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Aminopyridines for the treatment of neurologic disorders.

ABSTRACT: PURPOSE OF REVIEW:To identify the different indications for the treatment of neurologic disorders with the potassium channel blockers 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP). RECENT FINDINGS:4-AP is an effective symptomatic treatment for downbeat nystagmus (DBN), episodic ataxia type 2 (EA2) (5-10 mg TID), and impaired gait in multiple sclerosis (MS) (10 mg BID). 3,4-DAP (5 mg/d-20 mg TID) improves symptoms in Lambert-Eaton myasthenic syndrome (LEMS) (randomized placebo-controlled trials for all 4 entities). 4-AP may also be effective in cerebellar gait ataxia of different etiologies (2 case series), upbeat nystagmus, and limb ataxia in MS (single cases). In the recommended dosages, they are well tolerated. The assumed mode of action is a blockade of mainly Kv1.5: in DBN, this increases the excitability of Purkinje cells (PC), and in EA2, restores the precision of resting discharge of PC. In MS, 4-AP improves the conduction of action potentials in demyelinated axons, and in LEMS, 3,4-DAP facilitates the transmission at the neuromuscular endplate by prolonging the action potential duration. SUMMARY:There is sufficient evidence that APs are indicated for the symptomatic treatment of DBN, EA2, gait ataxia due to MS and cerebellar disorders, and LEMS with a reasonable risk-benefit profile.

SUBMITTER: Strupp M

PROVIDER: S-EPMC5310209 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Aminopyridines for the treatment of neurologic disorders.

Strupp Michael M Teufel Julian J Zwergal Andreas A Schniepp Roman R Khodakhah Kamran K Feil Katharina K

Neurology. Clinical practice 20170201 1

<h4>Purpose of review</h4>To identify the different indications for the treatment of neurologic disorders with the potassium channel blockers 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP).<h4>Recent findings</h4>4-AP is an effective symptomatic treatment for downbeat nystagmus (DBN), episodic ataxia type 2 (EA2) (5-10 mg TID), and impaired gait in multiple sclerosis (MS) (10 mg BID). 3,4-DAP (5 mg/d-20 mg TID) improves symptoms in Lambert-Eaton myasthenic syndrome (LEMS) (randomized p ...[more]

PMID: 28243504

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Project description:ObjectiveTo investigate whether nonsurgical treatment can reduce muscle contractures in individuals with neurologic disorders. The primary outcome measure was muscle contractures measured as joint mobility or passive stiffness.Data sourcesEmbase, MEDLINE, Cumulative Index to Nursing and Allied Health, and Physiotherapy Evidence Database in June-July 2019 and again in July 2020.Study selectionThe search resulted in 8020 records, which were screened by 2 authors based on our patient, intervention, comparison, outcome criteria. We included controlled trials of nonsurgical interventions administered to treat muscle contractures in individuals with neurologic disorders.Data extractionAuthors, participant characteristics, intervention details, and joint mobility/passive stiffness before and after intervention were extracted. We assessed trials for risk of bias using the Downs and Black checklist. We conducted meta-analyses investigating the short-term effect on joint mobility using a random-effects model with the pooled effect from randomized controlled trials (RCTs) as the primary outcome. The minimal clinically important effect was set at 5°.Data synthesisA total of 70 trials (57 RCTs) were eligible for inclusion. Stretch had a pooled effect of 3° (95% CI, 1-4°; prediction interval (PI)=-2 to 7°; I 2=66%; P<.001), and robot-assisted rehabilitation had an effect of 1 (95% CI, 0-2; PI=-8 to 9; I 2=73%; P=.03). We found no effect of shockwave therapy (P=.56), physical activity (P=.27), electrical stimulation (P=.11), or botulinum toxin (P=.13). Although trials were generally of moderate to high quality according to the Downs and Black checklist, only 18 of the 70 trials used objective measures of muscle contractures. In 23 trials, nonobjective measures were used without use of assessor-blinding.ConclusionsWe did not find convincing evidence supporting the use of any nonsurgical treatment option. We recommend that controlled trials using objective measures of muscle contractures and a sufficiently large number of participants be performed.

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Aminopyridines for the treatment of neurologic disorders.

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Aminopyridines for the treatment of neurologic disorders.

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