Background: Persons with MS (PwMS) commonly present ambulatory and manual dysfunctions. While ambulation is recognized as important to PwMS, manual dysfunction is only lately gaining attention. Fampridine-PR was approved for MS ambulatory impairments. Anecdotal evidences indicate possible therapeutic effects on manual function. Objective: To comprehensively assess the effect of Fampridine-PR on manual functions of PwMS. Methods: Twenty six PwMS with ambulatory and manual dysfunction assessed before, 1 and 3months after treatment with Fampridine-PR, applying Timed 25-Foot Walk (T25FW) for ambulation while manual functions were evaluated by several tools addressing the International Classification of Functioning (ICF) concepts. This includes hand grip and pinch strength, 9 Hole Peg Test (9HPT), Arthritis Hand Function Test (AHFT), activities of daily life (ADL) tests, ABILHAND questionnaire and Computerized Penmanship Evaluation Tool (ComPET). Results: Fampridine-PR increased dominant hand grip and pinch strength 1month following treatment initiation by 12% and 10% (p<0.05), respectively. 9HPT improved by 11.3% after 3months of treatment (p<0.05%) and ABILHAND improved by 16% and 31% (p<0.05%) after 1 and 3months of treatment. Mean stroke duration in air of the name writing task improved by 21% (p<0.05) following 3months of treatment. T25FW results were similar to previous reports. Conclusion: The results of this pilot study suggest that Fampridine-PR improves manual function of PwMS. Methods herein indicate that an integrative approach may be useful for evaluation of manual function in MS and in additional neurological diseases.