2019 journal article
Predictors of Response to 4-Aminopyridine in Chronic Canine Spinal Cord Injury
JOURNAL OF NEUROTRAUMA, 36(9), 1428–1434.
4-Aminopyridine (4AP), a potassium channel antagonist, can improve hindlimb motor function in dogs with chronic thoracolumbar spinal cord injury (SCI); however, individual response is variable. We hypothesized that injury characteristics would differ between dogs that do and do not respond to 4AP. Our objective was to compare clinical, electrodiagnostic, gait, and imaging variables between dogs that do and do not respond to 4AP, to identify predictors of response. Thirty-four dogs with permanent deficits after acute thoracolumbar SCI were enrolled. Spasticity, motor and sensory evoked potentials (MEPs, SEPs), H-reflex, F-waves, gait scores, and magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) were evaluated at baseline and after 4AP administration. Baseline variables were assessed as predictors of response; response was defined as ≥1 point change in open field gait score. Variables were compared pre- and post-4AP to evaluate 4AP effects. Fifteen of 33 (45%) dogs were responders, 18/33 (55%) were non-responders and 1 was eliminated because of an adverse event. Pre-H-reflex threshold <1.2 mA predicted non-response; pre-H-reflex threshold >1.2 mA and Canine Spasticity Scale overall score <7 were predictive of response. All responders had translesional connections on DTI. MEPs were more common post-4AP than pre-4AP (10 vs. 6 dogs) and 4AP decreased H-reflex threshold and increased spasticity in responders. 4-AP impacts central conduction and motor neuron pool excitability in dogs with chronic SCI. Severity of spasticity and H-reflex threshold might allow prediction of response. Further exploration of electrodiagnostic and imaging characteristics might elucidate additional factors contributing to response or non-response.