Predicting responsiveness to fampridine in gait‐impaired patients with multiple sclerosis

Filli, Linard; Werner, Jana; Beyer, Gerrit; Reuter, Katja; Petersen, Jens A.; Weller, Michael; Zörner, Björn; Linnebank, Michael

doi:10.1111/ene.13805

Cited by 9 publications

(11 citation statements)

References 32 publications

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“…KA group) were diagnosed with secondary progressing MS and revealed higher EDSS scores compared to non-responding patients. This is in line with previous findings reporting that PwMS with higher levels of functional disability show enhanced responsiveness to PR-fampridine compared to mildly impaired PwMS [24][25][26]. Superior positive drug responses in patients with severe MS-related impairments might be attributed to more pronounced axonal demyelination and neural damage in these patients.…”

Section: Discussionsupporting

confidence: 92%

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

Weller

Lőrincz

Sutter

et al. 2020

Journal of the Neurological Sciences

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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 fampridineinduced 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.

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Section: Discussionsupporting

confidence: 92%

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

Weller

Lőrincz

Sutter

et al. 2020

Journal of the Neurological Sciences

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“…EDSS only weakly correlated with the outcome. In this study, reduced walking endurance as measured by the 6MWT was the best predictor of a good outcome with an accuracy of 80% [7]. In comparison, we found that EDSS correlated with improvement in T25wt; however, we did not test walking endurance, since we included patients with advanced gait impairment who were unable to complete the 6MWT.…”

Section: Discussionmentioning

confidence: 67%

“…The positive impact of fampridine on gait speed is now well established, but only 40% of patients are expected to experience a clinically meaningful improvement [15,21]. Proper selection of patients most likely to experience clinical benefits from fampridine has been the subject of rare dedicated studies [6][7][8]. It has been suggested that patients with more disability at baseline have the best outcome.…”

Section: Discussionmentioning

confidence: 99%

“…This seems logical, since advanced ambulatory impairment in MS is associated with a higher amount of axonal demyelination within the neural locomotor networks, providing more targets for fampridine to reinforce gait function [6,8]. Filli and collaborates tested the predictive value of a set of demographic and clinical criteria including T25wt, walking endurance 6-min walk test (6MWT), and the 12-item multiple sclerosis walking scale (MSWS-12) [7]. Their findings suggest that walking function at baseline (6MWT and T25wt) accurately predicts the responder status.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, only a subset of patients with MS and walking disabilities are responders to fampridine [5]. Limited data suggest that more advanced walking disability [6,7] and prolonged central conduction times [6,8] are predictive of a favorable response to treatment. The predictive value of more advanced measurements of cortical dysfunction have not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Cortical Excitability Measures May Predict Clinical Response to Fampridine in Patients with Multiple Sclerosis and Gait Impairment

Ahdab

Shatila

et al. 2019

Brain Sciences

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Background: Most multiple sclerosis (MS) patients will develop walking limitations during the disease. Sustained-release oral fampridine is the only approved drug that will improve gait in a subset of MS patients. Objectives: (1) Evaluate fampridine cortical excitability effect in MS patients with gait disability. (2) Investigate whether cortical excitability changes can predict the therapeutic response to fampridine. Method: This prospective observational study enrolled 20 adult patients with MS and gait impairment planned to receive fampridine 10 mg twice daily for two consecutive weeks. Exclusion criteria included: Recent relapse (<3 months), modification of disease modifying drugs (<6 months), or Expanded Disability Status Scale (EDSS) score >7. Neurological examination, timed 25-foot walk test (T25wt), EDSS, and cortical excitability studies were performed upon inclusion and 14 days after initiation of fampridine. Results: After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, p = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS (r = 0.57; p < 0.01) and ΔT25wt (r = 0.57, p = 0.01). rMT above 52% of the maximal stimulator output was found to be a good predictor of a favorable response to fampridine (accuracy: 75%). Discussion: Fampridine was found to have a significant modulatory effect on the cerebral cortex, demonstrated by an increase in excitatory intracortical processes as unveiled by paired-pulse transcranial magnetic stimulation. rMT could be useful in selecting patients likely to experience a favorable response to fampridine.

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A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis – An explorative study

Mamoei

Jensen

Dalgas

et al. 2020

Journal of Clinical Neuroscience

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Predicting responsiveness to fampridine in gait‐impaired patients with multiple sclerosis

Abstract: Initial walking impairment is a good predictor of therapeutic responsiveness to PR-fampridine. Valid predictors of patients' responsiveness to PR-fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.

Cited by 9 publications

References 32 publications

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

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

Cortical Excitability Measures May Predict Clinical Response to Fampridine in Patients with Multiple Sclerosis and Gait Impairment

A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis – An explorative study

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