4-Aminopyridine-sensitive neurologic deficits in patients with spinal cord injury.
4-Aminopyridine (4-AP) is a potassium channel blocking agent with the ability to restore conduction in demyelinated internodes of axons of the spinal cord. The present investigation sought to obtain electrophysiologic evidence of the effect of 4-AP in ameliorating central conduction deficits in a group of patients (n = 6) with spinal cord injury (SCI). The group was selected on the basis of having temperature-dependent central conduction deficits. 4-AP (24-25 mg total dose) was delivered intravenously at 6 mgh-1 or 15 mgh-1 while somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were recorded as indices of central conduction. Two patients exhibited marked increases in the amplitude of cortical SEPs, and in one of these, 4-AP brought about a reduced central conduction time from L1 to cortex. Four patients revealed increased amplitude MEPs with concomitant reduction in latency indicative of enhanced conduction in corticospinal or corticobulbospinal pathways. Two of these patients demonstrated increased voluntary motor unit recruitment following 4-AP. Clinical examination revealed reduced spasticity (n = 2), reduced pain (n = 1), increased sensation (n = 1), improved leg movement (n = 3), and restored voluntary control of bowel (n = 1). These results support the hypothesis that 4-AP induces neurologic benefits in some patients with SCI. They are also consistent with the emerging concept that pharmaceutical amelioration of central conduction deficits caused by focal demyelination may contribute to the management of a select group of patients with compressive or contusive SCI.
Department of Physical Medicine & Rehabilitation, Parkwood Hospital, University of Western Ontario, London, Canada.
K C
KC
Hayes
P J
PJ
Potter
D L
DL
Wolfe
J T
JT
Hsieh
G A
GA
Delaney
A R
AR
Blight
D015761:4-Aminopyridine / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D004558:Electric Stimulation; D004576:Electromyography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005260:Female; D006801:Humans; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000294:innervation; D009431:Neural Conduction / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D011999:Recruitment, Neurophysiological / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D015761:4-Aminopyridine