Longitudinal assessment of hand function in individuals with multiple sclerosis.

OBJECTIVE: Little is known about the frequency and severity of hand dysfunction in individuals with multiple sclerosis (MS). Hence, we sought to determine the extent that quantitative tests of hand function detect changes over time, evaluate their relationship to global disability measures, and identify predictors of hand function. METHODS: One-hundred and forty-seven individuals with MS were included (96 women, 84 relapsing-remitting MS [RRMS]) along with 35 age-and-sex matched controls. Quantitative tests of hand function (grip strength, pinch strength, 9 hole peg test [9HPT], finger tapping) and leg strength were acquired and normalized to age and sex. Expanded Disability Status Scale (EDSS) and timed 25 foot walk were also obtained. Spearman correlations, multivariate regression models and mixed effects linear regression were used for analysis. RESULTS: Our cohort had an EDSS of 3.6 ±â€¯2.2 (median ± SD) and age 44.6 ±â€¯11.9 years. Follow up time was up to 5 years. At baseline, 14/63 individuals with progressive MS (PMS) required more than twice as much time to complete the 9HPT using their dominant hand, compared to controls. Similarly, 11 individuals with PMS had less than 50% of grip strength and 6 had less than 50% of pinch strength, compared to controls. Additionally, 7 individuals with PMS were found to be at least 50% slower than controls in finger tapping. Over two years, 27/85 individuals with MS had more than 20% worsening in their 9HPT results from baseline (17 RRMS, 10 PMS) and 37/74 (20 RRMS, 17 PMS) had more than 20% worsening in their grip strength compared to baseline. CONCLUSIONS: Hand function is commonly impaired in individuals with MS. Assessing hand dysfunction with dynamometry and the 9HPT could help improve the precision of detecting changes in hand function over time in MS, and may be more sensitive in detecting changes in PMS. These quantitative tests may be useful as outcome measures in clinical trials using neuroprotective or reparative therapies and rehabilitative interventions.

Distinguishing among multiple sclerosis fallers, near-fallers and non-fallers.

BACKGROUND: Fall rates among adults with multiple sclerosis are consistently greater than 50%, but near-falls (i.e. a trip or stumble) are often undocumented. Furthermore, little is known about the circumstances surrounding fall and near-fall events. The purpose of this study was to examine the similarities and differences among non-fallers, near-fallers and fallers with multiple sclerosis, including the circumstances that surround falls and near-falls. METHODS: In a single visit, 135 multiple sclerosis participants completed the Hopkins Falls Grading Scale, a custom questionnaire investigating circumstances surrounding falls and near-falls, and performed the Timed Up and Go and Timed 25-Foot Walk tests. Mann-Whitney tests were used to examine differences between fallers, near-fallers and non-fallers. Multiple logistic regression with AIC criterion was used to examine associations of circumstances with the odds of falling vs. near-falling. Cumulative odds ordinal logistic regression was used to analyze the association between each of the walking tests and the susceptibility of the individual for falls or near-falls. RESULTS: 30% of individuals reported falls, while 44% reported near-falls over a 1-year period. Non-fallers completed the walking tests more quickly than near-fallers (p < 0.0045), and fallers (p < 0.0001); near-fallers and fallers demonstrated similar motor profiles. Individuals were more likely to sustain a fall rather than a near-fall under the following circumstances: transferring outside the home (p = 0.015) and tripping over an obstacle (p = 0.025). Performing 1-second slower on the walking tests increased the odds of a history of a fall by 6-20%. CONCLUSION: Near-falls occur commonly in individuals with MS; near-fallers and fallers reported similar circumstances surrounding fall events and demonstrated similar performance on standard timed walking tests. Clinicians monitoring individuals with MS should consider evaluation of the circumstances surrounding falls in combination with quantitative walking measures to improve determination of fall risk and appropriate rehabilitation interventions.

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis.

OBJECTIVE: To study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS). METHODS: In this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months. RESULTS: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17(+)CD4(+) T cells (p = 0.016), CD161(+)CD4(+) T cells (p = 0.03), and effector memory CD4(+) T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4(+) T cells (p = 0.018) and naive CD4(+) T cells (p = 0.04). These effects were not observed in the low-dose group. CONCLUSIONS: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4(+) T cells and decreased proportion of effector memory CD4(+) T cells with concomitant increase in central memory CD4(+) T cells and naive CD4(+) T cells. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects.