Effectiveness of 4-Aminopyridine for the Management of Spasticity in Spinal Cord Injury: A Systematic Review

Background: Spasticity is a common secondary complication of spinal cord injury (SCI), which can severely impact functional independence and quality of life. 4-Aminopyridine (4-AP) is a potassium channel blocker that has been studied as an intervention for spasticity in individuals with SCI. Objective: To conduct a systematic review of the available evidence regarding the effectiveness of 4-AP for the management of spasticity in individuals with SCI. Methods: A comprehensive literature search was conducted on five electronic databases for articles published in English up to January 2017. Studies were included if (1) the sample size was three or more subjects, (2) the population was >= 50% SCI, (3) the subjects were >= 18 years old, (4) the treatment was 4-AP via any route, and (5) spasticity was assessed before and after the intervention. Subject characteristics, study design, intervention protocol, assessment methods, side effects, adverse events, and outcomes were extracted from selected studies. Randomized controlled trials (RCTs) were evaluated for methodological quality using the Physiotherapy Evidence Database (PEDro) tool. Levels of evidence were assigned using a modified Sackett scale. Results: Nine studies met inclusion criteria with a pooled sample size of 591 subjects. Six studies were RCTs (PEDro = 6-10, Level 1 evidence) and three studies were pre-post tests (Level 4 evidence). There was a wide range in duration, severity, and level of SCI across subjects. Oral 4-AP was investigated in five studies; one study reported significant improvements on the Ashworth Scale (AS), while the remaining four studies found no improvement. Three studies found no significant improvements on the Spasm Frequency Scale. Intravenous 4-AP was investigated in three studies; no significant improvements were found on the AS or in the Reflex Score. Intrathecal 4-AP was investigated in one study, which did not find significant improvements on the AS. Conclusion: There is weak evidence supporting the effectiveness of 4-AP in reducing spasticity post SCI. Future research should utilize contemporary measures of spasticity and address methodological limitations such as small sample sizes.