title: Efficacy and safety of 4-aminopyridine in patients with long-term spinal cord injury: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  To study the efficacy and safety of 4-aminopyridine (4-AP), and to document sensorimotor changes after discontinuation of the drug in patients with long-term spinal cord injury.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Clinical research unit.
  
  
  METHODS
  Twenty-seven patients with long-term spinal cord injury.
  
  
  METHODS
  Patients were randomized to receive either oral 4-AP 5 mg/day, which was increased by 5 mg/week to a maximum dosage of 30 mg/day, or placebo for 12 weeks. They switched to the opposite treatment for the next 12 weeks.
  
  
  RESULTS
  Twenty-five patients finished the study. The results from the first 12 weeks were used to test efficacy. Positive gains in motor function, sensation, and independence occurred more frequently in patients receiving 4-AP (69%) than those receiving placebo (46%). Significant functional improvement was also noted in those treated with 4-AP (chi2, p=0.042). When each evaluation scale was considered separately, significant improvement was seen only in motor function (4-AP 92% vs placebo 46%, Fisher exact test, p=0.03). Persistent effects of the drug were assessed at week 24 in the group that initially received 4-AP. A persistent, significant 4-AP effect was observed in evaluations of sensation and independence (67% and 83% of patients, respectively; Wilcoxon signed rank test, p=0.032 and 0.042, respectively). Fourteen (56%) patients had 26 adverse reactions. One moderate adverse reaction--posterior tibial artery vasospasm--and 25 mild adverse reactions, such as dry mouth, dizziness, nausea, gastritis, oral and peripheral paresthesia, resolved adequately. Six (24%) patients experienced transitory alterations of enzyme levels (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and creatine kinase) and thrombocytopenia.
  
  
  CONCLUSIONS
  Patients who received 4-AP showed significant improvement in motor function, and a persistent effect on sensation and independent function occurred. The drug is safe; however, after starting 4-AP therapy, patients must be carefully monitored for the possible occurrence of peripheral vasospasm.
authors.affiliation: Research Medical Unit for Neurological Diseases, Specialties Hospital, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México City, México. igrijalvao@yahoo.com
authors.forename: Israel
authors.initials: I
authors.lastname: Grijalva
authors.forename: Gabriel
authors.initials: G
authors.lastname: Guízar-Sahagún
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
authors.forename: Dolores
authors.initials: D
authors.lastname: Mino
authors.forename: Héctor
authors.initials: H
authors.lastname: Maldonado-Julián
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Vidal-Cantú
authors.forename: Antonio
authors.initials: A
authors.lastname: Ibarra
authors.forename: Omar
authors.initials: O
authors.lastname: Serra
authors.forename: Hermelinda
authors.initials: H
authors.lastname: Salgado-Ceballos
authors.forename: Rita
authors.initials: R
authors.lastname: Arenas-Hernández
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012684:Sensory Thresholds / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine