19 May

Multicentre analysis of seizure outcome predicted by removal of high-frequency oscillations

In drug-resistant focal epilepsy, planning surgical resection can involve presurgical intracranial EEG (iEEG) recordings to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high-frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. In eight international epilepsy centres, iEEG was recorded during the presurgical evaluation of patients. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis, we applied a fully automated definition of HFO that was independent of the dataset. Using an observational cohort design that was blinded to postsurgical seizure outcome, we analysed HFO rates during non-rapid-eye-movement sleep. If channels had consistently high rates over multiple epochs, they were labelled the 'HFO area'. After HFO analysis, centres provided the electrode contacts located in the resected volume and the seizure outcome at follow-up ≥24 months after surgery. The study was registered at www.clinicaltrials.gov (NCT05332990). We received 160 iEEG datasets. In 146 datasets (91%), the HFO area could be defined. The patients with a completely resected HFO area were more likely to achieve seizure freedom in comparison to those without [odds ratio 2.61, 95% confidence interval (CI) 1.15-5.91, P = 0.02].

19 May

Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase 3 OCARINA II Study

Background and objectives: IV-administered ocrelizumab (OCR) is approved for the treatment of relapsing and primary progressive multiple sclerosis (RMS/PPMS). OCARINA II (NCT05232825) was designed to demonstrate noninferiority in drug exposure of OCR subcutaneous (SC) vs IV administration.

Methods: This phase 3, randomized, open-label study enrolled OCR-naive patients aged 18-65 years with RMS/PPMS and an Expanded Disability Status Scale score of 0-6.5. Patients received OCR IV 600 mg or OCR SC 920 mg (controlled period), followed by OCR SC 920 mg every 24 weeks, up to week 96 (OCR IV/SC and OCR SC/SC). The primary end point was OCR area under the serum concentration-time curve from day 1 to week 12 (AUC_W1‒12); other end points included clinical, biomarker, and pharmacodynamic outcomes and safety data.

Results: Baseline demographics were balanced across OCR IV/SC and OCR SC/SC arms (N = 118/118, 40.0 ± 11.9/39.9 ± 11.4 years, 59.3%/65.3% female, 89.0%/89.0% with RMS). The study demonstrated noninferiority of OCR SC 920 mg to OCR IV 600 mg for the primary end point AUC_W1-12 and also over the dosing interval for AUC_W1‒24 (geometric mean ratios [90% CI] 1.29 [1.23-1.35] and 1.27 [1.21-1.34], respectively). At week 48, 111 of 118 (OCR IV/SC) and 114 of 118 (OCR SC/SC) had received OCR SC.

12 May

Epilepsia Open® Prize 2025 Clinical Science

Congratulations!

5 May

A Systematic Review of Current Terminology for Conditions Preceding Degenerative Cervical Myelopathy: Evidence Synthesis to Inform an AO Spine Expert Opinion Statement

Study DesignSystematic review.ObjectivesThe pre-symptomatic state of Degenerative Cervical Myelopathy (DCM), wherein degenerative changes and spinal cord compression are seen without clinical findings, is poorly understood and inconsistently categorised. Clear identification may elucidate the temporality of DCM development. Therefore, a systematic assessment was undertaken of current terminology for pre-DCM states, with the objective of standardising definitions and informing an AO Spine expert position statement.MethodsMedline and Embase were searched for all studies on asymptomatic spinal compression or clinical findings preceding DCM, returning 3585 studies. After screening, 96 studies were included in the final analysis. The terminology used for pre-DCM states and their definitions were extracted, along with their frequencies or speciality/country of author in the literature.ResultsMultiple terms were used to represent pre-DCM stages, including "asymptomatic" (86 studies), "non-myelopathic" (26 studies), "without myelopathy" (15 studies), "pre-symptomatic" (9 studies) and "sub-clinical" (7 studies). "asymptomatic" was associated with the greatest inconsistency. Some defined this as patients with radiological signs of spinal degeneration with/without spinal cord compression but no clinical signs of myelopathy, whereas others used the term synonymously with healthy controls.

5 May

Search for Mutations Connected With Non-Response to Anti-EGFR Therapy in mCRC in the Morphologically Defined Regions of Primary Tumours

Background: Emerging evidence suggests that tumour morphological heterogeneity may influence mutational profiles relevant to therapy response. In this pilot study, we aimed to assess whether mutations identified within specific morphological patterns or at the invasion front correlate with shorter time to progression after anti-EGFR therapy, as compared to whole-tissue analysis.

Methods: We investigated genetic mutations in 142 samples from primary tumours of 39 KRAS wild-type metastatic colorectal cancer (CRC) patients receiving anti-EGFR therapy. Deep next-generation sequencing was performed on whole-tumour sections and six morphology-defined tumour regions.

Results: Mutations in genes linked to anti-EGFR therapy response (KRAS, BRAF, NRAS, PTEN and PI3KCA) were found uniquely in the non-responder group, with substantial variability across morphological sub-regions. BRAF mutations were aligned with serrated and mucinous morphologies, while KRAS mutations (p.Lys147Glu and p.Ala146Thr) were associated with mucinous and desmoplastic morphologies. In all cases, the cumulative mutational profile from sub-regions provided more details than that of the whole-tumour profile.

24 Apr

Non-invasive therapeutic drug monitoring: LC-MS validation for lamotrigine quantification in dried blood spot and oral fluid/saliva

Epilepsy, affecting over 50 million people globally, presents a significant neurological challenge. Effective prevention of epileptic seizures relies on proper administration and monitoring of Anti-Seizure Medication (ASMs). Therapeutic Drug Monitoring (TDM) ensures optimal dosage adjustment, minimizing adverse effects and potential drug interactions. While traditional venous blood collection for TDM may be stressful, emerging alternative sampling methods, particularly Dried Blood Spot (DBS) or oral fluid offer less invasive way of sampling. This study aimed to develop and validate an analytical method for the determination of lamotrigine in such alternative samples. The sample, either DBS or oral fluid, was subjected to extraction, evaporation, and reconstitution in 15 % acetonitrile containing 0.1 % formic acid. A Kinetex C18 Polar column was used for liquid chromatographic separation and MS in ESI+ mode was used for detection and quantitation of lamotrigine using an isotopically labelled internal standard according to EMA guidelines. The calibration range of the developed method enables the determination of lamotrigine in the concentration range of 1-30 μg/mL in DBS and 0.5-20 μg/mL in oral fluid. Oral fluid and DBS samples from patients treated with lamotrigine analysed by the developed method were compared to plasma concentrations measured by the hospital's accredited laboratory.

24 Apr

Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice

Neuropathic pain after spinal cord injury lacks any effective treatments, often leading to chronic pain. This study tested whether the daily administration of fully characterized polyphenolic extracts from grape stalks and coffee could prevent both reflexive and non-reflexive chronic neuropathic pain in spinal cord-injured mice by modulating the neuroimmune axis. Female CD1 mice underwent mild spinal cord contusion and received intraperitoneal extracts in weeks one, three, and six post-surgery. Reflexive pain responses were assessed weekly for up to 10 weeks, and non-reflexive pain was evaluated at the study's end. Neuroimmune crosstalk was investigated, focusing on glial activation and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 in supraspinal pain-related areas, including the periaqueductal gray, rostral ventromedial medulla, anterior cingulate cortex, and amygdala. Repeated treatments prevented mechanical allodynia and thermal hyperalgesia, and also modulated non-reflexive pain. Moreover, they reduced supraspinal gliosis and regulated CCL2/CCR2 and CX3CL1/CX3CR1 signaling.

24 Apr

FGFR2 residence in primary cilia is necessary for epithelial cell signaling

Primary cilium projects from cells to provide a communication platform with neighboring cells and the surrounding environment. This is ensured by the selective entry of membrane receptors and signaling molecules, producing fine-tuned and effective responses to the extracellular cues.

In this study, we focused on one family of signaling molecules, the fibroblast growth factor receptors (FGFRs), their residence within cilia, and its role in FGFR signaling. We show that FGFR1 and FGFR2, but not FGFR3 and FGFR4, localize to primary cilia of the developing mouse tissues and in vitro cells. For FGFR2, we demonstrate that the ciliary residence is necessary for its signaling and expression of target morphogenic genes. We also show that the pathogenic FGFR2 variants have minimal cilium presence, which can be rescued for the p.P253R variant associated with the Apert syndrome by using the RLY-4008 kinase inhibitor.

Finally, we determine the molecular regulators of FGFR2 trafficking to cilia, including IFT144, BBS1, and the conserved T429V430 motif within FGFR2.

24 Apr

Dietary inflammatory index during pregnancy and its relationship with gyrification and IQ in young adult offspring

Maternal diet during pregnancy has been associated with brain development and cognitive function in offspring, but the mechanisms mediating these relationships remain poorly understood. We conducted a longitudinal neuroimaging follow-up of a prenatal birth cohort and used Food Frequency Questionnaires completed by the mother in mid-pregnancy to calculate prenatal Dietary Inflammatory Index (DII) and tested its relationship with brain gyrification, an index of early brain development, and IQ in young adults (n = 179, age 28-30). The longitudinal gyrification data were available for a subset of these individuals (n = 77, age 23-24). A higher maternal pro-inflammatory diet during pregnancy, as represented by higher DII, was associated with worse verbal IQ but not performance IQ in young adulthood. These findings were independent of sex and remained significant after adjusting for maternal education, maternal stressful life events during pregnancy, maternal smoking during pregnancy, prenatal supplements (e.g. folic acid, iron, zinc, calcium, vitamins), and maternal age at birth. Moreover, higher DII was associated with altered cortical gyrification in the early as well as the late 20, particularly in men. Gyrification of the anterior middle and inferior frontal gyrus mediated the relationship between prenatal DII and verbal IQ in young adulthood. These findings support the use of cortical gyrification as a proxy marker of early brain development and suggest it may underlie the relationship between maternal diet during pregnancy and its long-term impact on cognitive skills in offspring.

24 Apr

Enhancing stroke response in school children: Efficacy of the HOBIT program - a cluster randomized trial

Objective: Stroke treatment is often hampered by delayed Emergency Medical Services activation. Public campaigns to improve the response to stroke symptoms are either costly or not working. We evaluate the effectiveness of a school-based HOBIT program in improving Emergency Medical Services activation. Methods: This cluster randomized trial was conducted from May to June 2023 at 13 schools in the South Moravian region of Czechia. Schools were randomized to the HOBIT intervention or control group with a 3:1 ratio. Both groups had knowledge assessments at baseline and follow-up. The primary outcome was the percentage change from the pretest to the follow-up test in the intervention group compared to the control group in 4 domains: 1) knowledge, 2) self-efficacy, 3) outcome expectations, 4) behavioral intentions. Results: The baseline knowledge was greater than 50 % in most metrics except for knowledge of the FAST test, which was only 16 %. The intervention effect was 16 % (95 % CI 12-21) for knowledge, 10 % (95 % CI 4-15) for self-efficacy,10 % (95 % CI 5-15) for outcome expectations, 8 % (95 % CI 2-11) for behavioral intentions. Conclusions: In school children, even those with high baseline, "HOBIT" intervention can improve determinants and behavioral intentions of Emergency Medical Services activation for suspected stroke.

Keywords: Children; Cluster randomized trial; Health education; Intervention; School; Stroke awareness.

11 Apr

Virtual Waiting Room: The New Narrative of Waiting in Oncology Care

This conceptual study introduces the "virtual waiting room," an innovative, interactive, web-based platform designed to enhance the waiting experience in oncology by providing personalized, educational, and supportive content. Central to our study is the implementation of the circular entry model, which allows for non-linear navigation of health information, empowering patients to access content based on their immediate needs and interests. This approach respects the individual journeys of patients, acknowledging the diverse pathways through which they seek understanding and manage their health. The virtual waiting room is designed not only to support patients but also to facilitate stronger communication and shared understanding between patients, caregivers, and families. By providing a shared digital space, the platform enables caregivers and family members to access the same information and resources, thereby promoting transparency and collective knowledge. This shared access is crucial in managing the emotional complexities of oncology care, where effective communication can significantly impact treatment outcomes and patient well-being. Furthermore, the study explores how the circular entry model within the virtual waiting room can enhance patient autonomy and engagement by offering customized interactions based on user feedback and preferences. This personalized approach aims to reduce anxiety, improve health literacy, and prepare patients more effectively for clinical interactions.

11 Apr

Noninvasive Temporal Interference Stimulation of the Subthalamic Nucleus in Parkinson's Disease Reduces Beta Activity

Background: Temporal interference stimulation (TIS) is a novel noninvasive electrical stimulation technique to focally modulate deep brain regions; a minimum of two high-frequency signals (f₁ and f₂ > 1 kHz) interfere to create an envelope-modulated signal at a deep brain target with the frequency of modulation equal to the difference frequency: Δf = |f₂ - f₁|.

Objective: The goals of this study were to verify the capability of TIS to modulate the subthalamic nucleus (STN) with Δf and to compare the effect of TIS and conventional deep brain stimulation (DBS) on the STN beta oscillations in patients with Parkinson's disease (PD).

Methods: DBS leads remained externalized after implantation, allowing local field potentials (LFPs) recordings in eight patients with PD. TIS was performed initially by two pairs (f₁ = 9.00 kHz; f₂ = 9.13 kHz, 4 mA peak-peak per pair maximum) of scalp electrodes placed in temporoparietal regions to focus the envelope signal maximum (Δf = 130 Hz) at the motor part of the STN target.

Results: The comparison between the baseline LFPs and recordings after TIS and conventional DBS sessions showed substantial suppression of high beta power peak after both types of stimulation in all patients.

24 Mar

Young Scientists from the MU Faculty of Medicine Receive Prestigious Award for Research in Medicine

24 Mar

Researching Alzheimer's disease through mini-brains. She was awarded the Werner von Siemens Prize for excellence in women's work

24 Mar

A Controlled Single-Centre Pilot Study to Evaluate the Effect of Prophylactic Surgery in Asymptomatic Degenerative Cervical Cord Compression

Study DesignSingle-centre controlled pilot study.ObjectivesTo evaluate the effect of prophylactic surgery and to review the biases of a therapeutic trial in asymptomatic degenerative cervical cord compression (ADCC) patients.MethodsPatients with ADCC and at least 1 predictor of progression to symptomatic degenerative cervical cord myelopathy (DCM) were offered either prophylactic surgery or standard structured rehabilitation. Recruited patients were clinically followed to detect the development of symptomatic DCM.ResultsForty-one patients treated surgically and 68 patients treated non-surgically completed the minimum 36 months' follow-up; 3 recruited patients were lost from evaluation. The surgical group had a higher Neck Disability Index score and more severe MRI compression. A matched subgroup of 41 non-surgical patients was created to reduce potential bias. During the follow-up period we observed progression to symptomatic DCM in 1 surgical case (2.4%) compared to 9 patients in the non-surgical group (13.2%, P = 0.054) and 7 cases in the matched non-surgical group (17.1%, P = 0.029). We observed non-serious early postoperative complications in 4 patients, which resolved spontaneously or after surgical revision. In 9 patients with progression to DCM, the myelopathy was mild with mJOA scale 15-17. One patient in the non-surgical group and 1 patient in the surgical group who progressed to DCM underwent surgery with a good outcome.ConclusionsProphylactic surgery led to a significant decrease in proportion of ADCC patients with progression to DCM.

24 Mar

Altered Patterns of Dynamic Functional Connectivity Underpin Reduced Expressions of Social-Emotional Reciprocity in Autistic Adults

To identify the neurocognitive mechanisms underpinning the social difficulties that characterize autism, we performed functional magnetic resonance imaging on pairs of autistic and non-autistic adults simultaneously whilst they interacted with one another on the iterated Ultimatum Game (iUG)-an interactive task that emulates the reciprocal characteristic of naturalistic interpersonal exchanges. Two age-matched sets of male-male dyads were investigated: 16 comprised an autistic Responder and a non-autistic Proposer, and 19 comprised non-autistic pairs of Responder and Proposer. Players' round-by-round behavior on the iUG was modeled as reciprocal choices, and dynamic functional connectivity (dFC) was measured to identify the neural mechanisms underpinning reciprocal behaviors. Behavioral expressions of reciprocity were significantly reduced in autistic compared with non-autistic Responders, yet no such differences were observed between the non-autistic Proposers in either set of dyads. Furthermore, we identified latent dFC states with temporal properties associated with reciprocity. Autistic interactants spent less time in brain states characterized by dynamic inter-network integration and segregation among the Default Mode Network and cognitive control networks, suggesting that their reduced expressions of social-emotional reciprocity reflect less efficient reconfigurations among brain networks supporting flexible cognition and behavior.

24 Feb

Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia

Dystonia is a rare-disease trait for which large-scale genomic investigations are still underrepresented. Genetic heterogeneity among patients with unexplained dystonia warrants interrogation of entire genome sequences, but this has not yet been systematically evaluated. To significantly enhance our understanding of the genetic contribution to dystonia, we (re)analyzed 2,874 whole-exome sequencing (WES), 564 whole-genome sequencing (WGS), as well as 80 fibroblast-derived proteomics datasets, representing the output of high-throughput analyses in 1,990 patients and 973 unaffected relatives from 1,877 families. Recruitment and precision-phenotyping procedures were driven by long-term collaborations of international experts with access to overlooked populations. By exploring WES data, we found that continuous scaling of sample sizes resulted in steady gains in the number of associated disease genes without plateauing. On average, every second diagnosis involved a gene not previously implicated in our cohort. Second-line WGS focused on a subcohort of undiagnosed individuals with high likelihood of having monogenic forms of dystonia, comprising large proportions of patients with early onset (81.3%), generalized symptom distribution (50.8%) and/or coexisting features (68.9%). We undertook extensive searches for variants in nuclear and mitochondrial genomes to uncover 38 (ultra)rare diagnostic-grade findings in 37 of 305 index patients (12.1%), many of which had remained undetected due to methodological inferiority of WES or pipeline limitations.

24 Feb

A new experimental model for studying peripheral nerve regeneration in dual innervated facial reanimation

Background: Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation. Although dual innervation approaches using two neurotizers have shown promise, there is a lack of evidence-based comparison in the literature. Furthermore, no animal model of dual reinnervation has yet been published. This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats.

Methods: Fifteen Wistar rats were divided into four experimental groups and one control group. The sural nerve was exposed and used as a cross-face nerve graft (CFNG), which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead. The CFNG, the masseteric nerve (MN), and the recipient nerve were coapted in one or two stages. The length and width of the utilized structures were measured under an operating microscope. Return of whisker motion was visually confirmed.

Results: Nine out of the eleven rats that underwent surgery survived the procedure. Whisker motion was observed in all experimental animals, indicating successful reinnervation. The mean duration of the surgical procedures did not differ significantly between the experimental groups, ensuring similar conditions for all groups.

18 Feb

Mapping conservative Fokker–Planck entropy in neural systems

Mapping the flow of information through the networks of the brain remains one of the most important challenges in computational neuroscience. In certain cases, this flow can be approximated by considering just two contributing factors—a predictable drift and a randomized diffusion. We show here that the uncertainty associated with such a drift-diffusion process can be calculated in terms of the entropy associated with the Fokker–Planck equation. This entropic evolution comprises two components: an irreversible entropic spread that always increases over time and a reversible entropic current that can increase or decrease locally within the system. We apply this dynamic entropy decomposition to two-photon imaging data collected in the murine visual cortex.

Our analysis reveals maps of conserved entropic flow emanating from lateral medial, anterolateral, and rostrolateral regions toward the primary visual cortex (V1).

These results highlight the role of V1 as an entropic sink, facilitating the redistribution of information throughout the visual cortex. These findings offer new insights into the hierarchical organization of cortical processing and provide a framework for exploring information dynamics in complex dynamical systems.

14 Feb

MicroRNA Analysis in Meningiomas with Different Degrees of Tissue Stiffness: A Potential Tool for Effective Preoperative Planning

Background and objectives: Meningioma, the most common primary intracranial tumor, presents challenges in surgical treatment because of varying tissue stiffness. This study explores the molecular background of meningioma stiffness, a critical factor in surgical planning and prognosis, focusing on the utility of microRNAs (miRNAs) as diagnostic biomarkers of tissue stiffness.

Methods: Patients with meningiomas treated surgically at the University Hospital Brno were included in this study. Total RNA, isolated from tumor tissue samples, underwent quality control and small RNA sequencing to analyze miRNA expression. Differentially expressed miRNAs were identified, and their association with tumor stiffness was assessed.

Results: This study identified specific miRNAs differentially expressed in meningiomas with different stiffness levels. Key miRNAs, such as miR-31-5p and miR-34b-5p, showed significant upregulation in stiffer meningiomas. These findings were validated using reverse transcription-quantitative polymerase chain reaction, revealing a potential link between miRNA expression and tumor consistency. The expression of miR-31-5p was most notably associated with the stiffness of the tumor tissue (sensitivity = 71% and specificity = 83%).

14 Feb

Maternal depression during the perinatal period and its relationship with emotion regulation in young adulthood: An fMRI study in a prenatal birth cohort

Background: Maternal perinatal mental health is essential for optimal brain development and mental health of the offspring. We evaluated whether maternal depression during the perinatal period and early life of the offspring might be selectively associated with altered brain function during emotion regulation and whether those may further correlate with physiological responses and the typical use of emotion regulation strategies.

Methods: Participants included 163 young adults (49% female, 28-30 years) from the ELSPAC prenatal birth cohort who took part in its neuroimaging follow-up and had complete mental health data from the perinatal period and early life. Maternal depressive symptoms were measured mid-pregnancy, 2 weeks, 6 months, and 18 months after birth. Regulation of negative affect was studied using functional magnetic resonance imaging, concurrent skin conductance response (SCR) and heart rate variability (HRV), and assessment of typical emotion regulation strategy.

Results: Maternal depression 2 weeks after birth interacted with sex and showed a relationship with greater brain response during emotion regulation in a right frontal cluster in women. Moreover, this brain response mediated the relationship between greater maternal depression 2 weeks after birth and greater suppression of emotions in young adult women (ab = 0.11, SE = 0.05, 95% CI [0.016; 0.226]).

4 Feb

Mitochondrial DNA variants and their impact on epigenetic and biological aging in young adulthood

The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood.

A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20. A subset of these participants (n = 69) also had epigenetic data to estimate epigenetic aging in the early 20s using Horvath's epigenetic clock.

The novel FI score was calculated based on 7 potentially pathogenic mtDNA variants. Greater FI score of mtDNA variants was associated with older epigenetic age in the early 20s and older biological age in the late 20s. These medium to large effects were independent of sex, current BMI, cigarette smoking, cannabis, and alcohol use. These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood.

4 Feb

Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation

Patient-derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment. We compared seven biomaterials, which included both published and custom-designed materials. The highest level of bone marrow niche was achieved with extracellular matrix gels and custom collagen fiber, both of which allowed for a simple non-surgical implantation. The biomaterial selection did not influence the following AML infiltration. Regarding xenotransplantation, standard intravenous administration produced the most robust engraftment, even for two out of four otherwise non-engrafting AML samples. In contrast, direct intra-scaffold xenotransplantation did not offer any advantage. In summary, we demonstrate that the combination of an injectable biomaterial for scaffold creation plus an intravenous route for AML xenotransplantation provide the most convenient and robust approach to produce AML PDX using a humanized niche.

Keywords: AML; T‐cell; collagen; mouse model; ossicles; patient‐derived xenografts.

4 Feb

The role of the somatosensory cortex in self-paced movement impairment in Parkinson's disease

Objective: The aim of this work was to study the differences at the whole-brain level between self-paced and cued movement processing in Parkinson's disease (PD).

Methods: High density electroencephalogram (HD-EEG) was recorded during the performance of self-paced movements (Bereitschaftspotential - BP) and visually cued movements (VMT) in PD patients (n = 38) and in a group of healthy controls (HC, n = 23). Oscillatory changes in the alpha, beta, and gamma frequencies were evaluated and correlated to the clinical scales- MDS-UPDRS and Freezing of Gait Questionnaire (FOGQ).

Results: The main difference in the alpha range was an activation in the basal ganglia area during VMT performance as compared to BP performance; this activation was present only in HC. The most important finding was observed in the high beta range: a higher activation of the right postcentral area during BP performance in PD subjects as compared to HC, correlating to the severity of FOG. Moreover, PD patients had lower gamma activation of the right frontal areas.

Conclusion: A simplification of motor circuits and a hyperactivation of the right somatosensory cortex were observed in PD subjects.

Significance: Future studies should be focused on this area to confirm or disprove its role in FOG.

4 Feb

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Methods: Vivacity-MG3 was a phase 3, randomised, double-blind, placebo-controlled, phase 3 study conducted at 81 outpatient centres with expertise in myasthenia gravis in 17 countries in Asia-Pacific, Europe, and North America. Adults (aged ≥18 years) with generalised myasthenia gravis inadequately controlled with standard-of-care therapy (MG-ADL score ≥6) were randomly assigned (1:1) to either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks. Randomisation was stratified by antibody status, day 1 MG-ADL total score, and region. The sponsor, investigators, clinical raters, and participants were masked to treatment assignment.

4 Feb

Breaking boundaries: role of the brain barriers in metastatic process

Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3-10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20-56%), breast (5-20%), and melanoma (7-16%) tumors, although they can arise from other cancer types less frequently. The metastatic cascade is a multistep process involving local invasion, intravasation into the bloodstream or lymphatic system, extravasation into normal tissue, and colonization of the distal site. After reaching the brain, circulating tumor cells (CTCs) breach the blood-brain barrier (BBB).The selective permeability of the BBB poses a significant challenge for therapeutic compounds, limiting the treatment efficacy of BMs. Understanding the mechanisms of tumor cell interactions with the BBB is crucial for the development of effective treatments. This review provides an in-depth analysis of the brain barriers, including the BBB, blood-spinal cord barrier, blood-meningeal barrier, blood-arachnoid barrier, and blood-cerebrospinal fluid barrier. It explores the molecular and cellular components of these barriers and their roles in brain metastasis, highlighting the importance of this knowledge for identifying druggable targets to prevent or limit BM formation.

Keywords: Blood-cerebrospinal fluid barrier; Blood-spinal cord barrier; Blood–brain barrier; Brain Metastasis; Cancer.

4 Feb

The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion

CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion. Intrathecal application of the CXCR4 inhibitor AMD3100 following CSNT reduced CXCL12 and CXCR4 protein levels in cervical DRG neurons, as well as the length of afferent axons regenerated distal to the ulnar nerve crush. Furthermore, treatment with the CXCR4 inhibitor decreased levels of activated Signal Transducer and Activator of Transcription 3 (STAT3), a critical transforming factor in the neuronal regeneration program. Administration of IL-6 increased CXCR4 levels, whereas the JAK2-dependent STAT3 phosphorylation inhibitor (AG490) conversely decreased CXCR4 levels. This indicates a link between the CXCL12/CXCR4 signaling axis and IL-6-induced activation of STAT3 in the sciatic nerve injury-induced pro-regenerative state of cervical DRG neurons.

29 Jan

Pre-implantation Scalp EEG Can Predict VNS Efficacy in Children

Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.

29 Jan

Revealing connectivity patterns of deep brain stimulation efficacy in Parkinson's disease

The aim of this work was to study the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on the subnetwork of subcortical and cortical motor regions and on the whole brain connectivity using the functional connectivity analysis in Parkinson's disease (PD). The high-density source space EEG was acquired and analyzed in 43 PD subjects in DBS on and DBS off stimulation states (off medication) during a cognitive-motor task. Increased high gamma band (50-100 Hz) connectivity within subcortical regions and between subcortical and cortical motor regions was significantly associated with the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III improvement after DBS. Whole brain neural correlates of cognitive performance were also detected in the high gamma (50-100 Hz) band. A whole brain multifrequency connectivity profile was found to classify optimal and suboptimal responders to DBS with a positive predictive value of 0.77, negative predictive value of 0.55, specificity of 0.73, and sensitivity of 0.60. Specific connectivity patterns related to PD, motor symptoms improvement after DBS, and therapy responsiveness predictive connectivity profiles were uncovered.

Keywords: Connectivity patterns; Deep brain stimulation; EEG; Functional connectivity; Parkinson’s disease; Subthalamic nucleus.

29 Jan

A roadmap toward promoting and improving brain health in Europe and closing the awareness and funding gap

Background and purpose: The global burden of neurological diseases exceeds 43.1%, imposing a significant burden on patients, caregivers and society. This paper presents a roadmap to reduce this burden and improve brain health (BH) in Europe.

Methods: The roadmap is based on the European Academy of Neurology's (EAN) five-pillar BH strategy: advancing a global BH approach (P1), supporting policymaking (P2), fostering research (P3), promoting education (P4), and raising awareness of prevention and treatment (P5). It reviews current efforts, collaborations and future directions aligned with the WHO Intersectoral Global Action Plan (iGAP) for Neurological Disorders and suggests future initiatives and call for action.

Results: P1: Support WHO-iGAP through defined action points, international collaborations, in particular, the WHO BH Unit, and the EAN Brain Health Mission. P2: Collaborate with 48 national neurological societies to promote National Brain Plans (NBPs), addressing local needs, and improving access to care. P3: Advocate for more research funding; identify determinants of BH; develop preventive measures. P4: Provide educational opportunities for neurologists, public education programs, and advocacy training, including tools to educate the public. P5: Spearhead global awareness campaigns, organize public educational activities, and train BH advocates to contribute toward sustainable and long-term public health campaigns and policy engagement.

29 Jan

Exploring medical error taxonomies and human factors in simulation-based healthcare education

This study aims to provide an updated overview of medical error taxonomies by building on a robust review conducted in 2011. It seeks to identify the key characteristics of the most suitable taxonomy for use in high-fidelity simulation-based postgraduate courses in Critical Care. While many taxonomies are available, none seem to be explicitly designed for the unique context of healthcare simulation-based education, in which errors are regarded as essential learning opportunities. Rather than creating a new classification system, this study proposes integrating existing taxonomies to enhance their applicability in simulation training. Through data from surveys of participants and tutors in postgraduate simulation-based courses, this study provides an exploratory analysis of whether a generic or domain-specific taxonomy is more suitable for healthcare education. While a generic classification may cover a broad spectrum of errors, a domain-specific approach could be more relatable and practical for healthcare professionals in a given domain, potentially improving error-reporting rates. Seven strong links were identified in the reviewed classification systems. These correlations allowed the authors to propose various simulation training strategies to address the errors identified in both the classification systems. This approach focuses on error management and fostering a safety culture, aiming to reduce communication-related errors by introducing the principles of Crisis Resource Management, effective communication methods, and overall teamwork improvement.

29 Jan

The Blood-Cerebrospinal Fluid Barrier as a Potential Entry Site for the SARS-CoV-2 Virus

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19). While SARS-CoV-2 primarily targets the lungs and airways, it can also infect other organs, including the central nervous system (CNS). The aim of this study was to investigate whether the choroid plexus could serve as a potential entry site for SARS-CoV-2 into the brain. Tissue samples from 24 deceased COVID-19-positive individuals were analyzed. Reverse transcription real-time PCR (RT-qPCR) was performed on selected brain regions, including the choroid plexus, to detect SARS-CoV-2 viral RNA. Additionally, immunofluorescence staining and confocal microscopy were used to detect and localize two characteristic proteins of SARS-CoV-2: the spike protein S1 and the nucleocapsid protein. RT-qPCR analysis confirmed the presence of SARS-CoV-2 viral RNA in the choroid plexus. Immunohistochemical staining revealed viral particles localized in the epithelial cells of the choroid plexus, with the spike protein S1 detected in the late endosomes. Our findings suggest that the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus serves as a route of entry for SARS-CoV-2 into the CNS. This study contributes to the understanding of the mechanisms underlying CNS involvement in COVID-19 and highlights the importance of further research to explore potential therapeutic strategies targeting this entry pathway.

Keywords: COVID‐19; SARS‐CoV‐2; blood‐cerebrospinal fluid barrier; choroid plexus; neuroinvasion.

29 Jan

Inflammatory changes in the choroid plexus following subarachnoid hemorrhage: the role of innate immune receptors and inflammatory molecules

Introduction: The choroid plexus is located in the cerebral ventricles. It consists of a stromal core and a single layer of cuboidal epithelial cells that forms the blood-cerebrospinal barrier. The main function of the choroid plexus is to produce cerebrospinal fluid. Subarachnoid hemorrhage due to aneurysm rupture is a devastating type of hemorrhagic stroke. Following subarachnoid hemorrhage, blood and the blood degradation products that disperse into the cerebrospinal fluid come in direct contact with choroid plexus epithelial cells. The aim of the current study was to elucidate the pathophysiological cascades responsible for the inflammatory reaction that is seen in the choroid plexus following subarachnoid hemorrhage.

Methods: Subarachnoid hemorrhage was induced in rats by injecting non-heparinized autologous blood to the cisterna magna. Increased intracranial pressure following subarachnoid hemorrhage was modeled by using artificial cerebrospinal fluid instead of blood. Subarachnoid hemorrhage and artificial cerebrospinal fluid animals were left to survive for 1, 3, 7 and 14 days. Immunohistochemical staining of TLR4, TLR9, FPR2, CCL2, TNFα, IL-1β, CCR2 and CX3CR1 was performed on the cryostat sections of choroid plexus tissue. The level of TLR4, TLR9, FPR2, CCL2, TNFα, IL-1β was detected by measuring immunofluorescence intensity in randomly selected epithelial cells.

10 Dec 2024

Diagnostic efficacy and clinical utility of whole-exome sequencing in Czech pediatric patients with rare and undiagnosed diseases

In the last decade, undiagnosed disease programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases. In our single-center study, we have launched a pilot program for pediatric patients with undiagnosed diseases in the second-largest university hospital in the Czech Republic. This study was prospectively conducted at the Department of Pediatrics at University Hospital Brno between 2020 and 2023. A total of 58 Czech patients with undiagnosed diseases were enrolled in the study. All children underwent singleton WES with targeted phenotype-driven analysis. We identified 28 variants, including 11 pathogenic, 13 likely pathogenic, and 4 VUS according to ACMG guidelines, as diagnostic of genetic diseases in 25 patients, resulting in an overall diagnostic yield of 43%. Eleven variants were novel and had not been previously reported in any public database. The overall clinical utility (actionability) enabling at least one type of change in the medical care of the patient was 76%, whereas the average number of clinical implications to individual patient care was two.

10 Dec 2024

Early Changes in the Locus Coeruleus in Mild Cognitive Impairment with Lewy Bodies

Background: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking.

Objectives: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts.

Methods: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes.

Results: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021).

10 Dec 2024

Metrics for evaluation of automatic epileptogenic zone localization in intracranial electrophysiology

Introduction: Precise localization of the epileptogenic zone is critical for successful epilepsy surgery. However, imbalanced datasets in terms of epileptic vs. normal electrode contacts and a lack of standardized evaluation guidelines hinder the consistent evaluation of automatic machine learning localization models.

Methods: This study addresses these challenges by analyzing class imbalance in clinical datasets and evaluating common assessment metrics. Data from 139 drug-resistant epilepsy patients across two Institutions were analyzed. Metric behaviors were examined using clinical and simulated data.

Results: Complementary use of Area Under the Receiver Operating Characteristic (AUROC) and Area Under the Precision-Recall Curve (AUPRC) provides an optimal evaluation approach. This must be paired with an analysis of class imbalance and its impact due to significant variations found in clinical datasets.

Conclusions: The proposed framework offers a comprehensive and reliable method for evaluating machine learning models in epileptogenic zone localization, improving their precision and clinical relevance.

13 Nov 2024

Masaryk University strengthens its position in neuroscience research with new partnership

13 Nov 2024

First in the Czech Republic – The Faculty of Medicine at Masaryk University launches a Master's degree program in Neuroscience.

5 Nov 2024

Pharmacotherapy for behavioural manifestations in frontotemporal dementia: An expert consensus from the European Reference Network for Rare Neurological Diseases (ERN-RND)

Background and purpose: Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by pervasive personality and behavioural disturbances with severe impact on patients and caregivers. In current clinical practice, treatment is based on nonpharmacological and pharmacological approaches. Unfortunately, trial-based evidence supporting symptomatic pharmacological treatment for the behavioural disturbances in FTD is scarce despite the significant burden this poses on the patients and caregivers.

Method: The study examined drug management decisions for several behavioural disturbances in patients with FTD by 21 experts across European expert centres affiliated with the European Reference Network for Rare Neurological Diseases (ERN-RND).

Results: The study revealed the highest consensus on drug treatments for physical and verbal aggression, impulsivity and obsessive delusions. Antipsychotics (primarily quetiapine) were recommended for behaviours posing safety risks to both patients and caregivers (aggression, self-injury and self-harm) and nightly unrest.

5 Nov 2024

Changes in Cx43 and AQP4 Proteins, and the Capture of 3 kDa Dextran in Subpial Astrocytes of the Rat Medial Prefrontal Cortex after Both Sham Surgery and Sciatic Nerve Injury

A subpopulation of astrocytes on the brain's surface, known as subpial astrocytes, constitutes the "glia limitans superficialis" (GLS), which is an interface between the brain parenchyma and the cerebrospinal fluid (CSF) in the subpial space. Changes in connexin-43 (Cx43) and aquaporin-4 (AQP4) proteins in subpial astrocytes were examined in the medial prefrontal cortex at postoperative day 1, 3, 7, 14, and 21 after sham operation and sciatic nerve compression (SNC). In addition, we tested the altered uptake of TRITC-conjugated 3 kDa dextran by reactive subpial astrocytes. Cellular immunofluorescence (IF) detection and image analysis were used to examine changes in Cx43 and AQP4 protein levels, as well as TRITC-conjugated 3 kDa dextran, in subpial astrocytes. The intensity of Cx43-IF was significantly increased, but AQP4-IF decreased in subpial astrocytes of sham- and SNC-operated rats during all survival periods compared to naïve controls. Similarly, the uptake of 3 kDa dextran in the GLS was reduced following both sham and SNC operations. The results suggest that both sciatic nerve injury and peripheral tissue injury alone can induce changes in subpial astrocytes related to the spread of their reactivity across the cortical surface mediated by increased amounts of gap junctions.

5 Nov 2024

Using Polycaprolactone Nanofibers for the Proof-of-Concept Construction of the Alveolar-Capillary Interface

The alveolar-capillary interface is the key functional element of gas exchange in the human lung, and disruptions to this interface can lead to significant medical complications. However, it is currently challenging to adequately model this interface in vitro, as it requires not only the co-culture of human alveolar epithelial and endothelial cells but mainly the preparation of a biocompatible scaffold that mimics the basement membrane. This scaffold should support cell seeding from both sides, and maintain optimal cell adhesion, growth, and differentiation conditions. Our study investigates the use of polycaprolactone (PCL) nanofibers as a versatile substrate for such cell cultures, aiming to model the alveolar-capillary interface more accurately. We optimized nanofiber production parameters, utilized polyamide mesh UHELON as a mechanical support for scaffold handling, and created 3D-printed inserts for specialized co-cultures. Our findings confirm that PCL nanofibrous scaffolds are manageable and support the co-culture of diverse cell types, effectively enabling cell attachment, proliferation, and differentiation. Our research establishes a proof-of-concept model for the alveolar-capillary interface, offering significant potential for enhancing cell-based testing and advancing tissue-engineering applications that require specific nanofibrous matrices.

31 Oct 2024

Dataset of DNA methylation profiles of 189 pediatric central nervous system, soft tissue, and bone tumors

Alterations in DNA methylation profiles belong to important mechanisms in cancer development, and their assessment can be utilized for rapid and precise diagnostics. Therefore, establishing datasets of methylation profiles can improve and deepen our understanding of the role of epigenetic changes in cancer development as well as improve our diagnostic capabilities. In this dataset, we generated NGS data for 189 samples of pediatric CNS, soft tissue, and bone tumors. The sequencing libraries were prepared using methyl capture bisulfite sequencing, an effective compromise between whole-genome bisulfite sequencing and array-based methods with a more limited scope of target regions. The larger part of the cohort was processed with the Agilent SureSelectXT Human Methyl-Seq kit (149 samples) and the rest with the Illumina TruSeq Methyl Capture EPIC Library Prep Kit (40 samples). The data presented in this article may help other researchers further elucidate the importance of methylation in diagnosing pediatric CNS tumors, soft tissue, and bone tumors.

Keywords: Epigenetics; Pediatric oncology; Precision medicine; Targeted methylation sequencing.

31 Oct 2024

Development of a stereo-EEG based seizure matching system for clinical decision making in epilepsy surgery

Objective.The proportion of patients becoming seizure-free after epilepsy surgery has stagnated. Large multi-center stereo-electroencephalography (SEEG) datasets can allow comparing new patients to past similar cases and making clinical decisions with the knowledge of how cases were treated in the past. However, the complexity of these evaluations makes the manual search for similar patients impractical. We aim to develop an automated system that electrographically and anatomically matches seizures to those in a database. Additionally, since features that define seizure similarity are unknown, we evaluate the agreement and features among experts in classifying similarity.Approach.We utilized 320 SEEG seizures from 95 consecutive patients who underwent epilepsy surgery. Eight international experts evaluated seizure-pair similarity using a four-level similarity score. As our primary outcome, we developed and validated an automated seizure matching system by employing patient data marked by independent experts. Secondary outcomes included the inter-rater agreement (IRA) and features for classifying seizure similarity.Main results.The seizure matching system achieved a median area-under-the-curve of 0.76 (interquartile range, 0.1), indicating its feasibility. Six distinct seizure similarity features were identified and proved effective: onset region, onset pattern, propagation region, duration, extent of spread, and propagation speed. Among these features, the onset region showed the strongest correlation with expert scores (Spearman's rho = 0.75,p< 0.001).

1 Oct 2024

Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry

Background: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS).

Objectives: Provide experience with cladribine therapy in a real-world setting.

Methods: This is a registry-based retrospective observational cohort study. First, using data from the Czech nationwide registry ReMuS, we analysed patients who initiated cladribine from September 1, 2018 to December 31, 2021. Second, we analysed a subgroup of patients who initiated cladribine between September 1, 2018 to June 30, 2020, thus possessing a follow-up period of at least 2 years. We evaluated demographic and MS characteristics including disease-modifying therapies (DMTs) before and after cladribine administration, relapses, Expanded Disability Status Scale (EDSS), and adherence.

Results: In total, 617 patients (335 with follow-up of at least 2 years) started cladribine therapy in the study period (mean age 37.0, mean disease duration 8.4 years, 74.1% females). In most cases, cladribine was administered as a second-line drug, a total of 80.7% had been escalated from a platform DMT. During 2 years before cladribine initiation, the average annualised relapse rate (ARR) was .67.

1 Oct 2024

Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly

Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues. In mouse brain, Nav3 is expressed throughout the nervous system, with more prominent signatures in postmitotic, excitatory, inhibiting, and sensory neurons. When overexpressed in HEK293T and COS7 cells, pathogenic variants impaired NAV3 ability to stabilize microtubules. Further, knocking-down nav3 in zebrafish led to severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, which were rescued with co-injection of WT NAV3 mRNA and not by transcripts encoding the pathogenic variants. Our findings establish the role of NAV3 in neurodevelopmental disorders, and reveal its involvement in neuronal morphogenesis, and neuromuscular responses.

1 Oct 2024

Genetic Landscape of Amyotrophic Lateral Sclerosis in Czech Patients

Background: Genetic factors are involved in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS) and constitute a link to its association with frontotemporal dementia (FTD). Gene-targeted therapies for some forms of ALS (C9orf72, SOD1) have recently gained momentum. Genetic architecture in Czech ALS patients has not been comprehensively assessed so far.

Objective: We aimed to deliver pilot data on the genetic landscape of ALS in our country.

Methods: A cohort of patients with ALS (n = 88), recruited from two Czech Neuromuscular Centers, was assessed for hexanucleotide repeat expansion (HRE) in C9orf72 and also for genetic variations in other 36 ALS-linked genes via next-generation sequencing (NGS). Nine patients (10.1%) had a familial ALS. Further, we analyzed two subgroups of sporadic patients - with concomitant FTD (n = 7) and with young-onset of the disease (n = 22).

Results: We detected the pathogenic HRE in C9orf72 in 12 patients (13.5%) and three other pathogenic variants in FUS, TARDBP and TBK1, each in one patient. Additional 7 novel and 9 rare known variants with uncertain causal significance have been detected in 15 patients. Three sporadic patients with FTD (42.9%) were harbouring a pathogenic variant (all HRE in C9orf72).

1 Oct 2024

A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single-cell suspension

The development of 3D organoids has provided a valuable tool for studying human tissue and organ development in vitro. Cerebral organoids, in particular, offer a unique platform for investigating neural diseases. However, current methods for generating cerebral organoids suffer from limitations such as labor-intensive protocols and high heterogeneity among organoids. To address these challenges, we present a microfluidic device designed to automate and streamline the formation and differentiation of cerebral organoids. The device utilizes microwells with two different shapes to promote the formation of a single aggregate per well and incorporates continuous medium flow for optimal nutrient exchange. In silico simulations supported the effectiveness of the microfluidic chip in replicating cellular microenvironments. Our results demonstrate that the microfluidic chip enables uniform growth of cerebral organoids, significantly reducing the hands-on time required for maintenance. Importantly, the performance of the microfluidic system is comparable to the standard 96-well plate format even when using half the amount of culture medium, and the resulting organoids exhibit substantially developed neuroepithelial buds and cortical structures. This study highlights the potential of custom-designed microfluidic technology in improving the efficiency of cerebral organoid culture.

1 Oct 2024

Virtual Waiting Room: The New Narrative of Waiting in Oncology Care

This conceptual study introduces the "virtual waiting room," an innovative, interactive, web-based platform designed to enhance the waiting experience in oncology by providing personalized, educational, and supportive content. Central to our study is the implementation of the circular entry model, which allows for non-linear navigation of health information, empowering patients to access content based on their immediate needs and interests. This approach respects the individual journeys of patients, acknowledging the diverse pathways through which they seek understanding and manage their health. The virtual waiting room is designed not only to support patients but also to facilitate stronger communication and shared understanding between patients, caregivers, and families. By providing a shared digital space, the platform enables caregivers and family members to access the same information and resources, thereby promoting transparency and collective knowledge. This shared access is crucial in managing the emotional complexities of oncology care, where effective communication can significantly impact treatment outcomes and patient well-being. Furthermore, the study explores how the circular entry model within the virtual waiting room can enhance patient autonomy and engagement by offering customized interactions based on user feedback and preferences.

13 Sep 2024

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Objective: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH.

Methods: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated.

6 Sep 2024

Assessment of lumbar paraspinal muscle morphology using mDixon Quant magnetic resonance imaging (MRI): a cross-sectional study in healthy subjects

Background: Lumbar paraspinal muscles (LPM) are a part of the deep spinal stabilisation system and play an important role in stabilising the lumbar spine and trunk. Inadequate function of these muscles is thought to be an essential aetiological factor in low back pain, and several neuromuscular diseases are characterised by dysfunction of LPM. The main aims of our study were to develop a methodology for LPM assessment using advanced magnetic resonance imaging (MRI) methods, including a manual segmentation process, to confirm the measurement reliability, to evaluate the LPM morphological parameters [fat fraction (FF), total muscle volume (TMV) and functional muscle volume (FMV)] in a healthy population, to study the influence of physiological factors on muscle morphology, and to build equations to predict LPM morphological parameters in a healthy population.

Methods: This prospective cross-sectional observational comparative single-centre study was conducted at the University Hospital in Brno, enrolling healthy volunteers from April 2021 to March 2023. MRI of the lumbar spine and LPM (erector spinae muscle and multifidus muscle) were performed using a 6-point Dixon gradient echo sequence. The segmentation of the LPM and the control muscle (psoas muscle) was done manually to obtain FF and TMV in a range from Th12/L1 to L5/S1.

6 Sep 2024

The moderating effect of perceived hope in the relationship between anxiety and posttraumatic growth during the Russian-Ukrainian war

Introduction: This study examines the relationships between perceived hope, posttraumatic growth, well-being, anxiety, and perceived threat of the Russian-Ukrainian War (RUW) in the Czech adult population. Drawing on the evidence of posttraumatic growth (PTG) amidst crisis, we hypothesized that perceived hope moderates the effects of perceived threat of war and anxiety on PTG.

Methods: Data were obtained from 1,000 Czech respondents via an online questionnaire ten months post-invasion. The form included measures of posttraumatic growth, perceived hope, well-being, anxiety and depression, and perceived threat of war.

Results: Our findings reveal that perceived hope acted as a moderator enhancing the positive effects of perceived threat and anxiety on PTG. However, perceived hope did not significantly moderate the direct effects of perceived threats and anxiety on well-being.

Discussion: This study highlights the significant role of hope amidst adversity and underscores its potential as a target for interventions aiming to foster PTG in populations who navigate traumatic experiences.

5 Sep 2024

Estimating the energy of dissipative neural systems

There is, at present, a lack of consensus regarding precisely what is meant by the term 'energy' across the sub-disciplines of neuroscience. Definitions range from deficits in the rate of glucose metabolism in consciousness research to regional changes in neuronal activity in cognitive neuroscience. In computational neuroscience virtually all models define the energy of neuronal regions as a quantity that is in a continual process of dissipation to its surroundings.

This, however, is at odds with the definition of energy used across all sub-disciplines of physics: a quantity that does not change as a dynamical system evolves in time. Here, we bridge this gap between the dissipative models used in computational neuroscience and the energy-conserving models of physics using a mathematical technique first proposed in the context of fluid dynamics.

We go on to derive an expression for the energy of the linear time-invariant (LTI) state space equation. We then use resting-state fMRI data obtained from the human connectome project to show that LTI energy is associated with glucose uptake metabolism. Our hope is that this work paves the way for an increased understanding of energy in the brain, from both a theoretical as well as an experimental perspective.

5 Sep 2024

The relationship between gadolinium enhancement and [18 F]fluorothymidine uptake in brain lesions with the use of hybrid PET/MRI

Background: To evaluate and compare the diagnostic power of [¹⁸F]FLT-PET with ceMRI in patients with brain tumours or other focal lesions.

Methods: 121 patients with suspected brain tumour or those after brain tumour surgery were enroled in this retrospective study (61 females, 60 males, mean age 37.3 years, range 1-80 years). All patients underwent [¹⁸F]FLT-PET/MRI with gadolinium contrast agent application. In 118 of these patients, a final diagnosis was made, verified by histopathology or by follow-up. Agreement between ceMRI and [¹⁸F]FLT-PET of the whole study group was established. Further, sensitivity and specificity of ceMRI and [¹⁸F]FLT-PET were calculated for differentiation of high-grade vs. low-grade tumours, high-grade vs. low-grade tumours together with non-tumour lesions and for differentiation of high-grade tumours from all other verified lesions.

Results: [¹⁸F]FLT-PET and ceMRI findings were concordant in 119 cases (98%). On closer analysis of a subset of 64 patients with verified gliomas, the sensitivity and specificity of both PET and ceMRI were identical (90% and 84%, respectively) for differentiating low-grade from high-grade tumours, if the contrast enhancement and [¹⁸F]FLT uptake were considered as hallmarks of high-grade tumour.

5 Sep 2024

Prognostic value of the 5-SENSE Score to predict focality of the seizure-onset zone as assessed by stereoelectroencephalography: a prospective international multicentre validation study

Introduction: Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions.

Methods and analysis: Non-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion.

5 Sep 2024

Interictal stereo-electroencephalography features below 45 Hz are sufficient for correct localization of the epileptogenic zone and postsurgical outcome prediction

Objective: Evidence suggests that the most promising results in interictal localization of the epileptogenic zone (EZ) are achieved by a combination of multiple stereo-electroencephalography (SEEG) biomarkers in machine learning models. These biomarkers usually include SEEG features calculated in standard frequency bands, but also high-frequency (HF) bands. Unfortunately, HF features require extra effort to record, store, and process. Here we investigate the added value of these HF features for EZ localization and postsurgical outcome prediction.

Methods: In 50 patients we analyzed 30 min of SEEG recorded during non-rapid eye movement sleep and tested a logistic regression model with three different sets of features. The first model used broadband features (1-500 Hz); the second model used low-frequency features up to 45 Hz; and the third model used HF features above 65 Hz. The EZ localization by each model was evaluated by various metrics including the area under the precision-recall curve (AUPRC) and the positive predictive value (PPV).

5 Sep 2024

Effectiveness of computed tomography perfusion imaging in stroke management

Objectives: Current guidelines do not support the use of computed tomography perfusion (CTP) in stroke, except when identifying the penumbra during an extended treatment window. Therefore, this study aimed to define the yield of CTP in diagnosing a stroke diagnosis beyond the imaging of the penumbra in the hyperacute phase (0-6 h) and an extended time window (6-24 h).

Materials and methods: All consecutive patients with acute onset of symptoms within a 24-h window underwent CTP imaging. The diagnostic value of CTP was calculated against the clinical and radiological diagnoses of stroke. A positive CTP result was determined by the presence of either a core or penumbra on the RAPID summary. Clinical diagnoses corresponded to discharge diagnoses of stroke. A radiological diagnosis was established if early ischemic changes [Alberta Stroke Program Early CT Score (ASPECTS) <10] were observed on the baseline CT scan, acute infarction was confirmed on follow-up imaging, or symptomatic occlusion was evident on baseline CTA.

Results: Between November 2018 and November 2019, 585 consecutive patients with an acute neurological deficit underwent multimodal CT imaging.

15 Jul 2024

Prenatal exposure to air pollution and maternal depression: Combined effects on brain aging and mental health in young adulthood

Introduction: Both maternal depression problems during pregnancy and prenatal exposure to air pollution have been associated with changes in the brain as well as worse mood and anxiety in the offspring in adulthood. However, it is not clear whether these effects are independent or whether and how they might interact and impact the brain age and mental health of the young adult offspring.

Methods: A total of 202 mother-child dyads from a prenatal birth cohort were assessed for maternal depression during pregnancy through self-report questionnaires administered in the early 90s, exposure to air pollutants (Sulfur dioxide [SO2], nitrogen oxides [NOx], and suspended particle matter [SPM]) during each trimester based on maternal address and air quality data, mental health of the young adult offspring (28-30 years of age; 52% men, all of European ancestry) using self-report questionnaires for depression (Beck Depression Inventory), mood dysregulation (Profile of Mood States), anxiety (State-Trait Anxiety Inventory), and psychotic symptoms (Schizotypal Personality Questionnaire), and brain age, estimated from structural magnetic resonance imaging (MRI) and previously published neuroanatomical age prediction model using cortical thickness maps.

15 Jul 2024

MicroRNA-mediated regulation of neurotransmitter receptors in epilepsy: A systematic review

Background: Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small non-coding RNAs known to play a crucial role in post-transcriptional regulation of gene expression.

Methods: The present review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, employing a comprehensive search strategy to identify and extract data from published research articles. Keywords suchas epilepsy, micro RNA (micro RNAs, miRNA, miRNAs, miR), neurotransmitters (specific names), and neurotransmitter receptors (specific names) were used to construct the query.

Results: A total of 724 articles were identified using the keywords epilepsy, microRNA along with select neurotransmitter and neurotransmitter receptor names. After exclusions, the final selection consisted of 17 studies, most of which centered on glutamate and gamma-aminobutyric acid (GABA) receptors. Singular studies also investigated miRNAs affecting cholinergic, purinergic, and glycine receptors.

15 Jul 2024

Cerebral air embolism: neurologic manifestations, prognosis, and outcome

Background: Cerebral air embolism (CAE) is an uncommon medical emergency with a potentially fatal course. We have retrospectively analyzed a set of patients treated with CAE at our comprehensive stroke center and a hyperbaric medicine center. An overview of the pathophysiology, causes, diagnosis, and treatment of CAE is provided.

Results: We retrospectively identified 11 patients with cerebral venous and arterial air emboli that highlight the diversity in etiologies, manifestations, and disease courses encountered clinically. Acute-onset stroke syndrome and a progressive impairment of consciousness were the two most common presentations in four patients each (36%). Two patients (18%) suffered from an acute-onset coma, and one (9%) was asymptomatic. Four patients (36%) were treated with hyperbaric oxygen therapy (HBTO), high-flow oxygen therapy without HBOT was started in two patients (18%), two patients (18%) were in critical care at the time of diagnosis and three (27%) received no additional treatment. CAE was fatal in five cases (46%), caused severe disability in two (18%), mild disability in three (27%), and a single patient had no lasting deficit (9%).

8 Jul 2024

Non-invasive stimulation for treating cognitive impairment in Alzheimer disease

Some device-based non-invasive brain stimulation methods have been recommended as probably effective for cognitive treatment in Alzheimer disease. New targets and novel transcranial electrical stimulation techniques enable physiology-inspired modulation of oscillatory activity and precise targeting of deep brain structures.

Various methods of non-invasive brain stimulation (NIBS) have been studied for the treatment of mild cognitive impairment (MCI) and dementia in people with Alzheimer disease (AD). Device-based NIBS techniques modulate brain function by inducing electric fields in the brain. Most studies have tested multiple sessions of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS); however, other emerging approaches have shown promising results, including transcranial alternating current stimulation (tACS) and temporal interference stimulation (TIS). Here, I summarize the various techniques and their individual benefits.

25 Jun 2024

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy

Background and purpose: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO).

Methods: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]).

Results: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points.

25 Jun 2024

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial

Background: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke.

Methods: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded.

25 Jun 2024

Migration of atrial catheter of ventriculo-cysto-atrial shunt into heart and pulmonary artery - case report and literature review

Ventriculoatrial shunts are the alternative treatments when it is impossible to use ventriculoperitoneal shunts. Limited indication for ventriculoatrial shunt is due to the possibility of very serious complications inherent with this procedure.

We present a case report of a young patient who suffered from disconnection of an atrial catheter from the valve after an accidental blow to his neck.

The atrial catheter was dislocated to the heart and pulmonary artery and it was extracted through the femoral vein in the groin area using an endovascular technique. The procedure went without complications.

A new atrial catheter was introduced under ultrasonic guidance during surgical revision.

Keywords: atrial catheter; hydrocephalus; rare complication; ventriculoatrial shunt.

25 Jun 2024

11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET)

Background: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of ¹¹C-methionine in optimizing radiotherapy for glioblastoma patients with REP.

Methods: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo ¹¹C-methionine positron emission tomography (PET/CT) examinations.

6 Jun 2024

Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson's Disease

Assessing imaging biomarker in the prodromal and early phases of Parkinson's disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT imaging with Ioflupane, more specific PET tracers to assess degeneration of the dopaminergic system are available. Furthermore, metabolic PET patterns can be used to anticipate a phenoconversion from prodromal PD to manifest PD. In this regard, it is worth mentioning that PET imaging of inflammation will gain significance.

Molecular imaging of neurotransmitters like serotonin, noradrenaline and acetylcholine shed more light on non-motor symptoms. Outside of the brain, molecular imaging of the heart and gut is used to measure PD-related degeneration of the autonomous nervous system.

Moreover, optical coherence tomography can noninvasively detect degeneration of retinal fibers as a potential biomarker in PD. In this review, we describe these state-of-the-art imaging modalities in early and prodromal PD and point out in how far these techniques can and will be used in the future to pave the way towards a biomarker-based staging of PD.

6 Jun 2024

Prenatal exposure to alcohol and its impact on reward processing and substance use in adulthood

Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less clear and any potential safe level of alcohol use during pregnancy is not known. We evaluated the effects of prenatal alcohol on reward-related behavior and substance use in young adulthood and the potential sex differences therein. Participants were members of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort who participated in its neuroimaging follow-up in young adulthood. A total of 191 participants (28-30 years; 51% men) had complete data on prenatal exposure to alcohol, current substance use, and fMRI data from young adulthood. Maternal alcohol drinking was assessed during mid-pregnancy and pre-conception. Brain response to reward anticipation and reward feedback was measured using the Monetary Incentive Delay task and substance use in young adulthood was assessed using a self-report questionnaire. We showed that even a moderate exposure to alcohol in mid-pregnancy but not pre-conception was associated with robust effects on brain response to reward feedback (six frontal, one parietal, one temporal, and one occipital cluster) and with greater cannabis use in both men and women 30 years later. Moreover, mid-pregnancy but not pre-conception exposure to alcohol was associated with greater cannabis use in young adulthood and these effects were independent of maternal education and maternal depression during pregnancy.

15 May 2024

Timing matters for accurate identification of the epileptogenic zone

Objective: Interictal biomarkers of the epileptogenic zone (EZ) and their use in machine learning models open promising avenues for improvement of epilepsy surgery evaluation. Currently, most studies restrict their analysis to short segments of intracranial EEG (iEEG).

Methods: We used 2381 hours of iEEG data from 25 patients to systematically select 5-minute segments across various interictal conditions. Then, we tested machine learning models for EZ localization using iEEG features calculated within these individual segments or across them and evaluated the performance by the area under the precision-recall curve (PRAUC).

Results: On average, models achieved a score of 0.421 (the result of the chance classifier was 0.062). However, the PRAUC varied significantly across the segments (0.323-0.493). Overall, NREM sleep achieved the highest scores, with the best results of 0.493 in N2. When using data from all segments, the model performed significantly better than single segments, except NREM sleep segments.

Conclusions: The model based on a short segment of iEEG recording can achieve similar results as a model based on prolonged recordings. The analyzed segment should, however, be carefully and systematically selected, preferably from NREM sleep.

24 Apr 2024

Inhibition of CD40L with Frexalimab in Multiple Sclerosis

Background: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis.

Methods: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment. The primary end point was the number of new gadolinium-enhancing T1-weighted lesions seen on magnetic resonance imaging at week 12 relative to week 8. Secondary end points included the number of new or enlarging T2-weighted lesions at week 12 relative to week 8, the total number of gadolinium-enhancing T1-weighted lesions at week 12, and safety. After 12 weeks, all the participants could receive open-label frexalimab.

Results: Of 166 participants screened, 129 were assigned to a trial group; 125 participants (97%) completed the 12-week double-blind period. The mean age of the participants was 36.6 years, 66% were women, and 30% had gadolinium-enhancing lesions at baseline.

17 Apr 2024

Striato-cortical functional connectivity changes in mild cognitive impairment with Lewy bodies

Background: Functional connectivity changes in clinically overt neurodegenerative diseases such as dementia with Lewy bodies have been described, but studies on connectivity changes in the pre-dementia phase are scarce.

Objectives: We concentrated on evaluating striato-cortical functional connectivity differences between patients with Mild Cognitive Impairment with Lewy bodies and healthy controls and on assessing the relation to cognition.

Methods: Altogether, we enrolled 77 participants (47 patients, of which 35 met all the inclusion criteria for the final analysis, and 30 age- and gender-matched healthy controls, of which 28 met all the inclusion criteria for the final analysis) to study the seed-based connectivity of the dorsal, middle, and ventral striatum. We assessed correlations between functional connectivity in the regions of between-group differences and neuropsychological scores of interest (visuospatial and executive domains z-scores).

Results: Subjects with Mild Cognitive Impairment with Lewy Bodies, as compared to healthy controls, showed increased connectivity from the dorsal part of the striatum particularly to the bilateral anterior part of the temporal cortex with an association with executive functions.

17 Apr 2024

Blind deconvolution decreases requirements on temporal resolution of DCE-MRI: Application to 2nd generation pharmacokinetic modeling

Purpose: Dynamic Contrast-Enhanced (DCE) MRI with 2nd generation pharmacokinetic models provides estimates of plasma flow and permeability surface-area product in contrast to the broadly used 1st generation models (e.g. the Tofts models). However, the use of 2nd generation models requires higher frequency with which the dynamic images are acquired (around 1.5 s per image). Blind deconvolution can decrease the demands on temporal resolution as shown previously for one of the 1st generation models. Here, the temporal-resolution requirements achievable for blind deconvolution with a 2nd generation model are studied.

Methods: The 2nd generation model is formulated as the distributed-capillary adiabatic-tissue-homogeneity (DCATH) model. Blind deconvolution is based on Parker's model of the arterial input function. The accuracy and precision of the estimated arterial input functions and the perfusion parameters is evaluated on synthetic and real clinical datasets with different levels of the temporal resolution.

Results: The estimated arterial input functions remained unchanged from their reference high-temporal-resolution estimates (obtained with the sampling interval around 1 s) when increasing the sampling interval up to about 5 s for synthetic data and up to 3.6-4.8 s for real data.

17 Apr 2024

Weak coupling of neurons enables very high-frequency and ultra-fast oscillations through the interplay of synchronized phase shifts

Recently, in the past decade, high-frequency oscillations (HFOs), very high-frequency oscillations (VHFOs), and ultra-fast oscillations (UFOs) were reported in epileptic patients with drug-resistant epilepsy. However, to this day, the physiological origin of these events has yet to be understood. Our study establishes a mathematical framework based on bifurcation theory for investigating the occurrence of VHFOs and UFOs in depth EEG signals of patients with focal epilepsy, focusing on the potential role of reduced connection strength between neurons in an epileptic focus. We demonstrate that synchronization of a weakly coupled network can generate very and ultra high-frequency signals detectable by nearby microelectrodes. In particular, we show that a bistability region enables the persistence of phase-shift synchronized clusters of neurons. This phenomenon is observed for different hippocampal neuron models, including Morris-Lecar, Destexhe-Paré, and an interneuron model. The mechanism seems to be robust for small coupling, and it also persists with random noise affecting the external current. Our findings suggest that weakened neuronal connections could contribute to the production of oscillations with frequencies above 1000 Hz, which could advance our understanding of epilepsy pathology and potentially improve treatment strategies.

17 Apr 2024

Short-term effects of transcranial direct current stimulation on motor speech in Parkinson's disease: a pilot study

Introduction: Hypokinetic dysarthria (HD) is a common motor speech symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated short-term effects of transcranial direct current stimulation (tDCS) on HD in PD using acoustic analysis of speech. Based on our previous studies we focused on stimulation of the right superior temporal gyrus (STG) - an auditory feedback area.

Methods: In 14 PD patients with HD, we applied anodal, cathodal and sham tDCS to the right STG using a cross-over design. A protocol consisting of speech tasks was performed prior to and immediately after each stimulation session. Linear mixed models were used for the evaluation of the effects of each stimulation condition on the relative change of acoustic parameters. We also performed a simulation of the mean electric field induced by tDCS.

Results: Linear mixed model showed a statistically significant effect of the stimulation condition on the relative change of median duration of silences longer than 50 ms (p = 0.015). The relative change after the anodal stimulation (mean = -5.9) was significantly lower as compared to the relative change after the sham stimulation (mean = 12.8), p = 0.014.

11 Apr 2024

Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study

Objective: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery.

Methods: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome.

Results: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios.

11 Apr 2024

Reply to: Questioning the cycad theory of Kii ALS-PDC causation

We read with great interest the Correspondence to our recent Review (Menšíková, K. et al. Endemic parkinsonism: clusters, biology and clinical features. Nat. Rev. Neurol. 19, 599–616 (2023)¹) by Kokubo and colleagues (Kokubo, Y., Morimoto, S. & Yoshida, M. Questioning the cycad theory of Kii ALS–PDC causation. Nat. Rev. Neurol. https://doi.org/10.1038/s41582-024-00936-0 (2024)²). We are aware that Kokubo — together with the late S. Kuzuhara — systematically studied amyotrophic lateral sclerosis–parkinsonism–dementia complex (ALS–PDC) on the Kii Peninsula for more than 30 years. They authored and co-authored numerous papers about this endemic disease, some of them with one of us (R.S.). We therefore considered the comments raised by Kokubo et al. carefully, and here we respond to the questions that they have raised.

Kokubo et al. state that the use of cycad seed in herbal and folk medicine, and as a tonic in children, is very rare. However, in the northeastern Kii (Hohara) focus of ALS–PDC, the seed of Cycas revoluta was prescribed throughout the 1980s by kitoshi (folk medicine practitioners) and dispensed by local pharmacies for the oral treatment of various ailments, including diarrhoea, dysmenorrhoea, gonorrhoea, tuberculosis and neuralgia, in accordance with published guidance³.

11 Apr 2024

Screening and differential diagnosis of delirium in neurointensive stroke patients

Diagnosing delirium in neurointensive care is difficult because symptoms of delirium, such as inappropriate speech, may be related to aphasia due to primary brain injury. Therefore, validated screening tools are needed. The aim of this study was to compare two Czech versions of already validated screening tools - the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) - in a cohort of acute stroke patients. We also aimed to assess the pitfalls of delirium detection in the context of non-convulsive status epilepticus (NCSE). We analysed 138 stroke patients admitted to the neurological intensive care unit (ICU) or stroke unit. According to expert judgement, which was used as the gold standard, 38 patients (27.54%) developed delirium. The sensitivity and specificity of the ICDSC were 91.60% and 95.33%, respectively, and the positive and negative predictive values were 76.76% and 98.54%, respectively. Similarly, the sensitivity and specificity of CAM-ICU were 75.63% and 96.74%, respectively, and the positive and negative predictive values were 79.65% and 95.93%, respectively. We did not detect an episode of NCSE mimicking delirium in any of our stroke patients who were judged to be delirious by expert assessment.

7 Mar 2024

EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies.

7 Mar 2024

Coupling between beta band and high frequency oscillations as a clinically useful biomarker for DBS

Beta hypersynchrony was recently introduced into clinical practice in Parkinson's disease (PD) to identify the best stimulation contacts and for adaptive deep brain stimulation (aDBS) sensing. However, many other oscillopathies accompany the disease, and beta power sensing may not be optimal for all patients. The aim of this work was to study the potential clinical usefulness of beta power phase-amplitude coupling (PAC) with high frequency oscillations (HFOs). Subthalamic nucleus (STN) local field potentials (LFPs) from externalized DBS electrodes were recorded and analyzed in PD patients (n = 19). Beta power and HFOs were evaluated in a resting-state condition; PAC was then studied and compared with the electrode contact positions, structural connectivity, and medication state. Beta-HFO PAC (mainly in the 200-500 Hz range) was observed in all subjects. PAC was detectable more specifically in the motor part of the STN compared to beta power and HFOs. Moreover, the presence of PAC better corresponds to the stimulation setup based on the clinical effect. PAC is also sensitive to the laterality of symptoms and dopaminergic therapy, where the greater PAC cluster reflects the more affected side and medication "off" state. Coupling between beta power and HFOs is known to be a correlate of the PD "off" state.

7 Mar 2024

Screening for dysphagia in patients with relapsing-remitting multiple sclerosis

Background: In multiple sclerosis (MS), dysphagia is an important and common clinical symptom. Although often overlooked and underdiagnosed, it can have a significant impact on a patient's life, including social integration, and it can lead to malnutrition, aspiration pneumonia, and suffocation, i.e., life-threatening complications. Early detection of dysphagia is essential to prevent these risks. However, the optimal screening method and the inter-relationship between different methods used for dysphagia screening are not clear. The aim of this study was to compare the diagnostic performance of a simple question about swallowing problems, the DYsphagia in MUltiple Sclerosis (DYMUS) swallowing questionnaire, and the Timed Water Swallowing Test (TWST) to detect dysphagia in people with relapsing-remitting MS (RRMS).

Methods: Patients with MS were asked about subjective swallowing difficulties and, regardless of their response, completed the DYMUS questionnaire and underwent the TWST at their routine follow-up visit. Patients with at least one positive screening method were offered an objective assessment of swallowing function using the Fiberoptic Endoscopic Evaluation of Swallowing (FEES). The results were statistically analyzed and correlated with demographic and MS-related parameters.

28 Feb 2024

Master´s Programme in Neuroscience

22 Feb 2024

A model of human neural networks reveals NPTX2 pathology in ALS and FTLD

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies¹, which involve human-specific mechanisms^2-5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors⁶. Single-cell transcriptomics and comparison to independent neural stem cells⁷ showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids⁸. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43.

22 Feb 2024

Facial emotion processing in patients with borderline personality disorder as compared with healthy controls: an fMRI and ECG study

Background: Maladaptive behaviors and interpersonal difficulties in patients with borderline personality disorder (BPD) seem connected to biased facial emotion processing. This bias is often accompanied by heightened amygdala activity in patients with BPD as compared to healthy controls. However, functional magnetic resonance imaging (fMRI) studies exploring differences between patients and healthy controls in facial emotion processing have produced divergent results. The current study explored fMRI and heart rate variability (HRV) correlates of negative facial emotion processing in patients with BPD and healthy controls.

Methods: The study included 30 patients with BPD (29 females; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 females; M = 24.66, SD = 5.28). All participants underwent the "faces" task, an emotional face perception task, in an fMRI session simultaneously with ECG. In this task, participants are presented with emotional expressions of disgust, sadness, and fear (as a negative condition) and with the same pictures in a scrambled version (as a neutral condition).

22 Feb 2024

Influence of metabolic state and body composition on the action of pharmacological treatment of migraine

Migraine is a disabling neurovascular disorder among people of all ages, with the highest prevalence in the fertile years, and in women. Migraine impacts the quality of life of affected individuals tremendously and, in addition, it is associated with highly prevalent metabolic diseases, such as obesity, diabetes mellitus and thyroid dysfunction. Also, the clinical response to drugs might be affected in patients with metabolic disease due to body composition and metabolic change. Therefore, the efficacy of antimigraine drugs could be altered in patients with both migraine and metabolic disease. However, knowledge of the pharmacology and the related clinical effects of antimigraine drugs in patients with metabolic disease are limited. Therefore, and given the clinical relevance, this article provides a comprehensive overview of the current research and hypotheses related to the influence of metabolic state and body composition on the action of antimigraine drugs. In addition, the influence of antimigraine drugs on metabolic functioning and, vice versa, the influence of metabolic diseases and its hormonal modulating medication on migraine activity is outlined. Future exploration on personalizing migraine treatment to individual characteristics is necessary to enhance therapeutic strategies, especially given its increasing significance in recent decades.

2 Feb 2024

Exploring the impact of intensified multiple session tDCS over the left DLPFC on brain function in MCI: a randomized control trial

Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention..

2 Feb 2024

Engineered human H-chain ferritin with reversed charge of the internal cavity exhibits RNA-mediated spongelike effect for loading RNA/DNA-binding molecules

Ferritins are globular proteins with an internal cavity that enables the encapsulation of a plethora of low-mass compounds. Unfortunately, the overall negative surface charge of ferritin's internal cavity hampers efficient loading of negatively charged molecules. Therefore, we produced a genetically engineered human H-chain ferritin containing a cationic RKRK domain, reversing the natural net charge of the cavity to positive, thus allowing for efficient encapsulation of negatively charged siRNA. Due to the reversed, positive charge mediated by RKRK domains, the recombinant ferritin produced in E. coli inherently carries a load of bacterial RNA inside its cavity, turning the protein into an effective sponge possessing high affinity for DNA/RNA-binding substances that can be loaded with markedly higher efficiency compared to the wildtype protein. Using doxorubicin as payload, we show that due to its loading through the RNA sponge, doxorubicin is released in a sustained manner, with a cytotoxicity profile similar to the free drug. In summary, this is the first report demonstrating a ferritin/nucleic acid hybrid delivery vehicle with a broad spectrum of properties exploitable in various fields of biomedical applications.

2 Feb 2024

Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study

bjective: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses.

Methods: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed.

Results: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]).

23 Jan 2024

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.

Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.

Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.

Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.

18 Jan 2024

How registry data are used to inform activities for stroke care quality improvement across 55 countries: A cross-sectional survey of Registry of Stroke Care Quality (RES-Q) hospitals

Background and purpose: The Registry of Stroke Care Quality (RES-Q) is a worldwide quality improvement data platform that captures performance and quality measures, enabling standardized comparisons of hospital care. The aim of this study was to determine if, and how, RES-Q data are used to influence stroke quality improvement and identify the support and educational needs of clinicians using RES-Q data to improve stroke care.

Methods: A cross-sectional self-administered online survey was administered (October 2021-February 2022). Participants were RES-Q hospital local coordinators responsible for stroke data collection. Descriptive statistics are presented.

Results: Surveys were sent to 1463 hospitals in 74 countries; responses were received from 358 hospitals in 55 countries (response rate 25%). RES-Q data were used "always" or "often" to: develop quality improvement initiatives (n = 213, 60%); track stroke care quality over time (n = 207, 58%); improve local practice (n = 191, 53%); and benchmark against evidence-based policies, procedures and/or guidelines to identify practice gaps (n = 179, 50%).

18 Jan 2024

Global stroke statistics 2023: Availability of reperfusion services around the world

Background: Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed.

Aims: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services.

Methods: We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary.

Results: Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review.

18 Jan 2024

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.

Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality.

18 Jan 2024

Levodopa may modulate specific speech impairment in Parkinson's disease: an fMRI study

Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003).

18 Jan 2024

Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks.

18 Jan 2024

Neural correlates of social exclusion and overinclusion in patients with borderline personality disorder: an fMRI study

Background: Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion.

Methods: The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions.

Results: Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did.

18 Jan 2024

A strategic neurological research agenda for Europe: Towards clinically relevant and patient-centred neurological research priorities

Background and purpose: Neurological disorders constitute a significant portion of the global disease burden, affecting >30% of the world's population. This prevalence poses a substantial threat to global health in the foreseeable future. A lack of awareness regarding this high burden of neurological diseases has led to their underrecognition, underappreciation, and insufficient funding. Establishing a strategic and comprehensive research agenda for brain-related studies is a crucial step towards aligning research objectives among all pertinent stakeholders and fostering greater societal awareness.

Methods: A scoping literature review was undertaken by a working group from the European Academy of Neurology (EAN) to identify any existing research agendas relevant to neurology. Additionally, a specialized survey was conducted among all EAN scientific panels, including neurologists and patients, inquiring about their perspectives on the current research priorities and gaps in neurology.

Results: The review revealed the absence of a unified, overarching brain research agenda.

15 Jan 2024

Neurosurgical treatment and outcome patterns in patients with meningioma in South Moravian region-a population-based study

Introduction: Meningiomas are usually slow-growing tumours, constituting about one third of all primary intracranial tumours. They occur more frequently in women. Clinical manifestation of meningiomas depends on their location, tumour size and growth rate. In most cases, surgical treatment is the procedure of choice. The success of this treatment is, however, associated with the radicality of the resection. Radiotherapy represents an additional or alternative treatment modality. Gamma knife surgery is another notable treatment method, especially in small and/or slow-growing tumours in eloquent areas or in elderly patients.

Material and methods: Authors describe their experience with the diagnosis, treatment and outcome of the patients with meningioma (n = 857). Furthermore, they also assess the postoperative morbidity/mortality and recurrence rate.

Results and conclusions: In view of the benign histology of meningiomas, the success of the treatment largely depends (besides the tumour grading) on the radicality of the resection.

15 Jan 2024

Water removal in MR spectroscopic imaging with Casorati singular value decomposition

Purpose: Water removal is one of the computational bottlenecks in the processing of high-resolution MRSI data. The purpose of this work is to propose an approach to reduce the computing time required for water removal in large MRS data.

Methods: In this work, we describe a singular value decomposition-based approach that uses the partial position-time separability and the time-domain linear predictability of MRSI data to reduce the computational time required for water removal. Our approach arranges MRS signals in a Casorati matrix form, applies low-rank approximations utilizing singular value decomposition, removes residual water from the most prominent left-singular vectors, and finally reconstructs the water-free matrix using the processed left-singular vectors.

Results: We have demonstrated the effectiveness of our proposed algorithm for water removal using both simulated and in vivo data. The proposed algorithm encompasses a pip-installable tool ( https://pypi.org/project/CSVD/), available on GitHub ( https://github.com/amirshamaei/CSVD), empowering researchers to use it in future studies.

10 Jan 2024

Sex differences in brain atrophy in dementia with Lewy bodies

Introduction: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI).

Methods: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males).

Results: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex.

Discussion: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75.

10 Jan 2024

Distance from main arteries influences microstructural and functional brain tissue characteristics

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ, and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing.

10 Jan 2024

Learn how to interpret and use intracranial EEG findings

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, as well as review available quantitative / signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples.

10 Jan 2024

Cyanobacterial anatoxin-a does not induce in vitro developmental neurotoxicity, but changes gene expression patterns in co-exposure with all-trans retinoic acid

Cyanobacterial blooms are increasing in frequency and intensity globally, and impacting recreational waters as well as waters used for drinking water provisioning. They are sources of bioactive metabolites including retinoids and the neurotoxin anatoxin-a. Here, we investigated the effects of anatoxin-a on a differentiating in vitro human neural stem cell model previously characterised with retinoic acids. Effects on protein and gene expression upon exposure for 9 or 18 days to anatoxin-a alone or in co-exposure with all-trans retinoic acid were evaluated using a panel of neural and glial differentiation biomarkers. Anatoxin-a did not cause distinct developmental neurotoxicity alone, or in co-exposure with retinoic acid. However, in line with its excitotoxicity, in co-exposure with 200 nM all-trans retinoic acid it reduced the differentiation of acetylcholinergic neuron subtypes in the culture at 1000 nM (highest tested concentration). While this could have substantial functional implications for the developing nervous system, there is no indication for developmental neurotoxicity beyond its (excito-)toxicity to acetylcholinergic neurons, which only occurred in co-exposure to all-trans retinoic acid.

10 Jan 2024

Generation of the Human iPSC Line from Spontaneous Late-Onset Alzheimer's Disease Patient with ApoE3/3 Genotype and Sex-, Age-, and ApoE-Matched Healthy Control

Human induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells (PBMCs) isolated from a patient diagnosed with spontaneous late-onset Alzheimer's disease (AD) carrying ApoE3/3 gene and one age-, sex-, and ApoE-matched healthy control.

Reprogramming was done using a commercially available Epi5 Reprogramming Kit containing OCT4, SOX2, KLF4, LIN28, and L-MYC as reprogramming factors. The pluripotency of the iPSC lines was verified by the expression of pluripotency markers and by their capacity to differentiate into all three embryonic germ layers in vitro.

These newly established iPSC lines offer a valuable platform for in vitro modeling of AD.

24 Nov 2023

Genetic findings in Czech patients with limb girdle muscular dystrophy

Limb girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of muscular dystrophies. The study presents an overview of molecular characteristics of a large cohort of LGMD patients who are representative of the Czech LGMD population. We present 226 LGMD probands in which 433 mutant alleles carrying 157 different variants with a supposed pathogenic effect were identified. Fifty-four variants have been described only in the Czech LGMD population so far. LGMD R1 caplain3-related is the most frequent subtype of LGMD involving 53.1% of patients with genetically confirmed LGMD, followed by LGMD R9 FKRP-related (11.1%), and LGMD R12 anoctamin5-related (7.1%). If we consider identified variants, then all but five were small-scale variants. One large gene deletion was identified in the LAMA2 gene and two deletions in each of CAPN3 and SGCG. We performed comparison our result with other published studies. The results obtained in the Czech LGMD population clearly differ from the outcome of other LGMD populations in two aspects-we have a more significant proportion of patients with LGMD R1 calpain3-related and a smaller proportion of LGMD R2 dysferlin-related.

24 Nov 2023

BODIPY-labelled acetylcholinesterase reactivators can be encapsulated into ferritin nanovehicles for enhanced bioavailability in the CNS

The BODIPY-labelled oxime reactivator was prepared and used to study its biodistribution into central nervous system. The newly synthesized oxime was found to be weak inhibitor of acetylcholinesterase and strong inhibitor of butyrylcholinesterase. Its reactivation ability for organophosphate inhibited acetylcholinesterase was found similar to a parent oxime. The BODIPY-labelled oxime was further encapsulated into recombinant human H-ferritin and evaluated in vitro and in vivo. The oxime or encapsulated oxime were found to be bioaccumulated primarily in liver and kidneys of mice, but some amount was distributed also to the brain, where it was detectable even after 24 h. The BODIPY-labelled oxime encapsulated to human H-ferritin showed better CNS bioaccumulation and tissue retention at 8 and 24 h time points compared to free oxime, although the fluorescence results might be biased due to BODIPY metabolites identified in tissue homogenates. Taken together, the study demonstrates the first utilization of recombinant ferritins for changing the unfavourable pharmacokinetics of oxime reactivators and brings promising results for follow-up studies.

24 Nov 2023

Multivariate linear mixture models for the prediction of febrile seizure risk and recurrence: a prospective case-control study

Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case-control study, we enrolled 162 children (age 25.8 ± 17.1 months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants' demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (p_FWE < 0.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity/specificity of 82%/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (p_FWE < 0.05) with a separating sensitivity/specificity of 72%/69%.

24 Nov 2023

Possibilities of Using Multi-b-value Diffusion Magnetic Resonance Imaging for Classification of Brain Lesions

In contrast to conventional diffusion magnetic resonance imaging (MRI), multi-b-value diffusion MRI methods are able to separate the signal from free water, pseudo-diffusion, and non-Gaussian components of water molecule diffusion. These approaches can then be utilised in so-called intravoxel incoherent motion imaging and diffusion kurtosis imaging.

Various parameters provided by these methods can describe additional characteristics of the tissue microstructure and potentially help in the diagnosis and classification of various pathological processes. In this review, we present the basic principles and methods of analysing multi-b-value diffusion imaging data and specifically focus on the known possibilities for its use in the diagnosis of brain lesions. We also suggest possible directions for further research.

Keywords: Brain tumours; DKI; DWI; IVIM.

24 Nov 2023

Interictal invasive very high-frequency oscillations in resting awake state and sleep

Interictal very high-frequency oscillations (VHFOs, 500-2000 Hz) in a resting awake state seem to be, according to a precedent study of our team, a more specific predictor of a good outcome of the epilepsy surgery compared to traditional interictal high-frequency oscillations (HFOs, 80-500 Hz). In this study, we retested this hypothesis on a larger cohort of patients. In addition, we also collected patients' sleep data and hypothesized that the occurrence of VHFOs in sleep will be greater than in resting state. We recorded interictal invasive electroencephalographic (iEEG) oscillations in 104 patients with drug-resistant epilepsy in a resting state and in 35 patients during sleep. 21 patients in the rest study and 11 patients in the sleep study met the inclusion criteria (interictal HFOs and VHFOs present in iEEG recordings, a surgical intervention and a postoperative follow-up of at least 1 year) for further evaluation of iEEG data. In the rest study, patients with good postoperative outcomes had significantly higher ratio of resected contacts with VHFOs compared to HFOs. In sleep, VHFOs were more abundant than in rest and the percentage of resected contacts in patients with good and poor outcomes did not considerably differ in any type of oscillations.

20 Nov 2023

Thank you to all who participated in the 35th Czech and Slovak Epileptology Congress and the 69th Czech and Slovak Congress of Clinical Neurophysiology.

We look forward to seeing you again next year.

9 Nov 2023

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.

Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality.

9 Nov 2023

Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid

Primary cilia are cellular surface projections enriched in receptors and signaling molecules, acting as signaling hubs that respond to stimuli. Malfunctions in primary cilia have been linked to human diseases, including retinopathies and ocular defects. Here, we focus on TMEM107, a protein localized to the transition zone of primary cilia. TMEM107 mutations were found in patients with Joubert and Meckel-Gruber syndromes. A mouse model lacking Tmem107 exhibited eye defects such as anophthalmia and microphthalmia, affecting retina differentiation. Tmem107 expression during prenatal mouse development correlated with phenotype occurrence, with enhanced expression in differentiating retina and optic stalk. TMEM107 deficiency in retinal organoids resulted in the loss of primary cilia, down-regulation of retina-specific genes, and cyst formation. Knocking out TMEM107 in human ARPE-19 cells prevented primary cilia formation and impaired response to Smoothened agonist treatment because of ectopic activation of the SHH pathway. Our data suggest TMEM107 plays a crucial role in early vertebrate eye development and ciliogenesis in the differentiating retina.

8 Nov 2023

Cerebral organoids derived from patients with Alzheimer's disease with PSEN1/2 mutations have defective tissue patterning and altered development

During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study human neural development and disease. Especially in the field of Alzheimer's disease (AD), remarkable effort has been put into investigating molecular mechanisms behind this disease. Then, with the advent of 3D neuronal cultures and cerebral organoids (COs), several studies have demonstrated that this model can adequately mimic familial and sporadic AD. Therefore, we created an AD-CO model using iPSCs derived from patients with familial AD forms and explored early events and the progression of AD pathogenesis. Our study demonstrated that COs derived from three AD-iPSC lines with PSEN1(A246E) or PSEN2(N141I) mutations developed the AD-specific markers in vitro, yet they also uncover tissue patterning defects and altered development. These findings are complemented by single-cell sequencing data confirming this observation and uncovering that neurons in AD-COs likely differentiate prematurely.

7 Nov 2023

Metabolic connectivity as a predictor of surgical outcome in mesial temporal lobe epilepsy

Objective: The study investigated metabolic connectivity (MC) differences between patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and healthy controls (HC), based on [18 F]-fluorodeoxyglucose (FDG)-PET data. We focused on the MC changes dependent on the lateralization of the epileptogenic lobe and on correlations with postoperative outcome.

Methods: FDG-PET scans of 47 patients with unilateral MTLE with histopathologically proven HS and 25 HC were included in the study. All the patients underwent a standard anterior temporal lobectomy and were more than two years after the surgery. MC changes were compared between the two HS groups (left HS, right HS) and HC. Differences between the metabolic network of seizure-free and non-seizure-free patients after surgery were depicted afterward. Network changes were correlated with clinical characteristics.

Results: The study showed widespread metabolic network changes in the HS patients as compared to HC.

7 Nov 2023

Parkinson´s disease cardiovascular symptoms: A new complex functional and structural insight

Background: The known impairments of the cardiovascular system in Parkinson´s disease (PD) are caused by autonomic dysfunction and manifested mainly in postural hypotension, chronotropic insufficiency, and reduced heart rate variability. Other dysfunctions, mainly stress response, arrhythmia occurrence, and heart morphology changes, are still the subject of research.

Objectives: To assess the heart rate and blood pressure reaction during exercise, advanced measurements of heart volumes and mass using cardiac magnetic resonance (CMR), and occurrence of arrhythmias in PD patients.

Methods: Thirty PD patients (19 men, mean age 57.5 years) without known cardiac comorbidities underwent bicycle ergometry, electrocardiogram Holter monitoring and CMR. Exercise and CMR parameters were compared with controls (24 subjects for ergometry, 20 for CMR).

7 Nov 2023

Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy

Vagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders.

7 Nov 2023

Selected neuroendocrine factors as potential molecular biomarkers of early non-affective psychosis course in relation to treatment outcome: A pilot study

The aim of this pilot study was to find whether the dysregulation of neuroendocrine biomarker signaling pathways in the first episode of non-affective psychosis is a predictive factor of treatment outcome. Patients with the first episode of non-affective psychosis (N = 29) were examined at admission, at discharge, and at follow-up (N = 23). The biomarkers included serum aldosterone, cortisol, free thyroxine, thyroid stimulating hormone, and prolactin. We revealed lower baseline aldosterone and higher baseline cortisol concentrations in patients with very good outcome compared to those with good outcome after one year. We failed to reveal any significant association between treatment outcome and neurohumoral biomarkers in the whole sample at 1-year follow-up. However, baseline aldosterone concentrations negatively correlated with total PANSS scores at the discharge. Lower baseline aldosterone and higher baseline cortisol concentrations have the potential to predict a more favorable outcome for patients with the first episode of psychosis.

19 Sep 2023

Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020

Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020.

Patients and methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively.

Results: The estimated mean number of acute SUs in 2019 was 3.68 (95% CI: 2.90-4.45) per one million inhabitants (MIH) with 7/44 countries having less than one SU per one MIH. The estimated mean annual number of IVTs was 21.03 (95% CI: 15.63-26.43) per 100,000 and 17.14% (95% CI: 12.98-21.30) of the AIIS in 2019, with highest country rates at 79.19 and 52.66%, respectively, and 15 countries delivering less than 10 IVT per 100,000. The estimated mean annual number of EVTs in 2019 was 7.87 (95% CI: 5.96-9.77) per 100,000 and 6.91% (95% CI: 5.15-8.67) of AIIS, with 11 countries delivering less than 1.5 EVT per 100,000.

19 Sep 2023

Endemic parkinsonism: clusters, biology and clinical features

The term 'endemic parkinsonism' refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region; one in the Caribbean islands of Guadeloupe and Martinique; and four in Europe. Some of these disease entities seem to be disappearing over time and therefore are probably triggered by unique environmental factors. By contrast, other types persist because they are exclusively genetically determined. Given the geographical clustering and potential overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism. Knowledge obtained from the study of these disease entities supports the hypothesis that both genetic and environmental factors contribute to the development of neurodegenerative diseases, not only in endemic parkinsonism but also in general.

29 Aug 2023

Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.

Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.

Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.

Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life.

29 Aug 2023

How registry data are used to inform activities for stroke care quality improvement across 55 countries: A cross-sectional survey of Registry of Stroke Care Quality (RES-Q) hospitals

Background and purpose: The Registry of Stroke Care Quality (RES-Q) is a worldwide quality improvement data platform that captures performance and quality measures, enabling standardized comparisons of hospital care. The aim of this study was to determine if, and how, RES-Q data are used to influence stroke quality improvement and identify the support and educational needs of clinicians using RES-Q data to improve stroke care.

Methods: A cross-sectional self-administered online survey was administered (October 2021-February 2022). Participants were RES-Q hospital local coordinators responsible for stroke data collection. Descriptive statistics are presented.

Results: Surveys were sent to 1463 hospitals in 74 countries; responses were received from 358 hospitals in 55 countries (response rate 25%).

29 Aug 2023

Interictal High-Frequency Oscillations, Spikes, and Connectivity Profiles: a Fingerprint of Epileptogenic Brain Pathologies

Introduction: Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for pre-resective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies.

Methods: Interictal awake SEEG recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone (SOZ) and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs.

29 Aug 2023

Eslicarbazepine-induced hyponatremia: A retrospective single-center real clinical practice study

Hyponatremia is a typical side effect of antiseizure drugs from the dibenzazepine family. The study investigated the prevalence of hyponatremia in patients with epilepsy who were treated with eslicarbazepine. We aimed to determine the prevalence of hyponatremia, reveal the factors leading to the discontinuation of treatment, and identify possible risk factors for the development of hyponatremia including the dose dependency. The medical records of 164 patients with epilepsy taking eslicarbazepine in our center were analyzed. The overall prevalence of hyponatremia was 30.5%. The prevalence of mild hyponatremia, seen in 14% to 20% of patients, was not dose dependent. The prevalence of moderate and severe hyponatremia was significantly dose dependent. The severity of hyponatremia was significantly dose dependent. Severe hyponatremia was found in 6.1% of patients. Hyponatremia was asymptomatic in the majority of cases, and in 48% did not require any management. Hyponatremia was the reason for discontinuation in 6.2% of patients. The major risk factor for developing hyponatremia was older age.

29 Aug 2023

EEG Microstates in Mood and Anxiety Disorders: A Meta-analysis

To reduce the psycho-social burden increasing attention has focused on brain abnormalities in the most prevalent and highly co-occurring neuropsychiatric disorders, such as mood and anxiety. However, high inter-study variability in these patients results in inconsistent and contradictory alterations in the fast temporal dynamics of large-scale networks as measured by EEG microstates. Thus, in this meta-analysis, we aim to investigate the consistency of these changes to better understand possible common neuro-dynamical mechanisms of these disorders.In the systematic search, twelve studies investigating EEG microstate changes in participants with mood and anxiety disorders and individuals with subclinical depression were included in this meta-analysis, adding up to 787 participants.The results suggest that EEG microstates consistently discriminate mood and anxiety impairments from the general population in patients and subclinical states. Specifically, we found a small significant effect size for B microstates in patients compared to healthy controls, with larger effect sizes for increased B presence in unmedicated patients with comorbidity. In a subgroup meta-analysis of ten mood disorder studies, microstate D showed a significant effect size for decreased presence.

29 Aug 2023

Lifelong effects of prenatal and early postnatal stress on the hippocampus, amygdala, and psychological states of Holocaust survivors

This study focuses on hippocampal and amygdala volume, seed-based connectivity, and psychological traits of Holocaust survivors who experienced stress during prenatal and early postnatal development. We investigated people who lived in Central Europe during the Holocaust and who, as Jews, were in imminent danger. The group who experienced stress during their prenatal development and early postnatal (PreP) period (n = 11) were compared with a group who experienced Holocaust-related stress later in their lives: in late childhood, adolescence, and early adulthood (ChA) (n = 21). The results of volumetry analysis showed significantly lower volumes of both hippocampi and the right amygdala in the PreP group. Seed-based connectivity analysis revealed increased connectivity from the seed in the right amygdala to the middle and posterior cingulate cortex, caudate, and inferior left frontal operculum in the PreP group. Psychological testing found higher levels of traumatic stress symptoms (TCS-40) and lower levels of well-being (SOS-10) in the PreP group than in the ChA group.

21 Aug 2023

Longitudinal study of epigenetic aging and its relationship with brain aging and cognitive skills in young adulthood

Introduction: The proportion of older adults within society is sharply increasing and a better understanding of how we age starts to be critical. However, given the paucity of longitudinal studies with both neuroimaging and epigenetic data, it remains largely unknown whether the speed of the epigenetic clock changes over the life course and whether any such changes are proportional to changes in brain aging and cognitive skills. To fill these knowledge gaps, we conducted a longitudinal study of a prenatal birth cohort, studied epigenetic aging across adolescence and young adulthood, and evaluated its relationship with brain aging and cognitive outcomes.

Methods: DNA methylation was assessed using the Illumina EPIC Platform in adolescence, early and late 20 s, DNA methylation age was estimated using Horvath's epigenetic clock, and epigenetic age gap (EpiAGE) was calculated as DNA methylation age residualized for batch, chronological age and the proportion of epithelial cells. Structural magnetic resonance imaging (MRI) was acquired in both the early 20 s and late 20 s using the same 3T Prisma MRI scanner and brain age was calculated using the Neuroanatomical Age Prediction using R (NAPR) platform.

4 Aug 2023

Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease

The biological basis of the neurodegenerative movement disorder, Parkinson's disease (PD), is still unclear despite it being 'discovered' over 200 years ago in Western Medicine. Based on current PD knowledge, there are widely varying theories as to its pathobiology.

The aim of this article was to explore some of these different theories by summarizing the viewpoints of laboratory and clinician scientists in the PD field, on the biological basis of the disease. To achieve this aim, we posed this question to thirteen "PD experts" from six continents (for global representation) and collated their personal opinions into this article.

The views were varied, ranging from toxin exposure as a PD trigger, to LRRK2 as a potential root cause, to toxic alpha-synuclein being the most important etiological contributor. Notably, there was also growing recognition that the definition of PD as a single disease should be reconsidered, perhaps each with its own unique pathobiology and treatment regimen.

4 Aug 2023

Consensus Paper: Cerebellum and Ageing

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks.

26 Jun 2023

Genetic algorithm designed for optimization of neural network architectures for intracranial EEG recordings analysis

Objective.The current practices of designing neural networks rely heavily on subjective judgment and heuristic steps, often dictated by the level of expertise possessed by architecture designers. To alleviate these challenges and streamline the design process, we propose an automatic method, a novel approach to enhance the optimization of neural network architectures for processing intracranial electroencephalogram (iEEG) data.Approach. We present a genetic algorithm, which optimizes neural network architecture and signal pre-processing parameters for iEEG classification.Main results. Our method improved the macroF1 score of the state-of-the-art model in two independent datasets, from St. Anne's University Hospital (Brno, Czech Republic) and Mayo Clinic (Rochester, MN, USA), from 0.9076 to 0.9673 and from 0.9222 to 0.9400 respectively. Significance. By incorporating principles of evolutionary optimization, our approach reduces the reliance on human intuition and empirical guesswork in architecture design, thus promoting more efficient and effective neural network models.

26 Jun 2023

Does initial high efficacy therapy in multiple sclerosis surpass escalation treatment strategy? A comparison of patients with relapsing-remitting multiple sclerosis in the Czech and Swedish national multiple sclerosis registries

Background: In relapsing-remitting multiple sclerosis (RRMS) the most common treatment strategy has been to start with low-moderate efficacy disease modifying therapy (LE-DMT) and to escalate to more efficacious treatments in cases of breakthrough disease activity. However, recent evidence suggests a better outcome in patients commencing with moderate-high efficacy DMT (HE-DMT) immediately after clinical onset.

Objective: The aim of this study is to compare disease activity and disability outcomes in patients treated with the two alternative strategies using the Swedish and Czech national multiple sclerosis registries, taking advantage of the fact that the relative frequency of each strategy differs markedly between these two countries.

26 Jun 2023

Is breastfeeding in MS harmful or not? An answer from real-world Czech data

Introduction: The influence of breastfeeding and it´s duration on the course of multiple sclerosis (MS) is unclear. Here we analyzed a real-world data for breastfeeding women with MS and their disease course collected from a Czech national registry ReMuS.

Objectives: To identify risk factors associated with not initiating breastfeeding after delivery, to analyze the impact of breastfeeding on the MS disease course, evaluate the assumption, that breastfeeding is not harmful in MS patients, and compare the disease course by breastfeeding status.

Materials and methods: Using propensity score matching we compared Expanded Disability Status Scale (EDSS), confirmed disease worsening (CDW) and annual relapse rate (ARR) in breastfeeding and non-breastfeeding MS patients according to disease duration, disease modifying treatment (DMT) before pregnancy, last EDSS score before conception, age, and ARR during pregnancy.

16 Jun 2023

Response: Can biomarkers of the epileptogenic zone be characterized in patients rendered seizure free alone?

The role ofpresurgical evaluation with intracranial elec-troencephalography (iEEG) is to localize the minimal amount ofbrain tissue which, ifresected, will achieve sei-zure freedom in the treated patient. From the definition ofthe epileptogenic zone (EZ)1being “the area ofcortex that is indispensable for the generation ofepileptic seizures,” it is the EZ that we want to localize. At the same time we will only know retrospectively in patients with seizure-free outcome that we were indeed able to identify the EZ.

This brings us to the localization dilemma. We either attempt to stick to the primary goal oflocalization ofthe EZ and use only good outcome patients or use something else as a localization target that is well defined in both good and poor outcomes. For poor outcome patients the latter remains less clear apart from the fact that at least part ofthe predicted target, localized by an algorithm, should be outside of the resection cavity.

16 Jun 2023

Six years of the Angels Initiative: Aims, achievements and future directions to improve stroke care worldwide

The rate of stroke-related death and disability is four times higher in low- and middle-income countries (LMICs) than in high-income countries (HICs), yet stroke units exist in only 18% of LMICs, compared with 91% of HICs. In order to ensure universal and equitable access to timely, guideline-recommended stroke care, multidisciplinary stroke-ready hospitals with coordinated teams of healthcare professionals and appropriate facilities are essential.Established in 2016, the Angels Initiative is an international, not-for-profit, public-private partnership. It is run in collaboration with the World Stroke Organization, European Stroke Organisation, and regional and national stroke societies in over 50 countries.

The Angels Initiative aims to increase the global number of stroke-ready hospitals and to optimise the quality of existing stroke units. It does this through the work of dedicated consultants, who help to standardise care procedures and build coordinated, informed communities of stroke professionals.

15 Jun 2023

Twenty-five years of epilepsy surgery at a Central European comprehensive epilepsy center-Trends in intervention delay and outcomes

Objective: We analyzed trends in patients' characteristics, outcomes, and waiting times over the last 25 years at our epilepsy surgery center situated in Central Europe to highlight possible areas of improvement in our care for patients with drug-resistant epilepsy.

Methods: A total of 704 patients who underwent surgery at the Brno Epilepsy Center were included in the study, 71 of those were children. Patients were separated into three time periods, 1996-2000 (n = 95), 2001-2010 (n = 295) and 2011-2022 (n = 314) based on first evaluation at the center.

Results: The average duration of epilepsy before surgery in adults remained high over the last 25 years (20.1 years from 1996 to 2000, 21.3 from 2001 to 2010, and 21.3 from 2011 to 2020, P = 0.718). There has been a decrease in rate of surgeries for temporal lobe epilepsy in the most recent time period (67%-70%-52%, P < 0.001).

15 Jun 2023

Editorial: The brain barriers in diseases of the nervous system

The central nervous system is protected against harmful substances from the blood by three major barriers: the blood–brain barrier, the choroid plexus blood–cerebrospinal fluid barrier, and the arachnoid blood–cerebrospinal fluid barrier. Under disease conditions (neurodegenerative, traumatic, oncologic, autoimmune), inflammatory responses within the brain barriers change their permeability. Therefore, the aim of this Research Topic was to provide new insights into (1) inflammatory responses within the brain barriers, (2) barrier changes associated with brain disorders, and (3) barrier modulation for drug delivery and treatment. This Research Topic consists of six articles, two reviews, and four original articles, written by authors with different expertise. All articles were focused on changes in the blood–brain barrier.

Keywords: blood-brain barrier; blood-cerebrospinal fluid barrier; choroid plexus; drug delivery; meningeal blood-cerebrospinal fluid barrier; stroke.

15 Jun 2023

Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate

Background: Apolipoprotein E (ApoE) ε4 genotype is the most prevalent risk factor for late-onset Alzheimer's Disease (AD). Although ApoE4 differs from its non-pathological ApoE3 isoform only by the C112R mutation, the molecular mechanism of its proteinopathy is unknown.

Methods: Here, we reveal the molecular mechanism of ApoE4 aggregation using a combination of experimental and computational techniques, including X-ray crystallography, site-directed mutagenesis, hydrogen-deuterium mass spectrometry (HDX-MS), static light scattering and molecular dynamics simulations. Treatment of ApoE ε3/ε3 and ε4/ε4 cerebral organoids with tramiprosate was used to compare the effect of tramiprosate on ApoE4 aggregation at the cellular level.

Results: We found that C112R substitution in ApoE4 induces long-distance (> 15 Å) conformational changes leading to the formation of a V-shaped dimeric unit that is geometrically different and more aggregation-prone than the ApoE3 structure.

1 Jun 2023

Single-center long-term results of vagus nerve stimulation for pediatric epilepsy: a 10-17-year follow-up study

Purpose: A retrospective study, based on a prospectively built database, presents the results of long-term follow-up care of pediatric vagus nerve stimulation (VNS) patients in terms of seizure outcome, surgical aspects, the potential impact of maturation, and medication changes.

Methods: From a prospectively built database, 16 VNS patients (median age 12.0 years, range 6.0 to 16.0 years; median seizure duration 6.5 years, range 2.0 to 15.5 years) followed for at least 10 years were graded as non-responder - NR (seizure frequency reduction < 50%), responder - R (reduction ≥ 50% and < 80%), and 80% responder - 80R (reduction ≥ 80%). Data about surgical aspects (battery replacement, system complications), seizure dynamics, and medication changes were taken from the database.

Results: The early percentages of good results (80R + R) were 43.8% (year 1), 50.0% (year 2), and 43.8% (year 3).

18 May 2023

A Pilot Study on the Functional Stability of Phonation in EEG Bands After Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative condition with constantly increasing prevalence rates, affecting strongly life quality in terms of neuromotor and cognitive performance. PD symptoms include voice and speech alterations, known as hypokinetic dysarthria (HD). Unstable phonation is one of the manifestations of HD. Repetitive transcranial magnetic stimulation (rTMS) is a rehabilitative treatment thathas been shown to improve some motor and non-motor symptoms of persons with PD (PwP). This study analyzed the phonation functional behavior of 18 participants (13 males, 5 females) with PD diagnosis before (one pre-stimulus) and after (four post-stimulus) evaluation sessions of rTMS treatment, to assess the extent of changes in their phonation stability. Participants were randomized 1:1 to receive either rTMS or sham stimulation.

18 May 2023

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%.

18 May 2023

Safety and Efficacy of Baseline Antiplatelet Treatment in Patients Undergoing Mechanical Thrombectomy for Ischemic Stroke

Purpose: Baseline use of antiplatelet medication before mechanical thrombectomy (MT) for acute ischemic stroke (AIS) can provide benefit on reperfusion and clinical outcome, but could also carry an increased risk of intracranial hemorrhage (ICH). This nationwide study investigates the safety and efficacy of baseline antiplatelet treatment in AIS patients undergoing MT.

Materials and methods: All consecutive AIS patients treated with MT with and without intravenous thrombolysis (IVT) between January 2012 and December 2019 in all centers performing MT nationwide were reviewed. Data were prospectively collected in national registries (SITS-TBY, RES-Q). Primary outcome was functional independence (modified Rankin Scale 0-2) at three months, secondary outcome was ICH.

26 Apr 2023

Physics-informed deep learning approach to quantification of human brain metabolites from magnetic resonance spectroscopy data

Purpose: While the recommended analysis method for magnetic resonance spectroscopy data is linear combination model (LCM) fitting, the supervised deep learning (DL) approach for quantification of MR spectroscopy (MRS) and MR spectroscopic imaging (MRSI) data recently showed encouraging results; however, supervised learning requires ground truth fitted spectra, which is not practical. Moreover, this work investigates the feasibility and efficiency of the LCM-based self-supervised DL method for the analysis of MRS data.

Method: We present a novel DL-based method for the quantification of relative metabolite concentrations, using quantum-mechanics simulated metabolite responses and neural networks. We trained, validated, and evaluated the proposed networks with simulated and publicly accessible in-vivo human brain MRS data and compared the performance with traditional methods.

26 Apr 2023

Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis using QuantiFERON Monitor

Background: The QuantiFERON®-Monitor (QFM) is an assay that measures interferon-γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing-remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN-γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function.

Methods: This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN-γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml.

26 Apr 2023

The effect of deep brain stimulation in Parkinson's disease reflected in EEG microstates

Mechanisms of deep brain stimulation (DBS) on cortical networks were explored mainly by fMRI. Advanced analysis of high-density EEG is a source of additional information and may provide clinically useful biomarkers. The presented study evaluates EEG microstates in Parkinson's disease and the effect of DBS of the subthalamic nucleus (STN). The association between revealed spatiotemporal dynamics of brain networks and changes in oscillatory activity and clinical examination were assessed. Thirty-seven patients with Parkinson's disease treated by STN-DBS underwent two sessions (OFF and ON stimulation conditions) of resting-state EEG. EEG microstates were analyzed in patient recordings and in a matched healthy control dataset. Microstate parameters were then compared across groups and were correlated with clinical and neuropsychological scores. Of the five revealed microstates, two differed between Parkinson's disease patients and healthy controls.

17 Apr 2023

Specialist Perspectives on the Imaging Selection of Large Vessel Occlusion in the Late Window

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window.

Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists.

17 Apr 2023

The interacting brain: Dynamic functional connectivity among canonical brain networks dissociates cooperative from competitive social interactions

We spend much our lives interacting with others in various social contexts. Although we deal with this myriad of interpersonal exchanges with apparent ease, each one relies upon a broad array of sophisticated cognitive processes. Recent research suggests that the cognitive operations supporting interactive behaviour are themselves underpinned by several canonical functional brain networks (CFNs) that integrate dynamically with one another in response to changing situational demands. Dynamic integrations among these CFNs should therefore play a pivotal role in coordinating interpersonal behaviour. Further, different types of interaction should present different demands on cognitive systems, thereby eliciting distinct patterns of dynamism among these CFNs. To investigate this, the present study performed functional magnetic resonance imaging (fMRI) on 30 individuals while they interacted with one another cooperatively or competitively.

17 Apr 2023

Predictive factors of multiple sclerosis relapse after the first demyelinating event: A 5-year follow-up

There is a growing need to discover the characteristics that predict prognostic factors after the first demyelinating event. In this study of 141 patients that met the 2017 McDonald criteria, a higher number of oligoclonal bands, cervical spinal cord demyelinating lesions, and sensory involvement were identified as independent predictors of the second demyelinating event during the 5-year follow-up period in patients who experienced the first demyelinating event. The identification of the aforementioned risk variables will make it possible to identify patients who are more likely to exhibit early second demyelinating event, implying more frequent monitoring and consideration of early application of highly effective disease-modifying treatment.

Keywords: Clinically isolated syndrome; Demyelinating diseases; Magnetic resonance imaging; Multiple sclerosis; Oligoclonal bands.

17 Apr 2023

Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro

Cyanobacterial blooms are known sources of environmentally-occurring retinoid compounds, including all-trans and 9-cis retinoic acids (RAs). The developmental hazard for aquatic organisms has been described, while the implications for human health hazard assessment are not yet sufficiently characterized. Here, we employ a human neural stem cell model that can differentiate in vitro into a mixed culture of neurons and glia. Cells were exposed to non-cytotoxic 8-1000 nM all-trans or 9-cis RA for 9-18 days (DIV13 and DIV22, respectively). Impact on biomarkers was analyzed on gene expression (RT-qPCR) and protein level (western blot and proteomics) at both time points; network patterning (immunofluorescence) on DIV22. RA exposure significantly concentration-dependently increased gene expression of retinoic acid receptors and the metabolizing enzyme CYP26A1, confirming the chemical-specific response of the model. Expression of thyroid hormone signaling-related genes remained mostly unchanged.

17 Apr 2023

Peripheral Inflammatory Markers in Subtypes and Core Features of Depression: A Systematized Review

Introduction: The aim of this work was to summarize relationships between two subtypes of major depressive disorder (melancholic and atypical) and four core features of depression that reflect the domains identified consistently in previous studies of major depressive disorder endophenotypes (exaggerated reactivity to negative information, altered reward processing, cognitive control deficits, and somatic symptoms) on the one hand and selected peripheral inflammatory markers (C-reactive protein [CRP], cytokines, and adipokines) on the other.

Methods: A systematized review was conducted. The database used for searching articles was PubMed (MEDLINE).

Results: According to our search, most peripheral immunological markers associated with major depressive disorder are not specific to a single depressive symptom group.

17 Apr 2023

Decompression alone versus decompression with instrumented fusion in the treatment of lumbar degenerative spondylolisthesis: a systematic review and meta-analysis of randomised trials

Objective: To determine the efficacy of adding instrumented spinal fusion to decompression to treat degenerative spondylolisthesis (DS).

Design: Systematic review with meta-analysis.

Data sources: MEDLINE, Embase, Emcare, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to May 2022.

Eligibility criteria for study selection: Randomised controlled trials (RCTs) comparing decompression with instrumented fusion to decompression alone in patients with DS.

17 Apr 2023

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications.

17 Apr 2023

Molecular Biomarkers of Neuronal Injury in Epilepsy Shared with Neurodegenerative Diseases

In neurodegenerative diseases, changes in neuronal proteins in the cerebrospinal fluid and blood are viewed as potential biomarkers of the primary pathology in the central nervous system (CNS). Recent reports suggest, however, that level of neuronal proteins in fluids also alters in several types of epilepsy in various age groups, including children. With increasing evidence supporting clinical and sub-clinical seizures in Alzheimer's disease, Lewy body dementia, Parkinson's disease, and in other less common neurodegenerative conditions, these findings call into question the specificity of neuronal protein response to neurodegenerative process and urge analysis of the effects of concomitant epilepsy and other comorbidities. In this article, we revisit the evidence for alterations in neuronal proteins in the blood and cerebrospinal fluid associated with epilepsy with and without neurodegenerative diseases.

17 Apr 2023

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF).

5 Apr 2023

MicroRNA Profiling of Self-Renewing Human Neural Stem Cells Reveals Novel Sets of Differentially Expressed microRNAs During Neural Differentiation In Vitro

The involvement of microRNAs (miRNAs) in orchestrating self-renewal and differentiation of stem cells has been revealed in a number of recent studies. And while in human pluripotent stem cells, miRNAs have been directly linked to the core pluripotency network, including the cell cycle regulation and the maintenance of the self-renewing capacity, their role in the onset of differentiation in other contexts, such as determination of neural cell fate, remains poorly described. To bridge this gap, we used three model cell types to study miRNA expression patterns: human embryonic stem cells (hESCs), hESCs-derived self-renewing neural stem cells (NSCs), and differentiating NSCs. The comprehensive miRNA profiling presented here reveals novel sets of miRNAs differentially expressed during human neural cell fate determination in vitro.

5 Apr 2023

Predictors of age at diagnosis in autism spectrum disorders: the use of multiple regression analyses and a classification tree on a clinical sample

The increasing prevalence of autism spectrum disorders (ASD) has led to worldwide interest in factors influencing the age of ASD diagnosis. Parents or caregivers of 237 ASD children (193 boys, 44 girls) diagnosed using the Autism Diagnostic Observation Schedule (ADOS) completed a simple descriptive questionnaire. The data were analyzed using the variable-centered multiple regression analysis and the person-centered classification tree method. We believed that the concurrent use of these two methods could produce robust results. The mean age at diagnosis was 5.8 ± 2.2 years (median 5.3 years). Younger ages for ASD diagnosis were predicted (using multiple regression analysis) by higher scores in the ADOS social domain, higher scores in ADOS restrictive and repetitive behaviors and interest domain, higher maternal education, and the shared household of parents.

4 Apr 2023

Infant attachment in the Czech Republic: Categorical and dimensional findings from a post-communist country

Infant attachment remains virtually unexplored in former Eastern Bloc countries. The dimensional approach to infant attachment, which could ease common obstacles in cross-cultural attachment research, necessitates more empirical support. This study explores infant attachment in the Czech Republic, a post-communist country with a unique family policy, using both the categorical and the dimensional models. It also compares the Czech infant attachment distribution to infant attachment distributions in other countries and compares infant attachment distributions in European countries to the Baltimore study sample. In the Strange Situation Procedure, forty-nine (74 %) out of sixty-six mother-infant dyads (35 boys, M = 13.8, SD = 0.9) received the B classification. Despite the generous family policy and cultural emphasis on close mother-infant relationships, the Czech distribution of insecure categories did not differ from the Baltimore study sample.

4 Apr 2023

Utility of quantitative MRI metrics in brain ageing research

The advent of new, advanced quantitative MRI metrics allows for in vivo evaluation of multiple biological processes highly relevant for ageing. The presented study combines several MRI parameters hypothesised to detect distinct biological characteristics as myelin density, cellularity, cellular membrane integrity and iron concentration. 116 healthy volunteers, continuously distributed over the whole adult age span, underwent a multi-modal MRI protocol acquisition.

Scatterplots of individual MRI metrics revealed that certain MRI protocols offer much higher sensitivity to early adulthood changes while plateauing in higher age (e.g., global functional connectivity in cerebral cortex or orientation dispersion index in white matter), while other MRI metrics provided reverse ability-stable levels in young adulthood with sharp changes with rising age (e.g., T1ρ and T2ρ).

4 Apr 2023

Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04).

4 Apr 2023

A color-tunable single-benzene fluorophore-based sensor for sensitive detection of palladium in solution and living cells

Single-benzene fluorophores are bright and the smallest fluorochromes known so far. In single-benzene fluorophores, the fluorescence is mediated by the push/pull effect of substituting groups. Despite a plethora of advantageous properties, this group of molecules has not been extensively studied for design of high-performance fluorescent sensors of catalytic or enzymatic activities. Thus, herein, new fluorescent probes based on the Tsuji-Trost reaction were developed for the selective detection of palladium and other transition metals (platinum and gold) in an aqueous/organic mixed solvent with the sensitivity down to 2.5 nM (for palladium). The relative flexibility in the synthesis of these probes allows for facile color tuning of the emitted fluorescence. In this study, we have successfully utilized a yellow emission variant for sensitive detection of palladium under cell-free conditions and in living cells, validating its possible applicability for high-throughput optical sensing of catalysts for bioorthogonal chemistry under physiological conditions.

21 Mar 2023

March 21 - Cluster headache awareness day

21 Feb 2023

Relative Entropy is an easy-to-use invasive EEG Biomarker of the Epileptogenic Zone

Objective: High-frequency oscillations are considered among the most promising interictal biomarkers of the epileptogenic zone in patients suffering from pharmaco-resistant focal epilepsy. However, there is no clear definition of pathological High-frequency oscillations and the existing detectors vary in methodology, performance, and computational costs. This study proposes Relative Entropy as an easy-to-use novel interictal biomarker of the epileptic tissue.

Methods: We evaluated Relative Entropy and High-frequency oscillations biomarkers on intracranial EEG data from 39 patients with seizure-free postoperative outcome (Engel Ia) from three Institutions. We tested their capability to localize the epileptogenic zone, defined as resected contacts located in seizure-onset zone. The performance was compared using areas under the receiver operating curves [AUROC] and precision-recall curves [AUPRC].

21 Feb 2023

Basilar artery occlusion management: Specialist perspectives from an international survey

Background and purpose: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties.

Methods: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics.

21 Feb 2023

Parental education, cognition and functional connectivity of the salience network

The aim was to investigate the association of parental education at birth with cognitive ability in childhood and young adulthood and determine, whether functional connectivity of the salience network underlies this association. We studied participants of the Czech arm of the European Longitudinal Study of Pregnancy and Childhood who underwent assessment of their cognitive ability at age 8 (Wechsler Intelligence Scale for Children) and 28/29 years (Wechsler Adult Intelligence Scale) and measurement with resting state functional MRI at age 23/24. We estimated the associations of parental education with cognitive ability and functional connectivity between the seeds in the salience network and other voxels in the brain. We found that lower education of both mothers and fathers was associated with lower verbal IQ, performance IQ and full-scale IQ of the offspring at age 8. Only mother´s education was associated with performance IQ at age 28/29.

21 Feb 2023

Interview with Milan Brázdil: Epilepsy and the Silent Epidemic of the Mind

9 Feb 2023

Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study

Background: Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke.

Aims: Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS).

Methods: We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score.

9 Feb 2023

Stroke Learning Health Systems: A Topical Narrative Review With Case Examples

To our knowledge, the adoption of Learning Health System (LHS) concepts or approaches for improving stroke care, patient outcomes, and value have not previously been summarized. This topical review provides a summary of the published evidence about LHSs applied to stroke, and case examples applied to different aspects of stroke care from high and low-to-middle income countries. Our attempt to systematically identify the relevant literature and obtain real-world examples demonstrated the dissemination gaps, the lack of learning and action for many of the related LHS concepts across the continuum of care but also elucidated the opportunity for continued dialogue on how to study and scale LHS advances. In the field of stroke, we found only a few published examples of LHSs and health systems globally implementing some selected LHS concepts, but the term is not common. A major barrier to identifying relevant LHS examples in stroke may be the lack of an agreed taxonomy or terminology for classification.

9 Feb 2023

Single Cerebral Organoid Mass Spectrometry of Cell-Specific Protein and Glycosphingolipid Traits

Cerebral organoids are a prolific research topic and an emerging model system for neurological diseases in human neurobiology. However, the batch-to-batch reproducibility of current cultivation protocols is challenging and thus requires a high-throughput methodology to comprehensively characterize cerebral organoid cytoarchitecture and neural development. We report a mass spectrometry-based protocol to quantify neural tissue cell markers, cell surface lipids, and housekeeping proteins in a single organoid. Profiled traits probe the development of neural stem cells, radial glial cells, neurons, and astrocytes. We assessed the cell population heterogeneity in individually profiled organoids in the early and late neurogenesis stages. Here, we present a unifying view of cell-type specificity of profiled protein and lipid traits in neural tissue. Our workflow characterizes the cytoarchitecture, differentiation stage, and batch cultivation variation on an individual cerebral organoid level.

9 Feb 2023

International study: Global impact of COVID-19 on stroke care - the Polish contribution

The most severe consequences of the COVID-19 pandemic were reported during its first wave in 2019. Although airway inflammation is part of the main clinical picture of COVID-19, the consequences of a SARS-Cov2 infection can also include coagulation disorders, cardiomyopathy and endotheliopathy, which lead to stroke in 1.5% of patients.
With the global reach of the pandemic came collaboration between scientists and clinicians from around the world.
This transfer of knowledge between various medical centres contributed to greatly improved understanding of the mechanisms of transmission and the different manifestations of infection.
To assess the global impact of the pandemic on stroke hospitalisations and outcomes, Prof. Nogueira inspired the international community of neurologists and neurointerventionalists from six continents, 70 countries and almost 500 hospital stroke centres to participate in large, cross-sectional, observational, retrospective studies

9 Feb 2023

A preliminary choroid plexus volumetric study in individuals with psychosis

The choroid plexus (ChP) is part of the blood-cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging-based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87).

9 Feb 2023

Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration

It is currently challenging to adequately model the growth and migration of glioblastoma using two-dimensional (2D) in vitro culture systems as they quickly lose the original, patient-specific identity and heterogeneity. However, with the advent of three-dimensional (3D) cell cultures and human induced pluripotent stem cell (iPSC)-derived cerebral organoids (COs), studies demonstrate that the glioblastoma-CO (GLICO) co-culture model helps to preserve the phenotype of the patient-specific tissue. Here, we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of co-cultured glioblastoma. Our data demonstrates that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration. We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model.

24 Jan 2023

Utilization of temporal autoencoder for semi-supervised intracranial EEG clustering and classification

Manual visual review, annotation and categorization of electroencephalography (EEG) is a time-consuming task that is often associated with human bias and requires trained electrophysiology experts with specific domain knowledge. This challenge is now compounded by development of measurement technologies and devices allowing large-scale heterogeneous, multi-channel recordings spanning multiple brain regions over days, weeks. Currently, supervised deep-learning techniques were shown to be an effective tool for analyzing big data sets, including EEG. However, the most significant caveat in training the supervised deep-learning models in a clinical research setting is the lack of adequate gold-standard annotations created by electrophysiology experts. Here, we propose a semi-supervised machine learning technique that utilizes deep-learning methods with a minimal amount of gold-standard labels. The method utilizes a temporal autoencoder for dimensionality reduction and a small number of the expert-provided gold-standard labels used for kernel density estimating (KDE) maps.

24 Jan 2023

Shadows of very high-frequency oscillations can be detected in lower frequency bands of routine stereoelectroencephalography

Very high-frequency oscillations (VHFOs, > 500 Hz) are more specific in localizing the epileptogenic zone (EZ) than high-frequency oscillations (HFOs, < 500 Hz). Unfortunately, VHFOs are not visible in standard clinical stereo-EEG (SEEG) recordings with sampling rates of 1 kHz or lower.

Here we show that "shadows" of VHFOs can be found in frequencies below 500 Hz and can help us to identify SEEG channels with a higher probability of increased VHFO rates.

Subsequent analysis of Logistic regression models on 141 SEEG channels from thirteen patients shows that VHFO "shadows" provide additional information to gold standard HFO analysis and can potentially help in precise EZ delineation in standard clinical recordings.

24 Jan 2023

Transient Reflexive Pain Responses and Chronic Affective Nonreflexive Pain Responses Associated with Neuroinflammation Processes in Both Spinal and Supraspinal Structures in Spinal Cord-Injured Female Mice

Central neuropathic pain is not only characterized by reflexive pain responses, but also emotional or affective nonreflexive pain responses, especially in women. Some pieces of evidence suggest that the activation of the neuroimmune system may be contributing to the manifestation of mood disorders in patients with chronic pain conditions, but the mechanisms that contribute to the development and chronicity of CNP and its associated disorders remain poorly understood. This study aimed to determine whether neuroinflammatory factor over-expression in the spinal cord and supraspinal structures may be associated with reflexive and nonreflexive pain response development from acute SCI phase to 12 weeks post-injury in female mice. The results show that transient reflexive responses were observed during the SCI acute phase associated with transient cytokine overexpression in the spinal cord.

12 Jan 2023

Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin

Background/aim: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs.

9 Jan 2023

Milan Brázdil in Forbes's TOP 50 Doctors of the Czech Republic

Forbes magazine has published a ranking of the top 50 doctors in the Czech Republic. Milan Brázdil, who is involved in teaching and research at the MU Faculty of Medicine, is among the best.

6 Jan 2023

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis

This study focuses on white matter alterations in pharmacoresistant epilepsy patients with no visible lesions in the temporal and frontal lobes on clinical MRI (i.e. MR-negative) with lesions confirmed by resective surgery. The aim of the study was to extend the knowledge about group-specific neuropathology in MR-negative epilepsy. We used the fixel-based analysis (FBA) that overcomes the limitations of traditional diffusion tensor image analysis, mainly within-voxel averaging of multiple crossing fibres. Group-wise comparisons of fixel parameters between healthy controls (N = 100) and: (1) frontal lobe epilepsy (FLE) patients (N = 9); (2) temporal lobe epilepsy (TLE) patients (N = 13) were performed. A significant decrease of the cross-section area of the fixels in the superior longitudinal fasciculus was observed in the FLE. Results in TLE reflected widespread atrophy of limbic, thalamic, and cortico-striatal connections and tracts directly connected to the temporal lobe (such as the anterior commissure, inferior fronto-occipital fasciculus, uncinate fasciculus, splenium of corpus callosum, and cingulum bundle).

6 Jan 2023

The decline in stroke hospitalization due to COVID-19 is unrelated to COVID-19 intensity

Background and purpose: During the coronavirus disease 2019 (COVID-19) pandemic many countries reported a decline in stroke volumes. The aim of this study was to analyze if the decline was related to the intensity of the COVID-19 pandemic.

Methods: The first pandemic year (1 March 2020 to 28 February 2021) overall and during the three COVID-19 waves were compared with the preceding year. Volumes of acute ischaemic stroke (AIS), subarachnoid hemorrhage, intracerebral hemorrhage and recanalization treatments (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) were obtained from the National Register of Reimbursed Health Services. Door-to-needle time, onset-to-door time and National Institutes of Health Stroke Scale at admission were obtained from the Registry of Stroke Care Quality.

Results: During the pandemic year compared to the preceding year there were 26,453 versus 28,771 stroke admissions, representing an 8.8% decline (p < 0.001).

6 Jan 2023

Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop

Background and purpose: In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks. We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation.

Methods: Patients were assigned to 10 sessions of real or sham 1-Hz stimulation over the right posterior superior temporal gyrus. Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by a speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at Weeks 6 and 10 after the baseline.

6 Jan 2023

Prolonged survival in patients with local chronic infection after high-grade glioma treatment: Two case reports

High-grade gliomas are primary brain tumors with poor prognosis, despite surgical treatment followed by radiotherapy and concomitant chemotherapy. We present two cases of long-term survival in patients treated for high-grade glioma and concomitant prolonged bacterial wound infection. The first patient treated for glioblastoma IDH-wildtype had been without disease progression for 61 months from the first resected recurrence. Despite incomplete chemotherapy-induced myelosuppression in the second patient with anaplastic astrocytoma IDH-mutant, she died without disease relapse after 14 years from the diagnosis due to other comorbidities. We assume that the documented prolonged survival could be related to the bacterial infection.

Keywords: anaplastic astrocytoma; glioblastoma; high-grade glioma; prolonged survival; wound infection.

23 Dec 2022

rTMS treatment for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop

Background: In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks.

Objectives: We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation.

Methods: Patients were assigned to ten sessions of real or sham 1 Hz stimulation over the right posterior superior temporal gyrus (STG). Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at week 6 and 10 after the baseline.

19 Dec 2022

Impact of analgesic regimen on patient outcome following subarachnoid hemorrhage: positive adjuvant effects of metamizole

Introduction: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects.

Methods: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes.

19 Dec 2022

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche.

9 Dec 2022

A new approach to the determination of tubular membrane capacitance: passive membrane electrical properties under reduced electrical conductivity of the extracellular solution

The transverse-axial tubular system (tubular system) of cardiomyocytes plays a key role in excitation-contraction coupling. To determine the area of the tubular membrane in relation to the area of the surface membrane, indirect measurements through the determination of membrane capacitances are currently used in addition to microscopic methods. Unlike existing electrophysiological methods based on an irreversible procedure (osmotic shock), the proposed new approach uses a reversible short-term intermittent increase in the electrical resistance of the extracellular medium. The resulting increase in the lumen resistance of the tubular system makes it possible to determine separate capacitances of the tubular and surface membranes. Based on the analysis of the time course of the capacitive current, computational relations were derived to quantify the elements of the electrical equivalent circuit of the measured cardiomyocyte including both capacitances.

9 Dec 2022

Use of free radial forearm and pronator quadratus muscle flap: Anatomical study and clinical application

The authors present an anatomical study and clinical experience with radial forearm flap (RFF) and pronator quadratus muscle (PQM) application in the reconstruction of various body areas. The aim was to describe the anatomical placement and proportions of the PQM, the anatomical location of the major arterial branch of the radial artery supplying the PQM, and the application of this knowledge in clinical practice. The anatomical study was based upon an analysis of 13 fresh adult cadaver upper extremities, of which nine were female and four male; both arms from the same donors were used in four cases. The study of the PQM was performed using a dye-containing intraarterial injection, standard macro- and micro-preparation techniques, and chemical digestion. The data on the PQM size in males and females, thickness of the radial artery branch (the principal artery nourishing the muscle), and its position were analysed. The radial artery branch nourishing the PQM was identified in all cadaveric specimens of the anatomical study.

9 Dec 2022

Immune system disorders in the early post-injury period in patients after severe brain injury from the perspective of the severity of the injury

Background: Brain injuries are the most common cause of death in productive age. Besides the extent of the injury, other systemic factors can also affect the outcome. Patients suffering from severe brain injury often experience extracranial inflammatory complications during the early period of treatment. Here, we investigate the changes in immunity in patients with brain injury.

Methods: 121 patients and 92 healthy controls were included in the research. Blood samples were collected on admission and analyzed by flow cytometry and biochemical methods. Multiple clusters of differentiation (CD) and antibody levels were investigated. The results were compared between patients and controls. In addition, results of two classes of severity (Glasgow Coma Scale, GCS, of 3-5 vs. 6-8) were also compared.

9 Dec 2022

Model-informed unsupervised deep learning approaches to frequency and phase correction of MRS signals

Purpose: A supervised deep learning (DL) approach for frequency and phase correction (FPC) of MRS data recently showed encouraging results, but obtaining transients with labels for supervised learning is challenging. This work investigates the feasibility and efficiency of unsupervised deep learning-based FPC.

Methods: Two novel deep learning-based FPC methods (deep learning-based Cr referencing and deep learning-based spectral registration), which use a priori physics domain knowledge, are presented. The proposed networks were trained, validated, and evaluated using simulated, phantom, and publicly accessible in vivo MEGA-edited MRS data. The performance of our proposed FPC methods was compared with other generally used FPC methods, in terms of precision and time efficiency. A new measure was proposed in this study to evaluate the FPC method performance.

9 Dec 2022

Perinatal maternal mental health and amygdala morphology in young adulthood

The pre- and perinatal environment is thought to play a critical role in shaping brain development. Specifically, maternal mental health and maternal care have been shown to influence offspring brain development in regions implicated in emotional regulation such as the amygdala. In this study, we used data from a neuroimaging follow-up of a prenatal birth-cohort, the European Longitudinal Study of Pregnancy and Childhood, to investigate the impact of early postnatal maternal anxiety/co-dependence, and prenatal and early-postnatal depression and dysregulated mood on amygdala volume and morphology in young adulthood (n = 103). We observed that in typically developing young adults, greater maternal anxiety/co-dependence after birth was significantly associated with lower volume (right: t = -2.913, p = 0.0045, β = -0.523; left: t = -1.471, p = 0.144, β = -0.248) and non-significantly associated with surface area (right: t = -3.502, q = 0.069, <10%FDR, β = -0.090, left: t = -3.137, q = 0.117, <10%FDR, = -0.088) of the amygdala in young adulthood.

7 Dec 2022

Inter-individual differences in baseline dynamic functional connectivity are linked to cognitive aftereffects of tDCS

Transcranial direct current stimulation (tDCS) has the potential to modulate cognitive training in healthy aging; however, results from various studies have been inconsistent. We hypothesized that inter-individual differences in baseline brain state may contribute to the varied results. We aimed to explore whether baseline resting-state dynamic functional connectivity (rs-dFC) and/or conventional resting-state static functional connectivity (rs-sFC) may be related to the magnitude of cognitive aftereffects of tDCS. To achieve this aim, we used data from our double-blind randomized sham-controlled cross-over tDCS trial in 25 healthy seniors in which bifrontal tDCS combined with cognitive training had induced significant behavioral aftereffects. We performed a backward regression analysis including rs-sFC/rs-dFC measures to explain the variability in the magnitude of tDCS-induced improvements in visual object-matching task (VOMT) accuracy. Rs-dFC analysis revealed four rs-dFC states.

29 Nov 2022

Geometric Control of Cell Behavior by Biomolecule Nanodistribution

Many dynamic interactions within the cell microenvironment modulate cell behavior and cell fate. However, the pathways and mechanisms behind cell-cell or cell-extracellular matrix interactions remain understudied, as they occur at a nanoscale level. Recent progress in nanotechnology allows for mimicking of the microenvironment at nanoscale <i>in vitro</i>; electron-beam lithography (EBL) is currently the most promising technique. Although this nanopatterning technique can generate nanostructures of good quality and resolution, it has resulted, thus far, in the production of only simple shapes (e.g., rectangles) over a relatively small area (100 × 100 μm), leaving its potential in biological applications unfulfilled. Here, we used EBL for cell-interaction studies by coating cell-culture-relevant material with electron-conductive indium tin oxide, which formed nanopatterns of complex nanohexagonal structures over a large area (500 × 500 μm).

16 Nov 2022

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: One-Year Follow-up

Background and objectives: Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

Methods: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers.

16 Nov 2022

Deep Brain Stimulation during Pregnancy and Delivery: Review of Current Literature

Deep brain stimulation (DBS) is an established method in the treatment of not only Parkinson's disease motor complications but also dystonia and tremor, and there are data supporting the efficacy of DBS in epilepsy and some psychiatric problems. The alleviation of the neurologic problems may enable females of childbearing age to consider pregnancy because of being able to take care of their child. The aim of the study is to provide a review of the data available on the effect of DBS on the course of pregnancy and delivery in patients suffering from diseases amenable for DBS treatment (Parkinson's disease, dystonia, obsessive compulsive disorder, Tourette's syndrome, epilepsy). Although data available in the literature on pregnancy and childbirth in patients with an implanted active DBS system are limited to small case series and case reports, the number of younger patients implanted with DBS systems will potentially require more attention beyond specialized DBS centers.

16 Nov 2022

A Randomized, Double-Blind, Placebo-Controlled Trial of the Corticosteroid-Sparing Effects of Immunoglobulin in Myasthenia Gravis

Background and objectives: Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CS) and intravenous immunoglobulin (IVIG). This study was conducted to determine if immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent MG patients.

Methods: In this randomized, double-blind, placebo-controlled trial, CS-dependent MG patients (MGFA class II-Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/day) or placebo at week 0 (baseline). Maintenance doses (1 g/kg IGIV-C or placebo) were administered every three weeks through week 36. Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (QMG score ≥ 4 points from baseline).

16 Nov 2022

Current Management of Generalized Convulsive Status Epilepticus in Children

Generalized convulsive status epilepticus (GCSE) in pediatric patients is an emergency condition with high morbidity and mortality and potentially irreversible brain damage, leading to cognitive deterioration, psychomotor retardation, chronic epilepsy with recurring seizures, and other complications.

Treatment must be initiated in the impending GCSE phase, within five minutes of the onset of a generalized convulsive seizure. Early initiation of treatment and adequate therapy is a prerequisite for a good patient outcome.

Keywords: burst-suppression pattern; children; generalized convulsive status epilepticus; management; propofol infuse syndrome.

16 Nov 2022

Incidence of Emergence Delirium in the Pediatric PACU: Prospective Observational Trial

Emergence delirium (ED) is a postoperative complication in pediatric anesthesia characterized by perception and psychomotor disorder and has a negative impact on morbidity in the form of maladaptive behavior, which can last weeks after anesthesia. Patients with developed ED present with psychomotor anxiety, agitation, and are at higher risk of unintentional extraction of an intravenous cannula, self-harm and nausea and vomiting. The described incidence of ED varies between 25-80%, with a higher prevalence among children younger than 6 years of age. We aimed to determine the incidence of ED in pediatric patients (>1 month) after general anesthesia in the post-anesthesia care unit (PACU), using Paediatric Anaesthesia Emergence Delirium (PAED) score, Watcha score and Richmond agitation and sedation scale (RASS). The incidence of ED was the highest in the PAED score with cutoff ≥10 points (89.0%, n = 1088). When using PAED score >12 points, ED incidence was 19.3% (n = 236). The lowest incidence was described by Watcha and RASS scores, 18.8% (n = 230) vs. 18.1% (n = 221), respectively.

11 Nov 2022

Astrocyte reactivity in the glia limitans superficialis of the rat medial prefrontal cortex following sciatic nerve injury

The glia limitans superficialis (GLS) on the rodent cortical surface consists of astrocyte bodies intermingled with their cytoplasmic processes. Many studies have observed astrocyte reactivity in the medial prefrontal cortex (mPFC) parenchyma induced by a peripheral nerve injury, while the response of GLS astrocytes is still not fully understood. The aim of our study was to identify the reactivity of rat GLS astrocytes in response to sciatic nerve compression (SNC) over different time periods.

The alteration of GLS astrocyte reactivity was monitored using immunofluorescence (IF) intensities of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and NFκBp65. Our results demonstrated that SNC induced GLS astrocyte reactivity seen as increased intensities of GFAP-IF, and longer extensions of cytoplasmic processes into lamina I. First significant increase of GFAP-IF was observed on post-operation day 7 (POD7) after SNC with further increases on POD14 and POD21.

11 Nov 2022

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry

Background and objectives: COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19.

Methods: Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).

20 Oct 2022

Teaching Video NeuroImage: Amaurosis Fugax Due to Recurrent Central Retinal Artery Occlusion by Microemboli

A previously healthy 71-year-old woman with hypercholesterolemia and current tobacco use presented with transient painless vision loss in the left eye without other neurologic abnormalities.

The 30-second episodes, followed by a recovery, repeated in 2- to 3-minute intervals.¹ Microemboli passing through central retinal artery (CRA) vasculature (Video 1) originated from a complicated atherosclerotic plaque in the left internal carotid artery (Figure).

After receiving intravenous thrombolysis 5 hours after symptom onset,² she reported a scotoma in the inferior part of her left eye, which persisted 2 years later.

Retinal embolism from carotid artery disease is the most common cause of CRA occlusion.

20 Oct 2022

Laterality in functional and metabolic state of the bulbectomised rat brain detected by ASL and 1H MRS: A pilot study

Objectives: Pilot study validating the animal model of depression - the bilateral olfactory bulbectomy in rats - by two nuclear magnetic resonance methods, indirectly detecting the metabolic state of the brain. Furthermore, the study focussed on potential differences in brain laterality.

Methods: Arterial spin labelling assessed cerebral brain flow in prefrontal, sensorimotor, and piriform cortices, nucleus accumbens, hippocampus, thalamus, circle of Willis, and whole brain. Proton magnetic resonance spectroscopy provided information about relative metabolite concentrations in the cortex and hippocampus.

Results: Arterial spin labelling found no differences in cerebral perfusion in the group comparison but revealed lateralisation in the thalamus of the control group and the sensorimotor cortex of the bulbectomized rats.

20 Oct 2022

Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydrocannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration.

14 Oct 2022

Wellbeing and national identity in three generations of Czech and Slovak Holocaust survivors

Subjective wellbeing (SWB) is an important factor of global adjustment. Intergenerational satisfaction in seriously traumatized people has not been studied so far in homogenous populations of Central and Eastern Europe. This study focuses on the SWB in three generations of survivors living in the Czech Republic and Slovakia after World War II (WWII). The focal groups were Holocaust survivors (ages 71-95, n = 47), Holocaust survivors' children (ages 30-73, n = 86), and their grandchildren (ages 15-48, n = 88), and they were compared to aged-matched groups without Holocaust history. The first and second generation of Holocaust survivors scored significantly lower than the comparison groups in wellbeing, as measured using the Schwartz Outcome Scale-10 (SOS-10). There was no significant difference in life satisfaction in any of the three generations. Within the focal group, identification as Jewish or as also Jewish was comparable in all three generations of Holocaust survivors (74% in the first, 79% in the second, and 66% in the third generation).

14 Oct 2022

Deep brain stimulation of the anterior nuclei of the thalamus in focal epilepsy

Objective: To review the therapeutic effects of deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) and the predictors of its effectiveness, safety, and adverse effects.

Methods: A comprehensive search of the medical literature (PubMed) was conducted to identify relevant articles investigating ANT-DBS therapy for epilepsy. Out of 332 references, 77 focused on focal epilepsies were reviewed.

Results: The DBS effect is probably due to decreased synchronization of epileptic activity in the cortex. The potential mechanisms from cellular to brain network levels are presented. The ANT might participate actively in the network elaborating focal seizures. The effects of ANT-DBS differed in various studies; ANT-DBS was linked with a 41% seizure frequency reduction at 1 year, 69% at 5 years, and 75% at 7 years.

14 Oct 2022

Perceptions on basilar artery occlusion management in China versus other countries: Analysis of the after the BEST of BASICS (ABBA) survey

Introduction: Uncertainty remains on the optimal management of basilar artery occlusion (BAO). Two large randomized controlled trials (RCTs) in 2019 and 2021 demonstrated neutral results with respect to the use of endovascular therapy (EVT) for BAO. This study aimed to understand regional variation in physicians' perceptions towards the treatment of BAO as stratified by physician respondents from China versus outside China, prior to the publication of studies demonstrating a benefit of EVT for BAO.

Methods: An international online survey was conducted of stroke neurologists and neurointerventionalists from January to March 2022. Survey questions evaluated physician opinions toward the use of EVT in BAO, as well as the clinical and imaging features underlying treatment decisions. Respondents were dichotomized as either from China or from other countries and differences between groups were analyzed.

14 Oct 2022

Is non-invasive brain stimulation effective for cognitive enhancement in Alzheimer's disease? An updated meta-analysis

Objective: Alzheimer's disease dementia (AD) and its preclinical stage, mild cognitive impairment (MCI), are critical issues confronting the aging society. Non-invasive brain stimulation (NIBS) techniques have the potential to be effective tools for enhancing cognitive functioning. The main objective of our meta-analysis was to quantify and update the status of the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS) when applied in AD and MCI.

Methods: The systematic literature search was conducted in PubMed and Web of Science according to PRISMA statement.

Results: Pooled effect sizes (Hedges' g) from 32 studies were analyzed using random effect models. We found both, rTMS and tDCS to have significant immediate cognition-enhancing effect in AD with rTMS inducing also beneficial long-term effects. We found no evidence for synergistic effect of cognitive training with NIBS.

5 Oct 2022

Diagnosis and classification of optic neuritis

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis.

21 Sep 2022

Multimodal combination of neuroimaging methods for localizing the epileptogenic zone in MR-negative epilepsy

The objective was to determine the optimal combination of multimodal imaging methods (IMs) for localizing the epileptogenic zone (EZ) in patients with MR-negative drug-resistant epilepsy. Data from 25 patients with MR-negative focal epilepsy (age 30 ± 10 years, 16M/9F) who underwent surgical resection of the EZ and from 110 healthy controls (age 31 ± 9 years; 56M/54F) were used to evaluate IMs based on 3T MRI, FDG-PET, HD-EEG, and SPECT. Patients with successful outcomes and/or positive histological findings were evaluated. From 38 IMs calculated per patient, 13 methods were selected by evaluating the mutual similarity of the methods and the accuracy of the EZ localization. The best results in postsurgical patients for EZ localization were found for ictal/ interictal SPECT (SISCOM), FDG-PET, arterial spin labeling (ASL), functional regional homogeneity (ReHo), gray matter volume (GMV), cortical thickness, HD electrical source imaging (ESI-HD), amplitude of low-frequency fluctuation (ALFF), diffusion tensor imaging, and kurtosis imaging.

13 Sep 2022

Continuum of sensory profiles in diabetes mellitus patients with and without neuropathy and pain

Background: Quantitative sensory testing (QST) assesses the functional integrity of small and large nerve fibre afferents and central somatosensory pathways; QST was assumed to provide insight into the mechanisms of neuropathy. We analysed QST profiles and phenotypes in diabetes mellitus patients to study whether these could differentiate patients with and without pain and neuropathy.

Methods: A standardised QST protocol was performed and 'loss and gain of function' abnormalities were analysed in four groups of subjects: diabetic patients with painful (pDSPN; n=220) and non-painful distal symmetric polyneuropathy (nDSPN; n=219), diabetic patients without neuropathy (DM; n=23), and healthy non-diabetic subjects (n=37).

9 Sep 2022

Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial

Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown.

Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation).

9 Sep 2022

Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the present work aimed to study preventive effects on SCI-induced CNP development by repeated administration of two vegetal polyphenolic extracts: grape stalk extract (GSE) and coffee extract (CE). Thermal hyperalgesia and mechanical allodynia were evaluated at 7, 14 and 21 days postinjury. Then, gliosis, ERK phosphorylation and the expression of CCL2 and CX3CL1 chemokines and their receptors, CCR2 and CX3CR1, were analyzed in the spinal cord. Gliosis and CX3CL1/CX3CR1 expression were also analyzed in the anterior cingulate cortex (ACC) and periaqueductal gray matter (PAG) since they are supraspinal structures involved in pain perception and modulation.

9 Sep 2022

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic.

9 Sep 2022

Relapsing MRI-negative myelitis associated with myelin-oligodendrocyte glycoprotein autoantibodies: a case report

Background: Serum antibodies to myelin-oligodendrocyte glycoprotein (MOG) are biomarkers of MOG-IgG-associated disorder (MOGAD), a demyelinating disease distinct from both multiple sclerosis and aquaporin-4-IgG neuromyelitis optica spectrum disorder. The phenotype of MOGAD is broad and includes optic neuritis, transverse myelitis, and acute demyelinating encephalomyelitis. Myelitis is common with MOGAD and typically results in acute and severe disability, although prospects for recovery are often favorable with prompt immunotherapy.

Case presentation: This contribution presents a unique case report of a young male patient exhibiting relapsing myelitis with normal spinal cord and brain magnetic resonance imaging.

9 Sep 2022

Cerebrovascular Complications of COVID-19 Disease in Children: A Single-Center Case Series

This work presents a case series of four children diagnosed with severe cerebrovascular disease in association with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet no patient from the group met typical diagnostic criteria for multisystem inflammatory syndrome in children. Our aim was to highlight the possible vascular involvement and coagulopathies associated with SARS-CoV-2 infection in the pediatric population. Further data are needed to better understand the pathophysiological basis of this condition in children and to ensure its optimal management.

Keywords: Brain vasculopathy; COVID-19; Children; SARS-CoV-2; Stroke.

11 Aug 2022

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Background: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown.

Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies.

Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination.

11 Aug 2022

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter

Purpose: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter.

Methods: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images.

10 Aug 2022

Increased occurrence of Treponema spp. and double-species infections in patients with Alzheimer's disease

Although the link between microbial infections and Alzheimer's disease (AD) has been demonstrated in multiple studies, the involvement of pathogens in the development of AD remains unclear. Here, we investigated the frequency of the 10 most commonly cited viral (HSV-1, EBV, HHV-6, HHV-7, and CMV) and bacterial (Chlamydia pneumoniae, Helicobacter pylori, Borrelia burgdorferi, Porphyromonas gingivalis, and Treponema spp.) pathogens in serum, cerebrospinal fluid (CSF) and brain tissues of AD patients. We have used an in-house multiplex PCR kit for simultaneous detection of five bacterial and five viral pathogens in serum and CSF samples from 50 AD patients and 53 healthy controls (CTRL). We observed a significantly higher frequency rate of AD patients who tested positive for Treponema spp. compared to controls (AD: 62.2 %; CTRL: 30.3 %; p-value = 0.007).

10 Aug 2022

The Significance of MicroRNAs in the Molecular Pathology of Brain Metastases

Brain metastases are the most frequent intracranial tumors in adults and the cause of death in almost one-fourth of cases. The incidence of brain metastases is steadily increasing. The main reason for this increase could be the introduction of new and more efficient therapeutic strategies that lead to longer survival but, at the same time, cause a higher risk of brain parenchyma infiltration. In addition, the advances in imaging methodology, which provide earlier identification of brain metastases, may also be a reason for the higher recorded number of patients with these tumors. Metastasis is a complex biological process that is still largely unexplored, influenced by many factors and involving many molecules. A deeper understanding of the process will allow the discovery of more effective diagnostic and therapeutic approaches that could improve the quality and length of patient survival.

10 Aug 2022

Blood-Brain Barrier Alterations and Edema Formation in Different Brain Mass Lesions

Differential diagnosis of brain lesion pathologies is complex, but it is nevertheless crucial for appropriate clinical management. Advanced imaging methods, including diffusion-weighted imaging and apparent diffusion coefficient, can help discriminate between brain mass lesions such as glioblastoma, brain metastasis, brain abscesses as well as brain lymphomas. These pathologies are characterized by blood-brain barrier alterations and have been extensively studied. However, the changes in the blood-brain barrier that are observed around brain pathologies and that contribute to the development of vasogenic brain edema are not well described. Some infiltrative brain pathologies such as glioblastoma are characterized by glioma cell infiltration in the brain tissue around the tumor mass and thus affect the nature of the vasogenic edema.

19 Jul 2022

Cathepsin B p.Gly284Val Variant in Parkinson's Disease Pathogenesis

Parkinson's disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort.

19 Jul 2022

Differential spatial distribution of white matter lesions in Parkinson's and Alzheimer's diseases and cognitive sequelae

White Matter Lesions (WML) are a radiological finding common in aged subjects. We explored the impact of WML on underlying neurodegenerative processes. We focused on the impact of WML on two neurodegenerative diseases with different pathology. In this cross-sectional study of 137 subjects (78 female, 59 men, mean age 67.2; 43-87 years), we compared WML in healthy controls (HC; n = 55), patients with Alzheimer's disease and amnestic Mild Cognitive Impairment (aMCI), and Parkinson's disease patients with normal cognition and with MCI. Subjects with AD and aMCI were treated as one group (n = 40), subjects with PD and PDMCI were another group (n = 42).

22 Jun 2022

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database.

22 Jun 2022

Comparison of CNN-Learned vs. Handcrafted Features for Detection of Parkinson's Disease Dysgraphia in a Multilingual Dataset

Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a noninvasive and inexpensive approach to monitoring the progress of the disease. However, although several approaches to supportive PDYS diagnosis have been proposed (mainly based on handcrafted features (HF) extracted from online handwriting or the utilization of deep neural networks), it remains unclear which approach provides the highest discrimination power and how these approaches can be transferred between different datasets and languages.

31 May 2022

Ultrashort Door-to-Needle Time for Intravenous Thrombolysis Is Safer and Improves Outcome in the Czech Republic: Nationwide Study 2004 to 2019

Background The benefit of intravenous thrombolysis is time dependent. It remains unclear, however, whether dramatic shortening of door-to-needle time (DNT) among different types of hospitals nationwide does not compromise safety and still improves outcome. Methods and Results Multifaceted intervention to shorten DNT was introduced at a national level, and prospectively collected data from a registry between 2004 and 2019 were analyzed. Generalized estimating equation was used to identify the association between DNT and outcomes independently from prespecified baseline variables. The primary outcome was modified Rankin score 0 to 1 at 3 months, and secondary outcomes were parenchymal hemorrhage/intracerebral hemorrhage (ICH), any ICH, and death.

17 May 2022

A high-density EEG investigation into the neurocognitive mechanisms underlying differences between personality profiles in social information processing

This study investigated whether differences between personality styles in the processing of social stimuli reflect variability in underlying general-purpose or social-specific neurocognitive mechanisms. Sixty-five individuals classified previously into two distinct personality profiles underwent high-density electroencephalography whilst performing tasks that tap into both aspects of cognitive processing - namely, two distinct facets of general-purpose response inhibition (interference resolution and action withholding) during social information processing. To determine the stage of processing at which personality differences manifest, we assessed event-related components associated with the early visual discrimination of social stimuli (N170, N190) and later more general conflict-related processes (N2, P3).

17 May 2022

Sick leave duration as a potential marker of functionality and disease severity in depression

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression.Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic.

Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work.

17 May 2022

Semi-automated detection of cervical spinal cord compression with the Spinal Cord Toolbox

Background: Degenerative cervical spinal cord compression is becoming increasingly prevalent, yet the MRI criteria that define compression are vague, and vary between studies. This contribution addresses the detection of compression by means of the Spinal Cord Toolbox (SCT) and assesses the variability of the morphometric parameters extracted with it.

Methods: Prospective cross-sectional study. Two types of MRI examination, 3 and 1.5 T, were performed on 66 healthy controls and 118 participants with cervical spinal cord compression. Morphometric parameters from 3T MRI obtained by Spinal Cord Toolbox (cross-sectional area, solidity, compressive ratio, torsion) were combined in multivariate logistic regression models with the outcome (binary dependent variable) being the presence of compression determined by two radiologists.

17 May 2022

Neuroplasticity in Motor Learning Under Variable and Constant Practice Conditions-Protocol of Randomized Controlled Trial

Background: There is numerous literature on mechanisms underlying variability of practice advantages. Literature includes both behavioral and neuroimaging studies. Unfortunately, no studies are focusing on practice in constant conditions to the best of our knowledge. Hence it is essential to assess possible differences in mechanisms of neuroplasticity between constant vs. variable practice conditions. The primary objectives of the study described in this protocol will be: (1) to determine the brain's structural and functional changes following constant and variable practice conditions in motor learning (structural and functional magnetic resonance imaging, MRI); (2) to determine the EEG activation and connectivity between cognitive, sensory, and motor cerebral cortex areas (central, temporal, parietal, occipital) in constant and variable practice conditions and as a function of practice time.

16 May 2022

Structural MRI-Based Schizophrenia Classification Using Autoencoders and 3D Convolutional Neural Networks in Combination with Various Pre-Processing Techniques

Schizophrenia is a severe neuropsychiatric disease whose diagnosis, unfortunately, lacks an objective diagnostic tool supporting a thorough psychiatric examination of the patient. We took advantage of today’s computational abilities, structural magnetic resonance imaging, and modern machine learning methods, such as stacked autoencoders (SAE) and 3D convolutional neural networks (3D CNN), to teach them to classify 52 patients with schizophrenia and 52 healthy controls. The main aim of this study was to explore whether complex feature extraction methods can help improve the accuracy of deep learning-based classifiers compared to minimally preprocessed data. Our experiments employed three commonly used preprocessing steps to extract three different feature types.

16 May 2022

Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin

Cardio- and cerebrovascular diseases are leading causes of death and disability, resulting in one of the highest socio-economic burdens of any disease type. The discovery of bacterial and human plasminogen activators and their use as thrombolytic drugs have revolutionized treatment of these pathologies. Fibrin-specific agents have an advantage over non-specific factors because of lower rates of deleterious side effects. Specifically, staphylokinase (SAK) is a pharmacologically attractive indirect plasminogen activator protein of bacterial origin that forms stoichiometric noncovalent complexes with plasmin, promoting the conversion of plasminogen into plasmin. Here we report a computer-assisted re-design of the molecular surface of SAK to increase its affinity for plasmin.

16 May 2022

Contribution of the multi-echo approach in accelerated functional magnetic resonance imaging multiband acquisition

We wanted to verify the effect of combining multi-echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi-slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole-brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single-echo (SE) data and ME data based on optimal combinations weighted by the contrast-to-noise ratio. Global metrics (temporal signal-to-noise ratio, signal-to-noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data.

16 May 2022

Prenatal stress and its association with amygdala-related structural covariance patterns in youth

Background: Prenatal stress influences brain development and mood disorder vulnerability. Brain structural covariance network (SCN) properties based on inter-regional volumetric correlations may reflect developmentally-mediated shared plasticity among regions. Childhood trauma is associated with amygdala-centric SCN reorganization patterns, however, the impact of prenatal stress on SCN properties remains unknown.

Methods: The study included participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with archival prenatal stress data and structural MRI acquired in young adulthood (age 23-24). SCNs were constructed based on Freesurfer-extracted volumes of 7 subcortical and 34 cortical regions.

16 May 2022

Is pregnancy in MS patients safe and what is its impact on MS course? Real World evidence of 1533 pregnancies in Czech Republic

Background: A special care of MS women planning a pregnancy is highly demanding especially in the terms of disease modifying treatment (DMD) decisions and counselling regarding periods of conception, pregnancy and postpartum period.

Objective: To provide data about impact of pregnancy, delivery or miscarriage/artificial abortion on MS disease course in Czech women with MS based on analysis of retrospective data from the Czech national registry ReMuS.

Methods: The analysis focused on women with MS with at least one record of pregnancy in the registry. Clinical data (EDSS, relapses) were collected prior to conception, during pregnancy and after delivery or miscarriage/artificial abortion.

16 May 2022

A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]: Mechanical Stress, Vulnerability and Time

Study design: Literature Review (Narrative).

Objective: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5.

Methods: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework.

16 May 2022

Degenerative Cervical Myelopathy: Development and Natural History [AO Spine RECODE-DCM Research Priority Number 2]

Study design: Narrative review.

Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM).

Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM.

Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals' risk for DCM development.

9 May 2022

EXPRESS: Association of statin pretreatment with baseline stroke severity and outcome in patients with acute ischemic stroke: an observational study

ABSTRACTBackground:Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke.

Aims: Our aim was to evaluate the association of statin pretreatment with the severity in acute ischemic stroke (AIS).

Methods: We analyzed SITS International Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with statin information at baseline. The primary outcome was baseline NIH stroke scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 hours, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention.

9 May 2022

Rationale and study design of a trial to assess r TMS add - on v alue for the amelioration of negative symptoms of schizophrenia (RADOVAN)

Background: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham.

Methods: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic.

9 May 2022

Intensive Circuit Class Therapy in Patients with Relapsing-Remitting Multiple Sclerosis

Objective: Long-term physiotherapy is of considerable benefit to patients with multiple sclerosis (MS) who have motor dysfunction or gait impairment. The aim of this study was to determine the effectiveness of a 12-week intensive circuit class therapy for patients with MS, with a wider focus on fatigue and gait ability.

Methods: A total of 46 patients with relapsing-remitting MS were divided randomly into 2 groups: 23 patients (mean Expanded Disability Status Scale (EDSS) 2.33 ± 0.74) participated in an intensive 12-week course of intensive circuit class therapy, and 23 patients (mean EDSS 2.04 ± 0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36).

22 Apr 2022

Bridging structural and functional biomarkers in functional movement disorder using network mapping

Background: There are gaps in our neurobiological understanding of functional movement disorder (FMD).

Objectives: We investigated gray matter volumetric profiles in FMD, and related findings to resting-state functional connectivity (rsFC) profiles using Human Connectome Project data.

Methods: Volumetric differences between 53 FMD patients and 50 controls were examined, as well as relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping was also used to probe whether FMD-related structural alterations preferentially impacted brain areas with dense rsFC.

Results: Compared to controls without neurological comorbidities (albeit with mild depression and anxiety as a group), the FMD cohort did not show any volumetric differences.

22 Apr 2022

LuminoCell: a versatile and affordable platform for real-time monitoring of luciferase-based reporters

Luciferase reporter assays represent a simple and sensitive experimental system in cell and molecular biology to study multiple biological processes. However, the application of these assays is often limited by the costs of conventional luminometer instruments and the versatility of their use in different experimental conditions. Therefore, we aimed to develop a small, affordable luminometer allowing continuous measurement of luciferase activity, designed for inclusion into various kinds of tissue culture incubators. Here, we introduce LuminoCell-an open-source platform for the construction of an affordable, sensitive, and portable luminometer capable of real-time monitoring in-cell luciferase activity. The LuminoCell costs $40, requires less than 1 h to assemble, and it is capable of performing real-time sensitive detection of both magnitude and duration of the activity of major signalling pathways in cell cultures, including receptor tyrosine kinases (EGF and FGF), WNT/β-catenin, and NF-κB.

14 Apr 2022

The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments

he response of the blood-brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has long-lasting consequences, but most changes in the pathophysiological cascades occur in the first few days following SAH. These changes determine the development of early brain injury as well as delayed cerebral ischemia. SAH-induced neuroprotection also plays an important role and weakens the negative impact of SAH.

4 Apr 2022

Functional Abilities of an International Post-Stroke Population: Standard Assessment of Global Everyday Activities (SAGEA) Scale

Background and objectives: Function is an important outcome after stroke; traditional assessments may not capture functional deficits important to patients. We examined the validity of the Standard Assessment of Global Everyday Activities (SAGEA), a patient-reported outcome that assesses activities important to patients and for use in international clinical trials.

Methods: The NAVIGATE-ESUS trial evaluated rivaroxaban compared to aspirin in preventing recurrent stroke in 7213 participants. The Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the SAGEA were collected at entry. Chi square tests were used to compare proportions and Spearman rank correlations were used to compare between measures. SAGEA was compared to the Modified Frailty Index (MFI) and the occurrence of infarct to examine criterion validity RESULTS:

17 Mar 2022

HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation

Background/aim: Glioblastoma (GBM) is one of the deadliest human cancers responding very poorly to therapy. Although the central nervous system has been traditionally considered an immunologically privileged site with an enhanced immune response, GBM appears to benefit from this immunosuppressive milieu. Immunomodulatory molecules play an important role in immune tumor-host interactions. Non-classical human leukocyte antigens (HLA) class Ib molecules HLA-E, HLA-F, and HLA-G have been previously described to be involved in protecting semi-allogeneic fetal allografts from the maternal immune response and in transplant tolerance as well as tumoral immune escape. Unfortunately, their role in GBM remains poorly understood. Our study, therefore, aimed to characterize the relationship between the expression of these molecules in GBM on the transcriptional level and clinicopathological and molecular features of GBM as well as the effect of ionizing radiation.

17 Mar 2022

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study

Importance: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, setting, and participants: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries.

17 Mar 2022

Clozapine Reverses Dysfunction of Glutamatergic Neurons Derived From Clozapine-Responsive Schizophrenia Patients

The cellular pathology of schizophrenia and the potential of antipsychotics to target underlying neuronal dysfunctions are still largely unknown. We employed glutamatergic neurons derived from induced pluripotent stem cells (iPSC) obtained from schizophrenia patients with known histories of response to clozapine and healthy controls to decipher the mechanisms of action of clozapine, spanning from molecular (transcriptomic profiling) and cellular (electrophysiology) levels to observed clinical effects in living patients. Glutamatergic neurons derived from schizophrenia patients exhibited deficits in intrinsic electrophysiological properties, synaptic function and network activity. Deficits in K⁺ and Na⁺ currents, network behavior, and glutamatergic synaptic signaling were restored by clozapine treatment, but only in neurons from clozapine-responsive patients.

4 Mar 2022

Successful AZV projects

The Ministry of Health has already announced the result of a one-stage public competition in research, experimental development and innovation for the years 2022-2025 for special-purpose support for medical research and development projects.

24 Feb 2022

Intensive circuit class therapy in patients with relapsing-remitting multiple sclerosis

Long-term physiotherapy is of considerable benefit to patients with motor dysfunction or gait impairment in patients with multiple sclerosis (MS). The aim of this study was to determine the effectiveness of 12-week intensive circuit class therapy (ICT) for patients with MS, with a wider focus on fatigue and gait ability. Methods: A total of 46 relapsing-remitting MS patients were divided randomly: Twenty-three of them (mean Expanded Disability Status Scale (EDSS) 2.33±0.74) took part in an intensive 12-week course of ICT and 23 (mean EDSS 2.04±0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36).

16 Feb 2022

Actions of a Shaken Heart: Interoception Interacts with Action Processing

In the present study, we investigated the modulatory influence of the unconscious, bodily arousal on motor-related embodied information. Specifically, we examined how the interoceptive prediction error interacts with the event-related potentials linked to action-effect processing. Participants were asked to perform a task with self-initiated or externally-triggered sounds while receiving synchronous or false auditory cardiac feedback. The results found that interaction of interoceptive manipulation and action-effect processing modulates the frontal subcomponent of the P3 response. During the synchronous cardiac feedback, the P3 response to self-initiated tones was enhanced. During the false cardiac feedback, the frontal cortical response was reversed. N1 and P2 components were affected by the interoceptive manipulation, but not by the interaction of interoception and action processing.

8 Feb 2022

Risk factors for depression and anxiety in painful and painless diabetic polyneuropathy: A multicentre observational cross-sectional study

Background: Despite the high prevalence of depression and anxiety in chronic pain conditions, current knowledge concerning emotional distress among painful diabetic polyneuropathy (pDSPN) and other diabetes mellitus (DM) sufferers is limited.

Methods: This observational multicentre cohort study employed the Hospital Anxiety and Depression Scale, the Beck Depression Inventory II and the State-Trait Anxiety Inventory to assess symptoms of depression and anxiety in several groups with diabetes, as well as in a control group. The study cohort included 347 pDSPN patients aged 63.4 years (median), 55.9% males; 311 pain-free diabetic polyneuropathy (nDSPN) patients aged 63.7 years, 57.9% males; 50 diabetes mellitus (DM) patients without polyneuropathy aged 61.5 years, 44.0% males; and 71 healthy controls (HC) aged 63.0 years, 42.3% males.

8 Feb 2022

Human iPSC-Derived Neural Models for Studying Alzheimer's Disease: from Neural Stem Cells to Cerebral Organoids

During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study mechanisms of human neural development, disease modeling, and drug discovery in vitro. Especially in the field of Alzheimer's disease (AD), where this treatment is lacking, tremendous effort has been put into the investigation of molecular mechanisms behind this disease using induced pluripotent stem cell-based models. Numerous of these studies have found either novel regulatory mechanisms that could be exploited to develop relevant drugs for AD treatment or have already tested small molecules on in vitro cultures, directly demonstrating their effect on amelioration of AD-associated pathology. This review thus summarizes currently used differentiation strategies of induced pluripotent stem cells towards neuronal and glial cell types and cerebral organoids and their utilization in modeling AD and potential drug discovery.

8 Feb 2022

The reduction of hippocampal volume in Parkinson's disease

The volume of the hippocampus decreases more slowly than the volume of the cortex during normal aging. We explored changes in the hippocampus-to-cortex volume (HV:CTV) ratio with increasing age in non-demented Parkinson's disease (PD) patients as compared to healthy controls (HC). We also evaluated the association between the HV:CTV ratio and cognitive outcomes. Altogether 130 participants without dementia aged 51-88 years were consecutively enrolled, including 54 PD patients (mean age 67, standard deviation (SD) 8 years) and 76 HC (mean age 69, SD 7 years). All participants underwent structural magnetic resonance examination and psychological evaluation. Hippocampal and cortex volumes were determined from T1 and FLAIR scans using FreeSurfer software, and the HV:CTV ratio was calculated. Regression lines for age-dependence of the HV:CTV ratio for PD and HC groups were calculated.

7 Feb 2022

Between-Center Variation in Outcome After Endovascular Treatment of Acute Stroke: Analysis of Two Nationwide Registries

Background: Insight in differences in patient outcomes between endovascular thrombectomy (EVT) centers can help to improve stroke care. We assessed between-center variation in functional outcome of patients with acute ischemic stroke who were treated with EVT. We analyzed to what extent this variation may be explained by modifiable center characteristics.

Methods: We used nationwide registry data of patients with stroke treated with EVT in the Netherlands and in the Czech Republic. Primary outcome was modified Rankin Scale score at 90 days as an indicator of disability. We used multilevel ordinal logistic regression to quantify the between-center variation in outcomes and the impact of patient and center characteristics.

7 Feb 2022

Emergency cesarean section is a risk factor for depressive symptoms when breastfeeding is limited

Objective: Previous studies indicated associations between cesarean section (CS), breastfeeding, and depressive symptoms. There is, however, little research integrating these variables into one model to analyze their interrelations. The aim of this observational prospective longitudinal study is to examine whether the effect of CS on postpartum depressive symptoms is mediated by difficulties with breastfeeding.

Methods: The participants were recruited in 5 maternity hospitals during their prenatal medical check-ups. Breastfeeding status was self-reported by the mothers six weeks postpartum. Screening for depressive symptoms was performed at six weeks (N = 404) and nine months (N = 234) postpartum using the Edinburgh Postnatal Depression Scale.

28 Jan 2022

Is the vertex a good control stimulation site? Theta burst stimulation in healthy controls

The vertex has been used as a suitable control stimulation site in repetitive transcranial magnetic stimulation studies. The objectives of this study are (1) to assess cognitive performance (CP) after theta burst stimulation (TBS); (2) to evaluate whether clinically relevant cortical areas might be reached by vertex stimulation and how that might influence CP. Twenty young healthy subjects performed a cognitive task prior to and immediately after intermittent TBS (iTBS) and continuous TBS (cTBS) of two active cortical stimulation sites and the vertex. We used the Wilcoxon signed-rank test to compare the pre- and post-stimulation reaction times (RTs) and a mixed ANOVA analysis to evaluate the effect of the stimulation on changes in RTs.

28 Jan 2022

Next-generation sequencing in children with epilepsy: The importance of precise genotype-phenotype correlation

Aim: The primary goal was to determine the yield of next-generation sequencing (NGS) epilepsy gene panels used for epilepsy etiology diagnosing using a multidisciplinary approach and to demonstrate the importance of genotype-phenotype correlations. The secondary goal was to evaluate the application of precision medicine in selected patients.

Methods: This single-center retrospective study included a total of 175 patients (95 males and 80 females) aged 0-19 years. They were examined between 2015 and 2020 using an NGS epilepsy gene panel (270 genes). A bioinformatic analysis was performed including copy number variation identification. Thorough genotype-phenotype correlation was performed.

28 Jan 2022

Evaluating Magnetic Resonance Diffusion Properties Together with Brain Volumetry May Predict Progression to Multiple Sclerosis

Rationale and objectives: Although the gold standard in predicting future progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) consists in the McDonald criteria, efforts are being made to employ various advanced MRI techniques for predicting clinical progression. This study's main aim was to evaluate the predictive power of diffusion tensor imaging (DTI) of the brain and brain volumetry to distinguish between patients having CIS with future progression to CDMS from those without progression during the following 2 years and to compare those parameters with conventional MRI evaluation.

Materials and methods: All participants underwent an MRI scan of the brain.

25 Jan 2022

Electrical brain stimulation and continuous behavioral state tracking in ambulatory humans

Objective: Electrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel devices capable of DBS and continuous intracranial EEG (iEEG) telemetry enable detailed assessments of therapy efficacy and tracking sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez's circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).

Approach: The iEEG recorded from HPC is used to classify sleep during concurent DBS targeting ANT.

17 Jan 2022

The role of central autonomic nervous system dysfunction in Takotsubo syndrome: a systematic review

Introduction: Takotsubo syndrome (TTS), also known as stress cardiomyopathy or "broken heart" syndrome, is a mysterious condition that often mimics an acute myocardial infarction. Both are characterized by left ventricular systolic dysfunction. However, this dysfunction is reversible in the majority of TTS patients.

Purpose: Recent studies surprisingly demonstrated that TTS, initially perceived as a benign condition, has a long-term prognosis akin to myocardial infarction. Therefore, the health consequences and societal impact of TTS are not trivial. The pathophysiological mechanisms of TTS are not yet completely understood. In the last decade, attention has been increasingly focused on the putative role of the central nervous system in the pathogenesis of TTS.

17 Jan 2022

Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS.

Methods: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13).

17 Jan 2022

Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry

Data comprise intracranial EEG (iEEG) brain activity represented by stereo EEG (sEEG) signals, recorded from over 100 electrode channels implanted in any one patient across various brain regions. The iEEG signals were recorded in epilepsy patients (N = 10) undergoing invasive monitoring and localization of seizures when they were performing a battery of four memory tasks lasting approx. 1 hour in total. Gaze tracking on the task computer screen with estimating the pupil size was also recorded together with behavioral performance. Each dataset comes from one patient with anatomical localization of each electrode contact. Metadata contains labels for the recording channels with behavioral events marked from all tasks, including timing of correct and incorrect vocalization of the remembered stimuli. The iEEG and the pupillometric signals are saved in BIDS data structure to facilitate efficient data sharing and analysis.

7 Jan 2022

Identification of Laminar Composition in Cerebral Cortex Using Low-Resolution Magnetic Resonance Images and Trust Region Optimization Algorithm

Pathological changes in the cortical lamina can cause several mental disorders. Visualization of these changes in vivo would enhance their diagnostics. Recently a framework for visualizing cortical structures by magnetic resonance imaging (MRI) has emerged. This is based on mathematical modeling of multi-component T₁ relaxation at the sub-voxel level. This work proposes a new approach for their estimation. The approach is validated using simulated data. Sixteen MRI experiments were carried out on healthy volunteers. A modified echo-planar imaging (EPI) sequence was used to acquire 105 individual volumes. Data simulating the images were created, serving as the ground truth. The model was fitted to the data using a modified Trust Region algorithm. In single voxel experiments, the estimation accuracy of the T₁ relaxation times depended on the number of optimization starting points and the level of noise.

3 Jan 2022

Insights into déjà vu: Associations between the frequency of experience and amplitudes of low-frequency oscillations in resting-state functional magnetic resonance imaging

The phenomenon of déjà vu (DV) has intrigued scientists for decades, yet its neurophysiological underpinnings remain elusive. Brain regions have been identified in which morphometry differs between healthy individuals according to the frequency of their DV experiences. This study built upon these findings by assessing if and how neural activity in these and other brain regions also differ with respect to DV experience. Resting-state fMRI was performed on 68 healthy volunteers, 44 of whom reported DV experiences (DV group) and 24 who did not (NDV group). Using multivariate analyses, we then assessed the (fractional) amplitude of low-frequency fluctuations (fALFF/ALFF), a metric that is believed to index brain tissue excitability, for five discrete frequency bands within sets of brain regions implicated in DV and those comprising the default mode network (DMN).

3 Jan 2022

Nationwide screening for Fabry disease in unselected stroke patients

Background and aims: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients.

Methods: A prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males-enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3.

Results: 986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%.

23 Dec 2021

Socioeconomic and Cognitive Roots of Trait Anxiety in Young Adults

In 54 participants (41% women) from the Czech arm of the European Longitudinal Study of Pregnancy and Childhood, a national birth cohort with prospectively collected data from their birth until young adulthood, we aimed to study the association between early-life socioeconomic deprivation, cognitive ability in adolescence, trait anxiety and resting state functional connectivity of the lateral prefrontal cortex in young adulthood. We found that early-life socioeconomic deprivation was associated with lower cognitive ability in adolescence (at age 13) as well as higher trait anxiety in young adulthood (at age 23/24). Higher cognitive ability in adolescence predicted lower trait anxiety in young adulthood. Resting state functional connectivity between the right lateral prefrontal cortex and a cluster of voxels including left precentral gyrus, left postcentral gyrus and superior frontal gyrus mediated the relationship between lower cognitive ability in adolescence and higher trait anxiety in young adulthood. These findings indicate that lower cognitive ability and higher trait anxiety may be both consequences of socioeconomic deprivation in early life.

23 Dec 2021

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as 'chemo fog'. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning.This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases.

16 Dec 2021

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

Introduction: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia.

Methods: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed.

Results: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1;

13 Dec 2021

Shannon entropy: A novel parameter for quantifying pentagon copying performance in non-demented Parkinson's disease patients

Introduction: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI).

Methods: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001.

10 Dec 2021

Development and Validation of the 5-SENSE Score to Predict Focality of the Seizure-Onset Zone as Assessed by Stereoelectroencephalography

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified.

Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated.

Design, setting, and participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year.

7 Dec 2021

Processing of emotionally ambiguous stimuli in eating disorders: an fMRI pilot study

Purpose: People with eating disorders (EDs) have difficulties understanding their own emotions and recognizing the emotions of others, especially in ambiguous settings. We examined the neuronal mechanisms underlying the emotion processing of ambiguous interpersonal stimuli in EDs and healthy controls (HCs).

Methods: The fMRI data were acquired by a blocked experimental design with 28 women (14 EDs) during the visual presentation of a modified Thematic Apperception Test.

Results: EDs showed very strong associations between experienced and inferred emotions evoked by the stimuli; no such relationship was found in HCs. HCs displayed elevated left anterior insula activity during the mentalizing condition; EDs showed increased activity in the right supramarginal gyrus and medial prefrontal cortex.

7 Dec 2021

Infantile status epilepticus disrupts myelin development

Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content.

11 Nov 2021

Applications of biomedical imaging in health and disease

Global BioImaging and Australia's National Imaging Facility (NIF) is jointly organizing a webinar series in the sphere of biomedical imaging focusing on health and disease.

5 Nov 2021

Primary progressive multiple sclerosis overlapping with anti-GAD and anti-Hu antibodies positive neurological syndromes

Although still rare, there have been reports describing autoimmune demyelinating disorders associated with specific antibodies which overlap with multiple sclerosis (MS) and other demyelinating syndromes in clinical, radiological and immunological features. A relationship between anti-myelin-associated glycoprotein (MOG) syndrome, anti-aquaporin-4 (AQ-4) neuromyelitis optica spectrum disorders, and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been described. The opportunity of discovering yet unknown associations is based on the presumption of the co-occurrence of immune mediated diseases [1]. The association of multiple sclerosis with glutamic acid decarboxylase (GAD) neurological syndromes has only been reported in one case [2, 3]. The associated neurological syndromes include stiff-person syndrome (SPS), cerebellar ataxia, epilepsy, and limbic encephalitis. Paraneoplastic origin is rare, and comorbidities include autoimmune thyreoiditis, pernicious anaemia and vitiligo [4].

3 Nov 2021

Diffusion magnetic resonance imaging reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression

Background and purpose: Non-myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract-specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM.

Methods: High-resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity.

3 Nov 2021

Contribution of the multi-echo approach in accelerated functional magnetic resonance imaging multiband acquisition

We wanted to verify the effect of combining multi-echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi-slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole-brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single-echo (SE) data and ME data based on optimal combinations weighted by the contrast-to-noise ratio. Global metrics (temporal signal-to-noise ratio, signal-to-noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data. ME results outperformed SE results in all runs; the differences became more apparent for higher acceleration, where a significant decrease in data quality is observed.

3 Nov 2021

Local and Systemic Expression Pattern of MMP-2 and MMP-9 in Complex Regional Pain Syndrome

Matrix metalloproteinases (MMP)-2 and MMP-9 play important roles in inflammation as well as in pain processes. For this reason, we compared the concentrations of these enzymes in skin and serum of patients with complex regional pain syndrome (CRPS), other pain diseases and healthy subjects. We analyzed ipsi- and contralateral skin biopsies of 18 CRPS patients, as well as in 10 pain controls and 9 healthy subjects. Serum samples were analyzed from 20 CRPS, 17 pain controls and 17 healthy subjects. All samples were analyzed with ELISA. Concentrations were then compared to clinical data as well as to quantitative sensory testing data.MMP-2 was increased in both ipsi- and contralateral skin biopsies of CRPS patients compared to healthy subjects. While low ipsilateral MMP-2 was associated with trophic changes, contralateral MMP-2 inversely correlated with the CRPS severity. MMP-9 was also locally increased in ipsilateral CRPS skin, and higher ipsi- and contralateral MMP-9 levels correlated with CRPS severity.

20 Oct 2021

Transduction profiles in minipig following MRI guided delivery of AAV-5 into thalamic and Corona Radiata areas

Background: As a step towards clinical use of AAV-mediated gene therapy, brains of large animals are used to settle delivery parameters as most brain connections, and relative sizes in large animals and primates, are reasonably common. Prior to application in the clinic, approaches that have shown to be successful in rodent models are tested in larger animal species, such as dogs, non-human primates, and in this case, minipigs.

New method: We evaluated alternate delivery routes to target the basal ganglia by injections into the more superficial corona radiata, and, deeper into the brain, the thalamus. Anatomically known connections can be used to predict the expression of the transgene following infusion of AAV5. For optimal control over delivery of the vector with regards to anatomical location in the brain and spread in the tissue, we have used magnetic resonance image-guided convection-enhanced diffusion delivery.

Results: While the transduction of the cortex was observed, only partial transduction of the basal ganglia was achieved via the corona radiata.

13 Oct 2021

Alterations in Sensorimotor and Mesiotemporal Cortices and Diffuse White Matter Changes in Primary Progressive Multiple Sclerosis Detected by Adiabatic Relaxometry

Background: The research of primary progressive multiple sclerosis (PPMS) has not been able to capitalize on recent progresses in advanced magnetic resonance imaging (MRI) protocols. Objective: The presented cross-sectional study evaluated the utility of four different MRI relaxation metrics and diffusion-weighted imaging in PPMS. Methods: Conventional free precession T1 and T2, and rotating frame adiabatic T1ρ and T2ρ in combination with diffusion-weighted parameters were acquired in 13 PPMS patients and 13 age- and sex-matched controls. Results: T1ρ, a marker of crucial relevance for PPMS due to its sensitivity to neuronal loss, revealed large-scale changes in mesiotemporal structures, the sensorimotor cortex, and the cingulate, in combination with diffuse alterations in the white matter and cerebellum. T2ρ, particularly sensitive to local tissue background gradients and thus an indicator of iron accumulation, concurred with similar topography of damage, but of lower extent.

13 Oct 2021

Effect of Apixaban Pretreatment on Alteplase-Induced Thrombolysis: An In Vitro Study

Benefit of thrombolytic therapy in patients with acute stroke, who are on anticoagulant treatment, is not well addressed. The aim of this study was to investigate whether apixaban can modify the thrombolytic efficacy of alteplase in vitro. Static and flow models and two variants of red blood cell (RBC) dominant clots, with and without apixaban, were used. Clots were prepared from the blood of healthy human donors and subsequently exposed to alteplase treatment. Apixaban and alteplase were used in clinically relevant concentrations. Clot lysis in the static model was determined both by clot weight and spectrophotometric determination of RBC release. Clot lysis in the flow model was determined by measuring recanalization time, clot length and spectrophotometric determination of RBC release. In the static model, clots without apixaban; compared to those with apixaban had alteplase-induced mass loss 54 ± 8% vs. 53 ± 8%, p = 1.00; RBC release 0.14 ± 0.04 vs. 0.12 ± 0.04, p = 0.14, respectively. Very similar results were obtained if plasma was used instead of physiological buffered saline as the incubation medium.

11 Oct 2021

Cognitive impairment and depression: Meta-analysis of structural magnetic resonance imaging studies

Longitudinal comorbidity of depression and cognitive impairment has been reported by number of epidemiological studies but the underlying mechanisms explaining the link between affective problems and cognitive decline are not very well understood. Imaging studies have typically investigated patients with major depressive disorder (MDD) and mild cognitive impairment (MCI) separately and thus have not identified a structural brain signature common to these conditions that may illuminate potentially targetable shared biological mechanisms. We performed a meta-analysis of. 48 voxel-based morphometry (VBM) studies of individuals with MDD, MCI, and age-matched controls and demonstrated that MDD and MCI patients had shared volumetric reductions in a number of regions including the insula, superior temporal gyrus (STG), inferior frontal gyrus, amygdala, hippocampus, and thalamus. We suggest that the shared volumetric reductions in the insula and STG might reflect communication deficits and infrequent participation in mentally or socially stimulating activities, which have been described as risk factors for both MCI and MDD.

1 Oct 2021

Self-compassion in medical students: a pilot study of its association with professionalism pressure

Background: To be a "good doctor" and have "good medical practices" are apparent goals for both medical students and medical faculties. However, the associated implicit and explicit standards could be a source of distress in the form of pressure to achieve professionalism. Self-compassion has been identified as a transtherapeutic factor that plays a crucial role in developing and maintaining mental health. It seems to be an essential meta-skill to learn, especially for medical students who often perceive imperfection as failure. In this pilot study, we investigated the qualities that medical students attribute to the "good doctor" concept, how they perceive themselves compared to this concept, and whether any possible discrepancy between these two perspectives could be associated with self-compassion.

Methods: Altogether, 301 medical students participated in the study (mean age 22.3 ± 2.1; 71.8 % female). The discrepancy between concepts was measured by a semantic differential consisting of a list of 36 adjectives and antonyms that students repeatedly mentioned in courses in their responses to the question "What should a doctor be like?" Self-compassion was measured by the Self-Compassion Scale.

1 Oct 2021

Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival

Background and purpose: Myasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID-19) mainly due to respiratory muscle weakness, older age and long-term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID-19 in MG patients and risk of MG exacerbation during COVID-19.

Methods: We evaluated clinical features and outcomes after COVID-19 in 93 MG patients.

Results: Thirty-five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID-19. Higher forced vital capacity (FVC) values tested before COVID-19 were shown to be protective against severe infection (95% CI 0.934-0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047-1.232). Long-term chronic corticosteroid treatment worsened the course of COVID-19 in MG patients (95% CI 1.784-111.43) and this impact was positively associated with dosage (p = 0.005).

1 Oct 2021

Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias.

22 Sep 2021

The City of Brno Award 2020

Ivan Rektor was one of the prize winners in The City of Brno Award in the field of medical sciences and pharmacy for 2020.

21 Sep 2021

Impact of cognitive reserve on dance intervention-induced changes in brain plasticity

Dance is a complex sensorimotor activity with positive effects on physical fitness, cognition, and brain plasticity in the aging population.

We explored whether individual levels of cognitive reserve (CR) proxied by education moderate dance intervention (DI)-induced plasticity assessed by resting-state functional connectivity (rs-FC) changes of the sensorimotor network (SMN), and between the dorsal attention network (DAN) and anterior default mode network (aDMN).

Our cohort consisted of 99 subjects, randomly assigned to either a DI group who underwent a 6-month intervention (n = 49, M_age = 69.02 ± 5.40) or a control group (n = 50, M_age = 69.37 ± 6.10). Moderation analyses revealed that CR moderated DI-induced increase of the SMN rs-FC with significant changes observed in participants with ≥ 15 years of education (b = 0.05, t(62) = 3.17, p = 0.002). Only DI alone was a significant predictor of the DAN-aDMN crosstalk change (b = 0.06, t(64) = 2.16, p = 0.035).

13 Sep 2021

MicroRNAs in the development of resistance to antiseizure drugs and their potential as biomarkers in pharmacoresistant epilepsy

Although many new antiseizure drugs have been developed in the past decade, approximately 30%-40% of patients remain pharmacoresistant. There are no clinical tools or guidelines for predicting therapeutic response in individual patients, leaving them no choice other than to try all antiseizure drugs available as they suffer debilitating seizures with no relief. The discovery of predictive biomarkers and early identification of pharmacoresistant patients is of the highest priority in this group. MicroRNAs (miRNAs), a class of short noncoding RNAs negatively regulating gene expression, have emerged in recent years in epilepsy, following a broader trend of their exploitation as biomarkers of various complex human diseases. We performed a systematic search of the PubMed database for original research articles focused on miRNA expression level profiling in patients with drug-resistant epilepsy or drug-resistant precilinical models and cell cultures. In this review, we summarize 17 publications concerning miRNAs as potential new biomarkers of resistance to antiseizure drugs and their potential role in the development of drug resistance or epilepsy.

6 Sep 2021

Ambassador for Epilepsy

Congratulations to prof. MUDr. Milan Brázdil, Ph.D., head of the 1st Department of Neurology, at St. Anne`s University Hospital Brno and LF MU with the Center for Epilepsy Brno to receive the prize Ambassador for Epilepsy.

3 Sep 2021

Cortical network organization reflects clinical response to subthalamic nucleus deep brain stimulation in Parkinson's disease

The degree of response to subthalamic nucleus deep brain stimulation (STN-DBS) is individual and hardly predictable. We hypothesized that DBS-related changes in cortical network organization are related to the clinical effect. Network analysis based on graph theory was used to evaluate the high-density electroencephalography (HDEEG) recorded during a visual three-stimuli paradigm in 32 Parkinson's disease (PD) patients treated by STN-DBS in stimulation "off" and "on" states. Preprocessed scalp data were reconstructed into the source space and correlated to the behavioral parameters. In the majority of patients (n = 26), STN-DBS did not lead to changes in global network organization in large-scale brain networks. In a subgroup of suboptimal responders (n = 6), identified according to reaction times (RT) and clinical parameters (lower Unified Parkinson's Disease Rating Scale [UPDRS] score improvement after DBS and worse performance in memory tests), decreased global connectivity in the 1-8 Hz frequency range and regional node strength in frontal areas were detected.

3 Sep 2021

Educational Program Improved Senior Preparedness to Call 911 as a Response to Stroke

Objectives: Stroke predominantly affects the elderly. Universities of the Third Age (U3A) are presented with an opportunity to target them. The goal of our study was to improve older adults' preparedness to call 911 as a response to symptoms of stroke.

Materials and methods: Participants were recruited from U3A in Brno, Czech Republic in year 2018. The program included an educational movie about stroke and testing with pretest posttest design. Stroke awareness was measured by Stroke Action Test and video-clips portraying stroke and stroke mimicking symptoms. Respondents had to answer close-ended questions. Composite scores were compared using paired t-test.

Results: Data were obtained from 206 attendees of the program, that is 2% of all students, from 4 of 5 U3A in Brno. The mean test score improved from 80% to 87% (paired p < 0.001). Participants with a lower baseline knowledge improved by 12% (95% CI 9% to 16%) and with a higher baseline knowledge by 0% (95% CI 3% to 4%). The score for calling 911 for stroke mimicking symptoms improved from 29% to 20% (paired p < 0.001).

27 Aug 2021

Multiple sclerosis and immune system biomarkers: Novel comparison in glatiramer acetate and interferon beta-1a-treated patient groups

Background: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). T cells and B lymphocytes are involved in the development of this disease.

Methods: The following biomarkers were determined in peripheral blood in 28 patients treated with glatiramer acetate (GA) and 21 patients treated with interferon beta 1-a (IFN): IL-10, BAFF, Mx1, IgG, IgG1, IgG2, IgG3 and IgG4 (at baseline and after 6 months of treatment). All participants had confirmed MS diagnosis.

Objectives: The primary objective is to assess a percentual change of biomarkers after 6 months since the first-line treatment initiation with GA or IFN. The secondary objective is to explore correlations between the baseline biomarkers' values (levels).

Results: A positive trend was observed in the increase in IL-10 concentration by 30.33 % (IFN) and by 15.65 % (GA). In the IFN group, we observed a statistically significant increase in the BAFF protein concentration by 29.9% (P < 0.001).

27 Aug 2021

In vivo molecular signatures of cervical spinal cord pathology in degenerative compression

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. MRS voxel was centered at C2 level. CSC volumes and neurochemicals were quantified and compared between HCNMDCDCM and HCMCSC, with general linear models adjusted for age and height effects (pFWE <0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p <0.05). Ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%).

27 Aug 2021

Tractography dissection variability: what happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation.

In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway.

27 Aug 2021

Autoimmune and limbic encephalitis: case series with some atypical variables in clinical practice

Autoimmune and limbic encephalitides are still rare diseases characterized by rapid diagnostics and treatment development in recent years. The incidence of anti-N-methyl-D- aspartate receptor [NMDAR] encephalitis is about 1.5 per million person per year, and the incidence of paraneoplastic neurological syndromes [PNS] including limbic encephalitis [LE] is about 1.22 per 100 000 person per year (Vogrig et al. J Neurol 267:26-35, 1; Dalmau et al. Ann Neurol 61:25-36, 2). The diagnostic criteria of anti-NMDAR encephalitis are already well established (Zuliani et al. Neurol Sci 40:2017-2030, 10). We provide immunological and clinical characteristics of anti-NMDAR encephalitis case series emphasizing unusual association with colon tumour in one case and complete recovery in two cases. Then we report two cases of onconeural and cell surface antibody negative limbic encephalitis [LE] associated with tumours, seizures, cognitive and behavioural changes resulting in severe cerebellar syndrome and fatal outcome. The clinical characteristics and results of selected paraclinical examinations as electroencephalography [EEG], magnetic resonance imaging [MRI] and cerebrospinal fluid [CSF] analysis are reviewed.

24 Aug 2021

Generic acquisition protocol for quantitative MRI of the spinal cord

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) presents many challenges, including a lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for users of 3T MRI systems from the three main manufacturers: GE, Philips and Siemens. The protocol provides guidance for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area computation, multi-echo gradient echo for gray matter cross-sectional area, and magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. In a companion paper from the same authors, the spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects. The key details of the spine generic protocol are also available in an open-access document that can be found at https://github.com/spine-generic/protocols . The protocol will serve as a starting point for researchers and clinicians implementing new SC imaging initiatives so that, in the future, inclusion of the SC in neuroimaging protocols will be more common. The protocol could be implemented by any trained MR technician or by a researcher/clinician familiar with MRI acquisition.

24 Aug 2021

Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens.

Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics.

Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics.

Full documentation and results can be found at https://spine-generic.rtfd.io/ . The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

24 Aug 2021

Hemodynamic and white blood cells parameters in patients with first-episode psychosis: a pilot longitudinal study

Objective: Patients with schizophrenia are at higher risk of cardiovascular (CVS) related mortality. Close attention is being paid to the clinical utility of readily available CVS markers.

Methods: A pilot one-year longitudinal study in inpatients with first-episode psychosis (FEP) was carried out to determine markers of inflammation and endothelial dysfunction (monocyte- and neutrophil-to-lymphocyte ratios) and basal blood pressure, pulse, and derived hemodynamic parameters (PP: pulse pressure; RPP: rate pressure product; and MAP: mean arterial pressure).

Results: After one year, PP and RPP increased, as did systolic blood pressure and heart rate. Systolic blood pressure, PP, total white blood cells, and neutrophils correlated with weight gain. After one year, correlations between monocyte-to-lymphocyte ratio and RPP and MAP were observed.

Conclusion: Our study indicates worsening CVS health over the first year of treatment and emphasises the importance of early monitoring of CVS status using easily accessible parameters to prevent CVS-related mortality.

23 Aug 2021

Impact of prenatal stress on amygdala anatomy in young adulthood: Timing and location matter

Background: Exposure to maternal stress in utero has long-term implications for the developing brain and has been linked with a higher risk of depression. The amygdala, which develops during the early embryonic stage and is critical for emotion processing, might be particularly sensitive.

Methods: Using data from a neuroimaging follow-up of the ELSPAC prenatal birth cohort (n=129, 47% men, 23-24 years old), we studied the impact of prenatal stress during the first and second half of pregnancy on the volume of the amygdala and its nuclei in young adult offspring. We further evaluated the relationship between amygdala anatomy and offspring depressive symptomatology. Amygdala nuclei were parcellated using FreeSurfer's automated segmentation pipeline. Depressive symptoms were measured via self-report using the Beck Depression Inventory (BDI).

Results: Exposure to stress during the first half of pregnancy was associated with smaller accessory basal (Cohen's f²=0.27, p(FDR)=0.03) and cortical (Cohen's f²=0.29, p(FDR)=0.03) nuclei volumes.

23 Aug 2021

Targeted mass spectrometry for monitoring of neural differentiation

Human multipotent neural stem cells could effectively be used for the treatment of a variety of neurological disorders. However, a defining signature of neural stem cell lines that would be expandable, non-tumorigenic, and differentiate into desirable neuronal/glial phenotype after in vivo grafting is not yet defined. Employing a mass spectrometry approach, based on selected reaction monitoring, we tested a panel of well-described culture conditions, and measured levels of protein markers routinely used to probe neural differentiation, i.e. POU5F1 (OCT4), SOX2, NES, DCX, TUBB3, MAP2, S100B, GFAP, GALC, and OLIG1. Our multiplexed assay enabled us to simultaneously identify the presence of pluripotent, multipotent, and lineage-committed neural cells, thus representing a powerful tool to optimize novel and highly specific propagation and differentiation protocols. The multiplexing capacity of this method permits the addition of other newly identified cell type-specific markers to further increase the specificity and quantitative accuracy in detecting targeted cell populations. Such an expandable assay may gain the advantage over traditional antibody-based assays, and represents a method of choice for quality control of neural stem cell lines intended for clinical use.

23 Aug 2021

Derivation and Molecular Characterization of a Morphological Subpopulation of Human iPSC Astrocytes Reveal a Potential Role in Schizophrenia and Clozapine Response

Astrocytes are the most abundant cell type in the human brain and are important regulators of several critical cellular functions, including synaptic transmission. Although astrocytes are known to play a central role in the etiology and pathophysiology of schizophrenia, little is known about their potential involvement in clinical response to the antipsychotic clozapine. Moreover, astrocytes display a remarkable degree of morphological diversity, but the potential contribution of astrocytic subtypes to disease biology and drug response has received little attention. Here, we used state-of-the-art human induced pluripotent stem cell (hiPSC) technology to derive a morphological subtype of astrocytes from healthy individuals and individuals with schizophrenia, including responders and nonresponders to clozapine. Using functional assays and transcriptional profiling, we identified a distinct gene expression signature highly specific to schizophrenia as shown by disease association analysis of more than 10 000 diseases.

23 Aug 2021

Posttraumatic Stress and Posttraumatic Growth in Three Generations of Czech and Slovak Holocaust Survivors

The psychological consequences of trauma related to the Holocaust have been primarily studied in samples derived from Israel, North America, and Western Europe. Few studies have examined postcommunist countries in Central and Eastern Europe. The present study focused on three generations living in the Czech Republic and Slovakia after World War II (WWII): Holocaust survivors (71-95 years of age), their children (30-73 years of age), and their grandchildren (15-48 years of age). We compared scores on measures of posttraumatic stress symptoms (PTSS; the Posttraumatic Stress Disorder Checklist-Civilian Version) and posttraumatic growth (PTG; the Posttraumatic Growth Inventory) derived from three focal samples with scores from age-matched comparison participants. Higher PTSS scores emerged for Holocaust survivors in all generations, η² _P=.087 but only participants in the first generation reported higher PTG scores relative to the comparison group, with small effect sizes for the overall group differences, η² _P=.029 . These results are discussed in the historical and political context of postwar Czechoslovakia.

23 Aug 2021

Altered Spatiotemporal Dynamics of the Resting Brain in Mild Cognitive Impairment with Lewy Bodies

Background: Electrophysiological markers of prodromal dementia with Lewy bodies were described in the spectral domain. The sub-second temporal resolution may provide additional information.

Objective: To evaluate electroencephalography (EEG) microstates in patients with mild cognitive impairment with Lewy bodies and to assess the association between their temporal dynamics and the spectral marker.

Methods: Temporal parameters of microstates were compared between 21 patients with mild cognitive impairment with Lewy bodies and 21 healthy controls. The dominant alpha frequency was correlated with microstate parameters.

Results: Microstates A-D showed higher occurrence in the patient group. Microstate B additionally revealed shorter mean duration and increased time coverage; its occurrence correlated with the dominant alpha frequency in the patient group.

23 Aug 2021

Modulation of Working Memory and Resting-State fMRI by tDCS of the Right Frontoparietal Network

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing.

23 Aug 2021

Divergent estimates of the ratio between Na+-Ca2+ current densities in t-tubular and surface membranes of rat ventricular cardiomyocytes

The ratio between Na+-Ca2+ exchange current densities in t-tubular and surface membranes of rat ventricular cardiomyocytes (JNaCa-ratio) estimated from electrophysiological data published to date yields strikingly different values between 1.7 and nearly 40. Possible reasons for such divergence were analysed by Monte Carlo simulations assuming both normal and log-normal distribution of the measured data. The confidence intervals CI95 of the mean JNaCa-ratios computed from the reported data showed an overlap of values between 1 and 3, and between 0.3 and 4.3 in the case of normal and log-normal distribution, respectively. Further analyses revealed that the published high values likely result from a large scatter of data due to transmural differences in JNaCa, dispersion of cell membrane capacitances and variability in incomplete detubulation. Taking into account the asymmetric distribution of the measured data, the reduction of mean current densities after detubulation and the substantially smaller CI95 of lower values of the mean JNaCa-ratio, the values between 1.6 and 3.2 may be considered as the most accurate estimates.

23 Aug 2021

Progressive Tumefactive Demyelination as the Only Result of Extensive Diagnostic Work-Up: A Case Report

Tumefactive demyelinating lesions belong to the rare variants of multiple sclerosis, posing a diagnostic challenge since it is difficult to distinguish them from a neoplasm or other brain lesions and they require a careful differential diagnosis. This contribution presents the case report of a young female with progressive tumefactive demyelinating brain and spinal cord lesions. An extensive diagnostic process including two brain biopsies and an autopsy did not reveal any explanatory diagnosis other than multiple sclerosis. The patient was treated by various disease-modifying treatments without significant effect and died from ascendent infection via ventriculoperitoneal shunt resulting in Staphylococcus aureus meningitis.

Keywords: case report; demyelinating diseases; multiple sclerosis; neuropathology; neuroradiology.

18 Aug 2021

Colour Categorization and its Effect on Perception: A Conceptual Replication

The presented study examines the question of colour categorization in relation to the hypothesis of linguistic relativity. The study is based on research conducted by Gilbert et al. (2006) and their claim that linguistic colour categorization in a particular language helps colour recognition and speeds the process of colour discrimination for colours from different linguistic categories but only for the right visual field. Our study approached the research question differently. We used the same methodology as Gilbert's team et al. (2006), but we used different colour categories in the Czech language and significantly enlarged the number of participants to 106 undergraduate psychology students. Our results show that the fastest reaction times were in trials when the target was located in the left visual field, quite opposite from the Gilbert's et al. (2006) study. We argue that this finding is based on different processes than simple colour linguistic categorisation and attentional processes actually play an important role in the task.

Keywords: Colour categorization; Language; The hypothesis of linguistic relativity.

18 Aug 2021

Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion

One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)-the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG.

26 Jul 2021

Diffusion MRI reveals tract-specific microstructural correlates of electrophysiological impairments in non-myelopathic and myelopathic spinal cord compression

Background: Non-myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical MRI and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract-specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM.

Methods: We acquired high-resolution 3T diffusion MRI in 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity.

26 Jul 2021

In vivo macromolecule signals in rat brain 1 H-MR spectra at 9.4T: Parametrization, spline baseline estimation, and T 2 relaxation times

Purpose: Reliable detection and fitting of macromolecules (MM) are crucial for accurate quantification of brain short-echo time (TE) ¹ H-MR spectra. An experimentally acquired single MM spectrum is commonly used. Higher spectral resolution at ultra-high field (UHF) led to increased interest in using a parametrized MM spectrum together with flexible spline baselines to address unpredicted spectroscopic components. Herein, we aimed to: (1) implement an advanced methodological approach for post-processing, fitting, and parametrization of 9.4T rat brain MM spectra; (2) assess the concomitant impact of the LCModel baseline and MM model (ie, single vs parametrized); and (3) estimate the apparent T₂ relaxation times for seven MM components.

Methods: A single inversion recovery sequence combined with advanced AMARES prior knowledge was used to eliminate the metabolite residuals, fit, and parametrize 10 MM components directly from 9.4T rat brain in vivo ¹ H-MR spectra at different TEs.

26 Jul 2021

Memory retrieval in temporal lobe epilepsy is related to functional segregation of the mesiotemporal structures

Objective: We analyzed the impact of temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) on functional connectivity (FC) between mesiotemporal structures. Functional connectivity modifications related to word retrieval were investigated.

Methods: High-density EEG of 21 patients with TLE with HS (12 left TLE and 9 right TLE) and 10 healthy controls (HCs) were recorded during a verbal subsequent memory paradigm. Electroencephalography data were reconstructed into the source space and FC was calculated from the source activity of regions of interest.

Results: A significant decrease in FC between the right- and left-sided mesiotemporal structures in TLE was observed. The decrease was significant only with words that were correctly recognized. The decrease in interhemispheric FC between mesiotemporal structures was found in the 8- to 20-Hz frequency range in both left and right TLE.

26 Jul 2021

Electrophysiological biomarkers for deep brain stimulation outcomes in movement disorders: state of the art and future challenges

Several neurological diseases are accompanied by rhythmic oscillatory dysfunctions in various frequency ranges and disturbed cross-frequency relationships on regional, interregional, and whole brain levels. Knowledge of these disease-specific oscillopathies is important mainly in the context of deep brain stimulation (DBS) therapy. Electrophysiological biomarkers have been used as input signals for adaptive DBS (aDBS) as well as preoperative outcome predictors. As movement disorders, particularly Parkinson's disease (PD), are among the most frequent DBS indications, the current research of DBS is the most advanced in the movement disorders field. We reviewed the literature published mainly between 2010 and 2020 to identify the most important findings concerning the current evolution of electrophysiological biomarkers in DBS and to address future challenges for prospective research.

26 Jul 2021

The benefit of the diffusion kurtosis imaging in presurgical evaluation in patients with focal MR-negative epilepsy

The effectivity of diffusion-weighted MRI methods in detecting the epileptogenic zone (EZ) was tested. Patients with refractory epilepsy (N=25) who subsequently underwent resective surgery were recruited. First, the extent of white matter (WM) asymmetry from mean kurtosis (MK) was calculated in order to detect the lobe with the strongest impairment. Second, a newly developed metric was used, reflecting a selection of brain areas with concurrently increased mean Diffusivity, reduced fractional Anisotropy, and reduced mean Kurtosis (iDrArK). A two-step EZ detection was performed as (1) lobe-specific detection, (2) iDrArK voxel-wise detection (with a possible lobe-specific restriction if the result of the first step was significant in a given subject). The method results were compared with the surgery resection zones. From the whole cohort (N=25), the numbers of patients with significant results were: 10 patients in lobe detection and 9 patients in EZ detection. From these subsets of patients with significant results, the impaired lobe was successfully detected with 100% accuracy; the EZ was successfully detected with 89% accuracy.

2 Jul 2021

Development and Testing of Thrombolytics in Stroke

Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage.

2 Jul 2021

MASARYK UNIVERSITY RECTOR´S AWARDS OF 2021

On 10^th June 2021, the Rector of Masaryk University, Martin Bareš, awarded the extraordinary achievements in science, research, pedagogical activities, art and civic activities.

11 Jun 2021

Diffusion kurtosis imaging detects the time-dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact.

Here we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS.

11 Jun 2021

Safety and Outcomes of Thrombectomy in Ischemic Stroke With vs Without Intravenous Thrombolysis

Objective: To test the hypothesis that intravenous thrombolysis (IVT) treatment prior to endovascular thrombectomy (EVT) is associated with better outcomes in patients with anterior circulation large artery occlusion (LAO) stroke, we examined a large real-world database, the SITS-International Stroke Thrombectomy Register (SITS-ISTR).

Methods: We identified centers recording ≥10 consecutive patients in the SITS-ISTR, with at least 70% available modified Rankin Scale (mRS) scores at 3 months during 2014-19. We defined LAO as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Main outcomes were functional independence (mRS 0-2) and death at 3 months and symptomatic intracranial hemorrhage (SICH) per modified SITS-MOST. We performed propensity score matched (PSM) and multivariable logistic regression analyses.

4 Jun 2021

Inferior parietal lobule involved in representation of “what” in a delayed-action Libet task

Intentional motor action is typically characterized by the decision about the timing, and the selection of the action variant, known as the “what” component. We compared free action selection with instructed action, where the movement type was externally cued, in order to investigate the action selection and action representation in a Libet’s task. Temporal and spatial locus of these processes was examined using the combination of high-density electroencephalography, topographic analysis of variance, and source reconstruction. Instructed action, engaging representation of the response movement, was associated with distinct negativity at the parietal and centro-parietal channels starting around 750 ms before the movement, which has a source particularly in the bilateral inferior parietal lobule.

Keywords: EEG; Intentional action; Action representation; Action selection; Prospective memory; Inferior parietal lobule; Libet task; Lateralized readiness potential; Delayed action

4 Jun 2021

The Practice of Electroconvulsive Therapy in Children and Adolescents in the Czech Republic

Objectives: The aim of this study was to describe the practice of electroconvulsive therapy (ECT) in child and adolescent patients in the Czech Republic.

Methods: We conducted a mail questionnaire survey among Czech facilities associated with the Association of Child and Adolescent Psychiatry, and university hospitals with inpatient psychiatric wards, focused on the practice of ECT between 2013 and 2017 in patients younger than 18 years.

Results: Of 18 approached facilities, 13 had access to ECT, and only 6 used ECT on 16 patients. The most common diagnosis was schizophrenia or related disorders (68.75% of patients), and the most common reason for ECT was catatonic symptoms (37.5%). The most common ECT methodology was bitemporal electrode placement with brief-pulse current (62.5%). In 2 patients, ECT was terminated because of ineffectiveness and in 1 patient because of adverse reaction. In other patients, ECT ended after achieving a clinical effect.

31 May 2021

Epileptogenic zone detection in MRI negative epilepsy using adaptive thresholding of arterial spin labeling data

Drug-resistant epilepsy is a diagnostic and therapeutic challenge, mainly in patients with negative MRI findings. State-of-the-art imaging methods complement standard epilepsy protocols with new information and help epileptologists to increase the reliability of their decisions. In this study, we investigate whether arterial spin labeling (ASL) perfusion MRI can help localize the epileptogenic zone (EZ). To that end, we developed an image processing method to detect the EZ as an area with hypoperfusion relative to the contralateral unaffected side, using subject-specific thresholding of the asymmetry index in ASL images. We demonstrated three thresholding criteria (termed minimal product criterion, minimal distance criterion, and elbow criterion) on 29 patients with MRI-negative epilepsy (age 32.98 ± 10.4 years). The minimal product criterion showed optimal results in terms of positive predictive value (mean 0.12 in postoperative group and 0.22 in preoperative group) and true positive rate (mean 0.71 in postoperative group and 1.82 in preoperative group). Additionally, we found high accuracy in determining the EZ side (mean 0.86 in postoperative group and 0.73 in preoperative group out of 1.00).

21 May 2021

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study

Background and objective: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies.

Methods: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST.

Results: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR).

17 May 2021

The State of Stroke Services across the Globe: Report of World Stroke Organization-World Health Organization Surveys

Background: Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization (WSO)-World Health Organisation (WHO)-Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle income countries (LMICs) compared to high income countries (HICs).

Methods: Using a validated WSO comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across WHO regions and economic strata. The WHO also conducted a survey of non-communicable diseases in 194 countries in 2019.

Results: Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys and participation in research) were reported in low-income countries (LICs) than HICs. The overall global score for prevention was 40.2%. Stroke units were present in 91% of HICs in contrast to 18% of LICs (p<0.001).

11 May 2021

A Novel Statistical Model for Predicting the Efficacy of Vagal Nerve Stimulation in Patients With Epilepsy (Pre-X-Stim) Is Applicable to Different EEG Systems

Background: Identifying patients with intractable epilepsy who would benefit from therapeutic chronic vagal nerve stimulation (VNS) preoperatively remains a major clinical challenge. We have developed a statistical model for predicting VNS efficacy using only routine preimplantation electroencephalogram (EEG) recorded with the TruScan EEG device (Brazdil et al., 2019). It remains to be seen, however, if this model can be applied in different clinical settings.

Objective: To validate our model using EEG data acquired with a different recording system.

Methods: We identified a validation cohort of eight patients implanted with VNS, whose preimplantation EEG was recorded on the BrainScope device and who underwent the EEG recording according to the protocol. The classifier developed in our earlier work, named Pre-X-Stim, was then employed to classify these patients as predicted responders or non-responders based on the dynamics in EEG power spectra.

7 May 2021

Dynamic miRNA changes during the process of epileptogenesis in an infantile and adult-onset model

Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy.

7 May 2021

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study

Background: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications.

Objectives: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity).

Methods: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses.

Results: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81.

23 Apr 2021

RAFF-4, Magnetization Transfer and Diffusion Tensor MRI of Lysophosphatidylcholine Induced Demyelination and Remyelination in Rats

Remyelination is a naturally occurring response to demyelination and has a central role in the pathophysiology of multiple sclerosis and traumatic brain injury. Recently we demonstrated that a novel MRI technique entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn) achieved exceptional sensitivity in detecting the demyelination processes induced by lysophosphatidylcholine (LPC) in rat brain. In the present work, our aim was to test whether RAFF4, along with magnetization transfer (MT) and diffusion tensor imaging (DTI), would be capable of detecting the changes in the myelin content and microstructure caused by modifications of myelin sheets around axons or by gliosis during the remyelination phase after LPC-induced demyelination in the corpus callosum of rats. We collected MRI data with RAFF4, MT and DTI at 3 days after injection (demyelination stage) and at 38 days after injection (remyelination stage) of LPC (n = 12) or vehicle (n = 9). Cell density and myelin content were assessed by histology.

23 Apr 2021

Editorial: Neuropsychology Through the MRI Looking Glass

Since its inception as a science, psychology has been explicitly preoccupied with the mind-body relationship, specifically with the role that the nervous system plays in shaping how we perceive the world around us and how we react in our interaction with it. The evidence in this regard are the second and third chapters of William James's 1890 “The Principle of Psychology” (Volume 1) (1), which explain the functions of the brain and the general conditions underlying its activity, as well as the entire work of Wilhelm Wundt's 1904 “Principles of Physiological Psychology” (2), which explicitly linked the evolution of various mental functions to the organization and physiology of the nervous system. Yet, it was not until 1980s when the neuropsychology has established itself as a branch of psychology in its own right, aiming to explain how the brain and the other parts of the nervous system influence one's cognition, emotions and behaviors using a variety of methods from observation and questionnaires to computerized tasks gathering reaction time and electrophysiology. The knowledge thus obtained in healthy individuals was then employed by neuropsychologists in assessing the impact of various diseases on brain structure and function.

23 Apr 2021

Memory outcomes of temporal lobe surgery in adults aged over 45 years

Objective: It is assumed that temporal lobe resection in older people is associated with worse seizure outcomes and potential postsurgical memory decline. We studied postsurgical memory development and surgical efficacy in patients over 45 years of age compared with younger patients.

Methods: We studied 88 patients (51 male and 37 female) after temporal lobe surgery, which involved hippocampal resection. The patients were evaluated before surgery and in the first (72 patients) and/or third (57 patients) postsurgical year. The Wechsler Memory Scale III test was performed to evaluate the MQ postsurgical development. Engel's classification was used to evaluate the postsurgical seizure outcome.

Results: The presurgical MQ (median 88) in ≥45 years age group was significantly lower than in both younger groups (median MQ = 100 for ≤30 years age group, p = 0.002; median MQ = 107 for 31-44 years age group, p = 0.002). Three years after the surgery, the MQ decreased significantly in ≤30 years age group (p = 0.012), while only non-significant MQ decline was observed in both older groups. We found no significant impact of age on the surgical outcome.

16 Apr 2021

Anomaly Detection Algorithm for Real-World Data and Evidence in Clinical Research

Background: Statistical analysis, which has become an integral part of evidence-based medicine, relies heavily on data quality that is of critical importance in modern clinical research. Input data are not only at risk of being falsified or fabricated, but also of being mishandled by investigators.

Objective: The urgent need to assure the highest data quality possible has led to the implementation of various auditing strategies designed to monitor clinical trials and detect errors of different origin that frequently occur in the field.

Methods: A particular electronic data capture (EDC) system, which is used for data management in clinical registries, is presented including its architecture and data structure. This EDC system features an algorithm based on machine learning designed to detect anomalous patterns in quantitative data. The detection algorithm combines clustering with a series of seven distance metrics that serve to determine the strength of an anomaly. For the detection process, the thresholds and combinations of the metrics were used and the detection performance was evaluated and validated in the experiments involving simulated anomalous data and real-world data.

12 Apr 2021

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients.

12 Apr 2021

Non-steroidal anti-inflammatory drugs in the pathophysiology of vasospasms and delayed cerebral ischemia following subarachnoid hemorrhage: a critical review

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm.

6 Apr 2021

Concentrating stroke care provision in the Czech Republic: The establishment of Stroke Centres in 2011 has led to improved outcomes

This article describes policy processes that have led to the re-organisation of stroke care in the Czech Republic since 2011, which has been part of a broader process of care concentration in several medical fields. Currently, stroke care is provided by 13 Comprehensive and 32 Primary Stroke Centres. The paper explains factors that supported the reform implementation, reviews implications, and discusses future challenges. Mandatory reporting of quality indicators, the introduction of a benchmarking system, integration with pre-hospital emergency care, and the introduction of countrywide patient triage have supported more timely treatment for stroke patients and better quality of care. Data from the Stroke Care Quality Indicators of the Czech Stroke Society show positive trends in many areas: the number of patients treated with intravenous thrombolysis quadrupled in eight years, with 26.4 % of all acute stroke patients receiving thrombolysis in 2018. Czech Republic now ranks third in Europe in the number of thrombolysis per population and second in the number of mechanical thrombectomies per population.

1 Apr 2021

ERASMUS+ COOPERATION PARTNERSHIPS 2021

The 2021 Erasmus+ programme calls for proposals are out. You can apply for funding in the field of education, training, youth and sport.

31 Mar 2021

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [¹⁸F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29 years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy.

31 Mar 2021

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue.

31 Mar 2021

Are Functional (Psychogenic Nonepileptic) Seizures the Sole Expression of Psychological Processes?

Functional [psychogenic nonepileptic/dissociative] seizures (FND-seiz) and related functional neurological disorder subtypes were of immense interest to early founders of modern-day neurology and psychiatry. Unfortunately, the divide that occurred between the both specialties throughout the mid-twentieth century placed FND-seiz at the borderland between the two disciplines. In the process, a false Cartesian dualism emerged that labeled psychiatric conditions as impairments of the mind and neurological conditions as disturbances in structural neuroanatomy. Excitingly, modern-day neuropsychiatric perspectives now consider neurologic and psychiatric conditions as disorders of both brain and mind. In this article, we aim to integrate neurologic and psychiatric perspectives in the conceptual framing of FND-seiz. In doing so, we explore emerging relationships between symptoms, neuropsychological constructs, brain networks, and neuroendocrine/autonomic biomarkers of disease. Evidence suggests that the neuropsychological constructs of emotion processing, attention, interoception, and self-agency are important in the pathophysiology of FND-seiz.

31 Mar 2021

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001).

31 Mar 2021

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus

We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of deep brain stimulation (DBS). We analyzed intracerebral electroencephalographic (EEG) recordings from externalized DBS electrodes targeted bilaterally in the anterior nuclei of the thalamus (ANT) in 12 patients (six responders, six nonresponders) with more than 1 year of follow-up care. In the bipolar local field potentials of the EEG, spectral power (PW) and power spectral entropy (PSE) were calculated in the passbands 1-4, 4-8, 8-12, 12-20, 20-45, 65-80, 80-200 and 200-500 Hz. The most significant differences between responders and nonresponders were observed in the BRIDGE area (bipolar recordings with one contact within the ANT and the second contact in adjacent tissue). In responders, PW was significantly decreased in the frequency bands of 65-80, 80-200, and 200-500 Hz (p < .05); PSE was significantly increased in all frequency bands (p < .05) except for 200-500 Hz (p = .06).

22 Mar 2021

Hyde Park Civilization about brain

You can watch the discussion of the following experts with Daniel Stach here.

22 Mar 2021

Trends and outcomes for non-elective neurosurgical procedures in Central Europe during the COVID-19 pandemic

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th-April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas.

16 Mar 2021

Czech-BioImaging call for research projects

The call for the Czech-BioImaging Open Access support for the period of July 2021 – June 2022 has been opened.

9 Mar 2021

Automated seizure detection using wearable devices: A clinical practice guideline of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology

The objective of this clinical practice guideline (CPG) is to provide recommendations for healthcare personnel working with patients with epilepsy, on the use of wearable devices for automated seizure detection in patients with epilepsy, in outpatient, ambulatory settings. The Working Group of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology developed the CPG according to the methodology proposed by the ILAE Epilepsy Guidelines Working Group. We reviewed the published evidence using The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and evaluated the evidence and formulated the recommendations following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

2 Mar 2021

A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence‐based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies.

Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web‐based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht‐like diseases. A consensus‐based questionnaire was generated for each disease.

2 Mar 2021

Sensory and pain modulation profiles of ongoing central neuropathic extremity pain in multiple sclerosis

Background: Central neuropathic extremity pain (CNEP) is the most frequent type of pain in multiple sclerosis (MS). The aim of the present study was to evaluate sensory and pain modulation profiles in MS patients with CNEP.

Methods: In a single-centre observational study, a group of 56 CNEP MS patients was compared with 63 pain-free MS patients and with a sex- and age-adjusted control group. Standardized quantitative sensory testing (QST) and dynamic QST (dQST) protocols comprising temporal summation and conditioned pain modulation tests were used to compare sensory profiles.

Results: Loss-type QST abnormalities in both thermal and mechanical QST modalities prevailed in both MS subgroups and correlated significantly with higher degree of disability expressed as Expanded Disability Status Scale (EDSS). Comparison of sensory phenotypes disclosed a higher frequency of the 'sensory loss' prototypic sensory phenotype in the CNEP subgroup (30%) compared with pain-free MS patients (6%; p = .003).

25 Feb 2021

Successful AZV projects

The results of the AZV call for proposals have been recently published.

19 Feb 2021

Contemporary clinical neurophysiology applications in dystonia

The complex phenomenological understanding of dystonia has transcended from the clinics to genetics, imaging and neurophysiology. One way in which electrophysiology will impact into the clinics are cases wherein a dystonic clinical presentation may not be typical or a "forme fruste" of the disorder. Indeed, the physiological imprints of dystonia are present regardless of its clinical manifestation. Underpinnings in the understanding of dystonia span from the peripheral, segmental and suprasegmental levels to the cortex, and various electrophysiological tests have been applied in the course of time to elucidate the origin of dystonia pathophysiology. While loss of inhibition remains to be the key finding in this regard, intricacies and variabilities exist, thus leading to a notion that perhaps dystonia should best be gleaned as network disorder. Interestingly, the complex process has now spanned towards the understanding in terms of networks related to the cerebellar circuitry and the neuroplasticity.

18 Feb 2021

Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel‐based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND‐seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within‐group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self‐reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between‐group interoceptive accuracy or FA differences.

5 Feb 2021

Representation of Parkinson's disease and atypical Parkinson's syndromes in the Czech Republic-A nationwide retrospective study

Background: Parkinson's disease is a progressive neurodegenerative disease which causes health problem that affects more patients in the past few years. To be able to offer appropriate care, epidemiological analyses are crucial at the national level and its comparison with the international situation.

Aim: The demographic description of reported patients with parkinsonism (including Parkinson's disease and atypical parkinsonian syndromes) according to the International Classification of Diseases (ICD-10) from the national health registries.

Methods: Retrospective analysis of data available from the National Health Information System-NHIS and the National Registry of Reimbursed Health Services (NRRHS). Analyzed epidemiological data are intending to determine the regional and specific prevalence of Parkinsonism in the Czech Republic.

5 Feb 2021

Mozart effect in epilepsy: Why is Mozart better than Haydn? Acoustic qualities-based analysis of SEEG

Background: We aimed to confirm the "Mozart effect" in epileptic patients using the intracerebral EEG recordings and the hypothesis that the reduction of epileptiform discharges (ED) can be explained by the music's acoustic properties.

Methods: Eighteen epilepsy surgery candidates were implanted with depth electrodes in the temporal medial and lateral cortex. Patients listened to the first movement of Mozart's Sonata for Two Pianos K. 448 and to the first movement of Haydn's Symphony No. 94. Musical features from each composition with respect to rhythm, melody, and harmony were analysed.

Results: ED in intracerebral EEG were reduced by Mozart's music. Listening to Haydn's music led to reduced ED only in the women; in the men, the ED increased. The acoustic analysis revealed that non-dissonant music with a harmonic spectrum and decreasing tempo with significant high-frequency parts has a reducing effect on ED in men. To reduce ED in women, the music should additionally be, in terms of loudness, gradually less dynamic.

5 Feb 2021

The Open Brain Consent: Informing research participants and obtaining consent to share brain imaging data

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation.

5 Feb 2021

Conducting composite films based on chitosan or sodium hyaluronate. Properties and cytocompatibility with human induced pluripotent stem cells

Novel composite films combining biocompatible polysaccharides with conducting polyaniline (PANI) were prepared via the in-situ polymerization of aniline hydrochloride in the presence of sodium hyaluronate (SH) or chitosan (CH). The composite films possess very good cytocompatibility in terms of adhesion and proliferation of two lines of human induced pluripotent stem cells (hiPSC). Moreover, the cardiomyogenesis and even formation of beating clusters were successfully induced on the films. The proportion of formed cardiomyocytes demonstrated excellent properties of composites for tissue engineering of stimuli-responsive tissues. The testing also demonstrated antibacterial activity of the films against E. coli and PANI-SH was able to reduce bacterial growth from 2 × 10⁵ to < 1 cfu cm^-2. Physicochemical characterization revealed that the presence of polysaccharides did not notably influence conductivities of the composites being ∼1 and ∼2 S cm^-1 for PANI-SH and PANI-CH respectively; however, in comparison with neat PANI, it modified their topography making the films smoother with mean surface roughness of 4 (PANI-SH) and 14 nm (PANI-CH).

1 Feb 2021

Dimensions of Impulsivity in Healthy People, Patients with Borderline Personality Disorder, and Patients with Attention-Deficit/Hyperactivity Disorder

Objective: Impulsivity, observed in patients with various psychiatric disorders, is a heterogeneous construct with different behavioral manifestations. Through confirmatory factor analysis (CFA), this study tests hypotheses about relationships between dimensions of impulsivity measured using personality questionnaires and behavioral tests. Method: The study included 200 healthy people, 40 patients with borderline personality disorder, and 26 patients with attention-deficit/hyperactivity disorder (ADHD) who underwent a comprehensive impulsivity test battery including the Barratt Impulsiveness Scale (BIS), UPPS-P Impulsive Behavior Scale, a Go-NoGo task, a stop-signal task, and a delay discounting task. Results: A CFA model comprising three self-reported and three behavioral latent variables reached a good fit. Both patient groups scored higher in the self-reported dimensions and impulsive choice; only the ADHD patients displayed impaired waiting and stopping impulsivity.

1 Feb 2021

Blood pressure excursions in acute ischemic stroke patients treated with intravenous thrombolysis

Objective: To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA).

Methods: We performed a post hoc analysis of the CLOTBUST-ER trial. Serial BP measurements were conducted using automated cuff recording according to the recommended BP protocol guidelines for tPA administration. The outcomes were prespecified efficacy and safety endpoints of CLOTBUST-ER.

Results: The mean number of serial BP recordings per patient was 37. Of the 674 patients, 227 (34%) had at least one BP excursion (>185/105 mmHg) during the first 24 h following tPA-bolus. The majority of BP excursions (46%) occurred within the first 75 min from tPA-bolus.

1 Feb 2021

The Direct Costs of Dravet's Syndrome before and after Diagnosis Assessment

The objective of this study was to estimate the direct cost before and after diagnosis assessment in patients with Dravet's syndrome (DS). The basis of the economic study was to calculate the costs of health care before and after diagnosis of DS. We retrospectively evaluated all SCN1A positive patients with phenotype of DS treated in our hospital. Statistical analyses were performed by IBM SPSS Statistics 24.0 software. After the diagnosis of DS, there was a significant decline of health care costs (-85.6%) an average of €29.4 ± 26.1 monthly per patient. We estimated the monthly costs at €204.5 ± 167 (median: €193.9, range: €35.5-534.4) per patient before DS diagnosis. The major cost was for hospitalization in neurological department: €43.3 ± 52 (median: €21.9, range: €9.5-179.4) per patient. Minimal cost per patient per months before DS diagnosis was cost of psychological testing/care and complementary rehabilitation (0.13 and 0.6% of total cost). After DS diagnosis, the major cost was focused on nonhospitalization care of patients (64.8%), minimal (€0) for genetic testing and major for outpatient care (18%, mean: €5.3, median: €7).

1 Feb 2021

Resting-State Phase-Amplitude Coupling Between the Human Subthalamic Nucleus and Cortical Activity: A Simultaneous Intracranial and Scalp EEG Study

It has been suggested that slow oscillations in the subthalamic nucleus (STN) reflect top-down inputs from the medial prefrontal cortex, thus implementing behavior control. It is unclear, however, whether the STN oscillations are related to cortical activity in a bottom-up manner. To assess resting-state subcortico-cortical interactions, we recorded simultaneous scalp electroencephalographic activity and local field potentials in the STN (LFP-STN) in 11 patients with Parkinson's disease implanted with deep brain stimulation electrodes in the on-medication state during rest. We assessed the cross-structural phase-amplitude coupling (PAC) between the STN and cortical activity within a wide frequency range of 1 to 100 Hz. The PAC was dominant between the δ/θ STN phase and β/γ cortical amplitude in most investigated scalp regions and between the δ cortical phase and θ/α STN amplitude in the frontal and temporal regions. The cross-frequency linkage between the slow oscillations of the LFP-STN activity and the amplitude of the scalp-recorded cortical activity at rest was demonstrated, and similar involvement of the left and right STNs in the coupling was observed.

22 Jan 2021

Successful asymmetrical deep brain stimulation using right subthalamic and left pallidal electrodes in a patient with Parkinson's disease

Purpose: Despite the best efforts of neurologists, the results of pharmacotherapy in the late stages of Parkinson's disease are often disappointing and accompanied by debilitating side effects. Under these circumstances, deep brain stimulation is a viable treatment option. The aim of the meticulous pre-surgical planning is not only precise electrode implantation, but also the avoidance of intraoperative vascular conflicts potentially causing intracerebral bleeding.

Material and methods: In this report, we present a patient with early-onset Parkinson's disease whose cerebral vascular anatomy precluded standard bilateral subthalamic nucleus electrode implantation. Initially, right subthalamic stimulation alone provided a very mild clinical benefit that was not reflected in the patient's quality of life. In this patient, an unusual configuration of intracerebral electrodes with right subthalamic and left pallidal stimulation electrodes was applied 15 months after the initial subthalamic electrode implantation.

15 Jan 2021

Imitation or Polarity Correspondence? Behavioural and Neurophysiological Evidence for the Confounding Influence of Orthogonal Spatial Compatibility on Measures of Automatic Imitation

During social interactions, humans tend to imitate one another involuntarily. To investigate the neurocognitive mechanisms driving this tendency, researchers often employ stimulus-response compatibility (SRC) tasks to assess the influence that action observation has on action execution. This is referred to as automatic imitation (AI). The stimuli used frequently in SRC procedures to elicit AI often confound action-related with other nonsocial influences on behaviour; however, in response to the rotated hand-action stimuli employed increasingly, AI partly reflects unspecific up-right/down-left biases in stimulus-response mapping. Despite an emerging awareness of this confounding orthogonal spatial-compatibility effect, psychological and neuroscientific research into social behaviour continues to employ these stimuli to investigate AI. To increase recognition of this methodological issue, the present study measured the systematic influence of orthogonal spatial effects on behavioural and neurophysiological measures of AI acquired with rotated hand-action stimuli in SRC tasks.

15 Jan 2021

Sex differences in the association of childhood socioeconomic position and later-life depressive symptoms in Europe: the mediating effect of education

Purpose: We aimed to study sex differences in the association of childhood socioeconomic position (SEP) with later-life depressive symptoms, the mediating effect of education and explore regional differences across Europe.

Methods: The study included 58,851 participants (55% women, mean age 65 years) from the multicentre, population-based Survey on Health, Ageing and Retirement in Europe. Interviews were conducted in six waves and included measurements of childhood SEP (household characteristics at the age of 10) and depressive symptoms (EURO-D scale). Linear regression was used to study the association of childhood SEP with depressive symptoms, adjusting for covariates, and structural equation modelling assessed the mediating effect of education.

Results: In the fully adjusted model, higher childhood SEP was associated with lower depressive symptoms with a greater magnitude in women (B = - 0.07; 95% CI - 0.08, - 0.05) than in men (B = - 0.02; 95% CI - 0.03, - 0.00).

5 Jan 2021

You took the words right out of my mouth: Dual-fMRI reveals intra- and inter-personal neural processes supporting verbal interaction

Verbal communication relies heavily upon mutual understanding, or common ground. Inferring the intentional states of our interaction partners is crucial in achieving this, and social neuroscience has begun elucidating the intra- and inter-personal neural processes supporting such inferences. Typically, however, neuroscientific paradigms lack the reciprocal to-and-fro characteristic of social communication, offering little insight into the way these processes operate online during real-world interaction. In the present study, we overcame this by developing a "hyperscanning" paradigm in which pairs of interactants could communicate verbally with one another in a joint-action task whilst both undergoing functional magnetic resonance imaging simultaneously. Successful performance on this task required both interlocutors to predict their partner's upcoming utterance in order to converge on the same word as each other over recursive exchanges, based only on one another's prior verbal expressions. By applying various levels of analysis to behavioural and neuroimaging data acquired from 20 dyads, three principle findings emerged: First, interlocutors converged frequently within the same semantic space, suggesting that mutual understanding had been established.

4 Jan 2021

Patterns of diffusion kurtosis changes in Parkinson's disease subtypes

Background: Diffusion kurtosis imaging has been applied to evaluate white matter and basal ganglia microstructure in mixed Parkinson's disease (PD) groups with inconclusive results.

Objectives: To evaluate specific patterns of kurtosis changes in PD and to assess the utility of diffusion imaging in differentiating between healthy subjects and cognitively normal PD, and between PD with and without mild cognitive impairment.

Methods: Diffusion scans were obtained in 92 participants using 3T MRI. Differences in white matter were tested by tract-based spatial statistics. Gray matter was evaluated in basal ganglia, thalamus, hippocampus, and motor and premotor cortices. Brain atrophy was also assessed. Multivariate logistic regression was used to identify a combination of diffusion parameters with the highest discrimination power between groups.

Results: Diffusion kurtosis metrics showed a significant increase in substantia nigra (p = 0.037, Hedges' g = 0.89), premotor (p = 0.009, Hedges' g = 0.85) and motor (p = 0.033, Hedges' g = 0.87) cortices in PD with normal cognition compared to healthy participants.

4 Jan 2021

Differential diagnosis of tremor syndromes using MRI relaxometry

Differential diagnosis of the most common tremor syndromes - essential tremor (ET) and Parkinson's disease (PD) is burdened with high error rate. However, diagnostic MRI biomarkers applicable in this clinically highly relevant scenario remain an unfulfilled objective. The presented study was designed in search for possible candidate MRI protocols relevant for differential diagnostic process in tremor syndromes.10 non-advanced tremor-dominant PD patients meeting diagnostic criteria for clinically established PD, 12 isolated ET patients and 16 healthy controls were enrolled into this study. The study focused on relaxation MRI protocols - T1, T2, adiabatic T1ρ and adiabatic T2ρ due to their relatively low post-processing requirements enabling implementation into routine clinical practice. Compared to ET, PD patients had significantly longer T2 relaxation times in striata with dominant findings in the putamen contralateral to the clinically more affected body side. This difference was driven by alterations in the PD group as confirmed in the complementary comparison with healthy controls. According to the receiver operating characteristic analysis, this region provided a reasonable sensitivity of 0.91 and specificity of 0.89 in the differential diagnosis of PD and ET.

4 Jan 2021

Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis

Background and purpose: Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes.

Methods: Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models.

Results: Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome.

4 Jan 2021

Incidence of Stroke and Ischemic Stroke Subtypes: A Community-Based Study in Brno, Czech Republic

Background: There are few contemporary epidemiological data on stroke for Central Europe. We performed a population-based study evaluating the incidence of stroke, stroke types, and ischemic stroke (IS) subtypes in Brno, the second biggest city in the Czech Republic (CR).

Methods: Using the National Registry of Hospitalized Patients, and hospital databases, we identified all patients hospitalized with a stroke diagnosis in Brno hospitals in 2011. For Brno residents with validated stroke diagnosis, we calculated (a) the overall incidence of hospitalized stroke, (b) incidence rates for IS, subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), and (c) incidence rates for IS subtypes. We calculated the average annual age- and sex-standardized incidence (European Standard Population and World Health Organization), to compare our results with other studies.

Results: The overall crude incidence of stroke in Brno was 213/100,000 population. The incidence of stroke for stroke types were as follows: SAH, 6.9; ICH, 26.4; and IS, 180 cases per 100,000 population, respectively.

18 Dec 2020

Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to Thrombus Targeting and Thrombolytic Studies

Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque^®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA).

18 Dec 2020

N-Formylated Peptide Induces Increased Expression of Both Formyl Peptide Receptor 2 (Fpr2) and Toll-Like Receptor 9 (TLR9) in Schwannoma Cells-An In Vitro Model for Early Inflammatory Profiling of Schwann Cells

Following nerve injury, disintegrated axonal mitochondria distal to the injury site release mitochondrial formylated peptides and DNA that can induce activation and inflammatory profiling of Schwann cells via formyl peptide receptor 2 (Fpr2) and toll-like receptor 9 (TLR9), respectively. We studied RT4 schwannoma cells to investigate the regulation of Fpr2 and TLR9 after stimulation with fMLF as a prototypical formylated peptide. RT4 cells were treated with fMLF at various concentrations and times with and without pretreatment with inhibitors (chloroquine for activated TLR9, PBP10 for Fpr2). Western blots of Fpr2, TLR9, p-p38, p-NFκB, and IL-6 were compared in relation to inflammatory profiling of RT4 cells and chemokine receptors (CCR2, CXCR4) as potential co-receptors of Fpr2. fMLF stimulation upregulated Fpr2 in RT4 cells at low concentrations (10 nM and 100 nM) but higher concentrations were required (10 µM and 50 µM) when the cells were pretreated with an activated TLR9 inhibitor.

18 Dec 2020

Socioeconomic deprivation in early life and symptoms of depression and anxiety in young adulthood: mediating role of hippocampal connectivity

Background: Experience of early-life socioeconomic deprivation (ELSD) may increase the risk of mental disorders in young adulthood. This association may be mediated by structural and functional alterations of the hippocampus.

Methods: We conducted a prospective cohort study on 122 participants of the European Longitudinal Study of Pregnancy and Childhood. Information about ELSD was collected via questionnaire from mothers during the first 18 months of participants' lives. At age 23-24, participants underwent examination by structural magnetic resonance imaging, resting-state functional connectivity and assessment of depressive symptoms (Mood and Feelings Questionnaire) and anxiety (Spielberger State-Trait Anxiety Inventory). The association of ELSD with brain outcomes in young adulthood was assessed with correlations, linear regression (adjusting for sex, socioeconomic position and mother's mental health) and moderated mediation analysis.

18 Dec 2020

Thrombectomy vs medical management in low NIHSS acute anterior circulation stroke

Objective: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature.

Methods: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation.

Results: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04).

18 Dec 2020

Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment: The INTERRSeCT Study

Background and purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke.

Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change.

11 Dec 2020

Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in perinatal Δ9-tetrahydrocannabinol occurs in schizophrenia: analyses in patients and in animal model of the disease

Perinatal exposure to Δ⁹-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems to be related to a dysregulation of endocannabinoid and/or dopaminergic systems. We here evaluated the transcriptional regulation of the genes encoding for the cannabinoid CB1 receptor (Cnr1) and the dopamine D2 receptor (Drd2) in perinatal THC-(pTHC) exposed male rats, focusing on the role of DNA methylation analyzed by pyrosequencing. Simultaneously, the molecular and behavioral abnormalities at two different time points (i.e., neonatal age and adulthood) and the potential preventive effect of peripubertal treatment with cannabidiol, a non-euphoric component of Cannabis, were assessed. The DRD2 methylation was also evaluated in a cohort of patients with schizophrenia.

7 Dec 2020

The reliability of a deep learning model in clinical out-of-distribution MRI data: A multicohort study

Deep learning (DL) methods have in recent years yielded impressive results in medical imaging, with the potential to function as clinical aid to radiologists. However, DL models in medical imaging are often trained on public research cohorts with images acquired with a single scanner or with strict protocol harmonization, which is not representative of a clinical setting. The aim of this study was to investigate how well a DL model performs in unseen clinical datasets-collected with different scanners, protocols and disease populations-and whether more heterogeneous training data improves generalization. In total, 3117 MRI scans of brains from multiple dementia research cohorts and memory clinics, that had been visually rated by a neuroradiologist according to Scheltens' scale of medial temporal atrophy (MTA), were included in this study. By training multiple versions of a convolutional neural network on different subsets of this data to predict MTA ratings, we assessed the impact of including images from a wider distribution during training had on performance in external memory clinic data.

4 Dec 2020

MR Diffusion Properties of Cervical Spinal Cord as a Predictor of Progression to Multiple Sclerosis in Patients with Clinically Isolated Syndrome

Background and purpose: This study's aim was to investigate diffusion properties of the cervical spinal cord in patients with clinically isolated syndrome (CIS) through analysis of diffusion tensor imaging (DTI) data and thereby to assess the capacity of this technique for predicting the progression of CIS to clinically definite multiple sclerosis (CDMS).

Methods: The study groups were comprised of 47 patients with CIS (15 of them with progression to CDMS within 2 years of follow-up) and 57 asymptomatic controls. All patients and controls had undergone magnetic resonance imaging (MRI) of the cervical spine including DTI and brain MRI. Methodological approaches included histogram analysis of the cervical cord's diffusion parameters and evaluation of T2 hyperintense lesions of the spinal cord and brain.

4 Dec 2020

Imagery-induced negative affect, social touch and frontal EEG power band activity

Social touch seems to modulate emotions, but its brain correlates are poorly understood. Here, we investigated if frontal power band activity in the electroencephalogram (EEG) during aversive mental imagery is modulated by social touch from one's romantic partner and a stranger. We observed the highest theta and beta power when imaging alone, next so when being touched by a stranger, with lowest theta and beta activity during holding hands with the loved one. Delta power was higher when being alone than with a stranger or a partner, with no difference between the two. Gamma power was highest during the stranger condition and lower both when being alone and with the partner, while alpha power did not change as a function of social touch. Theta power displayed a positive correlation with electrodermal activity supporting its relation to emotional arousal. Attachment style modulated the effect of touch on the EEG as only secure but not insecure partner bonding was associated with theta power reductions.

27 Nov 2020

Contribution of macromolecules to brain 1 H MR spectra: Experts' consensus recommendations

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice.

27 Nov 2020

Novel polygenic risk score as a translational tool linking depression-related changes in the corticolimbic transcriptome with neural face processing and anhedonic symptoms.

Convergent data from imaging and postmortem brain transcriptome studies implicate corticolimbic circuit (CLC) dysregulation in the pathophysiology of depression. To more directly bridge these lines of work, we generated a novel transcriptome-based polygenic risk score (T-PRS), capturing subtle shifts toward depression-like gene expression patterns in key CLC regions, and mapped this T-PRS onto brain function and related depressive symptoms in a nonclinical sample of 478 young adults (225 men; age 19.79 +/- 1.24) from the Duke Neurogenetics Study. First, T-PRS was generated based on common functional SNPs shifting CLC gene expression toward a depression-like state. Next, we used multivariate partial least squares regression to map T-PRS onto whole-brain activity patterns during perceptual processing of social stimuli (i.e., human faces).

18 Nov 2020

Cognitive Processing Impacts High Frequency Intracranial EEG Activity of Human Hippocampus in Patients With Pharmacoresistant Focal Epilepsy

The electrophysiological EEG features such as high frequency oscillations, spikes and functional connectivity are often used for delineation of epileptogenic tissue and study of the normal function of the brain. The epileptogenic activity is also known to be suppressed by cognitive processing. However, differences between epileptic and healthy brain behavior during rest and task were not studied in detail. In this study we investigate the impact of cognitive processing on epileptogenic and non-epileptogenic hippocampus and the intracranial EEG features representing the underlying electrophysiological processes. We investigated intracranial EEG in 24 epileptic and 24 non-epileptic hippocampi in patients with intractable focal epilepsy during a resting state period and during performance of various cognitive tasks.

18 Nov 2020

The impact of lymphocytosis and CD4/CD8 ratio on the anti-JCV antibody index and clinical data in patients treated with natalizumab

Background: Natalizumab is an effective therapy in the treatment of relapsing-remitting multiple sclerosis; it induces lymphocytosis (NIL, natalizumab-induced lymphocytosis) and changes the peripheral lymphocyte pattern.

Methods: This study aims to evaluate NIL, peripheral blood lymphocyte subsets, CD4/CD8 ratio, and their impacts on JCV index and clinical data-No Evidence of Disease Activity (NEDA-3) and annualized relapse rate (ARR) in patients treated with natalizumab.

18 Nov 2020

Mindfulness-Based Programs for Patients With Cancer via eHealth and Mobile Health: Systematic Review and Synthesis of Quantitative Research

Background: eHealth mindfulness-based programs (eMBPs) are on the rise in complex oncology and palliative care. However, we are still at the beginning of answering the questions of how effective eMBPs are and for whom, and what kinds of delivery modes are the most efficient.

Objective: This systematic review aims to examine the feasibility and efficacy of eMBPs in improving the mental health and well-being of patients with cancer, to describe intervention characteristics and delivery modes of these programs, and to summarize the results of the included studies in terms of moderators, mediators, and predictors of efficacy, adherence, and attrition.

18 Nov 2020

Sex differences in diagnosis and diagnostic revision of suspected minor cerebral ischemic events

Objective: To describe sex differences in the presentation, diagnosis, and revision of diagnosis after early brain MRI in patients who present with acute transient or minor neurological events.

Methods: We performed a secondary analysis of a prospective multicenter cohort study of patients referred to neurology between 2010 and 2016 with a possible cerebrovascular event and evaluated with brain MRI within 8 days of symptom onset. Investigators documented the characteristics of the event, initial diagnosis, and final diagnosis. We used multivariable logistic regression analyses to evaluate the association between sex and outcomes.

18 Nov 2020

Rapid Eye Movement Sleep Sawtooth Waves Are Associated with Widespread Cortical Activations

Sawtooth waves (STW) are bursts of frontocentral slow oscillations recorded in the scalp electroencephalogram (EEG) during rapid eye movement (REM) sleep. Little is known about their cortical generators and functional significance. Stereo-EEG performed for presurgical epilepsy evaluation offers the unique possibility to study neurophysiology in situ in the human brain. We investigated intracranial correlates of scalp-detected STW in 26 patients (14 women) undergoing combined stereo-EEG/polysomnography. We visually marked STW segments in scalp EEG and selected stereo-EEG channels exhibiting normal activity for intracranial analyses.

9 Nov 2020

Retinal arteriolar and venular diameters are widened in patients with schizophrenia

Cerebrovascular abnormalities have been discussed as pathological mechanisms involved in schizophrenia, particularly in the context of the genetic–inflammatory–vascular hypothesis.¹ The cerebral and retinal microcirculation have similarities with respect to morphology and physiology. It can therefore be tested if retinal vessel changes occur in patients with schizophrenia. Larger diameters of retinal venules have been noted in schizophrenia,^2, 3 while smaller retinal arteriolar diameters were recently shown in psychoses.³ Our study aimed to contribute new information to further test the hypothesis of the ‘eye as a window to the brain’ in the context of schizophrenia.

9 Nov 2020

Toward more accurate data in cardiac cellular electrophysiology

The divergence of published data is a well-recognised problem of experimental sciences including cardiac cellular electrophysiology. Differences in experimental conditions as well as in experimental models are commonly known to be potential reasons for this. Properties of individual cardiac myocytes vary depending on their localisation in the heart muscle, but also differ among species and strains, age and gender groups, housing and health conditions, to name the most often discussed sources of variability. However, limits of accuracy of experimental data arising from sub-optimal measurement and evaluation methods represent another important and often neglected source of data inconsistency.

9 Nov 2020

Structural Alterations in Deep Brain Structures in Type 1 Diabetes

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels, including macrostructural, microstructural cerebral damage, and blood flow alterations. In this cross-sectional study, we compared a cohort of 61 patients with T1D with an average disease duration of 21 years with 54 well-matched control subjects without diabetes in a multimodal MRI protocol providing macrostructural metrics (cortical thickness and structural volumes), microstructural measures (T1-weighted/T2-weighted [T1w/T2w] ratio as a marker of myelin content, inflammation, and edema), and cerebral blood flow.

9 Nov 2020

Voxelwise analysis of diffusion MRI of cervical spinal cord using tract-based spatial statistics

Robust voxelwise analysis using tract-based spatial statistics (TBSS) together with permutation statistical method is standardly used in analyzing diffusion tensor imaging (DTI) of brain. A similar analytical method could be useful when studying DTI of cervical spinal cord. Based on anatomical data of sixty-four healthy volunteers, white (WM) and gray matter (GM) masks were created and subsequently registered into DTI space. Using TBSS, two skeleton types were created (single line and dilated for WM as well as GM).

29 Oct 2020

Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial

Importance: The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging.

Objective: To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy.

29 Oct 2020

The Practice of Electroconvulsive Therapy in Children and Adolescents in the Czech Republic

Objectives: The aim of this study was to describe the practice of electroconvulsive therapy (ECT) in child and adolescent patients in the Czech Republic.

Methods: We conducted a mail questionnaire survey among Czech facilities associated with the Association of Child and Adolescent Psychiatry, and university hospitals with inpatient psychiatric wards, focused on the practice of ECT between 2013 and 2017 in patients younger than 18 years.

29 Oct 2020

High frequency oscillations in epileptic and non-epileptic human hippocampus during a cognitive task

Hippocampal high-frequency electrographic activity (HFOs) represents one of the major discoveries not only in epilepsy research but also in cognitive science over the past few decades. A fundamental challenge, however, has been the fact that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs. We investigated the impact of a cognitive task on HFOs with the aim of improving differentiation between epileptic and non-epileptic hippocampi in humans. Hippocampal activity was recorded with depth electrodes in 15 patients with focal epilepsy during a resting period and subsequently during a cognitive task. HFOs in ripple and fast ripple frequency ranges were evaluated in both conditions, and their rate, spectral entropy, relative amplitude and duration were compared in epileptic and non-epileptic hippocampi.

20 Oct 2020

The Direct Costs of Dravet's Syndrome before and after Diagnosis Assessment

The objective of this study was to estimate the direct cost before and after diagnosis assessment in patients with Dravet's syndrome (DS). The basis of the economic study was to calculate the costs of health care before and after diagnosis of DS. We retrospectively evaluated all SCN1A positive patients with phenotype of DS treated in our hospital. Statistical analyses were performed by IBM SPSS Statistics 24.0 software. After the diagnosis of DS, there was a significant decline of health care costs (-85.6%) an average of €29.4 ± 26.1 monthly per patient. We estimated the monthly costs at €204.5 ± 167 (median: €193.9, range: €35.5-534.4) per patient before DS diagnosis.

20 Oct 2020

Blood pressure excursions in acute ischemic stroke patients treated with intravenous thrombolysis

Objective: To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA).

Methods: We performed a post hoc analysis of the CLOTBUST-ER trial. Serial BP measurements were conducted using automated cuff recording according to the recommended BP protocol guidelines for tPA administration. The outcomes were prespecified efficacy and safety endpoints of CLOTBUST-ER.

20 Oct 2020

Temporally and sex-specific effects of maternal perinatal stress on offspring cortical gyrification and mood in young adulthood

Maternal stress during pregnancy and shortly thereafter is associated with altered offspring brain development that may increase risk of mood and anxiety disorders. Cortical gyrification is established during the prenatal period and the first 2 years of life and is altered in psychiatric disorders. Here, we sought to characterize the effects of perinatal stress exposure on offspring gyrification patterns and mood dysregulation in young adulthood.

20 Oct 2020

Epilepsy miRNA Profile Depends on the Age of Onset in Humans and Rats

Temporal lobe epilepsy (TLE) is a severe neurological disorder accompanied by recurrent spontaneous seizures. Although the knowledge of TLE onset is still incomplete, TLE pathogenesis most likely involves the aberrant expression of microRNAs (miRNAs). miRNAs play an essential role in organism homeostasis and are widely studied in TLE as potential therapeutics and biomarkers. However, many discrepancies in discovered miRNAs occur among TLE studies due to model-specific miRNA expression, different onset ages of epilepsy among patients, or technology-related bias.

8 Oct 2020

Simple compensation method for improved half-pulse excitation profile with rephasing gradient

Purpose: To improve the slice profile quality obtained by RF half-pulse excitation for 2D-UTE applications.

Methods: The overall first-order and zero-order phase errors along the slice-selection direction were obtained with the help of an optimization task to minimize the out-of-slice signal contamination from the calibration 1-dimenisonal (1D) profile data.

7 Oct 2020

Suboptimal response to STN-DBS in Parkinson's disease can be identified via reaction times in a motor cognitive paradigm

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) is generally a successful therapy, adverse events and insufficient clinical effect can complicate the treatment in some patients. We studied clinical parameters and cortical oscillations related to STN-DBS to identify patients with suboptimal responses.

7 Oct 2020

Use of high-density EEG in patients with Parkinson's disease treated with deep brain stimulation

The number of reports on cognitive changes related to deep brain stimulation (DBS) surgery in Parkinson's disease (PD) is growing. The aim of the review was to assess whether high-density electroencephalography (HD EEG) in patients with DBS treatment for PD is used and mentioned as a research method for the assessment of cognitive function changes after DBS of the subthalamic nucleus.

7 Oct 2020

Thrombectomy vs medical management in low NIHSS acute anterior circulation stroke

Background: Endovascular thrombectomy (EVT) is highly effective for acute ischemic stroke with large vessel occlusion (LVO) and moderate to severe neurologic deficits.

Objective: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIHSS ≤6 using datasets of multicentre and multinational nature.

6 Oct 2020

Medical Students' Career Choice and Attitudes Toward Psychiatry: Case of the Czech Republic

A survey among medical students of all medical schools in the Czech Republic was conducted to investigate attitudes and views of psychiatry and career choice of psychiatry.

6 Oct 2020

Cerebrocerebellar structural covariance in temporal lobe epilepsy with hippocampal sclerosis

Purpose: The purpose of the study was to evaluate cerebral morphological changes in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and their relationship to the cerebellum.

1 Oct 2020

1.-2. October 2020 - Course Cognitive Disorders and Dementia XVII

Where: Online stream

Progamme

19 Sep 2020

9. October 2020 – PhD Day

Where: Bohunice University Campus

19 Sep 2020

The first workshop of Masaryk Neuroscience Hub took place on 17. Sept. 2020

On the 17^thSeptember 2020 the first workshop on shared infrastructures took place. See enclosed video from the workshop.

18 Sep 2020

Internal Grant Agency of the Faculty of Medicine MUNI awarded researches with Start-up grants

The internal grant agency announced the results of the Start-up Grants competition.
The following applicants have been successful in obtaining grants with a neuroscience theme.

15 Sep 2020

Cognitive task-related functional connectivity alterations in temporal lobe epilepsy

We investigated cognitive task-related functional connectivity (FC) in patients with temporal lobe epilepsy (TLE). Using a visual three-stimulus paradigm (VTSP), we studied cognitive large-scale networks and the impact of TLE on connectivity outside the temporal lobe.

15 Sep 2020

Orientation-selective and directional deep brain stimulation in swine assessed by functional MRI at 3T

Functional MRI (fMRI) has become an important tool for probing network-level effects of deep brain stimulation (DBS). Previous DBS-fMRI studies have shown that electrical stimulation of the ventrolateral (VL) thalamus can modulate sensorimotor cortices in a frequency and amplitude dependent manner. Here, we investigated, using a swine animal model, how the direction and orientation of the electric field, induced by VL-thalamus DBS, affects activity in the sensorimotor cortex.

15 Sep 2020

Simple compensation method for improved half-pulse excitation profile with rephasing gradient

The overall first-order and zero-order phase errors along the slice-selection direction were obtained with the help of an optimization task to minimize the out-of-slice signal contamination from the calibration 1-dimenisonal (1D) profile data. The time-phase-error evolution was approximated from the k-space readout data, which were acquired primarily for correction of the readout trajectories during data regridding to the rectilinear grids. The correction of the slice profile was achieved by rephasing gradient pulses applied immediately after the end of excitation. The total prescan calibration typically took less than 2 minutes.

15 Sep 2020

Structural Alterations in Deep Brain Structures in Type 1 Diabetes

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels including macrostructural, microstructural cerebral damage and blood flow alterations.

15 Sep 2020

Detection of ischemic changes on baseline multimodal computed tomography: expert reading vs. Brainomix and RAPID software

The aim of the study was to compare the assessment of ischemic changes by expert reading and available automated software for non-contrast CT (NCCT) and CT perfusion on baseline multimodal imaging and demonstrate the accuracy for the final infarct prediction.

14 Sep 2020

miR‐183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids

MicroRNAs (miRNAs), a class of small, non-coding RNA molecules represent important regulators of gene expression. Recent reports have implicated their role in the cell specification process acting as "fine-tuners" to ensure the precise gene expression at the specific stage of cell differentiation. Here we used retinal organoids differentiated from human pluripotent stem cells (hPSCs) as a model to closely investigate the role of a sensory organ-specific and evolutionary conserved miR-183/96/182 cluster.

14 Sep 2020

Intracranial and systemic atherosclerosis in the NAVIGATE ESUS trial: Recurrent stroke risk and response to antithrombotic therapy

Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.

14 Sep 2020

Pre-Radiotherapy Progression after Surgery of Newly Diagnosed Glioblastoma: Corroboration of New Prognostic Variable

The aim of this retrospective study is to assess the incidence, localization, and potential predictors of rapid early progression (REP) prior to initiation of radiotherapy in newly diagnosed glioblastoma patients and to compare survival outcomes in cohorts with or without REP in relation to the treatment.

14 Sep 2020

Impulsivity in patients with borderline personality disorder: a comprehensive profile compared with healthy people and patients with ADHD

Impulsivity is a core symptom of borderline personality disorder (BPD). Impulsivity is a heterogeneous concept, and a comprehensive evaluation of impulsivity dimensions is lacking in the literature. Moreover, it is unclear whether BPD patients manifest impaired cognitive functioning that might be associated with impulsivity in another patient group, such as ADHD, a frequent comorbidity of BPD.

10 Sep 2020

16. Oct. 2020 - 20 Years of FMRI in Brno

Postponed to the spring.

10 Sep 2020

Looking for PhD candidate in the field of Retinal Organoids

Research topic: Human retinal organoids as a tool for investigating mechanisms of circadian clock control.

28 Aug 2020

New MASARYK NEUROSCIENCE HUB website has been released.

We are happy to announce that our new website has been released.

28 Aug 2020

A unique research cluster for the treatment of stroke has been established in Brno

STROKE BRNO is an interdisciplinary research cluster with the aim of connecting the knowledge and expertise of academic and industrial partners and ensuring the effective use of knowledge from basic research in clinical practice.