Fampridine-induced changes in walking kinetics are associated with clinical improvements in patients with multiple sclerosis

• Published in: Journal of the neurological sciences 2020-09, Vol.416, p.116978-116978, Article 116978
• Main Authors: Weller, D., Lörincz, L., Sutter, T., Reuter, K., Linnebank, M., Weller, M., Zörner, B., Filli, L.
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - therapeutic use; Dalfampridine; Fampridine; Gait; Humans; Kinetics; Locomotor mechanisms; Multiple sclerosis; Multiple Sclerosis - drug therapy; Potassium Channel Blockers - therapeutic use; Treatment Outcome; Walking; Walking pattern
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2020.116978

Gait dysfunction is common in patients with multiple sclerosis (PwMS). Treatment with prolonged-release fampridine (PR-fampridine) improves walking ability in some PwMS. Associated fampridine-induced changes in the walking pattern are still poorly understood but may provide a better understanding of the mechanisms underlying the beneficial drug effects. 61 PwMS were treated with PR-fampridine in a randomized, monocentric, double-blind and placebo-controlled clinical trial with crossover design (FAMPKIN). Drug-induced improvements in walking speed (Timed-25-Foot Walk; T25FW) and endurance (6-Minute Walk Test; 6MWT) were quantified. In this sub-study of the FAMPKIN trial, fampridine-induced changes in kinetic gait patterns were analyzed by pressure-based foot print analysis during treadmill walking. Vertical ground reaction forces were analyzed during different gait phases. Kinetic data of 44 PwMS was eligible for analysis. During double-blind treatment with PR-fampridine, patients performed significantly better in the T25FW and 6MWT than during placebo treatment (p < 0.0001 for both). At the group level (n = 44), there were no significant changes of gait kinetics under PR-fampridine vs. placebo. However, we found relevant changes of walking kinetics regarding forces during loading, single limb and pre-swing phase in a patient sub-group (n = 8). Interestingly, this sub-group demonstrated superior responsiveness to PR-fampridine in the clinical walking tests compared to those patients without any fampridine-induced changes in kinetics (n = 36). Our results demonstrate fampridine-induced changes in gait kinetics in a sub-group of PwMS. These gait pattern changes were accompanied by improved clinical walking performance under PR-fampridine. These results shed some light on the biomechanical changes in walking patterns underlying enhanced fampridine-induced gait performance. •PR-fampridine enhances clinical walking function in persons with multiple sclerosis.•Fampridine-induced changes in gait kinetics were observed in a subset of patients.•Patients with kinetic adaptations showed superior drug effects in clinical walking tests.•This data sheds light onto the mechanisms underlying fampridine-induced gait improvements.