22 Jan

GLP-1 Receptor Agonists for Secondary Prevention After Myocardial Infarction and Stroke in Type 2 Diabetes: Nationwide Real-World Evidence

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischemic stroke and examined trends and disparities.

Methods: Using nationwide Czech registry data (2015-2024), we identified patients with incident nonfatal MI or ischemic stroke and confirmed T2D. GLP-1RA users-initiating therapy within 12 months post-event-were propensity score-matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality.

Results: GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126,845 MI survivors, 28,206 had T2D; the matched cohort comprised 2,271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR:0.7; 95%CI:0.52-0.93), all-cause (HR:0.61;95%CI:0.47-0.80) and cardiovascular death (HR:0.54, 95%CI:0.36-0.80). Among 177,115 stroke survivors, 73,750 had T2D; the matched cohort comprised 2,235 patients (385 GLP-1RA; median follow-up 27 months). 

22 Jan

The Assessment of RAB32 p.Ser71Arg Variant Prevalence in Parkinson's Disease Across Selected African, European, and South American Cohorts

Monogenic forms of Parkinson's disease (PD) have demonstrated a heterogeneous disorder involving multiple biological pathways.¹ Familial forms of PD have been linked to variants in LRRK2, SNCA, VPS35, PARKIN, and PINK1.¹ Heterozygous GBA mutation carriers are associated with higher disease risk, earlier onset, and accelerated clinical progression.¹

Recently, RAB32 has emerged as a nominated PD gene. It encodes a Rab GTPase involved in mitochondrial and vesicular trafficking pathways. A rare substitution, p.Ser71Arg (rs200251693), has been proposed as a potential susceptibility factor.^2, 3 Reported carriers exhibit late-onset, levodopa-responsive parkinsonism with familial clustering; the only available autopsy case lacked Lewy bodies.^1-3 Across published studies, RAB32 c.213C>G was detected in 0.22% to 2.3% of patients, primarily within Mediterranean and North American cohorts, and was absent in large East Asian datasets. This pattern suggests regional specificity and a possible shared Mediterranean haplotype.^2-6 Limited data exist from several regions, including Eastern Europe, Ireland, sub-Saharan Africa, and South America.

22 Jan

Influence of hypokinetic dysarthria severity level on the long-term outcome of repetitive transcranial magnetic stimulation therapy

Introduction: Hypokinetic dysarthria (HD) is a common and disabling symptom of Parkinson's disease (PD) for which established pharmacological and surgical treatments bring only limited, often short-term improvement in speech. The aim of this study was to investigate whether the long-term acoustic effects of repetitive transcranial magnetic stimulation (rTMS) over the right superior temporal gyrus (STG) depend on the baseline severity of HD.

Methods: 26 PD patients were randomized to active STG-targeted rTMS (n = 15) or sham stimulation (n = 11) and followed across five recording sessions over 14 weeks, alongside one session of matched healthy controls. HD severity at baseline was quantified using 3F test subscores and used to stratify patients into milder (0) and more severe (1) subgroups. The STG 1 subgroup combined greater motor and speech impairment with shorter disease duration. Multiple acoustic features from sustained phonation and free monologue were extracted, normalized to controls, adjusted for sex, and analyzed using non-parametric statistics and descriptive visualisations.

Results: Patients with more severe HD receiving active stimulation (STG 1) showed consistent, long-lasting improvements in phonation-related parameters, whereas milder HD (STG 0) and sham groups (SHAM 0, SHAM 1) exhibited only limited or transient changes.

5 Jan

Network hubs supporting memory encoding: Implications for cognitive preservation in epilepsy surgery

Objective: Memory impairments are common in neurological disorders, especially drug-resistant epilepsy, where cognitive deficits such as accelerated long-term forgetting may occur before surgery due to interictal/ictal discharges, antiseizure medications, and disease progression. Postsurgical memory decline affects 40%-60% of patients. Understanding the neural mechanisms of memory encoding is essential for identifying critical network hubs and guiding surgical interventions that preserve cognitive function.

Methods: We analyzed intracranial electroencephalographic recordings from epilepsy patients (n = 15) performing a verbal memory encoding task to identify key structures involved in successful memory formation. Functional connectivity was computed using multiple features across several frequency bands. Temporal dynamics of connectivity were examined to characterize pre-encoding and encoding phases.

Results: The middle temporal gyrus (MTG) consistently emerged as a verbal memory hub across features and frequency bands. The inferior frontal gyrus (IFG) was identified as a beta-band-specific hub via phase synchrony. Temporal analyses revealed that MTG exhibited stable and widespread connectivity differences across all encoding phases, suggesting a role in pre-encoding network priming. 

5 Jan

Functional Impact Score of Mitochondrial Variants and Its Relationship With Functional Connectivity of the Brain: Potential Origins of Premature Aging in Young Adulthood

Alterations in mitochondrial DNA (mtDNA) have been associated with worse cognitive abilities in older adults and premature epigenetic aging in young adulthood. However, it is not clear how mitochondrial dysfunction affects brain function in young adulthood and whether cognition-related networks might be most affected. We tested whether mtDNA functional impact (FI) score might map onto specific patterns of between-network functional connectivity in young adults from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). We also tested whether these relationships might be mediated by accelerated epigenetic aging, calculated using Horvath's epigenetic clock, CheekAge clock, and AltumAge clock. General connectivity method was used as a reliable marker of individual differences in brain function. We showed that a greater mtDNA FI score was associated with lower connectivity between the dorsal attention and language networks (beta = -0.41, p = 0.0007, AdjR² = 0.15) and that there was suggestive evidence that this relationship might be mediated by accelerated epigenetic aging calculated using Horvath's epigenetic clock in young adulthood (ab = -0.061, SE = 0.04, 95% CI [-0.163; 0.001], 90% CI [-0.142; -0.002]). These findings were independent of sex, current BMI, and current substance use. 

10 Dec 2025

Limitations of multiexponential T1 mapping of cortical myeloarchitecture

Neuropsychiatric malignancies frequently manifest at the level of individual cortical layers. The resolutions currently available for medical magnetic resonance imaging (MRI) prevent the study of these pathologies at clinically available field strengths of 3 T. Previous studies have claimed to have overcome these issues by extensions of quantitative MRI. Following this, the feasibility of multiexponential T1 relaxometry was assessed as a basis for in vivo delineation of cortical lamination. Three methods of non-linear least-squares-based multiexponential analysis were examined across key degrees of freedom identified in the literature. The methods employ a wide variety of ways to overcome the common pitfalls of multiexponential analysis, such as regularization, bound constraints, and repeated optimization from multiple starting points. A custom MRI phantom was 3D-printed and filled with various MnCL2 mixtures that represent the spin-lattice relaxation times that commonly occur in neocortical gray and white matter at 3 T. A 96 × 96-voxel image consisting of a single slice was acquired using a FLASH sequence and used to create 10 composite datasets with known distributions of T1 decay constants. The results showed that lowest relative error achieved across multiexponential models was approximately 20%. 

10 Dec 2025

Ultra-refractory epilepsy: The newly described entity

Objective: Drug-resistant epilepsy (DRE) is defined as the failure of two antiseizure medications (ASMs) to achieve complete seizure control, affecting approximately 30% of epilepsy patients. In some cases, additional ASMs and surgical approaches are also unsuccessful. Ultra-Refractory Epilepsy (URE) is a newly described entity, characterized by the failure of six distinct epilepsy treatment strategies, including ASMs, surgical resection, and neurostimulation techniques. This study aimed to analyze demographic and clinical data of URE patients managed at the Brno Epilepsy Center, a member of the European Reference Network (ERN)-EpiCARE.

Methods: We conducted a retrospective cohort study with a prospective follow-up component. Adult patients hospitalized for epilepsy at the Brno Epilepsy Center between 2017 and 2023 were retrospectively identified, and their outcomes were prospectively assessed in February 2025 through medical record review and structured telephone interviews. URE patients were identified, and their demographic and clinical data were analyzed.

Results: In this study, 1034 patients' charts were reviewed, and 62 patients (6%) met the criteria for URE. In the URE cohort, the median age of epilepsy onset was 9 years (range 1-60 years), and the median age at the time of evaluation was 35 years (range 21-67 years).

28 Nov 2025

Sentence comprehension in Lewy body diseases: a functional magnetic resonance imaging study

Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies, often involve mild cognitive impairment at diagnosis (mild cognitive impairment with Lewy bodies (MCI-LB). Language dysfunction in MCI-LB patients is often unrecognized. This study aimed to assess syntactic comprehension deficits in MCI-LB patients and to explore their neural correlates. A total of 25 MCI-LB patients (mean ± sd: 72 ± 5.6 years old, 10 women) and 25 healthy controls (HC, mean ± sd: 66 ± 4.0 years old, 12 women) performed task functional MRI Test of Sentence Comprehension (ToSC). Functional connectivity was analysed using psychophysiological interaction (PPI) method, focusing on the striatum and language networks. MCI-LB patients had lower ToSC scores than HC (MCI-LB: 74.7 ± 15.7, HC: 88.5 ± 9.0, P < 0.001) and their PPI analysis revealed decreased connectivity from the striatum to the cuneus, precuneus, and left supramarginal gyrus, and reduced connectivity particularly in the dorsal pathway during noncanonical (syntactically more complex) sentence processing. Taken together, in this cross-sectional study MCI-LB patients showed impaired sentence comprehension related to decreased subcortical-cortical and dorsal language network connectivity.