18 May

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

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

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

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

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

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

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

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

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

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

17 Apr

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

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

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

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

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

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

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

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

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

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

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

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

March 21 - Cluster headache awareness day

21 Feb

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

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

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

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

9 Feb

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 (&gt;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 &gt;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

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

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. 

16 Nov 2021

Master´s Programme in Neuroscience

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.

11 Oct 2021

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. The roles played in emotional distress were explored in terms of the biological, the clinical (diabetes-, neuropathy- and pain-related), the socio-economic and the cognitive factors (catastrophizing).

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

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

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

18 Aug 2021

Colour Categorization and its Effect on Perception: A Conceptual Replication

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

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.

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^th September 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.