Effects of prolonged-release fampridine on multiple sclerosis-related gait impairments. A crossover, double-blinded, placebo-controlled study

Background: People with multiple sclerosis have reduced walking speed and impaired gait pattern. Prolonged release-fampridine is a potassium channel blocker that improves nerve conduction in patients with multiple sclerosis, leading to walking benefits. Whether fampridine alters gait pattern is unknown. Methods: In this crossover, randomized controlled trial, patients with multiple sclerosis were tested for responder status during a 4-week run-in period. Patients were considered responders if they improved their 25-ft walk test by 10% and improved their perceived walking capacity. Responders were randomized to prolonged release- fampridine (10 mg b.i.d.) or placebo for a 6-week period. After a 2-week wash-out period, they were allo- cated to the other treatment for 6 weeks. Participants were assessed before and after both conditions. Three- dimensional gait analysis assessed kinematic, kinetic, mechanic and energetic variables while walking on a treadmill at comfortable speed. Six-minute walk test and 25-ft walk test were used to assess walking speed on middle and short-distances, respectively. Patient-reported outcome measures were also used. Repeated measures ANCOVAs were applied to assess the treatment effects. Findings: Out of 39 included patients, 24 responders (12 women; Expanded Disability Status Scale:4.25[4–5]; age:46 ± 10 years; maximal speed:0.93 ± 0.38 m⋅s− 1) were identified. Among them, prolonged release- fampridine reduced the external mechanical work (− 0.039 J⋅kg− 1⋅m− 1;p = 0.02), and improved knee flexion during swing phase (+5.3◦; p = 0.02). No differences were found in other walking tests and patient-reported outcomes, at group-level. Interpretation: Prolonged release-fampridine increases knee flexion during swing phase and lowers mechanical external work. Whether these changes are related to clinically meaningful improvements in walking capacity and other functional variables should be further investigated