Background: Natalizumab (NZB) is a disease-modifying treatment (DMT) used in persons with MS (PwMS) with an active relapsing course, either as a first-line, or after previous treatments The principal biological effect of NZB is thought to be the blockade of the molecular interaction between β4β1-integrin (also known as very late antigen-4) expressed by mononuclear inflammatory cells, and vascular cell adhesion molecule-1 (CAM-1) expressed by cerebral vascular endothelial cells NZB is a potent DMT which must be monitored with caution, its use being hampered by the risk of opportunistic infections, mostly progressive multifocal leukoencephalopathy (PML) Objectives: To document the efficacy and safety of NZB for the treatment of RRMS in a population of persons with MS (PwMS) followed in a regular MS Clinic setting Methods: We report our single-centre experience over a period of 13 years: from JAN 2007 through the end of May 2020 All PwMS treated with NZB were included, regardless of the treatment duration The retainment of patients in our MS Clinic is 95% We use the iMed database, an international MS registry Results: We report on 230 PwMS, 159 women, 71 men treated with NZB since 2007, up to 30 April 2020 We had no PML case We had 2 PML 'clinical alerts', but CSF search for JC virus (JCV) was negative There was no rebound of activity, nor IRIS, after NZB cessation, as we usually quickly switch to an alternative DMT Median age at MS onset: 26 3 years Median age at NZB initiation: 35 years Median disease duration before treatment: 8 07 years First line use: 94 Previous BRACE DMT: 136 Risk factors: previous immuno-suppression: 7;NZB duration > 24 months: 112;JCV index > 1: 81 Median treatment duration: 23 months;still active: 71 including 7 after > 6 years ARR at NZB onset: 1 5;during NZB: 0 27;current: 0 89 Median EDSS at NZB start: 3 0 Current median EDSS: 2 8 EDSS stable: 65, worsened: 58;improved: 60 MRI: stable: 133 (58%) ;improved: 5 (2%);worsened: 35 (25%) Conversion to SPMS: 48 (20%) 29 W, 19 M Reasons for NZB cessation: planned: 27;pregnancy: 3;loss of efficacy: 39;increased JCV index: 62 No blood toxicity (CBC, ALT) We had 9 pregnancies: 4 planned interruptions;5 full term, with normal babies Treatment after NZB cessation: 48 fingolimod, glatiramer: 17;ocrelizumab: 16;others: 29;none: 32 (no rebound observed) One patient had COVID 1 year after NZB: complete recovery;needed only nasal O2 during 3 day hospital admission Conclusions: NZB, when used with caution, is an effective and safe MS DMT during the RRMS phase, even after extended disease and treatment durations NZB is most effective to reduce relapse frequency, less effective against progression, as 20% of PwMS transited to the secondary progressive phase Gender, disease duration, and age do not influence outcomes We encountered no significant toxicity, in particular no PML Clinical, JCV index measures, and MRI monitoring are paramount to maintain safety

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH). Methods: In a randomized, double-blind trial (NCT01746342), MS patients with fatigue, poor subjective sleep quality, and OSAH (apnea-hypopnea index of ⩾ 15 events per hour/sleep), but without severe OSAH (apnea-hypopnea index > 30, and 4% oxygen desaturation index > 15 events/hour or severe somnolence), were randomized to fixed CPAP or sham CPAP for 6 months. Outcome assessments were performed at 3 and 6 months. Results: Of 49 randomized patients, 34 completed the protocol. Among completers, FSS did not improve with CPAP compared to sham at 6 months. FSS tended to improve (p = 0.09), and sleepiness (Epworth Sleepiness Scale) improved significantly (p = 0.03) at 3 months with CPAP compared to sham, but there were no other improvements with CPAP at either study evaluation. Conclusion: In non-severe OSAH patients, CPAP did not significantly improve the primary outcome of FSS change at 6 months. In secondary analyses, we found a trend to improved FSS, and a significant reduction in somnolence with CPAP at 3 months.

Background: Several studies have concluded that the lifespan of a person with multiple sclerosis (MS) is 6 years less than that of the general population. However these studies did not reflect the latest advancements in disease-modifying therapies. Little is known about the impact of factors such as gender, disease course, date of onset by decades, or age at onset on longevity. Methods: The Montreal-based CHUM MS Clinic was established in 1975. Since its inception, cohorts of 3771 patients have been followed and, in April 2016, their vital status was obtained through the provincial health care system database. Mortality rates, per 1000 person-years, were estimated according to gender, disease course at baseline, and age at onset. Follow-ups were carried out from the first clinic visit until death, or up to April 2016. Results: This cohort consists of 3771 patients with a median follow-up of 13.7 years, representing 55,339 person-years. A total of 482 (13%) patients were deceased at the end of the follow-up period. The overall mortality rate was 8.7 per 1000 person-years. The mortality rate was higher among men (11.6 per 1000 person-years) than women (7.6 per 1000 person-years). Disease course at baseline greatly influenced mortality. Mortality rates were 5.5 among patients who had a persistent clinically isolated syndrome (n=750), 7.2 among those with a relapsing course (n=2465), 18.2 among those with secondary progressive (n=127) and 19.1 per 1000 person-years among patients with primary progressive course (n=429). In a subgroup of subjects who started their follow-up at the clinic within a maximum of 3 years after onset, age at onset was strongly related to mortality. Mortality rates were 2.9, 4.3, and 11.6 per 1000 person-years respectively among patients who were ≤20, 20-40, and >40 years at onset. Discussion: Our observed results are in agreement with those published from similar cohorts in Canada and in Europe. Striking differences in mortality rates were observed according to gender, disease course at baseline, and age at onset. As the lifespan of the MS population increases, so does the need for global strategies for the care of aging MS patients. Conclusion: This work is a first step in a study on the impact of aging in MS. Further work will be conducted on other factors that may impact mortality such as comorbidities, lifestyle, and treatment.