Using Neurology Trainees as Standardized Patients in a Neurological Emergency Simulation Curriculum for Medical Students.

Purpose: Simulation manikins have limited ability to mimic neurological exam findings, which has historically constrained their use in neurology education. We developed a cased-based simulation curriculum in which neurology trainees acted as standardized patients (SPs) and portrayed the neurologic exam for medical students. Materials/Methods: We ran monthly simulations of two cases (acute stroke and seizure) with resident/fellow SPs. Pre-/post-session surveys assessed students' self-rated confidence in neurological clinical skills (gathering a history, performing an exam, presenting a case) and knowledge domains. Questions about students' attitudes about neurology were adapted from a validated assessment tool. Paired t-tests were performed for quantitative items. Qualitative thematic analysis identified key themes. Results: Sixty-one students participated. Post-session, students reported significantly higher self-confidence in all neurological clinical skills and knowledge domains (p < 0.002). Greater than ninety-five percent agreed the session met the learning objectives; 95% recommended it to others. Resident/fellow SPs were cited as the most effective educational component. Students appreciated evaluating acute emergencies and reported an increased interest in neurology careers. Conclusions: A case-based simulation curriculum with neurology trainees portraying the SP increased students' self-reported knowledge, skills, and confidence in managing neurological emergencies. Our intervention may improve medical student neurology education and increase interest in the field. Future research should evaluate clinical skills objectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02016-w.

Sexual dysfunction and commonly used drugs in neurology.

Sexual dysfunction is common in men and women with neurological diseases. Medications used in neurology can cause sexual dysfunction independently of the disease process and this may adversely affect patients' quality of life. This review focuses on medications commonly prescribed to neurological patients that may contribute to altered sexual function, and discusses how they may differ in men and women.

Integrating Virtual Teaching in a New Era of Medical Education: Lessons from a Neurology Course.

The COVID-19 pandemic has led to a sudden shift toward virtual learning in neurology education, which presents challenges for educators. However, virtual learning is here to stay for three key reasons: demand among students, ease of dissemination, and potential to improve educational quality. Despite challenges, educators can teach effectively using appropriate virtual tools and methods, with innovative approaches that will ultimately lead to sustained improvements in neurology education. Here, we aim to help educators effectively incorporate virtual instruction into their "new normal" by offering practical, evidence-based tips for balancing in-person and virtual learning, selecting the appropriate tools and methods for virtual teaching, and creating a supportive virtual learning environment. Using a systematic approach, educators can identify specific, achievable goals, determine the content's scope, appropriate assessments, select appropriate teaching methods, and create the session schedule and materials. Here we described evidence-based strategies for best practices, developing virtual material, and creating the appropriate virtual learning environment.

Navigating the acute to post-acute transition with patients: a first characterization of medical student knowledge gaps in rehabilitation and post-acute care.

PURPOSE: Clinical rehabilitation and post-acute care (PAC) learning experiences are not uniformly required within medical school core curricula in the United States or internationally. This study aims to characterize what medical students might know/need to know to support patients in the transition from acute hospitalization to post-acute rehabilitation settings. MATERIALS/METHODS: The medical student cohort completing required clinical rotations in a United States quaternary care hospital system was provided a voluntary survey prompting reflection on experiences discharging patients to rehabilitation/PAC and related learning needs. Data were analyzed using descriptive statistics and qualitative grounded theory. RESULTS: Response rate was 72% (39/54). All respondents reported at least one gap in rehabilitation/PAC knowledge, falling into 8 themes: daily experience of rehabilitation/PAC; determination of eligibility/screening processes; distinctions among levels of rehabilitation/PAC; insurance coverage/equity; rehabilitation/PAC clinical practice environment; post-rehabilitation/PAC discharge support; medical capabilities within PAC settings; developing rehabilitation goals. CONCLUSIONS: Despite caring for patients discharged to post-acute rehabilitation settings, medical students lack essential knowledge about the process of rehabilitation and recovery, including patient eligibility for and service availability across PAC settings. Explicit rehabilitation/PAC education for medical students could enhance their ability to counsel and advocate for patients with disability and rehabilitation needs through care transitions.Implications for rehabilitationMedical students lack knowledge about rehabilitation and post-acute care that is important for helping patients navigate the acute to post-acute transition.Dedicated rehabilitation/post-acute care education could prepare trainees for counseling and advocating for patients during care transitions.Knowledge gaps identified in this study could inform development of curricular interventions to address medical student learning needs.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination. Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab. Results: After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (P = 5.7 × 10-11) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (P = 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (P < 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (P < 0.0001). Conclusions: MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination. Clinical Trials Registration: NCT05060354.

Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era.

BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse. METHODS: Patients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported. RESULTS: One hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI. DISCUSSION: In this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

Transitioning immunotherapy in neuromyelitis optica spectrum disorder - when and how to switch.

INTRODUCTION: Newly approved immunotherapies for neuromyelitis optica spectrum disorder (NMOSD) have transformed the treatment landscape and improved disability outcomes. However, there are many remaining questions regarding transitioning immunotherapies in NMOSD that have not been addressed by randomized controlled trials. AREAS COVERED: This review focuses on the practical questions of managing and switching immunotherapies for NMOSD, including how to transition between immunotherapies, deciding when and if therapy should be discontinued, and transitioning during pregnancy or breastfeeding. EXPERT OPINION: Clinical experience and retrospective studies of real-world outcomes and complications associated with therapy, as well as therapy transitions, will help inform practice patterns moving forward. Strategies for transitioning between immunotherapies should consider the pharmacokinetics and the onset of clinical efficacy for each drug. Despite all the currently approved preventative immunotherapies, there are limited treatment options for those suffering from significant disability after their initial attack, and remyelination therapies are an important area for future research.

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood. METHODS: In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls. Demographic data, serum immune profiles including lymphocyte count, B-cell count, and immunoglobulins, and clinical outcome of COVID-19 infection were collected. RESULTS: 254 patients (73.2% female, mean (SD) age 52.9 (11.2) years) were identified. When controlling for age, time since vaccination, and vaccine type, patients on fingolimod, ocrelizumab, rituximab, mycophenolate mofetil, natalizumab and teriflunomide had significantly lower levels of spike antibodies compared to healthy controls (n = 34). Longer duration of treatment was associated with lower spike antibody levels in patients on anti-CD20 therapy (p = 0.016) and S1P modulators (p = 0.016) compared to healthy controls. In patients on anti-CD20 therapy, higher spike antibody levels were associated with higher CD20 cell count (p<0.001), and longer time since last anti-CD20 therapy infusion (p<0.001). 92.8% (13/14) vaccine responders (spike antibody titer >100 ug/dL) on anti-CD20 therapy demonstrated B-cell reconstitution (mean CD20 3.6%). Only 1 out of 86 patients with CD20 of 0% had a measurable spike antibody response to vaccination. During follow-up (mean 270 days), five patients were diagnosed with COVID-19 after vaccination (incidence 1.9%), all of whom had spike antibody < 20 ug/dL. No patients required ICU care or died. CONCLUSIONS: Patients on some DMTs demonstrate reduced humoral immunity after Sars-CoV-2 vaccination. Longer duration of anti-CD20 therapy and reduced CD20 cell count is associated with blunted humoral response to vaccination. CD20 reconstitution >0.1% appears necessary, but not always sufficient, for humoral response to vaccination. Breakthrough COVID-19 infection in our cohort of MS patients on DMT was higher than in population studies. We propose that adjustment of B-cell therapy administration to allow for B-cell reconstitution prior to vaccination should be considered.

COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders.

BACKGROUND: Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19. METHODS: This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudorelapse, new brain MRI activity, worsening of preexisting MSRD symptoms, or development of other long-term neurologic symptoms. RESULTS: 111 patients, 85 (76.6%) females, with a mean [SD] age of 49.3 [12.2] years and median [range] EDSS of 2.5 [0, 8.5] were identified. 41 patients (36.9%) had neurologic worsening post-COVID-19. Of those, 19 (46.3%) had pseudorelapses, 2 (4.8%) had relapses, and 24 (58.5%) patients reported worsening of preexisting MSRD symptoms, or other new long-term neurologic symptoms. Neurologic worsening was associated with hospitalized (moderate or severe) COVID-19 (p = 0.001), treatment for COVID-19 (p = 0.006), and incomplete COVID-19 recovery (p = 0.0267) but not with age, sex, MS type, race, disease duration, EDSS, vitamin D use, or disease modifying therapy use. CONCLUSIONS: COVID-19 severity and lack of complete systemic recovery were associated with new or worsening neurologic symptoms in 36.9% of MSRD patients.

Disease modifying therapy management of multiple sclerosis after stem cell therapies: A retrospective case series.

BACKGROUND: Stem cell therapies (SCT) have not received formal regulatory approval for the treatment of people with multiple sclerosis (PwMS), but PwMS may seek various options on their own accord. The current literature largely focuses on the efficacy and safety of SCT in PwMS in clinical trials, in particular autologous hematopoietic stem cell transplantation (aHSCT), in carefully selected participants. There is little reported on the MS disease modifying therapy (DMT) management of PwMS who choose to undergo SCT outside of these trials. METHODS: We identified PwMS from two academic centers who had MS diagnosis fulfilling 2017 McDonald criteria and received SCT (methodologies permitted: aHSCT, umbilical-derived mesenchymal stem cells and/or adipose-derived mesenchymal stem cells (AdMSC)), with the goal to treat MS, between 1/1/2015 and 11/30/2021. RESULTS: Nine PwMS (five females; age range at SCT treatment 25-69 years old; MS disease duration 1-12 years; six relapsing-remitting, three secondary progressive, one primary progressive) underwent a total of eleven SCTs (nine aHSCT, two AdMSC, one umbilical-derived MSC) with the goal to treat MS. Two of six PwMS who underwent SCT <10 years from MS diagnosis, and one of three PwMS who underwent stem cell therapies >10 years from MS diagnosis were clinically stable thereafter. An MS DMT was resumed in five PwMS afterwards, including rituximab, ocrelizumab, siponimod, and glatiramer acetate: one remained clinically stable, whereas four clinically progressed. Four PwMS remained off of a DMT: three were clinically stable, whereas one clinically progressed. All nine patients demonstrated radiographic stability by MRI after SCT. Only one met formal criteria to consider aHSCT for MS. CONCLUSIONS: We demonstrate the heterogeneous real-world experience of treating MS after patient-chosen experimental SCTs, detailing the range of DMT management in various patient circumstances. Limitations of our study include its small sample size and the variety of stem cell therapies received.

Challenges to Longitudinal Characterization of Lower Urinary Tract Dysfunction in Multiple Sclerosis.

BACKGROUND: Neurogenic lower urinary tract dysfunction (LUTD) results in lower urinary tract symptoms (LUTS) that impact quality of life in people with multiple sclerosis (PwMS). The risk factors and the contribution of LUTD to multiple sclerosis (MS) disease progression are under-researched. OBJECTIVE: To identify clinical and demographic predictors of LUTS in PwMS and gaps in clinical ascertainment. METHODS: Participants were adults with MS enrolled in a prospective, multicenter study (SUMMIT, N=802), including a subset of N = 258 patients in the UCSF EPIC study for whom medical records were further reviewed. Demographic (age, sex, race, ethnicity), clinical (disease duration, MS type), and female-specific reproductive factors (e.g., parity) were evaluated to determine associations with bowel/bladder functional system score. Participants' medical records were analyzed to understand the patterns of LUTS ascertainment by physicians and the specific contribution of LUTS to overall bowel/bladder functional system scores. RESULTS: 802 participants (71.3% female) contributed to these analyses. Higher bowel/bladder functional system scores, indicating worsening symptoms and function, were significantly associated with female sex (p=0.001) and progressive MS type (p≤ 0.001). In the EPIC participants, female-specific reproductive exposures (parity, menopause) were not significantly associated with worse bowel/bladder functional system scores. Most (98%) bowel/bladder functional system scores reflected the severity of LUTS (relative to bowel dysfunction). LUTS were under-ascertained clinically, and more so in women (X2 = 5.02, p=0.08). CONCLUSIONS: Female sex and MS type are predictive of worsening LUTS. Symptoms may be less likely to be ascertained by clinicians in females compared to males.

Electronic pill bottles to monitor and promote medication adherence for people with multiple sclerosis: A randomized, virtual clinical trial.

OBJECTIVE: We perform a randomized trial to test the impact of electronic pill bottles with audiovisual reminders on oral disease modifying therapy (DMT) adherence in people with MS (PwMS). METHODS: Adults with multiple sclerosis (MS) taking an oral DMT were randomized 1:1 for 90 days to remote smartphone app- and pill bottle-based (a) adherence monitoring, or (b) adherence monitoring with audiovisual medication reminders. Optimal adherence was defined as the proportion of doses taken ±3 h of the scheduled time. Numbers of missed pills and pills taken early, on time, late, and extra were recorded. A multivariable regression model tested possible associations between optimal adherence and age, MS duration, cognitive functioning, and number of daily prescription pills. RESULTS: 85 participants (66 female; mean age 44.9 years) took dimethyl/diroximel fumarate (n = 49), fingolimod (n = 26), or teriflunomide (n = 10). Optimal adherence was on average higher in the monitoring with reminders arm (71.4%) than the monitoring only arm (61.6%; p = 0.033). In a multivariable model, optimal adherence was less likely in younger participants (p < 0.001) and those taking more daily prescription pills (p < 0.001). In the monitoring only arm, 4.0% of doses were taken early, 61.6% on time, 5.6% late, 4.4% in excess, and 24.4% were missed. In the reminders arm, these proportions were 3.4%, 71.4%, 3.7%, 8.7%, and 12.8%, respectively. CONCLUSION: We map real-world oral DMT adherence patterns using mHealth technology. PwMS who received medication reminders had higher optimal adherence. Nonadherence was more nuanced than simply missing pills. Developing strategies to improve adherence remains important in longitudinal MS care.

MRI activity in MS and completed pregnancy: Data from a tertiary academic center.

OBJECTIVE: To evaluate postpartum MRI activity in patients with MS and a completed pregnancy and to compare these results to an age-matched untreated nonpregnant MS cohort. METHODS: Patient with MS from a tertiary care MS center between 2006 and 2015, with prepartum and postpartum neurologic follow-ups and MRI scans were analyzed. Clinical activity and inflammatory brain MRI activity (new T2-hyperintense or gadolinium-enhancing [Gd+] lesions) were assessed peripartum. The results were compared with untreated reproductive-age patients with MS from the placebo arm of the clinical trials. RESULTS: A total of 123 pregnancies in 123 women (median Expanded Disability Status Scale 1.0) were analyzed. Approximately 7.2% relapsed during pregnancy and 48.7% relapsed postpartum. Of pregnancies with prepartum and postpartum gadolinium (Gd)-enhanced MRI (n = 112), 8% had Gd+ lesions prepartum and 33% had new Gd+ lesions postpartum. Overall, 54.4% had either new T2 or Gd+ lesions postpartum. Seventy-nine percent of subjects with postpartum relapse had new MRI activity compared with 37.1% without relapse (p < 0.001). Twenty-five percent had both clinical and radiographic activity and only 24.9% maintained no evidence of disease activity status postpartum. There was no association between postpartum MRI activity and disease-modifying treatments (DMTs) (p > 0.5). MRI and clinical outcomes were also assessed for 126 nonpregnant untreated female patients with MS. Comparing pregnancy and no pregnancy groups, there was no difference in MRI activity at follow-up. CONCLUSIONS: There was a high level of inflammatory radiographic disease activity which was related to relapses in postpartum patients with MS. Further studies are needed to determine whether hormonal fluctuations vs extended time off DMTs may be the underlying cause of our observations.

Light therapy for multiple sclerosis-associated fatigue: a randomized, controlled phase II trial.

BACKGROUND: Bright white light therapy (LT) can improve fatigue in several disease states but has not been studied in multiple sclerosis (MS). OBJECTIVE: To determine whether controlled home-based LT is feasible, tolerable, and well-adhered to in MS-associated fatigue. METHODS: A randomized, controlled trial of twice-daily 1-h bright white LT (BWLT) (10,000 lx, active arm) versus dim red LT (DRLT) (< 300 lx, control arm) was performed. Adults with MS-associated fatigue were enrolled for 10 weeks: 2-week baseline, 4-week intervention, 4-week washout. RESULTS: 41 participants were enrolled; 35 were randomized (average age 42 years, 80% female; BWLT n = 20; DRLT n = 15). 31 were in the intention to treat analysis. The average duration of LT sessions was similar between groups (BWLT 60.9 min, DRLT 61.5 min, p = 0.70). The most commonly reported adverse event was headache. There were no events that led to discontinuation. Baseline fatigue was severe in both arms (each 53/63 points on the Fatigue Severity Scale (FSS), p = 0.92). FSS was lower following BWLT (FSS 45.8 post-LT, p = 0.04; 44.9 post-washout, p = 0.02 intra-group compared to baseline FSS) and DRLT (FSS 46.7 post-LT, p = 0.03; 43.9 post-washout, p = 0.002 intragroup compared to baseline FSS). There was no difference between BWLT and DRLT groups in the magnitude of reduction of FSS scores (p = 0.81 after LT; p = 0.77 after washout for between group comparisons). Similarly, MS quality of life metrics improved in both arms but were not significantly different between groups after LT (p = 0.22) or washout. CONCLUSIONS: LT is safe, feasible, and well-tolerated in people with MS-associated fatigue. Improvement in both light spectra likely indicates a strong placebo effect for the DRLT group.

Management of Demyelinating Disorders in Pregnancy.

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are chronic inflammatory demyelinating disorders of the central nervous system that often affect women during childbearing years. Therefore, issues of conception, pregnancy, and delivery are of significant importance to patients and treating physicians. The current review provides updated information regarding the effects of pregnancy on MS and NMO, as well as the available safety data on immunomodulatory MS therapies for pregnant and lactating women. Management issues of women with MS and NMO during conception, gestation, and the postpartum period also are addressed.

Paraneoplastic Neuromyelitis Optica Spectrum Disorder as Presentation of Esophageal Adenocarcinoma.

Neuromyelitis optica spectrum disorders are a group of relapsing, inflammatory, demyelinating neurologic syndromes involving the central nervous system associated with antibodies against aquaporin-4. Although most commonly an idiopathic autoimmune condition, neuromyelitis optica may occur as a paraneoplastic syndrome in rare instances. We report a case of transverse myelitis caused by paraneoplastic neuromyelitis optica as the presenting clinical syndrome in a patient with esophageal adenocarcinoma.

Reproductive Issues in MS.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, predominantly affecting women of childbearing age. Therefore, issues of conception, pregnancy, and delivery are of significant importance to patients and treating physicians. We discuss immunologic and clinical effects of pregnancy on the course of MS including both immunosuppression on a local level and a heightened state of immunocompetence on a global level. Clinical outcomes of the Pregnancy in Multiple Sclerosis trials are reported. We analyze and update the available data on safety and efficacy of immunomodulating MS treatments and symptomatic treatments for pregnant and lactating women, and address specific issues of MS management at the time of pregnancy. We review the data related to estrogen-based MS therapies currently or previously in trials. Pregnancy does not appear to be associated with adverse outcomes in MS patients. Some evidence suggests possible beneficial effects, although clear prospective data of sufficient length and quality are limited. Long-term relapse rates or disability progression do not seem to be affected by pregnancy in MS patients. The use of immunosuppressive or immunomodulatory agents in pregnancy is not routinely advisable but could be considered under special circumstances.

The effect of alcohol and red wine consumption on clinical and MRI outcomes in multiple sclerosis.

BACKGROUND: Alcohol and in particular red wine have both immunomodulatory and neuroprotective properties, and may exert an effect on the disease course of multiple sclerosis (MS). OBJECTIVE: To assess the association between alcohol and red wine consumption and MS course. METHODS: MS patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) who completed a self-administered questionnaire about their past year drinking habits at a single time point were included in the study. Alcohol and red wine consumption were measured as servings/week. The primary outcome was the Expanded Disability Status Scale (EDSS) at the time of the questionnaire. Secondary clinical outcomes were the Multiple Sclerosis Severity Score (MSSS) and number of relapses in the year before the questionnaire. Secondary MRI outcomes included brain parenchymal fraction and T2 hyperintense lesion volume (T2LV). Appropriate regression models were used to test the association of alcohol and red wine intake on clinical and MRI outcomes. All analyses were controlled for sex, age, body mass index, disease phenotype (relapsing vs. progressive), the proportion of time on disease modifying therapy during the previous year, smoking exposure, and disease duration. In the models for the MRI outcomes, analyses were also adjusted for acquisition protocol. RESULTS: 923 patients (74% females, mean age 47 ± 11 years, mean disease duration 14 ± 9 years) were included in the analysis. Compared to abstainers, patients drinking more than 4 drinks per week had a higher likelihood of a lower EDSS score (OR, 0.41; p = 0.0001) and lower MSSS (mean difference, - 1.753; p = 0.002) at the time of the questionnaire. Similarly, patients drinking more than 3 glasses of red wine per week had greater odds of a lower EDSS (OR, 0.49; p = 0.0005) and lower MSSS (mean difference, - 0.705; p = 0.0007) compared to nondrinkers. However, a faster increase in T2LV was observed in patients consuming 1-3 glasses of red wine per week compared to nondrinkers. CONCLUSIONS: Higher total alcohol and red wine intake were associated with a lower cross-sectional level of neurologic disability in MS patients but increased T2LV accumulation. Further studies should explore a potential cause-effect neuroprotective relationship, as well as the underlying biological mechanisms.