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Journal of Neurology

, Volume 265, Issue 5, pp 1016–1025 | Cite as

Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years

  • Sarah D. BroicherEmail author
  • Linard Filli
  • Olivia Geisseler
  • Nicole Germann
  • Björn Zörner
  • P. Brugger
  • M. Linnebank
Original Communication

Abstract

Objective

To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS).

Methods

Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue.

Results

We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients’ perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders.

Conclusions

Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS.

Keywords

Multiple sclerosis PR-fampridine Dalfampridine Cognition Fatigue Depression 

Notes

Acknowledgements

We thank the subjects who participated in this study and the institutions supporting the trial (Betty and David Koetser Foundation, the Clinical Research Priority Program (CRPP) “NeuroRehab” of the University of Zurich, the Swiss MS Society and Biogen).

Compliance with ethical standards

Conflicts of interest

Dr. Zörner received honoraria, travel grants and funding from Biogen. Prof. Linnebank received honoraria, travel grants and funding from Biogen. He is a consultant to Biogen.

Ethical standard

This study was approved by the cantonal ethics committee Zurich, Switzerland, and the regulatory agency for medicines (Swissmedic), and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Supplementary material

415_2018_8796_MOESM1_ESM.pdf (86 kb)
Supplementary material 1 (PDF 86 kb)
415_2018_8796_MOESM2_ESM.tif (17.2 mb)
Fig e-2 Efficacy of PR-fampridine on cognitive function in responders and non-responders (Goodman’s criteria). a-c: Efficacy of PR-fampridine on cognitive function in the subpopulation fulfilling (responders; red data points) and failing (non-responders; blue data points) the responder criteria as defined by Goodman and colleagues (Goodman et al., 2009, 2010). Responder criteria are based on the consistency of drug effects on maximal gait speed during the core study. Data points represent group mean values ± SEM. D: Statistical analysis of drug efficacy during the open-label (V2 vs V3; n = 32) and double-blind, placebo-controlled treatment (Famp vs. Plac; n = 20) with PR-fampridine in different neuropsychological assessments in responders and non-responders (analogous to Table 2). Only patients completing the open-label (V2 and V3) or the double-blind (Plac and Famp) treatment phase were included in the analysis (two-tailed, paired Wilcoxon signed-rank test). (TIFF 17565 kb)
415_2018_8796_MOESM3_ESM.tif (12.5 mb)
Figure e-3 Efficacy of PR-fampridine on cognitive performance in locomotor responders and non-responders during randomized, double-blind, placebo-controlled treatment with PR fampridine. PR-fampridine-induced effects on different neuropsychological domains in the subpopulation of locomotor responders (black bars; n = 8) and non-responders (gray bars; n = 11). Locomotor responders were defined as patients improving ≥ 15% in either maximal walking speed (T25FW) or endurance (6MWT) during the double-blind assessments at the end of the second year of the extension study. Bars represent group mean values ± SEM. p values reflect statistical differences between functional responders and non-responders as tested by the two-tailed, paired Wilcoxon signed-rank test. Abbreviations: T25FW: Timed 25-Foot Walk; 6MWT: 6-Minute Walk Test. (TIFF 12802 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Sarah D. Broicher
    • 1
    Email author
  • Linard Filli
    • 1
  • Olivia Geisseler
    • 1
  • Nicole Germann
    • 1
  • Björn Zörner
    • 2
  • P. Brugger
    • 1
  • M. Linnebank
    • 3
  1. 1.Department of NeurologyUniversity Hospital ZurichZurichSwitzerland
  2. 2.Spinal Cord Injury CenterBalgrist University HospitalZurichSwitzerland
  3. 3.Department of NeurologyHelios-Klinik Hagen-AmbrockHagenGermany

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