Dalfampridine benefits ambulation but not cognition in multiple sclerosis

Mult Scler. 2020 Jan;26(1):91-98. doi: 10.1177/1352458518815795. Epub 2018 Dec 19.

Abstract

Background: Impaired cognition and ambulation are common in multiple sclerosis (MS). Dalfampridine is the first Food and Drug Administration (FDA)-approved medication to treat impaired ambulation in MS. Dalfampridine may benefit patients with cognitive impairment, given its effects on saltatory conduction and the association between cognitive and motor function.

Objective: To examine the effects of dalfampridine on cognition in MS. To determine if the anticipated improved cognition is grounded in dalfampridine's effects on ambulation.

Methods: Adults with MS were randomized to dalfampridine (n = 45) or placebo (n = 16) for 12 weeks. Cognition and motor function were assessed at baseline and end-point.

Results: T25FW and 6-minute walk (6MW) performance improved at end-point in the treatment group but not in the placebo group (p < 0.05). Our primary outcome, performance on the Symbol Digit Modalities Test, did not improve. About 30% (n = 12) of the dalfampridine group demonstrated ⩾20% improved ambulation and were categorized "responders." Among "responders", Symbol Digit Modalities test performance did not improve. However, performance on the Paced Auditory Serial Addition Test improved among "responders" (p < 0.05).

Conclusion: Dalfampridine benefits timed ambulation but not cognition. Some improvement among ambulation "responders" is consistent with prior reports of cognition-motor coupling in MS ( ClinicalTrials.gov #: NCT02006160).

Keywords: Multiple sclerosis; ambulation; aminopyradine; cognition; cognitive processing speed; dalfampridine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology*
  • Adult
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mobility Limitation
  • Movement Disorders / drug therapy*
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / physiopathology
  • Outcome Assessment, Health Care*
  • Potassium Channel Blockers / pharmacology*

Substances

  • Potassium Channel Blockers
  • 4-Aminopyridine

Associated data

  • ClinicalTrials.gov/NCT02006160