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

D Weller, L Lörincz, T Sutter, K Reuter, M Linnebank, M Weller, B Zörner, L Filli

Journal: Journal of the neurological sciences 2021;416():116978

PMID: 32559515

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Abstract

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.

Address: Department of Neurology, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.; Department of Neurology, University Witten/Herdecke and Evangelische Kliniken Gelsenkirchen, Munckelstraße 32, 45879 Gelsenkirchen, Germany.; Spinal Cord Injury Center, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.; Department of Neurology, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland; Spinal Cord Injury Center, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland; Swiss Center for clinical Movement Analysis (SCMA), Balgrist Campus AG, Lengghalde 5, 8008 Zurich, Switzerland. Electronic address: [email protected].

DOI: 10.1016/j.jns.2020.116978