Abstract
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 report describes three patients with SCI who responded favourably in preclinical 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 patients (two male: 1 female) all had incomplete tetraplegia (ASIA levels C and D) with the neurological level of the lesion between C5-C7. Following the administration of 4-AP the patients demonstrated marked and sustained reductions in upper (n=1) or lower extremity (n=2) spasticity. 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 patients exhibited improved hand function (n=1), enhanced mobility in transfers and gait (n=2), with improved energy and endurance. Only trivial side effects (transient lightheadedness) were observed. In one case, the enhanced neurological function allowed the patient to stand with support for the first time post injury (16 years). The time course of therapeutic response to the initial dose matched the pharmacokinetic elimination profile derived from serum and urine analysis. There was no evidence of renal or hepatic toxicity with prolonged use. These results indicate a therapeutic benefit of oral 4-Aminopyridine in the management of various neurological deficits in a select group of SCI patients.
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Potter, P., Hayes, K., Hsieh, J. et al. Sustained improvements in neurological function in spinal cord injured patients treated with oral 4-aminopyridine: three cases. Spinal Cord 36, 147–155 (1998). https://doi.org/10.1038/sj.sc.3100559
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DOI: https://doi.org/10.1038/sj.sc.3100559
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