Objective: To evaluate the direct and indirect influences of physical comorbidity, symptoms of depression and anxiety, fatigue, and disability on health-related quality of life (HRQoL) in persons with multiple sclerosis (MS).Methods: A large (n 5 949) sample of adults with MS was recruited from 4 Canadian MS clinics.HRQoL was assessed using the patient-reported Health Utilities Index Mark 3. Expanded Disability Status Scale scores, physical comorbidity, depression, anxiety, and fatigue were evaluated as predictors of HRQoL in a cross-sectional path analysis.Results: All predictors were significantly associated with HRQoL and together accounted for a large proportion of variance (63%). Overall, disability status most strongly affected HRQoL (b 5 20.52) but it was closely followed by depressive symptoms (b 5 20.50). The direct associations of physical comorbidity and anxiety with HRQoL were small (b 5 20.08 and 20.10, respectively), but these associations were stronger when indirect effects through other variables (depression, fatigue) were also considered (physical comorbidity: b 5 20.20; anxiety: b 5 20.34).Conclusions: Increased disability, depression and anxiety symptoms, fatigue, and physical comorbidity are associated with decreased HRQoL in MS. Disability most strongly diminishes HRQoL and, thus, interventions that reduce disability are expected to yield the most substantial improvement in HRQoL. Yet, interventions targeting other factors amenable to change, particularly depression but also anxiety, fatigue, and physical comorbidities, may all result in meaningful improvements in HRQoL, as well. Our findings point to the importance of further research confirming the efficacy of such interventions.

Presence of psychiatric comorbidities, which were common in our incident MS cohort, increased the severity of subsequent neurologic disability. Optimizing management of psychiatric comorbidities should be explored as a means of potentially mitigating disability progression in MS.

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ObjectiveTo evaluate long-term disability progression in pediatric-onset multiple sclerosis (POMS) and compare to adult-onset multiple sclerosis (AOMS).MethodsThis was a retrospective cohort study using prospectively collected clinical information from the Swedish MS Registry. Clinical features were compared and Kaplan-Meier and Cox proportional hazards regression were used to assess the risk of reaching sustained Expanded Disability Status Scale (EDSS) 3, 4, and 6 in POMS (multiple sclerosis [MS] onset <18 years) and AOMS (MS onset ≥18 years).ResultsA total of 12,482 persons were included; 549 (4.4%) were classified as POMS. The POMS cohort took longer to reach all 3 disability milestones from their MS onset, but did so at a younger age than the AOMS cohort. Primary progressive course (hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.46–14.7), higher relapse rate in the first 5 years of disease (HR 5.35; 95% CI 3.37–8.49), and complete remission from the initial relapse (HR 0.41; 95% CI 0.18–0.94) were associated with an altered risk of progression to EDSS 4 among POMS cases. The same pattern emerged for the risk of reaching EDSS 3 and 6.ConclusionsPatients with pediatric-onset MS follow a distinctive clinical course, which should be considered in the treatment and management of the disease.

Multiple sclerosis (MS) is a chronic central nervous system disease with a highly heterogeneous course. The aetiology of MS is not well understood but is likely a combination of both genetic and environmental factors. Approximately 85% of patients present with relapsing-remitting MS (RRMS), while 10–15% present with primary progressive MS (PPMS). PPMS is associated with an older onset age, a different sex ratio, and a considerably more rapid disease progression relative to RRMS. We systematically reviewed the literature to identify modifiable risk factors that may be associated with these different clinical courses. We performed a search of six databases and integrated twenty observational studies into a descriptive review. Exposure to Epstein-Barr virus (EBV) appeared to increase the risk of RRMS, but its association with PPMS was less clear. Other infections, such as human herpesvirus-6 and chlamydia pneumoniae, were not consistently associated with a specific disease course nor was cigarette smoking. Despite the vast literature examining risk factors for the development of MS, relatively few studies reported findings by disease course. This review exposes a gap in our understanding of the risk factors associated with the onset of PPMS, our current knowledge being predominated by relapsing-onset MS.

Individuals with migraine, hyperlipidemia, or a high comorbidity burden (3 or more conditions) had an increased relapse rate over 2 years. These findings have potential implications for understanding the pathophysiology of MS relapses, and suggest that closer monitoring of individuals with specific or multiple comorbidities may be needed. Future research is needed to understand if the presence of comorbidity warrants a tailored approach to MS management.

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IMPORTANCE Cognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term. OBJECTIVE To compare long-term information-processing efficiency between patients with POMS and adult-onset MS (AOMS). DESIGN, SETTING, AND PARTICIPANTS This population-based longitudinal cohort study accessed the Swedish MS Registry (SMSreg), which collates information from all 64 neurology clinics in Sweden. Registered cases with definite MS in the SMSreg with an onset before April 15, 2018, and at least 2 Symbol Digit Modalities Test (SDMT) scores recorded were included. Only persons aged 18 to 55 years and with duration of disease of less than 30 years at the time of SDMT administration were included, to ensure comparable ranges between patients with POMS and AOMS. Of 8247 persons with an SDMT recorded in the SMSreg, 5704 met inclusion criteria, 300 (5.