Safety and efficacy of 4-aminopyridine in humans with spinal cord injury: A long-term, controlled trial

Study Objective. To determine the effects of the long-term administration o f 4-aminopyridine (4-AP) on sensorimotor function in humans with longstandi ng spinal cord injury (SCI). Design. Randomized, open-label, active-treatment control, dosage-blinded st udy. Setting. University-affiliated, tertiary-level care, Department of Veterans Affairs Medical Center. Patients. Twenty-one healthy men and women outpatients suffering from traum atic SCI (14 tetraplegic, 7 paraplegic) for 2 years or more. Interventions. Dosages of an immediate-release formulation of 4-AP were tit rated. 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 stati stically significant increases at 3 months. Maximal expiratory pressure, ma ximal inspiratory pressure, forced vital capacity, and forced expiratory vo lume in 1 second showed clinically meaningful and/or statistically signific ant increases among patients receiving 4-AP 30 mg/day. These subjects also had significant decreases in spasticity (modified Ashworth Scale). Serial b iochemical 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 as sociated with improvement in and recovery of sensory and motor function, en hanced pulmonary function, and diminished spasticity in patients with long- standing SCI. Lf-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 ou tcome measures.