Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury: A double-blinded, placebo-controlled crossover trial

4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been shown to reduce the latency and increase the amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) in patients with chronic spinal cord injury (SCI). These effects on MEPs are thought to reflect enhanced conduction in long tract axons brought about by overcoming conduction deficits due to focal demyelination and/or by enhanc ing neuroneuronal transmission at one or more sites of the neuraxis. The pr esent study was designed to obtain further evidence of reduced central moto r conduction time (CMCT) and to determine whether MEPs could be recorded fr om paretic muscles in which they were not normally elicited. MEPs were elic ited with TMS being delivered to subjects (n = 25) pre- and post-administra tion of 4-AP (10 mg capsule) or placebo. The principal finding was that 4-A P lowered the stimulation threshold, increased the amplitude and reduced th e latency of MEPs in all muscles tested, including those that were unimpair ed, but did not alter measures of the peripheral nervous system (i.e., M-wa ve, H-reflex, F-wave). These 4-AP-induced changes in MEPs were significantl y greater than those seen with placebo (p < 0.05). The primary implication of these results is that a low dose of 4-AP (immediate-release formulation) appears to improve the impaired central motor conduction of some patients with incomplete SCI. This is most likely attributable to overcoming conduct ion deficits at the site of injury but may also involve an increase in cort ical excitability.