This review summarizes the existing knowledge regarding the effects of physical exercise in patients suffering from multiple sclerosis (MS). Furthermore, recommendations are given regarding exercise prescription for MS patients and for future study directions. Previously, MS patients were advised not to participate in physical exercise. During recent years, it has been increasingly acknowledged that exercise benefits MS patients. The requirement for exercise in MS patients is emphasized by their physiological profile, which probably reflects both the effects of the disease per se and the reversible effects of an inactive lifestyle. To date the effects of exercise have only been studied in moderately impaired MS patients with an EDSS score of less than 7. Evidence exists for recommending participation in endurance training at low to moderate intensity, as the existing literature demonstrates that MS patients can both tolerate and benefit from this training modality. Also, resistance training of moderate intensity seems to be well tolerated and to have beneficial effects on MS patients, but the methodological quality of the existing evidence is in general low and the number of studies is limited. Only two studies have evaluated the effects of combined resistance- and endurance training, making solid conclusions regarding this training modality impossible. Multiple Sclerosis 2008; 14: 35—53. http://msj.sagepub.com

Background: Obesity in late adolescence has been associated with an increased risk of multiple sclerosis (MS); however, it is not known if body size in childhood is associated with MS risk. Methods: Using a prospective design we examined whether body mass index (BMI) at ages 7–13 years was associated with MS risk among 302,043 individuals in the Copenhagen School Health Records Register (CSHRR). Linking the CSHRR with the Danish MS registry yielded 774 MS cases (501 girls, 273 boys). We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among girls, at each age 7–13 years, a one-unit increase in BMI z-score was associated with an increased risk of MS (HR_{age 7}=1.20, 95% CI: 1.10–1.30; HR_{age 13}=1.18, 95% CI: 1.08–1.28). Girls who were ≥95^th percentile for BMI had a 1.61–1.95-fold increased risk of MS as compared to girls <85^th percentile. The associations were attenuated in boys. The pooled HR for a one-unit increase in BMI z-score at age 7 years was 1.17 (95% CI: 1.09–1.26) and at age 13 years was 1.15 (95% CI: 1.07–1.24). Conclusion: Having a high BMI in early life is a risk factor for MS, but the mechanisms underlying the association remain to be elucidated.

Background: Epidemiologic studies have suggested different prevalence of neuromyelitis optica (NMO) in different ethnic groups. However, data on the incidence and prevalence of NMO in Caucasians are scarce. Objective: To estimate the incidence and prevalence of NMO in a predominantly Caucasian population based on the Wingerchuk 2006 criteria. Methods: The study was a population-based retrospective case series with longitudinal follow-up. Patients with multiple sclerosis (MS), optic neuritis (ON), acute transverse myelitis (TM), and NMO from the 4 neurology and 3 ophthalmology departments in the Region of Southern Denmark having been diagnosed between 1998 and 2008 were investigated. Patients were included based on 1) episodes of ON or TM and 2) an initial brain MRI not diagnostic for MS. An immunofluorescence assay was used to determine aquaporin-4 (AQP-4) antibodies. Results: A total of 477 patients with MS, TM, or ON were evaluated: 163 fulfilled the inclusion criteria, 42 (26%) qualified for the diagnosis of NMO, 26 (62.0%) of these were AQP4 antibody positive. All except one were Caucasian, the female:male ratio was 2.8:1, and mean age at onset was 35.6 years (range 15–64 years). The clinical presentation was heterogeneous including TM, longitudinally extensive TM, ON, and brainstem syndromes. The yearly incidence rate of NMO in the population was estimated to be 0.4 per 10⁵ person-years (95% confidence interval [CI] 0.30–0.54) and the prevalence was 4.4 per 10⁵ (95% CI 3.1–5.7). Conclusions: Despite being a rare disease, NMO is more common in a Caucasian population than earlier believed.

The Danish Multiple Sclerosis Registry contains information about all Danish patients in whom multiple sclerosis has been diagnosed since 1948. The purpose of this study was to analyse trends in survival and causes of death of these patients and to compare them with those of the general population. The study comprised all patients with onset in the period 1949–1996. All case records were validated and classified according to standardized diagnostic criteria. Data on emigration and death were obtained by record linkage to official registers. The end of follow‐up was 1 January 2000 for emigration and death, and 1 January 1999 for cause‐specific deaths. Standardized mortality ratios and excess death rates were calculated for various causes of death and periods after multiple sclerosis onset, and time trends in survival probability were analysed by Cox regression. The study comprised 9881 patients, of whom 4254 had died before end of follow‐up. The median survival time from onset was ∼10 years shorter for multiple sclerosis patients than for the age‐matched general population, and multiple sclerosis was associated with an almost threefold increase in the risk for death. According to death certificates, more than half (56.4%) of the patients had died from multiple sclerosis. They also had excess mortality rates from other diseases, except cancer, and from accidents and suicide. The probability for survival improved significantly during the observation period. Thus, the 10‐year excess mortality was almost halved in comparison with that in the middle of the 1900s.

Objective: To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether the improvements are maintained after the trial. Methods: The present study was a 2-arm, 12-week, randomized controlled trial including a poststudy follow-up period of 12 weeks. Thirty-eight moderately impaired patients with MS were randomized to a PRT exercise group (n = 19) or a control group (n = 19). The exercise group completed a biweekly 12-week lower extremity PRT program and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score of 4 tests) were evaluated. Results: KE MVC and FS improved after 12 weeks of PRT in the exercise group (KE MVC: 15.7% [95% confidence interval 4.3–27.0], FS: 21.5% [95% confidence interval 17.0–26.1]; p < 0.05), and the improvements were better than in the control group (p < 0.05). The improvements of KE and FS in the exercise group persisted at follow-up after 24 weeks. Also, the exercise effects were reproduced in the control group during the 12-week posttrial PRT period. Conclusions: Twelve weeks of intense progressive resistance training of the lower extremities leads to improvements of muscle strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity. Level of evidence: The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle strength and functional capacity in patients with multiple sclerosis.