Potassium channel antagonists 4-aminopyridine and the T-butyl carbamate derivative of 4-aminopyridine improve hind limb function in chronically non-ambulatory dogs; a blinded, placebo-controlled trial.

4-Aminopyridine (4-AP) blocks voltage gated potassium channels, restoring conduction to demyelinated axons and improving function in demyelinating conditions, but its use is associated with adverse effects and benefit in spinal cord injury is limited. Derivatives of 4-AP have been developed to improve clinical efficacy while reducing toxicity. We compared the therapeutic effects of orally administered 4-AP and its t-butyl carbamate derivative (t-butyl) with placebo in dogs that had suffered an acute spinal cord injury that left them chronically paralyzed. Nineteen dogs were entered into the trial, conducted in two-week treatment blocks starting with placebo, followed by random assignment to 4-AP or t-butyl, a washout and then the opposite medication followed by placebo. Investigators and owners were blinded to treatment group. Primary outcome measures included open field gait score (OFS), and treadmill based stepping score and regularity index, with additional secondary measures also considered. Thirteen of 19 dogs completed the protocol. Two were euthanized due to unrelated heath problems, two developed side effects and two were unable to complete for unrelated reasons. Dogs showed significant improvement in supported stepping score (from 17.39 to 37.24% with 4-AP; 16.85 to 29.18% with t-butyl p<0.0001) and OFS (from 3.63 to 4.73 with 4-AP; 3.78 to 4.45 with t-butyl, p = 0.005). Response was individually variable and most dramatic in three dogs that were able to walk without support with treatment. No significant difference was found between 4-AP and t-butyl. No adverse effects were reported with t-butyl but gastrointestinal upset and seizures were observed in two dogs with 4-AP. In conclusion, both 4-AP and t-butyl significantly improved supported stepping ability in dogs with chronic spinal cord injury with no adverse effects noted with t-butyl. Drug response varied widely between individuals, highlighting the need to understand the factors that influence canine and human patients' response to therapy.

The cutaneous trunci muscle reflex: a predictor of recovery in dogs with acute thoracolumbar myelopathies caused by intervertebral disc extrusions.

OBJECTIVE: To determine whether changes in the cutaneous trunci muscle (CTM) reflex are an early predictor of outcome in dogs with severe acute thoracolumbar intervertebral disc extrusion (IVDE). STUDY DESIGN: Multicenter prospective cohort study. ANIMALS: Dogs (n = 36) with acute IVDE causing paraplegia, loss of nociception in pelvic limbs and tail, and an abnormal CTM reflex postoperatively. METHODS: The caudal border of the CTM reflex was established 24 hours after surgery and at discharge, and was reported as moving cranially, caudally, or staying static. Dogs were re-evaluated at 12-20 weeks and at 7-36 months postoperatively. Outcome was classified as improved or unimproved, successful or unsuccessful, and ascending myelomalacia or not, and compared with early movement of the CTM reflex by construction of contingency tables and performing a Fisher's exact test. RESULTS: By discharge (mean, 4.7 days; SD = 2.10), CTM reflex progression was caudal in 19 dogs, static in 11, and cranial in 6. Five of 6 dogs with cranial movement developed ascending myelomalacia (P < .0001). Seventeen of 19 dogs with caudal movement showed an improvement by 12-20 weeks (P = .0046) and none developed ascending myelomalacia (P = .0013). CONCLUSIONS: Postoperative changes of the caudal border of the CTM reflex are an early indicator of outcome in dogs with severe acute IVDE. Cranial movement of the CTM reflex is significantly associated with the development of ascending myelomalacia. Caudal movement is significantly associated with improvement, but not associated with a long-term successful outcome.

The sensory field and repeatability of the cutaneous trunci muscle reflex of the dog.

OBJECTIVE: To describe the cutaneous trunci muscle (CTM) reflex in dogs. STUDY DESIGN: Prospective descriptive study. ANIMALS: Normal dogs (n = 155) and 10 dogs with thoracolumbar myelopathies. METHODS: The CTM reflex caudal border was assessed from the ilial crests moving cranially until a CTM contraction was elicited. The lateral borders were evaluated at 4 levels and the distance from the midline to the lateral border was expressed asa percentage of the trunk hemicircumference. The caudal border was assessed in 10 dogs with myelopathies by 4 different observers and by 1 observer on 3 occasions;the inter- and intraobserver kappa coefficient was calculated. RESULTS: The CTM reflex was elicited in all dogs. Its caudal border was at L5 or L6 in 153 dogs and at L1 and L3 in 2 dogs. The lateral field of the reflex occupied>50%of the hemicircumference of the trunk at each level tested. The mean difference in measurement of the reflex caudal border was 0.55 cm between observers and 0.28 cm for the same observer. The inter- and intraobserver kappa coefficient was 0.67 and 0.87, respectively. CONCLUSIONS: The CTM reflex is elicited caudal to L5 in most normal dogs, and the lateral sensory field extends to 50% or more of the circumference of the trunk.Inter- and intraobserver differences in assessment of the caudal border are low.