BACKGROUND:Fitness tracking, facilitated by wearable devices, has emerged as a popular method for monitoring physical activity levels in the general population; however, its usage, acceptance and utility in patients with multiple sclerosis (pwMS) remain understudied. OBJECTIVE:To investigate the prevalence of fitness tracking device usage in pwMS and to explore acceptance and willingness to share data for use in healthcare. METHODS:We surveyed a cohort of consecutively and prospectively included pwMS diagnosed according to revised McDonald criteria 2017 in MS outpatient departments from two centers in Bern, Switzerland and Vienna, Austria. RESULTS:Out of a total of 200 pwMS (70% female) with a mean age of 43.1 years (SD 12.3 years), 161/200 (80.5%) had relapsing MS. Overall, 34.0% pwMS reported wearing a fitness tracker and when asked how often they actually wear their fitness tracker, 54.4% reported wearing it always and 27.9% reported wearing it often, whereas only 16.2% reported infrequent use. Asked whether they would share the data gathered by their respective fitness tracker, 93.9% reported a willingness to share their health data for both clinical routine care and research. CONCLUSION:In a representative cohort of pwMS in Central Europe, about one third are already actively and frequently tracking their physical activities with a strong dedication to utilizing their tracking data within healthcare settings including research. This underscores the feasibility and significant potential utility of monitoring physical activity by fitness tracking in the realm of MS care.

Background: Different definitions of disability progression by Expanded Disability Status Scale (EDSS) may influence frequency and/or time to event. Methods: In this multicenter cohort study, we included PPMS patients with follow-up >= 24 months and >= 3 available EDSS scores overall (>= 1 per year). We applied 672 definitions of disability progression including different minimal EDSS increase, required confirmation and fixed/roving-baseline score. Results: We analyzed follow-up periods from 131 PPMS patients (median age at baseline 53.0 years [45.0 - 63.0], 51.9 % female, median follow-up 3.9 years [2.6 - 6.0], median baseline EDSS 4.0 [2.5 - 6.0]). The most sensitive definition of a progression event was an unconfirmed increase of >= 0.5 points with a roving baseline (81.8 % event rate). The least sensitive definition was an increase of >= 1.0 points with a fixed baseline, minimal distance to reference 48 weeks, and confirmed at >= 48 weeks (28.4 % event rate). Comparing roving vs. fixed baseline over all cutoffs and confirmation definitions, average time to progression was 227 days shorter applying the roving baseline (1405 days [550 - 2653] vs. 1632 days [760 - 2653]). Conclusions: Different definitions of disability progression result in significantly differing rates of disability progression, which may influence study results and create confusion in clinical practice.

Background: Reporting of sex-specific analyses in multiple sclerosis (MS) is sparse. Disability accrual results from relapses (relapse-associated worsening) and independent thereof (progression independent of relapses). Objectives: A population of MS patients during relapse treated per standard of care was analyzed for sex differences and short-term relapse outcome (3–6 months) as measured by Expanded Disability Status Scale (EDSS) change. Design: Single-center retrospective study. Methods: We analyzed 134 MS relapses between March 2016 and August 2020. All events required relapse treatment (steroids and/or plasma exchange). Demographic, disease, and paraclinical characteristics [cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI)] were displayed separated by sex. Multivariable linear regression was run to identify factors associated with short-term EDSS change. Results: Mean age at relapse was 38.4 years (95% confidence interval: 36.3–40.4) with a proportion of 71.6% women in our cohort. Smoking was more than twice as prevalent in men (65.8%) than women (32.3%). In- and after-relapse EDSSs were higher in men [men: 3.3 (2.8–3.9), women: 2.7 (2.4–3.0); men: 3.0 (1.3–3.6); women: 1.8 (1.5–2.1)] despite similar relapse intervention. Paraclinical parameters revealed no sex differences. Our primary model identified female sex, younger age, and higher EDSS at relapse to be associated with EDSS improvement. A higher immunoglobulin G (IgG) quotient (CSF/serum) was associated with poorer short-term outcome [mean days between first relapse treatment and last EDSS assessment 130.2 (79.3–181.0)]. Conclusion: Sex and gender differences are important in outcome analyses of MS relapses. Effective treatment regimens need to respect putative markers for a worse outcome to modify long-term prognosis such as clinical and demographic variables, complemented by intrathecal IgG synthesis. Prospective trials should be designed to address these differences and confirm our results.

Introduction Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 (cluster of differentiation) monoclonal antibodies (mAbs) such as ocrelizumab (OCR) and ofatumumab (OFA) show a reduction mainly of B-lymphocytes, but also other lymphocyte subsets can be affected by these treatments. There is limited data on differences between lymphocyte subset counts of pwMS after treatment initiation with OCR or OFA. Objective To compare lymphocyte subset counts after treatment initiation in pwMS treated with OCR and OFA. Methods We analyzed 22 pwMS initiated on OFA and 56 sex-, age- and MS course matched pwMS initiated on OCR from 2 prospectively collected observational MS databases (Bern [n: OFA 14, OCR 44] and Vienna [n: OFA 8, OCR 12]) statistically comparing lymphocyte subset counts (Mann Whitney Test). Results We found that pwMS treated with OCR showed a stronger reduction of CD20 B-lymphocytes ( P = .001), and a trend towards lower counts of CD8 + T cells ( P = .056) compared to pwMS treated with OFA, whereas reduction of total lymphocyte, CD4 + lymphocyte and NK cell count was equally distributed between both treatments. Conclusion Different effects on lymphocyte subpopulations appear to be present in pwMS after treatment initiation with different anti-CD20 mAbs. Further studies are needed to determine potential effects on anti-CD20 treatment efficacy as well as treatment associated risks such as failed vaccinations and infections.

A large number of disease-modifying immunotherapies are available for the treatment of people with multiple sclerosis. Many disease-modifying immunotherapies show scarce or no safety data in pregnancy and breastfeeding and are labeled as being contraindicated during these periods in the Swiss summary of product characteristics. Some disease-modifying immunotherapies also have restrictions for male patients. Hence, family planning should always be considered in treatment decisions. If clinically necessary, the continuation of immunotherapy during pregnancy can be considered for some substances. In these situations, the “Good Off-Label Use Practice”, careful consideration of the benefit–risk profile, and interprofessional cooperation between the treating neurologist, obstetrician–gynecologist, and pharmacist/pharmacologist, ideally with the involvement of experienced centers, is necessary. Here, we present an update on disease-modifying immunotherapies in multiple sclerosis with a focus on family planning, pregnancy, and breastfeeding and provide consensus recommendations of the Medico-Scientific Advisory Board of the Swiss Multiple Sclerosis Society, the Swiss Neurological Society, and the Swiss Society for Gynecology and Obstetrics (represented by the Academy of Fetomaternal Medicine). These unified national recommendations are necessary, as guidelines from other countries differ and because of separate approval/reimbursement situations in Switzerland.

Introduction: The differences in vascular risk factors’ and stroke burden across Europe are notable, however there is limited understanding of the influence of socioeconomic environment on the quality of secondary prevention and outcome after acute ischemic stroke. Patients and methods: In this observational multicenter cohort study, we analyzed baseline characteristics, reperfusion treatment, outcome and secondary prevention in patients with acute ischemic stroke from three tertiary-care teaching hospitals with similar service population size in different socioeconomic environments: Bern/CH/ n = 293 (high-income), Gdansk/PL/ n = 140 (high-income), and Lutsk/UA/ n = 188 (lower-middle-income). Results: We analyzed 621 patients (43.2% women, median age = 71.4 years), admitted between 07 and 12/2019. Significant differences were observed in median BMI (CH = 26/PL = 27.7/UA = 27.8), stroke severity [(median NIHSS CH = 4(0-40)/PL = 11(0-33)/UA = 7(1-30)], initial neuroimaging (CT:CH = 21.6%/PL = 50.7%/UA = 71.3%), conservative treatment (CH = 34.1%/PL = 38.6%/UA = 95.2%) (each p < 0.001), in arterial hypertension (CH = 63.8%/PL = 72.6%/UA = 87.2%), atrial fibrillation (CH = 28.3%/PL = 41.4%/UA = 39.4%), hyperlipidemia (CH = 84.9%/PL = 76.4%/UA = 17%) (each p < 0.001) and active smoking (CH = 32.2%/PL = 27.3%/UA = 10.2%) ( p < 0.007). Three-months favorable outcome (mRS = 0–2) was seen in CH = 63.1%/PL = 50%/UA = 59% (unadjusted- p = 0.01/adjusted- p CH-PL/CH-UA = 0.601/0.981), excellent outcome (mRS = 0–1) in CH = 48.5%/PL = 32.1%/UA = 27% (unadjusted- p < 0.001/adjusted- p CH-PL/CH-UA = 0.201/0.08 and adjusted-OR CH-UA = 2.09). Three-months mortality was similar between groups (CH = 17.2%/PL = 15.7%/UA = 4.8%) (unadjusted- p = 0.71/adjusted- p CH-PL/CH-UA = 0.087/0.24). Three-months recurrent stroke/TIA occurred in CH = 3.1%/PL = 10.7%/UA = 3.1%, adjusted- p/OR CH-PL = 0.04/0.32). Three-months follow-up medication intake rates were the same for antihypertensives. Statin/OAC intake was lowest in UA = 67.1%/25.5% (CH = 87.3%/39.2%/unadjusted- p < 0.001/adjusted- p CH-UA = 0.02/0.012/adjusted-OR CH-UA = 2.33/2.18). Oral intake of antidiabetics was lowest in CH = 10.8% (PL = 15.7%/UA = 16.1%/unadjusted- p = 0.245/adjusted- p CH-PL/CH-UA = 0.061/0.002/adjusted-OR CH-UA = 0.25). Smoking rates decreased in all groups during follow-up. Discussion and conclusion: Substantial differences in presentation, treatment and secondary prevention measures, are linked to a twofold difference in adjusted 3-months excellent outcome between Switzerland and Ukraine. This underscores the importance of socioeconomic factors that influence stroke outcomes, emphasizing the necessity for targeted interventions to address disparities in treatment and secondary prevention strategies.

Background and ObjectivesIsolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome.MethodsCombining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for >= 12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for >= 2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses.ResultsA total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given >= 3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with >= 3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%.DiscussionIn our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred.Classification of EvidenceThis study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with >= 3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.

BACKGROUND AND PURPOSE:Relapse presentation in relapsing multiple sclerosis (RMS) differs between sexes, leading to differential outcomes. An influence of age seems likely but is less well investigated separately for women and men. METHODS:Using the large well-defined dataset of the pivotal trials of ocrelizumab in RMS, OPERA I and II, and their open-label extension, we performed a post hoc analysis to investigate relapse phenotypes for sex- and age-related differences in n = 929 relapses in 534 subjects (171 men, 363 women). Frequencies of affected functional systems were analyzed separated by sex and for three age strata (<35, 35-44, ≥45 years). Exact p-values are given for this exploratory analysis. RESULTS:Frequencies of mono- versus polysymptomatic relapse presentations were different neither between sexes nor in different age groups. Cerebellar symptoms were more frequent in relapses in men (female [f]: 23.1%, male [m]: 33.0%, p = 0.002), and women's relapses included more sensory (f: 53.8%, m: 32.3%, p < 0.001) and fatigue symptoms (f: 22.6%, m: 14.7%, p = 0.006). Whereas the sex difference for sensory involvement was present over all age groups (<35 years: f: 58.3%, m: 30.4%, p < 0.001; 35-44 years: f: 53.7%, m: 36.0%, p = 0.003; ≥45 years: f: 47.8%, m: 28.8%, p = 0.009), the difference for cerebellar involvement diminished with age (<35 years: f: 20.1%, m: 33.3%, p = 0.009; 35-44 years: f: 22.7%, m: 34.2%, p = 0.034; ≥45 years: f: 27.8%, m: 30.3%, p = 0.750). Relapse presentation seemed to shift with age in women only. CONCLUSIONS:We describe sex-specific relapse presentations and an influence of age only for women. Underlying causal factors warrant further investigations.

Aim The aim of this study was to investigate baseline characteristics and outcome of patients after endovascular therapy (EVT) for acute large vessel occlusion (LVO) in relation to their history of symptomatic vascular disease and sex.Methods Consecutive EVT-eligible patients with LVO in the anterior circulation admitted to our stroke center between 04/2015 and 04/2020 were included in this observational cohort study. All patients were treated according to a standardized acute ischaemic stroke (AIS) protocol. Baseline characteristics and successful reperfusion, recurrent/progressive in-hospital ischaemic stroke, symptomatic in-hospital intracranial hemorrhage, death at discharge and at 3 months, and functional outcome at 3 months were analyzed according to previous symptomatic vascular disease and sex.Results 995 patients with LVO in the anterior circulation (49.4% women, median age 76 years, median admission NIHSS score 14) were included. Patients with multiple vs. no previous vascular events showed higher mortality at discharge (20% vs. 9.3%, age/sex - adjustedOR = 1.43, p = 0.030) and less independency at 3 months (28.8% vs. 48.8%, age/sex - adjustedOR = 0.72, p = 0.020). All patients and men alone with one or multiple vs. patients and men with no previous vascular events showed more recurrent/progressive in-hospital ischaemic strokes (19.9% vs. 6.4% in all patients, age/sex - adjustedOR = 1.76, p = 0.028) (16.7% vs. 5.8% in men, age-adjustedOR = 2.20, p = 0.035). Men vs. women showed more in-hospital symptomatic intracranial hemorrhage among patients with one or multiple vs. no previous vascular events (23.7% vs. 6.6% in men and 15.4% vs. 5.5% in women, OR = 2.32, p = 0.035/age - adjustedOR = 2.36, p = 0.035).Conclusions Previous vascular events increased the risk of in-hospital complications and poorer outcome in the analyzed patients with EVT-eligible LVO-AIS. Our findings may support risk assessment in these stroke patients and could contribute to the design of future studies.

This cross-sectional study examines the geographical and socioeconomic factors associated with trial distribution and outcome of treatment for multiple sclerosis (MS).

Multiple sclerosis (MS) is a neuroinflammatory disease that affects millions of people worldwide. Since dysarthria is prominent in people with MS (pwMS), this paper aims to identify acoustic features that differ between people with MS and healthy controls (HC). Additionally, we develop automatic classification methods to distinguish between pwMS and HC. In this work, we present a new dataset of a German-speaking cohort which contains 39 patients with low disability of relapsing MS and 16 HC. Findings suggest that certain interpretable speech features could be useful in diagnosing MS, and that machine learning methods could potentially support fast and unobtrusive screening in clinical practice. The study emphasises the importance of analysing free speech compared to read speech

Background: Leptomeningeal inflammation in patients with multiple sclerosis (MS) mainly affects meningeal B-cell follicle-like structures linked to cortical and subpial lesions and can be visualized as leptomeningeal enhancement (LME). Objective: To evaluate the evolution of LME under different MS immunotherapies. Methods: A total of 214 MS patients treated with anti-CD20 therapies or fingolimod at the university hospital Bern were screened for LME. Magnetic resonance imaging (MRI) and medical records were retrospectively evaluated, and comparative statistics were applied. Results: We compared MS patients treated with anti-CD20 therapies (128 patients (59.8%)) or fingolimod (86 patients (40.2%)). Of 128 anti-CD20-treated patients, 108 (84.4%) had no LME, 11 (8.6%) had persistent LME, and 9 (7.0%) showed resolution of LME. Of 86 fingolimod-treated MS patients, 81 (94.2%) had no LME and 5 (5.8%) persistent LME. Patients with LME persistence were older than those without or resolution of LME (p = 0.039). Resolution of LME was more frequent during anti-CD20 compared with fingolimod treatment (p = 0.019). Conclusion: We observed LME resolution under treatment with anti-CD20 therapies. As LME might play an important role in cerebral gray matter pathology in MS, further investigations including extensions to higher field strengths, correlation with clinical phenotypes, and comparison with other immunotherapies are needed.

Kelchlike protein 11 antibodies (KLHL11‐IgGs) were first described in 2019 as a marker of paraneoplastic neurological syndromes (PNSs). They have mostly been associated with testicular germ cell tumors (tGCTs).

The SARS-CoV-2 pandemic is still ongoing and will remain a major health concern and challenge for the health care systems in the upcoming years. To address this threat, our research group has been studying this issue.

Multiple sclerosis (MS), Neuromyelitis optica spectrum disorder (NMOSD) and Myelin-Oligodendrocyte-Glycoprotein antibody associated disorder (MOGAD) are demyelinating disorders of the central nervous system (CNS) of autoimmune origin. Here, we summarize general considerations on sex-specific differences in the immunopathogenesis and hormonal influences as well as key clinical and epidemiological elements. Gender-specific issues are widely neglected starting with the lacking separation of sex as a biological variable and gender comprising the sociocultural components. As for other autoimmune diseases, female preponderance is common in MS and NMOSD. However, sex distribution in MOGAD seems equal. As in MS, immunotherapy in NMOSD and MOGAD is crucial to prevent further disease activity. Therefore, we assessed data on sex differences of the currently licensed disease-modifying treatments for efficacy and safety. This topic seems widely neglected with only fragmented information resulting from post-hoc analyses of clinical trials or real-world post-marketing studies afflicted with lacking power and/or inherent sources of bias. In summary, biological hypotheses of sex differences including genetic factors, the constitution of the immune system and hormonal influences are based upon human and preclinical data, especially for the paradigmatic disease of MS whereas specific data for NMOSD and MOGAD are widely lacking. Epidemiological and clinical differences between men and women are well described for MS and to some extent for NMOSD, yet, with remaining contradictory findings. MOGAD needs further detailed investigation. Sex-specific analyses of safety and efficacy of long-term immunotherapies need to be addressed in future studies designed and powered to answer the pressing questions and to optimize and individualize treatment.

Survival analysis of reaching EDSS ≥4.0 based on RoAD score ≥4 (dashed line) and <4 (solid line) by Cox regression analysis. (A) Unadjusted regression analysis. (B) Regression controlled for sex and immunotherapy groups, and the trajectory of treatment changes during follow-up.

INTRODUCTION: Post-COVID-19 syndrome affects approximately 10-25% of people suffering from COVID-19 infection, irrespective of initial COVID-19 severity. Fatigue is one of the major symptoms, occurring in 30-90% of people with post-COVID-19 syndrome. This study aims at describing factors associated with fatigue in people with Post-COVID-19 seen in our newly established Post-Covid clinic. METHODS: This retrospective single center study included 42 consecutive patients suffering from Post-COVID-19 syndrome treated at the Department of Neurology, University Hospital Bern, between 11/2020 and05/2021. Clinical phenomenology of Post-COVID-19 syndrome with a special focus on fatigue and risk factor identification was performed using Mann-Whitney U Test, Pearson Correlation, and Chi-Quadrat-Test. RESULTS: Fatigue (90.5%) was the most prevalent Post-COVID-19 symptom followed by depressive mood (52.4%) and sleep disturbance (47.6%). Fatigue was in mean severe (Fatigue severity scale (FSS) mean 5.5 points (95% Confidence interval (95CI) 5.1 - 5.9, range .9 - 6.9, n = 40), and it was unrelated to age, COVID-19 severity or sex. The only related factors with fatigue severity were daytime sleepiness and depressed mood. CONCLUSION: Fatigue is the main symptom of the Post-COVID-19 syndrome in our cohort. Further studies describing this syndrome are needed to prepare the healthcare systems for the challenge of treating patients with Post-COVID-19 syndrome.

BACKGROUND AND PURPOSE:Neuronal autoantibodies can support the diagnosis of primary autoimmune cerebellar ataxia (PACA). Knowledge of PACA is still sparce. This article aims to highlight the relevance of anti-neurochondrin antibodies and possible therapeutical consequences in people with PACA.METHODS:This is a case presentation and literature review of PACA associated with anti-neurochondrin antibodies.RESULTS:A 33-year-old man noticed reduced control of the right leg in May 2020. During his first clinic appointment at our institution in September 2021, he complained about gait imbalance, fine motor disorders, tremor, intermittent diplopia and slurred speech. He presented a pancerebellar syndrome with stance, gait and limb ataxia, scanning speech and oculomotor dysfunction. Within 3 months the symptoms progressed. An initial cerebral magnetic resonance imaging, June 2020, was normal, but follow-up imaging in October 2021 and July 2022 revealed marked cerebellar atrophy (29% volume loss). Cerebrospinal fluid analysis showed lymphocytic pleocytosis of 11 x 103 /L (normal range 0-4) and oligoclonal bands type II. Anti-neurochondrin antibodies (immunoglobulin G) were detected in serum (1:10,000) and cerebrospinal fluid (1:320, by cell-based indirect immunofluorescence assay and immunoblot, analysed by the EUROIMMUN laboratory). After ruling out alternative causes and neoplasia, diagnosis of PACA was given and immunotherapy (steroids and cyclophosphamide) was started in January 2022. In March 2022 a stabilization of disease was observed.CONCLUSION:Cerebellar ataxia associated with anti-neurochondrin antibodies has only been described in 19 cases; however, the number of unrecognized PACAs may be higher. As anti-neurochondrin antibodies target an intracellular antigen and exhibit a mainly cytotoxic T-cell-mediated pathogenesis, important therapeutic implications may result. Because of the severe and rapid clinical progression, aggressive immunotherapy was warranted. This case highlights the need for rapid diagnosis and therapy in PACA, as stabilization and even improvement of symptoms are attainable.