SUSTAINED IMPROVEMENTS IN NEUROLOGICAL FUNCTION IN SPINAL-CORD INJURED PATIENTS TREATED WITH ORAL 4-AMINOPYRIDINE - 3 CASES

Preclinical trials of intravenously administered 4-Aminopyridine (4-AP ) have demonstrated transient improvements in neurological function in patients with longstanding spinal cord injury (SCI). The present repo rt describes three patients with SCI who responded favourably in precl inical trials and who were subsequently administered oral (capsule) 4- AP (10 mg b.i.d. or t.i.d.) over a 4 month interval. The three patient s (two male: 1 female) all had incomplete tetraplegia (ASIA levels C a nd D) with the neurological level of the lesion between C5-C7. Followi ng the administration of 4-AP the patients demonstrated marked and sus tained reductions in upper (n = 1) or lower extremity (n = 2) spastici ty. Other clinical benefits of 4-AP were reduced pain (n=1), restored muscle strength (n=3), improved sensation (n=2), voluntary control of bowel function (n=1), and sustained penile tumescence (n=2). The patie nts exhibited improved hand function (n=1), enhanced mobility in trans fers and gait (n=2), with improved energy and endurance. Only trivial side effects (transient light-headedness) were observed. In one case, the enhanced neurological function allowed the patient to stand with s upport for the first time post injury (16 years). The time course of t herapeutic response to the initial dose matched the pharmacokinetic el imination profile derived from serum and urine analysis. There was no evidence of renal or hepatic toxicity with prolonged use, These result s indicate a therapeutic benefit of oral 4-Aminopyridine in the manage ment of various neurological deficits in a select group of SCI patient s.