BackgroundThe presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE. MethodsCharts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied. CSF and serum kappa free light chains were determined using the Freelite assay (The Binding Site Group) and the turbidimetric Optilite analyzer. ResultsWe identified 34 patients with “definite” AE (9 anti-NMDAR AE and 25 limbic AE) and nine patients with “possible” AE. Five patients (15%) with definite AE had pleocytosis and twelve (34%) showed CSF-restricted oligoclonal bands (OCB) at isoelectric focusing. The Kappa index was >6 in 29.4% and > 3 in 50% of the definite AE patients. It was elevated (>3) in 36.4% of patients with definite AE who resulted negative to OCB testing and was the only altered parameter suggestive of an ongoing inflammatory process in the CNS in three definite AE patients with otherwise normal CSF findings (i.e. normal cell count and protein levels, no OCBs). In the possible AE group, one patient had a Kappa index >3 in the absence of OCB. ConclusionsThe Kappa index could be useful, as a more sensitive marker of IS and as a supportive marker of neuroinflammation, in the diagnostic work-up of suspected AE.

Sleep apnea is an independent risk factor for cerebrovascular diseases. Its prevalence in stroke survivors is high and the disorder negatively affects patients' outcomes. Despite the importance of sleep apnea assessment is highlighted also in the current guidelines, a high proportion of patients remain undiagnosed and lose the potential benefit of positive airway pressure treatment. The current paper describes links between sleep apnea and stroke. It focuses on the challenges of the diagnostic and therapeutical process and provides a brief insight into ongoing trials that could help to identify appropriate diagnostic and therapeutic approaches, their timing, and the patient population for whom treatment could be most beneficial.

BackgroundThe Myasthenia Gravis–Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score. MethodsCross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure. ResultsCorrelations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution. DiscussionPsychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling.Registration: MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).

ObjectiveDespite high COVID-19 vaccination rates in many populations, concerns persist about potential adverse events, including concerns about involuntary movements. While case studies have shown occurrences of involuntary movements following COVID-19 vaccination, no systematic studies have explored this association. Our study aims to investigate the relationship between COVID-19 vaccination and involuntary movements. MethodsThis study employs a longitudinal panel design. The study population consists of 165,834 responses from a total of 97,537 unique individuals sourced from the BiCoVac cohort, which is a randomly sampled cohort of Danish individuals aged 16 to 65. Data were collected through a combination of questionnaires and national registers, and analyses were conducted using mixed effects logistic regression. ResultsVaccinated individuals had lower odds of reporting involuntary movements compared to non-vaccinated individuals. Although adjustments attenuated the results, a consistent pattern of lower odds was observed among the vaccinated individuals. The strongest association for the first dose was observed in individuals who received the vaccine within the last 4 weeks before reporting symptoms (OR = 0.72 (0.60; 0.85)). For the second dose, the strongest association was found in individuals who received the second vaccine dose >4 weeks before reporting symptoms (OR = 0.77 (0.65; 0.91)). ConclusionThe results of the study do not indicate involuntary movements as an adverse reaction to the COVID-19 vaccine. These findings support the safety profile of the COVID-19 vaccine concerning involuntary movements and contribute to enhancing public trust in vaccination programs.

The WFN Needs Registry survey was developed and conducted over two and a half years commencing in 2020 to investigate the accessibility and affordability of neurological services and therapeutics and the most urgent needs. Method: An experienced neurologist responded in each of 118 societies to an online electronic survey comprising 13 questions. General data sought comprised the respondent's training, place of practice, duration in practice, number of neurologists in the society, health care system and types of neurological practice available. Specific data collected comprised neurological facilities, specialist services available, resources, therapeutics accessibility, challenges and three most urgent needs. ResultsResponding neurologists spent a median of 26 years in practice and represented a median of 225 neurologists per society. Of 13 classes of neuromedicines deemed readily available to 70% of the population, 41 societies listed ≥1 and 14 societies ≥3 unavailable. The three most frequent unavailable neuromedicines were second level AEDs, Dopamine agonists and MS DMTs. Of 14 neurological services, 15 societies had all services accessible and affordable, 13 had none and 72 had ≥1 services either inaccessible or unaffordable. EEG, Epilepsy, Headache and EMG services were most available; Neurogenetics, Neuropsychology, Neurorehabilitation and Neurodevelopmental services were least available. Of 13 specified challenges, lack of subspecialists and specialty centers were both identified by 60% of societies followed by costs of neurological care, neuromedicines availability and stigma. Ten societies had no challenges. ConclusionA unique insight into the inequities of neurological care globally and a potential tool to assist their remedy.

IntroductionSmartphone applications (apps) are instruments that assist with objective measurements during the clinical assessment of patients with movement disorders. We aim to test the hypothesis that PD patients will exhibit an increase in tapping variability and a decrease in tapping speed over a one-year period, compared to healthy controls (HC). MethodsData was prospectively collected from participants enrolled in our Cincinnati Cohort Biomarker Program, in 2021–2023. Participants diagnosed with PD and age-matched HC were examined over a one-year-interval with a tapping test performed with customized smartphone app. Tapping speed (taps/s), inter-tap intervals and variability (movement regularity), and sequence effect were measured. ResultsWe included 295 PD patients and 62 HC. At baseline, PD subjects showed higher inter-tap variability than HC (coefficient-of-variation-CV, 37 ms [22–64] vs 26 ms [8–51])(p = 0.007). Conversely, there was no difference in inter-tap intervals (411 ms [199–593] in PD versus 478 ms [243–618] in HC) and tapping speed (3.42[2.70–4.76] taps/s in PD versus 3.21 taps/s [2.57–4.54] in HC)(p > 0.05). Only PD subjects (n = 135), at the one-year follow-up, showed a decreased tapping speed vs baseline (3.44 taps/s[2.86–4.81] versus 3.39 taps/s [2.58,4.30])(p = 0.036), without significant changes in inter-tap variability (CV, 32 ms[18,55] baseline versus 34 ms[22,59] follow-up)(p = 0.142). No changes were found in HC at the one-year follow up (all p values>0.05). ConclusionsOur results provided reliable one-year longitudinal information about PD patients, with the aim of improving objective assessment of bradykinesia. Longer follow-up studies may allow to better describe dysrhythmia progression over time and to distinguish between different subtypes of PD progression.

The global shortage and inequitable distribution of neurologists has led to significant gaps not only in neurology care, but also in neurology education. In order to increase access to neurology education, we developed neurology virtual morning report (NVMR), a virtual, open-access, case-based clinical reasoning conference available to learners worldwide. To evaluate NVMR's impact on participants' perception of, interest in, and confidence in neurology, we conducted a survey. Respondents represented 25 different countries of various income levels. The majority of respondents reported that NVMR decreased their perception of difficulty in understanding neurology and increased confidence in various clinical reasoning domains in neurology. Additionally, the majority of medical student participants showed an increased interest in pursuing neurology as a future specialty after participating in NVMR. NVMR represents a potential model for virtual educational conferences and highlights the opportunities digital education has to improve equitable access to neurology education.

BackgroundGuillain-Barré Syndrome (GBS) can lead to significant functional impairments, yet little is understood about the recovery phase and long-term consequences for patients in low- and medium-income countries. ObjectiveTo evaluate the functional status and identify factors influencing outcomes among patients with GBS in Colombia. MethodsBetween 2016 and 2020, telephone interviews were conducted with GBS patients enrolled in the Neuroviruses Emerging in the Americas Study. The investigation encompassed access to health services and functional status assessments, utilizing the modified Rankin Scale (mRS), GBS Disability Score (GDS), Barthel Index (BI), and International Classification of Functioning (ICF). Univariate analysis, principal component analysis, linear discriminant analysis, and linear regression were employed to explore factors influencing functional status. ResultsForty-five patients (mean age = 50[±22] years) with a median time from diagnosis of 28 months (IQR = 9–34) were included. Notably, 22% and 16% of patients did not receive rehabilitation services during the acute episode and post-discharge, respectively. Most patients demonstrated independence in basic daily activities (median BI = 100, IQR = 77.5–100), improved disability as the median mRS at follow-up was lower than at onset (1 [IQR = 0–3] vs. 4.5 [IQR = 4–5], p < 0.001), and had better ability to walk without assistance (median GDS = 2, IQR = 0–2). A shorter period from disease onset to interview was associated with worse mRS (p = 0.015) and ICF (p = 0.019). Negative outcomes on GDS and ICF were linked to low socioeconomic status, ICF to the severity of weakness at onset, and BI to an older age. ConclusionsThis study underscores that the functional recovery of GBS patients in Colombia is influenced not only by the natural course of the disease but also by socioeconomic factors, emphasizing the crucial role of social determinants of health.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke.In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays).VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04).Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

Patients with amyotrophic lateral sclerosis (ALS) do not develop oculomotor disturbances and vesicorectal dysfunction until end-stage disease owing to the survival of certain motor neurons (MNs), including oculomotor neurons and MNs within Onuf's nucleus. In sporadic ALS, adenosine deaminase acting on RNA 2 (ADAR2)-mediated editing of GluA2 mRNA at the Q/R site is compromised in lower MNs. We previously developed genetically modified mice with a conditional knockout of ADAR2 in cholinergic neurons (ADAR2flox/flox/VAChT-Cre, Fast; AR2). These mice displayed slow and progressive lower motor neuron death with TAR DNA-binding protein 43 (TDP-43) pathology, attributable to insufficient editing at the GluA2 Q/R site due to ADAR2 deficiency. MN death was more common in fast-fatigable MNs owing to differential vulnerability under conditions of ADAR2 deficiency. Although facial and hypoglossal nerves were impaired in AR2 mice, cell death did not occur within the oculomotor nerve nucleus, as observed in patients with sporadic ALS. Since the basis for avoiding cystorectal damage in ALS is unknown, we compared the features of Onuf's nucleus MNs in 12-month-old AR2 mice with those in age-matched wild-type mice. Although the number of MNs was not significantly lower in AR2 mice, the neurons exhibited a shrunken morphology and TDP-43 pathology. Onuf's nucleus MNs could survive in an ADAR2-deficient state and mainly included fast fatigue-resistant (FR) and slow (S) MNs. In summary, FR and S MNs show increased resilience to ADAR2 deficiency, potentially participating in an important neuronal death avoidance mechanism in ALS.