title: High doses of 4-aminopyridine improve functionality in chronic complete spinal cord injury patients with MRI evidence of cord continuity.
abstract: OBJECTIVE
  Many patients with complete spinal cord injury (SCI) exhibit demyelinated and poorly myelinated nerve fibers traversing the lesion site. Conventional doses of 4-aminopyridine (4-AP, 30 mg/day) have shown to provide no or minor functional improvement in these patients. We undertook this study to test the functional effect of high doses of 4-AP on patients with chronic complete SCI with cord continuity at the site of injury demonstrated by magnetic resonance imaging.
  
  
  METHODS
  Fourteen patients were included in a double-blind, randomized, placebo-controlled trial followed by an open label long-term follow-up. Initially, patients received 4-AP or placebo orally, with 4-AP being increased gradually (5 mg/week) to reach 30 mg/day. For long-term treatment, 4-AP was increased 10 mg periodically according to negative electroencephalogram and blood test abnormalities and minor adverse reactions. Pre-treatment, 12 and 24 weeks of the controlled trial, and 6 and 12 months of open trial evaluations, or with the highest doses reached were obtained.
  
  
  RESULTS
  Three of 12 patients were able to walk with the assistance of orthopedic devices, 1/12 became incomplete (AIS B), 7/12 improved their somatosensory evoked potentials, 5/12 had sensation and control of bladder and anal sphincters, and 4/9 male patients had psychogenic erection.
  
  
  CONCLUSIONS
  Positive changes were seen mainly in patients with cyst (4/5) or atrophy (3/5) of the injury site. Two patients withdrew from the study: one had seizures and one had intolerant adverse reactions. We conclude that high doses of 4-AP in the studied population produced several functional benefits not observed using lower doses.
authors.affiliation: Medical Research Unit for Neurological Diseases, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico, D.F., Mexico. igrijalvao@cis.gob.mx
authors.forename: Israel
authors.initials: I
authors.lastname: Grijalva
authors.forename: Angélica
authors.initials: A
authors.lastname: García-Pérez
authors.forename: Jenaro
authors.initials: J
authors.lastname: Díaz
authors.forename: Sergio
authors.initials: S
authors.lastname: Aguilar
authors.forename: Dolores
authors.initials: D
authors.lastname: Mino
authors.forename: Efraín
authors.initials: E
authors.lastname: Santiago-Rodríguez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Guizar-Sahagún
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
authors.forename: Héctor
authors.initials: H
authors.lastname: Maldonado-Julián
authors.forename: Ignacio
authors.initials: I
authors.lastname: Madrazo
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010919:Placebos / Q000627:therapeutic use; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D020127:Recovery of Function; D013116:Spinal Cord / Q000033:anatomy & histology* / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D010919:Placebos; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine