Changes in Cognitive Processing Speed, Mood, and Fatigue in an Observational Study of Persons With Multiple Sclerosis Treated With Dalfampridine-ER

Triche, Elizabeth W.; Ruiz, Jennifer A.; Olson, Kayla M.; Lo, Albert

doi:10.1097/wnf.0000000000000130

Cited by 15 publications

(11 citation statements)

References 31 publications

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“…In line with a number of previous studies, we did observe a beneficial effect of dalfampridine on the cognitive function of MS patients (Jensen et al., 2014; Ruck et al., 2014; Triche, Ruiz, Olson, & Lo, 2016). In our cohort, the improvement of the performance in the PASAT test was independent of the responder status.…”

Section: Discussionmentioning

confidence: 99%

“…(2001) who reported a significant improvement of fatigue in patients showing adequate blood concentrations of 4‐aminopyridine. This finding was also supported by subsequent observational studies using dalfampridine (Allart et al., 2015; Pavsic et al., 2015; Ruck et al., 2014; Triche et al., 2016). In our cohort, no significant overall effect of dalfampridine on fatigue was detected but the responder group had a better treatment response than the nonresponders.…”

Section: Discussionmentioning

confidence: 99%

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Dalfampridine effects on cognition, fatigue, and dexterity

et al. 2016

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ObjectivesDalfampridine exerts beneficial effects on walking ability in a subgroup of patients with multiple sclerosis (MS). These patients are termed “responders”. Here, we investigated whether the responder status with respect to mobility measures would determine whether dalfampridine treatment exerts a beneficial effect on other MS symptoms. We therefore assessed walking ability, upper limb function, cognition, fatigue, visual evoked potentials (VEPs), depression, and quality of life in patients before and after dalfampridine treatment.MethodsPatients with MS and impaired mobility were recruited. Maximal walking distance, timed 25 Foot Walk, nine hole peg test, paced auditory serial addition test (PASAT), fatigue severity scale (FSS), VEPs, Beck Depression Inventory (BDI), EuroQol five dimensional questionnaire, and quality of life visual analogue scale were determined before and after 12–14 days of dalfampridine treatment. Repeated measures analysis of variance was applied to determine the effect of dalfampridine treatment.ResultsOf the 34 patients who completed the study, 22 patients were responders and 12 patients nonresponders, according to their performance in mobility measures. Treatment effects for the entire patient cohort were observed for PASAT (p = .029) and BDI (p = .032). Belonging to the responder cohort did not predict the response to treatment in these tests. For the FSS, response to dalfampridine treatment was dependent on the responder status (p = .001) while no effects in the total patient cohort were observed (p = .680). Other neurological functions remained unaltered. For VEP latencies, no significant improvements were detected.ConclusionIn this study, we observed beneficial effects of dalfampridine on cognition, depression, and fatigue. These effects were not limited to patients who responded to dalfampridine with improved mobility measures. These findings underscore the need to assess the beneficial effects of dalfampridine on neurological deficits in MS patients in additional randomized clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dalfampridine effects on cognition, fatigue, and dexterity

et al. 2016

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“…11 A more recent, yet smaller observational study of 39 adults with MS reported that performance on the SDMT improved with 14 weeks of treatment. 7 These findings are encouraging and warrant more in-depth examination. However, several design issues such as smaller sample sizes, lack of a placebo control group, and/or lack of blinding of assessments in pre- and post-trials without a placebo arm, leave little that can be concluded from these trials.…”

Section: Introductionmentioning

confidence: 79%

“…However, thus far only a handful of studies have investigated its impact on cognition. 7–11 Results from these limited observational studies are inconsistent. Some studies have investigated change in auditory processing speed using the Paced Auditory Serial Addition Test (PASAT).…”

Section: Introductionmentioning

confidence: 99%

Dalfampridine benefits ambulation but not cognition in multiple sclerosis

et al. 2018

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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).

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“… 18 These results in MS are similar to our findings in the TM patient population and likely suggest that larger studies might have yielded similar positive outcomes with increased statistical power. D-ER has been tested for benefits in other neurological functions besides walking, including cognition, 19 fatigue, 20 mood, 21 visual acuity, 22 nystagmus, dexterity and strength in the arms, 23 balance, 24 and language. 25 The trends toward improvement observed in these trials are similar to trends seen for some of the secondary outcomes in this study, including endurance, strength and balance.…”

Section: Discussionmentioning

confidence: 99%

Randomized, Placebo-controlled Crossover Study of Dalfampridine Extended-release in Transverse Myelitis

Schwartz

Wymbs

Huang

et al. 2017

Multiple Sclerosis Journal - Experimental, Translational and Cl

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BackgroundDalfampridine has the potential to be effective in patients with transverse myelitis (TM) as this rare disorder shares some clinical and pathogenic similarities with multiple sclerosis.MethodsThis is a randomized, double-blind, placebo-controlled crossover study of dalfampridine extended-release (D-ER, Ampyra®). Sixteen adult study participants with monophasic TM confirmed by MRI were enrolled if their baseline timed 25-foot walking speed was between 5 and 60 seconds. Participants were randomized to receive 10 mg twice-daily doses of either D-ER or placebo control for eight weeks, then crossed over to the second arm of placebo or dalfampridine for eight weeks. The primary outcome measure was the timed 25-foot walk.ResultsOf 16 enrolled participants, three withdrew and 13 completed the trial. Among the 13 completers, nine individuals showed an average timed walk that was faster in the D-ER arm compared to the placebo arm, but only four participants met the stricter statistical threshold to be classified as a responder. Analyses of secondary clinical outcome measures including strength, balance assessments, spasticity, and Expanded Disability Status Scale (EDSS) score showed trends toward improvement with D-ER.ConclusionsD-ER may be beneficial in TM to improve walking speed and other neurological functions.

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Changes in Cognitive Processing Speed, Mood, and Fatigue in an Observational Study of Persons With Multiple Sclerosis Treated With Dalfampridine-ER

Abstract: Dalfampridine-extended release may improve cognition and fatigue in persons with MS, especially among timed walk responders.

Cited by 15 publications

References 31 publications

Dalfampridine effects on cognition, fatigue, and dexterity

Dalfampridine effects on cognition, fatigue, and dexterity

Dalfampridine benefits ambulation but not cognition in multiple sclerosis

Randomized, Placebo-controlled Crossover Study of Dalfampridine Extended-release in Transverse Myelitis

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