Dalfampridine to Improve Balance in Multiple Sclerosis: Substudy from a Randomized Placebo-Controlled Trial

Abstract

This was a substudy of a randomized, double-blind, placebo-controlled trial originally designed to explore the effect of dalfampridine on information processing speed (2013-002558-64 EU Clinical Trials Register) in patients with multiple sclerosis (MS). A total of 120 patients were originally randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. Here, we sought to explore the effect of dalfampridine on static balance in single-task and dual-task conditions in a subgroup of 41 patients. They underwent static posturography in quiet standing (single-task) and while performing the Stroop test (dual-task) at randomization (baseline), after 12 weeks and after a 4-week wash-out period. Baseline characteristics of active group (n = 27) did not differ from those of placebo group (n = 14). Dalfampridine treatment was associated with better balance control than placebo in both single-task (F = 4.80, p = 0.034) and dual-task (F = 6.42, p = 0.015) conditions, with small-tomoderate effect sizes (Cohen's f 2 = 0.122-0.162). The beneficial effect of dalfampridine was not retained 4 weeks after its discontinuation. The rate of accidental falls per month did not differ between the two groups (p = 0.12). Our preliminary findings suggest that dalfampridine can be considered a potential option to treat balance impairment due to MS. Larger sample sizes are needed to verify if the beneficial effect of dalfampridine on balance can be translated into a reduced risk of accidental falls.

Dalfampridine improves slowed processing speed in multiple sclerosis patients with mild motor disability: post hoc analysis of a randomized controlled trial

“… 34 Conversely, temporal network and relay areas the cerebellum and brainstem correlated with cognitive performances. 34 – 36 Prosperini et al 11 in a sub-study of the present trial demonstrated that patients classified as responders to DA according to SDMT improved also their postural sway, thus confirming the hypothesis of an overlap between the two networks connecting balance and information processing speed. 37 , 38 …”

“… 1 , 2 More recent experiences with DA showed that benefits to MS patients may be broader than just on walking speed, with improvements in gait pattern, manual dysfunction, walking endurance, balance, fatigability, cognitive dysfunction and quality of life. 3 – 12 …”

“…1,2 More recent experiences with DA showed that benefits to MS patients may be broader than just on walking speed, with improvements in gait pattern, manual dysfunction, walking endurance, balance, fatigability, cognitive dysfunction and quality of life. [3][4][5][6][7][8][9][10][11][12] Recently, we demonstrated in a randomized, double-blind, placebo-controlled trial the efficacy of DA treatment in improving information processing speed in patients with MS and a documented deficit in this cognitive domain. 13 This was the only randomized, double-blind, placebocontrolled trial of class I which demonstrated the cognitive efficacy of DA with a medium effect size.…”

Approach to Symptom Management in Multiple Sclerosis With a Focus on Wellness

“…A 2021 meta-analysis of nine randomized controlled trials (1691 participants) found additional significant benefits in walking duration, self-reported walking ability on the 12-Item Multiple Sclerosis Walking Scale, finger dexterity on the 9-hole peg test, and cognitive function on the Symbol Digit Modalities Test. 43 Emerging data suggest that dalfampridine improves fatigue, depression, and imbalance in people with MS. 44,45 Dalfampridine may also treat eye movement abnormalities, including horizontal saccadic pursuit due to internuclear ophthalmoplegia, and central and upbeat nystagmus from cerebellar lesions, which are typically treated with gabapentin, memantine, and baclofen. 46,47 Because seizures are a risk of dalfampridine, both a history of seizure and low creatinine clearance (≤50 mL/min) are contraindications for treatment.…”

Pharmacotherapy of cerebellar and vestibular disorders

“…In a recent substudy among patients with multiple sclerosis and impaired sustained attention, a 12-week treatment with dalfampridine was associated with improved standing balance when compared to placebo, in both single-task ( F = 4.80, P = 0.034) and dual-task ( F = 6.42, P = 0.015) conditions. However, such improvement had small-to-moderate effect sizes (Cohen's f 2 = 0.122–0.162) and did not translate directly into a reduced incidence of accidental falls [12 ▪ ]. Patients with spinocerebellar ataxia (SCA) might also benefit from riluzole, while SCA type 3 patients in particular, might benefit from valproic acid [13].…”