Objective To develop and validate a large language model (LLM) prompt capable of ascertaining a patient’s depression from their multiple sclerosis (MS) neurologist’s note and to explore its potential for earlier detection of depression in MS care.Materials and methods This single-center retrospective study analysed prospectively collected electronic health record notes. In phase I, an institutionally secure ChatGPT-4 prompt was iteratively refined to infer the presence of depression using the neurologist’s note and compared with manual annotation of the neurologist’s impression (depression: present, absent, no mention) and patient-reported outcomes (PROs): Hospital Anxiety and Depression Scale or Patient Health Questionnaire-9. In phase II, longitudinal analysis compared timing of depression detection by the prompt and the neurologist across 5 years of notes for 250 patients.Results In phase I (n=278 adults with MS), the LLM prompt detected depression in 60.4% of notes (168/278). When compared with neurologist impression in the clinical notes, the prompt achieved 97.3% sensitivity and 84.4% accuracy. Specificity was more modest (68.3%): when neurologists did not mention depression, the prompt inferred depression based on symptoms, history and medications. When PRO and neurologist impression disagreed, the prompt aligned with PROs 61.9% of the time. In phase II, the LLM inferred depression earlier than the neurologist in 18.8% of patients, at an average of 2.45 (SD 1.54) years earlier.Conclusion The prompt was highly sensitive to neurologist documentation of depression in clinical notes; it inferred both present/treated depression from other note components. Potential applications include quality improvement initiatives aiming to improve depression care on a cohort level.

Purpose of Review:As the life expectancy of people with multiple sclerosis (PwMS) increases, the importance of recognizing and addressing specific needs and challenges faced by those undergoing age-related sex hormone changes and hypogonadism is becoming increasingly evident. We present expert-led, practical recommendations from a consensus program that address gaps in age-related sex hormone changes and hypogonadism in PwMS not sufficiently addressed in current literature and guidelines. A multidisciplinary steering committee (SC) of 15 international experts identified 18 key clinical questions across 6 themes: climacteric symptoms in women with MS; impact of MS on the climacteric stage; impact of menopause on MS disease activity and progression; treatment and management of climacteric symptoms in women with MS; late-onset hypogonadism (LOH) in men with MS; and patient-centered care. After thorough review of the evidence from a systematic literature review, the SC formulated 18 clinical recommendations to address the questions. These recommendations were voted on by the SC and an extended faculty of 23 health care professionals from 16 countries, including 2 nurses and 1 patient association representative. Recent Findings:Consensus was reached when ≥75% of respondents expressed agreement, with a score of 7-9 on a 9-point scale. After a single voting round, all 18 recommendations reached consensus (14 reaching consensus at 90%-100% and 4 at 80%-90%). The clinical recommendations addressed the following: the potential overlap and exacerbation of MS symptoms during the climacteric stage; the need for preventive care and screening during the menopausal transition; the potential for, and a paucity of data on, differential efficacy and tolerability of MS medications in menopausal/postmenopausal women; the complex causal interplay between hormonal and/or immunologic changes and natural aging in PwMS switching to a more progressive phase of disease; consideration of behavioral/lifestyle interventions alongside pharmacologic treatments; effects of hormonal treatments on MS symptoms; and management of LOH in men with MS. Summary:These recommendations were based on a robust modified Delphi consensus approach and present a valuable framework for improved patient care. These results emphasize the need to address critical gaps in our understanding and management of PwMS undergoing age-related sex hormone changes and hypogonadism.

BACKGROUND:The ORATORIO trial showed that ocrelizumab reduced the risk of disability progression versus placebo in patients with primary progressive multiple sclerosis (PPMS). We aimed to elucidate the effect of ocrelizumab in older and more disabled patients with PPMS, particularly regarding hand function preservation. METHODS:ORATORIO-HAND was a multicentre, double-blind, randomised, placebo-controlled, phase 3b study with 138 sites across 22 countries. Patients with PPMS aged 18-65 years and Expanded Disability Status Scale (EDSS) score of 3·0-8·0 were randomly assigned 1:1 to intravenous ocrelizumab 600 mg or placebo every 6 months for 144 weeks or until a prespecified number of progression events occurred. Masking was achieved by use of a placebo solution administered in the same manner as ocrelizumab. Double-blinding across all periods was maintained through separation of investigators responsible for efficacy and safety assessments. MRI scans were evaluated by a masked central reader, and laboratory parameters that could reveal treatment allocation were masked to site personnel until the primary analysis. Two coprimary estimands were defined, with the endpoint of time to onset of 12-week composite confirmed disability progression (12W-cCDP) in 9-Hole Peg Test or EDSS evaluated in all randomly assigned patients, and the same endpoint evaluated in a subset of patients with MRI activity at baseline. This study is registered with ClinicalTrials.gov, NCT04035005 and is ongoing and not recruiting. FINDINGS:Between Aug 12, 2019, and Dec 10, 2024, of 1360 patients assessed for eligibility, 1013 were randomly assigned (ocrelizumab [n=505]; placebo [n=508]). The proportion of patients with 12W-cCDP was 165 (33%) of 505 with ocrelizumab and 205 (40%) of 508 with placebo (hazard ratio, 95% CI 0·70 0·57-0·86; relative risk reduction=30%; p=0·0007). In the MRI-active subgroup, a significant risk reduction was also observed in 12W-cCDP (risk reduction=55%; p<0·0001). The overall safety profile was similar in both groups. More infections (245 [48%] of 506 vs 226 [45%] of 506) were observed with ocrelizumab, but not after COVID-19 was excluded (38% vs 37%). Rates of serious adverse events and serious infections were similar between groups. INTERPRETATION:Ocrelizumab was superior to placebo in delaying disability progression, with stronger effect on hand function, in a broad PPMS population including older patients and those with more advanced disease, while maintaining a manageable safety profile. FUNDING:F Hoffmann-La Roche.

Initiating high-efficacy disease-modifying therapies (DMTs) early in relapsing multiple sclerosis (RMS) can reduce inflammation and limit disability progression; however, moderate-efficacy oral DMTs remain common first-line treatments. Ofatumumab demonstrated superior efficacy and tolerable safety in the phase 3 ASCLEPIOS trials, although few participants (≤ 5

Menopause is under-recognized as a biological and sociocultural contributor to brain health, and scientific understanding of the impact that the menopausal transition has on the brain is minimal. This knowledge gap is particularly detrimental for women who live with neurological conditions. We lack sufficient data to understand the experience of women with established neurological conditions during perimenopause, the mechanisms associated with postmenopausal changes in disease course and how to improve management of neurological conditions in a sex-specific way. Furthermore, approximately two thirds of women experience cognitive concerns during the menopausal transition. Although earlier menopause is associated with a greater risk of cognitive decline, the influence of the menopausal transition on subsequent risk of neurological conditions remains unclear. In this Roadmap, we identify key areas in which research is limited and highlight historical and scientific challenges that have hindered progress in understanding brain health in the context of menopause. To address these challenges, we consider existing knowledge and propose priorities and future research directions to advance our understanding of the relationship between menopause and neurological health and disease.

Research indicates that pregnancy does not negatively impact the long-term progression of multiple sclerosis (MS); however, women with MS (WwMS) often do not have access to consistent and reliable information on reproductive health, particularly in settings with limited resources. This scoping review aims at providing an overview of the current evidence on knowledge gaps and information needs on reproductive health by WwMS in childbearing age globally. The review was conducted in May 2025 by searching three databases for peer-reviewed studies involving adult women with a diagnosis of MS and/or addressing their knowledge on reproductive health. Studies on professionals engaged in MS care as providers of information about reproductive health were also included. Data were categorized according to 13 key reproductive health indicators. Finally, of 545 records screened, 29 studies met the inclusion criteria. Most studies included only WwMS (59%) and were based in high-income countries (72%). Results are presented in an interactive scoping map showing the distribution of key health indicators across study characteristics such as geographic area, study design, and methods. This review highlights gaps in studies targeting the experience of WwMS in managing reproductive health in low- and middle-income countries.Systematic review registrationThe scoping review was registered on Zenodo at the following link: https://zenodo.org/records/13866567.

Background Multiple sclerosis (MS)–related bladder dysfunction (BD) affects up to 80% of people with MS (PwMS) and substantially impacts mobility, safety, and quality of life. Pelvic Health Physical Therapy (PHPT) is an evidence-based, noninvasive treatment for MS-related BD. This retrospective study compared screening and PHPT referral rates at two time points to evaluate longitudinal changes in BD management. Methods Data were analyzed from two prospective studies (2015 and 2023) enrolling adults with MS from a large subspecialty outpatient clinic. Bladder dysfunction–specific patient-reported outcomes, clinic notes, treatment plans, and referral histories were assessed at baseline, 6 and 12 months. Between 2015 and 2023, many BD-targeted changes were made, including a quality improvement initiative and embedding a physical therapist in the MS-clinic. Results The 2015 ( N = 65) and 2023 ( N = 80) cohorts were similar in demographics, MS duration, and Expanded Disability Status Scale. Bladder dysfunction prevalence was comparable (84% of 2015; 94% in 2023). However, BD-related care increased significantly in 2023: BD-specific treatment plans doubled, and PHPT referrals increased by 100%. Conclusion Greater BD treatment utilization and PHPT referrals likely reflect increased awareness of BD management and expanded system capacity. Further evaluation of PHPT practices and quality improvement efforts is needed to identify the most influential contributors of increasing BD-specific treatment in PwMS.

The aging of the global population has profound implications for multiple sclerosis (MS), a disease increasingly affecting older adults. Motor and cognitive impairments are common in both aging and MS, strongly predicting fall risk, independence, and quality of life. Yet chronological age, the most common clinical proxy, does not capture how disease-specific pathology and biological processes shape these outcomes. This review evaluates biological aging as a framework for understanding how motor and cognitive trajectories in MS diverge from typical aging. Evidence from telomere length, epigenetic clocks, cellular senescence, reproductive aging, and neuroimaging-derived brain age was synthesized. A targeted literature search of PubMed and related databases was conducted to identify relevant studies on biological aging in MS, with emphasis on motor and cognitive outcomes. Outcomes indicate accelerated biological aging in MS, with brain-predicted age showing the strongest functional associations, linking older-appearing brains to slower gait, greater disability, and reduced processing speed. Integrating biological-age frameworks could enable earlier detection of decline, guide targeted interventions, and improve quality of life in older adults with MS.

OBJECTIVE:Neurofilament light chain (NfL) is a biomarker of neuroaxonal injury in multiple sclerosis (MS), yet associations with functional outcomes remain unclear. Longitudinal associations between serum NfL (sNfL) and daily step count (STEPS) from wearable devices were assessed in a large international progressive MS cohort. METHODS:A post hoc analysis of the Phase III randomized controlled trial SPI2 (high-dose biotin vs. placebo RCT) pooled treatment arms due to no observed therapeutic benefit. Participants with sNfL and step count data were included. STEPS were calculated within ±15-days of baseline, 6, 12, 15, and 27-month visits. Mixed-effects models with 1000 bootstrap iterations assessed contemporaneous associations with each measure alternately specified as the outcome, adjusting for age and sex. Lagged models evaluated whether 0-6-month sNFL changes predicted subsequent 6-12-month STEPS changes. RESULTS:Among 506 participants (53.8% female; mean age 52.7 [SD: 7.7] years; median EDSS 6.0 [4.5-6.0]), mean sNfL z-score was 1.00 (SD: 0.95), and median STEPS were 3029 [1708-5210]. Higher sNfL was associated with lower STEPS (IRR = 0.97, p = 0.014), consistent across sex, treatment, disability, and disease-modifying treatment status. Conversely, higher STEPS were associated with lower sNfL z-scores; a 10% increase in STEPS corresponded to a 0.015 decrease in sNfL z-score (95% CI -0.022 to -0.008; p < 0.001). Greater prior 6-month increases in sNfL were associated with a lower subsequent STEPS (β = -141; 95% CI -302 to 21; p = 0.088; trend), corresponding to 141 fewer steps per 1-SD sNfL increase. INTERPRETATION:Higher sNfL was associated with reduced daily ambulatory activity in progressive MS, and vice versa. Rising sNfL may precede mobility decline, highlighting sNfL as a potential indicator of functional worsening. TRIAL REGISTRATION:ClinicalTrials.gov NCT02936037; EudraCT database 2016-000700-29.

Multiple sclerosis (MS) is a chronic, immune-mediated disorder that predominantly affects women, with an average age of onset between 20 and 50 years. As a result of the early age of onset and increasing life expectancies of women, owing to improvements in disease-modifying treatments (DMTs), recommendations regarding disease and symptom management may vary depending on their life stage and should be tailored to the individual. In addition, in recent years, new data regarding the management of MS from the preconception to postpartum period has led to evolving recommendations from both neuroimmunologists and national drug agencies alike. Similarly, an aging MS population has led to questions regarding the effect of menopause on MS and guidance regarding DMTs as patients age. The purpose of this review is to provide an up-to-date, comprehensive summary of the clinical course and management of the disease and commonly experienced symptoms during puberty, preconception and pregnancy, postpartum, menopause, and life after menopause.

While advances in anti-inflammatory disease-modifying therapies (DMTs) have transformed multiple sclerosis (MS) care, treatment recommendations are not necessarily applicable or uniform across all populations. This narrative review synthesizes contemporary evidence on DMT selection in people with MS (pwMS) from diverse backgrounds and life stages, accounting for race and ethnicity, reproductive status, age, and sexual and gender identity. We highlight emerging data from clinical trials, post-hoc analyses, and observational studies, offering potential treatment approaches based on the available evidence. We also underscore gaps in current knowledge of DMT use across MS sub-populations, highlighting areas needing further investigation.

Background:Motor disturbances are common in neurologic and neurodegenerative syndromes. A standard motor speed and dexterity measure is the finger tapping test (FTT). The FTT has traditionally been administered in clinic using a mechanical FTT, limiting accessibility and early motor change quantification. This study assessed the validity of a smartphone app-based FTT, which may expand access and enable more frequent testing. Methods:The cohort was diagnostically diverse, including participants with frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal syndrome, primary progressive aphasia, multiple sclerosis, and clinically unimpaired controls. Participants completed a 20-second ALLFTD Mobile App (mApp)-FTT with each hand. Tapping speed metrics were extracted. Participants completed the gold-standard mechanical FTT, a neurologist-administered finger tapping exam, the PSP Rating Scale (PSPRS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Correlations assessed mApp-FTT and mechanical FTT relationships; regressions evaluated associations with neurologist-rated finger tapping impairment, PSPRS and UPDRS, adjusting for age and sex. Results:The mApp-FTT showed moderate-to-strong correlations with the mechanical FTT (dominant: r=0.63, p<0.001; non-dominant: r=0.55, p<0.001). Taps per second were associated with PSPRS motor severity (dominant hand: std. β=-0.59, 95% CI [-0.91, -0.27], p<0.001) and the UPDRS (dominant hand: std. β=-0.41, 95% CI [-0.82, 0.00], p=0.049). Flight time was modestly associated with neurologist-rated finger tapping impairment (dominant hand: std. β=0.15, 95% CI [0.00, 0.29], p=0.044). Conclusion:These findings support mApp-FTT validity as a measure of motor function across neurodegenerative conditions. Validation in longitudinal and unsupervised remote settings is warranted to understand scalability and evaluate change over time.