Multiple sclerosis (MS) is one of the most frequently observed neurological conditions in Switzerland, but data sources for country-wide epidemiological trend monitoring are lacking. Moreover, while clinical and laboratory MS research are generally well established, there is a gap in patient-centered MS research to inform care management, or treatment decisions and policy making not only in Switzerland but worldwide. In light of these research gaps, the Swiss Multiple Sclerosis Society initiated and funded the Swiss Multiple Sclerosis Registry (SMSR) an open-ended, longitudinal and prospective, nationwide, patient-centered study. The SMSR recruits adult persons with a suspected or confirmed MS diagnosis who reside or receive care in Switzerland. The SMSR has established a governance structure with clear rules and guidelines. It follows a citizen-science approach with direct involvement of persons with MS (PwMS), who contribute actively to registry development, operations, and research. Main scientific goals entail the study of MS epidemiology in Switzerland, health care access and provision, as well as life circumstances and wellbeing of persons with MS. The innovative study design (“layer model”) offers several participation options with different time commitments. Data collection is by means of regular surveys and medical record abstraction. Survey participation is offered in different modes (web, paper & pencil) and in the three main national languages (German, French, Italian). Participants also receive regular data feedbacks for personal use and self-monitoring, contextualized in the whole population of study participants. Data feedbacks are also used to solicit data corrections of key variables from participants. The SMSR combines the advantages of traditional and novel research methods in medical research and has recruited over 1600 PwMS in its first year. The future-oriented design and technology will enable a response not only to future technological innovations and research trends, but also to challenges in health care provision for MS. ClinicalTrials.gov NCT02980640 ; December 6, 2016; retrospectively registered.

Background and purpose: Fatigue is amongst the most frequent and disabling symptoms of multiple sclerosis and a close relation between fatigue and sleep quality has been hypothesized. In this study the contribution of sleep disturbances measured by clinical and polysomnographic parameters to fatigue in multiple sclerosis was investigated.Methods: This was a prospective instrumental study performed at the Neurocenter of Southern Switzerland. Demographic data and clinical characteristics including fatigue (as measured by the modified fatigue impact scale [MFIS]), neurological disability, psychiatric symptoms, medications and sleep‐related variables were collected at baseline visit and by a home full‐night polysomnography. The associations between sleep‐related variables and the MFIS were tested using partial correlations adjusted by demographic and sleep‐unrelated clinical factors.Results: Seventy‐six patients were included in the study, of whom 53 (69.7%) had an MFIS ≥38 points (median 49.5, interquartile range 31.0–62.0). MFIS scores were positively associated with age, neurological disability, symptoms of depression and anxiety, and use of benzodiazepines and selective serotonin reuptake inhibitors. When adjusting for these variables, the presence of restless legs syndrome (RLS) (r = 0.37, p = 0.005) and periodic leg movements index (r = −0.33, p = 0.014) were associated with MFIS. Excessive daytime sleepiness, total sleep time, sleep efficiency, respiratory disturbances, and percentage of time spent in the different sleep stages (N1, N2, N3 and rapid eye movement) were not associated with fatigue.Conclusions: Multiple sclerosis patients with a diagnosis of RLS had significantly higher global fatigue scores compared to those without RLS. Future studies should investigate whether medical treatment of RLS can ameliorate fatigue.

Spinal magnetic resonance imaging (MRI) is currently not recommended for the routine monitoring of clinically stable multiple sclerosis (MS) patients. We aimed to investigate the occurrence of asymptomatic spinal lesions (a-SL) in clinically stable MS patients, and their association with clinical and radiological outcomes, including the recurrence of spinal lesions. The hospital MS registry was searched for clinically stable MS patients (no relapses, no disability progression) with spinal MRIs performed at T1 (baseline) and T2 (9–36 months after T1). Information on relapses, disability and new brain/spinal MRI lesions at T3 (≥6 months after T2) was collected and analyzed. Out of 300 MS patients, 45 showed a-SL between T1 and T2. The presence of a-SL was not associated with the subsequent occurrence of relapses or disability progression at T3, but did correlate with the risk of new brain (rate ratio (RR) = 1.63, 95% CI = 1.16−2.25, p = 0.003) and recurrent spinal lesions (RR = 7.28, 95% CI = 4.02–13.22, p < 0.0001). Accounting for asymptomatic brain lesions (a-BL), the presence of either a-BL or a-SL was associated with subsequent risk for new brain (OR = 1.81, 95% CI = 1.25–2.60, p = 0.001) or spinal (RR = 2.63, 95% CI = 1.27–5.45, p = 0.009) lesions. Asymptomatic spinal demyelinating lesions occurred in 15% of clinically stable MS patients within a median period of 14 months and conferred an increased risk of future radiological activity at the brain and spinal level.

Objective: Prognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age‐ and BMI‐adjusted) with absolute concentrations for the prediction of response to disease‐modifying therapy. Methods: Observational cohort study including the first serum sample of participants after the start of fingolimod therapy. We estimated hazard ratios for future relapses comparing participants with high (upper quartile) versus lower neurofilament light chain levels, based on either absolute concentration or Z score cutoffs. We compared the prognostic/predictive performance of these two measures for the occurrence of new/enlarging T2w lesions in longitudinal MRI. Results: We included 447 participants (median [IQR] age, 41.3 [32.1–49.2] years; 65.1% female); median follow‐up 8.3 years [6.0–10.3]. Participants with a high neurofilament light chain Z score ( Z ≥ 1.2/88.5 percentile) were more likely to experience future relapses (HR: 1.80, 95% CI 1.27–2.54, p < 0.001) compared to those below this threshold while this dichotomy could not be demonstrated with absolute concentration cutoffs (≥ vs. < 10.8 pg/mL; HR: 0.94, 95% CI 0.64–1.38, p = 0.75). Furthermore, patients with upper quartile Z scores were associated with a higher incidence of new/enlarging T2w lesions compared with those below this threshold (OR: 1.88, 95% CI 1.31–2.70, p < 0.001); again, absolute concentration cutoffs failed to identify this risk (OR: 1.20, 95% CI 0.82–1.77, p = 0.34). These findings were confirmed when patients having started alternative oral treatments were also included ( n = 713). Interpretation: Serum neurofilament light chain Z scores consistently outperformed absolute concentration cutoffs for prognostication of clinical/radiological disease activity and may facilitate individual prediction of treatment response.

It is widely acknowledged that month of birth influences the risk for developing multiple sclerosis (MS) later in life. This has been consistently shown in a number of countries and regions including England, Scotland, Canada, Denmark, Sweden, Sardinia, Finland, and Australia (eReferences). The month of birth effect is particularly evident in England, where the risk for MS peaks in May and drops in November for those born in those months.¹ The biological basis of this month of birth effect is not yet known. Because thymic development mainly occurs in utero and is susceptible to intrauterine exposures,² we sought to assess whether the month of birth has any effect on thymic function. Given the evidence accumulating for vitamin D deficiency in the etiology of MS,³ we also investigated whether vitamin D levels were associated with thymic output.

Background: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application. Objective: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs). Methods: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios. sNfL levels were defined as “high” (>90th percentile) vs “normal” (<80th percentile), based on normative values of control persons. In three rounds, 10 international and 18 Swiss MS experts, and 3 patient consultants rated their agreement on treatment algorithms. Consensus thresholds were defined as moderate (50%–79%), broad (80%–94%), strong (≥95%), and full (100%). Results: The Delphi provided 9 escalation algorithms (e.g. initiating treatment based on high sNfL), 11 horizontal switch (e.g. switching natalizumab to another high-efficacy DMT based on high sNfL), and 3 de-escalation (e.g. stopping DMT or extending intervals in B-cell depleting therapies). Conclusion: The consensus reached on typical clinical scenarios provides the basis for using sNfL to inform treatment decisions in a randomized pragmatic trial, an important step to gather robust evidence for using sNfL to inform personalized treatment decisions in clinical practice.