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Safety and Efficacy of 4‐Aminopyridine in Humans with Spinal Cord Injury: A Long‐Term, Controlled Trial

1999; Wiley; Volume: 19; Issue: 6 Linguagem: Inglês

10.1592/phco.19.9.713.31540

1875-9114

Jack L. Segal, Mayank Pathak, Jesús Pérez Hernández, Peter L. Himber, Sherry R. Brunnemann, Richard S. Charter,

Stroke Rehabilitation and Recovery

Study Objective. To determine the effects of the long‐term administration of 4‐aminopyridine (4‐AP) on sensorimotor function in humans with longstanding spinal cord injury (SCI). Design. Randomized, open‐label, active‐treatment control, dosage‐blinded study. Setting. University‐affiliated, tertiary‐level care, Department of Veterans Affairs Medical Center. Patients. Twenty‐one healthy men and women outpatients suffering from traumatic SCI (14 tetraplegic, 7 paraplegic) for 2 years or more. Interventions. Dosages of an immediate‐release formulation of 4‐AP were titrated. At 3 months, 16 subjects were receiving 4‐AP 30 mg/day (high dose); 5 subjects were receiving 4‐AP 6 mg/day (low dose) and served as an active‐treatment control group. Measurements and Main Results. Composite motor and sensory scores had statistically significant increases at 3 months. Maximal expiratory pressure, maximal inspiratory pressure, forced vital capacity, and forced expiratory volume in 1 second showed clinically meaningful and/or statistically significant increases among patients receiving 4‐AP 30 mg/day. These subjects also had significant decreases in spasticity (modified Ashworth Scale). Serial biochemical profiles and electroencephalographs were unchanged from baseline, and no clinically significant drug toxicity was encountered. Conclusions. Long‐term oral administration of immediate‐release 4‐AP was associated with improvement in and recovery of sensory and motor function, enhanced pulmonary function, and diminished spasticity in patients with long‐standing SCI. 4‐Aminopyridine appears to be safe and relatively free from toxicity when administered orally over 3 months. Each patient who received immediate‐release 4‐AP 30 mg/day showed a response in one or more of the outcome measures.