Passive assessment of tapping speed through smartphone is useful for monitoring multiple sclerosis.

INTRODUCTION: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS. METHODS: Single-center prospective study in patients with MS. We passively assessed TS during first week, measured by an "in house" smartphone application. Reliability was assessed by intraclass correlation coefficient (ICC). Correlations between median and maximum keys/s of first week of assessment and baseline disability measures were explored. RESULTS: One-hundred three patients were included: 62.1 % women, with a median (IQR) age of 47 (40.4-54.8) years-old and an EDSS score of 3.0 (2.0-4.0). Distribution by MS subtypes was: 77.7 % relapsing-remitting MS (RRMS), 17.5 % secondary-progressive MS (SPMS) and 4.9 % primary-progressive MS (PPMS). ICC during first week was 0.714 (p < 0.00001). Both median and maximum keys/s showed a negative correlation with Expanded Disability Status Score, 9-hole peg test and timed 25-foot walk and a positive correlation with Processing Speed Test CogEval® raw and Z-score. Median and maximum keys/s were lower in patients diagnosed with SPMS than in RRMS. Both measures of tapping speed were associated with MS phenotype independently of age. CONCLUSION: TS measured through our application is reliable and correlates with baseline disability scales.

Emerging biomarkers for improving pregnancy planning in multiple sclerosis.

Background: Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy. Methods: This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys® Anti-Müllerian Hormone Assay. Results: We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = -0.67, p < 0.0001; rho HCW = -0.43, p = 0.0006). Interestingly, among the 76 MS participants under 40 years old, we identified ten individuals (13.1%) with AMH levels below 0.7 ng/ml, indicative of a low ovarian reserve, and an additional six individuals (7.8%) with AMH levels between 0.7 ng/ml and 0.9 ng/ml, suggesting a potential risk of premature ovarian failure. Conversely, sNfL and GFAP levels in the MS group exhibited high variability but showed no significant association with age intervals. Conclusion: We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women.

Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.

BACKGROUND: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. OBJECTIVE: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. METHODS: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. RESULTS: ARR decreased from 1.9 (95% confidence interval 1.60-2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17-0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13-0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18-0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. CONCLUSIONS: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.