As a first step toward understanding which changes should be considered as meaningful, the authors assessed the reliability of quantitative functional tests on 5 consecutive days in 63 patients with MS, determining the range of measurement variability present when patients are clinically stable. Time to walk 25 feet (T25FW) and the 9-hole peg test (9HPT) varied by <20% of individual mean scores on repeated testing. Therefore, a 20% change on these tests can be considered to be the threshold that reliably indicates a true change in function for an individual.

In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone) reduced the relapse rate and slowed accumulation of disability for patients with relapsing - remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 - 0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis. Multiple Sclerosis (2000) 6 255 - 266

We studied a large kindred with a chronic progressive neurologic disorder affecting at least 10 men and 11 women in four generations in a pattern compatible with autosomal dominant inheritance. In 20 of the affected subjects, evaluated before the availability of computerized tomography and without regard to family history, the diagnosis was multiple sclerosis. Symptoms of the neurologic disorder begin in the fourth and fifth decades and include cerebellar, pyramidal, and autonomic abnormalities. The autonomic symptoms, which involve bowel and bladder regulation and orthostatic hypotension, may be the earliest changes but are frequently disregarded. Survival for 20 years after onset is common. The CT scan is striking and shows a symmetrical decrease in white-matter density, beginning in the frontal lobes but extending to all of the centrum ovale and the cerebellar white matter. Limited pathological observation reveals gross white-matter degeneration with microscopic vacuolation, preservation of U fibers and cortical structures, and no inflammatory changes or reactive gliosis. Because of its hereditary basis, the disorder should be susceptible to genetic definition and ultimately to treatment or prevention.

Background: Current evidence suggests that sun exposure and vitamin D intake, during childhood and adolescence, are associated with a reduced risk of multiple sclerosis (MS). However, the role of these environmental agents in the timing of disease symptom onset remains to be investigated. Methods: Using a cross-sectional study design, we recruited participants from the Veterans Health Administration – Multiple Sclerosis Surveillance Registry. Self-reported histories of residential locations, sun exposure and intake of vitamin D were used to estimate vitamin-D-related exposures. Multivariable linear regression analysis was used to examine the associations between these variables and age at MS onset. Results: Among veterans with relapsing MS who resided in low-to-medium solar radiation areas (n = 540), low sun exposure in the fall/winter during the ages of 6–15 years was significantly associated with earlier symptom onset by 2.1 years (p = 0.02). Intake of cod liver oil during the same age period was associated with later onset of MS symptoms by 4 years (p = 0.02). Conclusions: The current study provides evidence for an association between vitamin-D-related exposures during childhood and early adolescence and the timing of MS symptom onset, and supports vitamin D as a potential modulator of the clinical course of this disease.

Backgrounds/Aim: Gestational and early life events have been suggested to contribute to multiple sclerosis (MS) susceptibility. We assessed the effects of time and place of birth on the age at onset of MS symptoms. Methods: We selected a national cohort of 967 veterans from the Multiple Sclerosis Surveillance Registry for whom month and season (time) of birth, and birthplace (city and state) were available. Multiple linear regression analyses were used to examine the association between time of birth, birthplace latitude and solar radiation, and the age at onset of MS symptoms among the study sample. Results: Patients with a relapsing form of the disease (R-MS), who were born in winter and whose birthplace was in low solar radiation areas, had disease symptom onset on average 2.8 years earlier than those born in seasons other than winter and in medium- and high-solar radiation areas (p = 0.02). Conclusions: These results suggest that exposure early in life to geographical and seasonal factors, possibly related to the protective effect of sunlight, and thus vitamin D, is associated with a delay in MS symptom onset. Other larger studies are required to examine the period-specific (from conception to adulthood) environmental factors that are associated with MS susceptibility.