Dalfampridine benefits ambulation but not cognition in multiple sclerosis

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).

Cognitive Efficacy of Pharmacologic Treatments in Multiple Sclerosis: A Systematic Review

“…The study was limited due to the large number of outcome measures administered without specification of one or two primary outcomes, as required by the AAN criteria. In contrast, another class II RCT did not find a significant treatment effect on the SDMT after 12 weeks among 57 cognitively impaired MS patients [50]. This study was classified as class II because it did not provide sufficient information regarding its inclusion criteria and randomization.…”

A Prospective, Observational, Cohort Study to Assess the Efficacy and Safety of Prolonged-Release Fampridine in Cognition, Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients: The FAMILY Study

“…Studies utilizing the Symbol Digit Modalities Test (SDMT) further corroborate these results by demonstrating an improvement in visual processing speed after short- and long-term treatment with PR-FAM [ 28 , 30 , 44 , 45 ] . In contrast, some studies failed to demonstrate an impact of PR-FAM on cognitive function, as assessed either by PASAT or SDMT [ 24 , 27 , 31 ] . Interestingly, in the study of Satchidanand et al (2020), while there was no effect of fampridine on cognitive outcomes when compared with placebo, performance in PASAT but not in SDMT improved significantly among “responders” in the treatment group compared with “non-responders”, reflecting a possible cognition–motor coupling [ 31 ].…”

“…In contrast, some studies failed to demonstrate an impact of PR-FAM on cognitive function, as assessed either by PASAT or SDMT [ 24 , 27 , 31 ] . Interestingly, in the study of Satchidanand et al (2020), while there was no effect of fampridine on cognitive outcomes when compared with placebo, performance in PASAT but not in SDMT improved significantly among “responders” in the treatment group compared with “non-responders”, reflecting a possible cognition–motor coupling [ 31 ]. A recently conducted meta-analysis showed conflicting results with regards to the effect of PR-FAM on cognitive function.…”

“…Apart from one randomized, placebo-controlled study describing PR-FAM's beneficial effects on different cognitive domains as well as on fatigue and depression over 2 years in a cohort of MS patients [18], most studies conducted so far, utilizing a randomized, placebo-controlled design, have failed to demonstrate fampridine's benefits in such non-walking outcomes [22][23][24][25]. On the other hand, a limited number of openlabel, uncontrolled studies have already described PR-FAM-induced improvements in fatigue, cognition, mood and overall QoL [4,17,19,[26][27][28][29][30][31]. Whereas these studies offer valuable information towards a possible role of PR-FAM on these functions, data remain unclear, with variabilities in study parameters, including study design, treatment algorithms and assessment protocols, do not allowing the drawing of univocal conclusions [32].…”

Esclerose Múltipla: Diagnóstico E Manejo

“…Entre os fármacos sintomáticos, o dalfampridine é um dos mais utilizados, auxiliando na melhora da mobilidade e velocidade de caminhada dos pacientes, ao bloquear canais de potássio (SATCHIDANAND et al, 2020). Aumento das aminotransferases séricas (ALT e AST) ocorre de forma constante com a maioria dos medicamentos usados para tratar a esclerose múltipla.…”