Effects of Dalfampridine in Hereditary Spastic Paraparesis (S50.007)

OBJECTIVE To assess the clinical efficacy of dalfampridine in Hereditary Spastic Paraparesis (HSP). BACKGROUND Dalfampridine, 4-aminopyridine, a voltage-dependent potassium channel blocker has been shown to improve walking ability in patients with multiple sclerosis (MS). The major pathology seen in HSP is the degeneration of axons of the pyramidal tract and dorsal column pathways and secondary demyelination occurs with axonal loss. Our purpose was to study the effect of dalfampridine in HSP patients with gait disorder due to pyramidal tract involvement. DESIGNS AND METHODS Five patients with a clinically definite diagnosis of HSP, of whom four had genetic confirmation were included. Dalfampridine-SR 10 mg was administered to the patients twice daily for 15 days. Patients were assessed by Timed 25-Foot Walk (T25FW) test, modified Ashworth Scale (MAS) and video taped timed nine-hole peg test (NHPT) which were repeated twice just before administration of dalfampridine and at the end of 15 days. RESULTS All patients were female [mean age 35.2±10.8 years (range: 22-49 years)]. Mean disease duration was 9.5±5.3 years. Timed 25-Foot Walk (T25FW) walking decreased significantly (18.3±5.8 vs 14.6±6.5, confidence interval: 1.4-5.9, p=0.014). Baseline mean MAS score was 2.0±0.7, and end-of-study MAS score was 1.0±0.0 (confidence interval: 0.122-1.878, p=0.034). Similarly, four patients had a MAS score of 2 or 3 in the pretreatment phase, which regressed to 1 in all patients (p=0.036). Time for nine-hole peg test was also shorter at end-of-study, compared to baseline which reached significant level for left hand (20.5±2.2 vs 18.5±2.5, p=0.025 for left hand and 19.4±3.3 vs 18.2±2.9, p=0.539 for right hand). CONCLUSION HSP patients treated with dalfampridine showed significantly improvement in T25FW, MAS and NHPT. However, this observation needs to be confirmed in a larger number of HSP patients. Disclosure: Dr. Siva has nothing to disclose. Dr. Uygunoglu has received personal compensation for activities with Merck Serono and Biogen Idec. Dr. Tutuncu has nothing to disclose. Dr. Gunduz has nothing to disclose. Dr. Akalin has nothing to disclose. Dr. Saip has nothing to disclose.