P.J. Early

Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial

BACKGROUND There is little evidence-based information available to guide treatment of refractory epilepsy in dogs. The antiepileptic drug levetiracetam (LEV) is administered to dogs, although its safety and efficacy are unknown. OBJECTIVE To evaluate the safety and efficacy of LEV as adjunctive therapy for refractory epilepsy in dogs. ANIMALS Thirty-four client-owned dogs with idiopathic epilepsy. METHODS Randomized, blinded trial involving dogs resistant to phenobarbital and bromide. Dogs received LEV (20 mg/kg PO q8h) or placebo for 16 weeks, and after a 4-week washout were crossed over to the alternate treatment for 16 weeks. Owners kept records on seizure frequency and adverse events. Hemogram, chemistry profile, urinalysis, and serum antiepileptic drug concentrations were evaluated at established intervals. RESULTS Twenty-two (65%) dogs completed the study. Weekly seizure frequency during the 1st treatment period decreased significantly during LEV administration relative to baseline (1.9 ± 1.9 to 1.1 ± 1.3, P = .015). The reduction in seizures with LEV was not significant when compared to placebo (1.1 ± 1.3 versus 1.5 ± 1.7, P = .310). The most common adverse event was ataxia, with no difference in incidence between LEV and placebo (45 versus 18%, P = .090). No changes in laboratory parameters were identified and owners reported an improved quality of life (QOL) with LEV compared to placebo (QOL score 32.7 ± 4.3 versus 29.4 ± 4.5, P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE Adjunctive treatment with LEV appears safe in epileptic dogs. Efficacy of LEV over placebo was not demonstrated, although the power of the study was limited. Further evaluation of LEV as treatment for epilepsy in dogs is warranted.

A Placebo-Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation

Background Acute intervertebral disk herniation (IVDH) is a common cause of spinal cord injury in dogs and currently there is no proven medical treatment to counter secondary injury effects. Use of methylprednisolone sodium succinate (MPSS) or polyethylene glycol (PEG) as neuroprotectants is advocated but controversial because neither treatment has been tested in placebo‐controlled, randomized, blinded trials in dogs. Hypothesis Polyethylene glycol will improve the outcome of severe spinal cord injury caused by IVDH compared to MPSS or placebo. Animals Client‐owned dogs with acute onset of thoracolumbar IVDH causing paralysis and loss of nociception for <24 hours. Methods Dogs were randomized to receive MPSS, PEG, or placebo; drugs appeared identical and group allocation was masked. Drug administration was initiated once the diagnosis of IVDH was confirmed and all dogs underwent hemilaminectomy. Neurologic function was assessed 2, 4, 8, and 12 weeks postoperatively using an open field gait score (OFS) as the primary outcome measure. Outcomes were compared by the Wilcoxon rank sum test. Results Sixty‐three dogs were recruited and 47.6% recovered ambulation. 17.5% developed progressive myelomalacia but there was no association with group. There was no difference in OFS among groups. Although full study power was not reached, conditional power analyses indicated the futility of continued case recruitment. Conclusions This clinical trial did not show a benefit of either MPSS or PEG in the treatment of acute, severe thoracolumbar IVDH when used as adjunctive medical treatment administered to dogs presenting within 24 hours of onset of paralysis.

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 Fishers 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.

Long‐Term Effect of Cervical Distraction and Stabilization on Neurological Status and Imaging Findings in Giant Breed Dogs With Cervical Stenotic Myelopathy

OBJECTIVES To assess long-term clinical and imaging outcomes in giant breed dogs with cervical stenotic myelopathy treated surgically. STUDY DESIGN Retrospective case series. ANIMALS Dogs (n = 7). METHODS All dogs had lateral or dorsolateral cord compression at 1 or more sites and were treated with cervical distraction and stabilization using PMMA plugs. Four dogs had follow-up CT or CT/myelography performed at least 6 months postoperatively. Spinal canal stenosis measurements were compared between pre- and postoperative CT images. Long-term clinical neurologic re-evaluation ranged from 4 to 7 years. Outcome was considered positive, satisfactory, or negative. Recurrence was defined as signs of a cervical myelopathy in dogs that initially improved or had stable disease postoperatively. RESULTS All dogs had immediate postoperative improvement. Recurrence (4 months to 4 years postoperatively) occurred in 3 dogs that had multiple sites of compression. Long-term outcome was positive in 4 of 7 dogs. Postoperative imaging revealed subjective regression of bony proliferation at surgical sites in 2 of 4 dogs that improved clinically but morphometric data showed no change in canal measurements. An adjacent site lesion was confirmed in 1 dog. CONCLUSIONS Distraction and stabilization with PMMA plugs and bone grafts is a safe surgical option for giant breed dogs with CSM with a single site of lateral or dorsolateral compression. Long-term recurrence was common among dogs with multiple sites of compression. Follow-up of 4 years or more among a larger population is indicated to fully assess implications of surgical intervention and determine recurrence rates.Objectives To assess long-term clinical and imaging outcomes in giant breed dogs with cervical stenotic myelopathy treated surgically. Study Design Retrospective case series. Animals Dogs (n = 7). Methods All dogs had lateral or dorsolateral cord compression at 1 or more sites and were treated with cervical distraction and stabilization using PMMA plugs. Four dogs had follow-up CT or CT/myelography performed at least 6 months postoperatively. Spinal canal stenosis measurements were compared between pre- and postoperative CT images. Long-term clinical neurologic re-evaluation ranged from 4 to 7 years. Outcome was considered positive, satisfactory, or negative. Recurrence was defined as signs of a cervical myelopathy in dogs that initially improved or had stable disease postoperatively. Results All dogs had immediate postoperative improvement. Recurrence (4 months to 4 years postoperatively) occurred in 3 dogs that had multiple sites of compression. Long-term outcome was positive in 4 of 7 dogs. Postoperative imaging revealed subjective regression of bony proliferation at surgical sites in 2 of 4 dogs that improved clinically but morphometric data showed no change in canal measurements. An adjacent site lesion was confirmed in 1 dog. Conclusions Distraction and stabilization with PMMA plugs and bone grafts is a safe surgical option for giant breed dogs with CSM with a single site of lateral or dorsolateral compression. Long-term recurrence was common among dogs with multiple sites of compression. Follow-up of 4 years or more among a larger population is indicated to fully assess implications of surgical intervention and determine recurrence rates.

In vitro biomechanical comparison of the flexion/extension mobility of the canine lumbosacral junction before and after dorsal laminectomy and partial discectomy.

The purpose of this canine cadaver study was to evaluate the range of flexion and extension of the canine lumbosacral spine before and after dorsal laminectomy and partial discectomy. Using a cantilever biomechanical system, a 3Nm bending moment was applied to flex and extend the lumbosacral segment. Motion in L7 (total range of motion [ROM] and neutral zone motion [NZ]) was recorded via a rotational potentiometer. There was a significant increase in NZ and ROM after the decompressive procedures (NZ before decompression 6.0±1.2°; NZ after decompression 7.6±2.1°; ROM before decompression 32.8±6.4°; ROM after decompression 40.2±5.6°). It is unknown whether dorsal laminectomy and partial discectomy will induce the same increased motion in clinical cases. Dogs with lumbosacral subluxation, active dogs with little radiographic degenerative changes and working dogs could benefit from lumbosacral stabilization. This cadaver study demonstrated that dorsal laminectomy and partial discectomy at the lumbosacral junction does lead to significant spinal instability.

Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial

Background Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. Hypothesis Cranberry extract reduces risk of bacteriuria in dogs after acute TL‐IVDH. Animals Client‐owned dogs with acute onset TL‐IVDH causing nonambulatory status. Methods Randomized, placebo‐controlled, blinded, prospective clinical trial. Dogs with acute TL‐IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi‐squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. Results Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). Conclusions and Clinical Importance This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Recovery of stepping and coordination in dogs following acute thoracolumbar intervertebral disc herniations.

Prospective data on the recovery of coordination in dogs suffering acute thoracolumbar intervertebral disc herniations (TL-IVDH) are limited. The purpose of this study was to use treadmill based and open field scores (OFS) to quantify recovery of stepping ability and forelimb, hindlimb coordination in the 6 weeks following surgical decompression of dogs with TL-IVDH. Sixty-three dogs were grouped at presentation as grades 3 (non-ambulatory paraparetic), 4 (paraplegic) or 5 (paraplegic without pain sensation) and were evaluated 2, 4, and 6 weeks post-operatively. Stepping scores and Regularity Index (RI), a measure of coordination, were calculated from treadmill walking, and an OFS incorporating supported and unsupported walking was assigned. Outcomes for the three measures were compared between groups and correlation between scoring methods was assessed. Grade 3 and 4 dogs recovered ambulation by 2 weeks, reaching median stepping scores of 96 and 90% by 6 weeks, respectively. Recovery of coordination differed between groups 3 and 4 with median RI scores of 93.9% and 63%, respectively, by 6 weeks. Eight grade 5 dogs failed to recover independent ambulation by 6 weeks. Nine dogs recovered with scores that were significantly worse than the grade 3 and 4 dogs at 6 weeks for stepping score (P < 0.001) and RI (P < 0.001). OFS correlated closely with stepping and RI scores and each group was significantly different using this ordinal scale. In conclusion, recovery of coordination was incomplete in dogs that showed good recovery of stepping. The data generated could be used for clinical trial design.

Associations Between Anesthetic Variables and Functional Outcome in Dogs With Thoracolumbar Intervertebral Disk Extrusion Undergoing Decompressive Hemilaminectomy

Background Outcome of acute experimental spinal cord injury is strongly associated with tissue perfusion and oxygenation. Cardiopulmonary depression could affect outcome in dogs undergoing general anesthesia for surgical treatment of thoracolumbar intervertebral disk extrusion (IVDE). Hypothesis/Objectives To evaluate the effects of general anesthesia on functional outcome in dogs undergoing surgery to treat thoracolumbar IVDE. Animals Eighty‐four client‐owned dogs with acute thoracolumbar IVDE treated by decompressive hemilaminectomy. Methods Exploratory, retrospective observational study. Medical records were reviewed for clinical presentation and anesthetic monitoring variables, including duration of anesthesia and surgery, hypotension, bradycardia, temperature, and respiratory parameters. Multivariable regression tree analysis was performed to explore associations between anesthetic variables and functional outcome scores after 6 weeks, as well as return to ambulatory status. Results Episodes of bradycardia (69%) and hypotension (57%) were frequent. Across all outcome measures, regression tree analysis highlighted functional grade at presentation as the primary determining factor, and among pain perception negative dogs, there was a possible association between increased duration of surgery and poorer outcome. In dogs with intact pain perception, duration of bradycardia, mean body temperature, and mean end‐tidal carbon dioxide were highlighted. Conclusions and Clinical Importance Exploratory statistical methods can facilitate hypothesis‐generating studies to inform prospective investigations in veterinary medicine. Although the mechanism is uncertain, increased duration of surgery might be associated with poorer outcome in pain perception negative dogs with thoracolumbar IVDE.

Clinical and Diagnostic Imaging Features of Brain Herniation in Dogs and Cats.

Background Quantification of brain herniation on MRI and its immediate clinical implications are poorly described. Objectives Define the normal position of caudal fossa structures on brain MRIs in dogs and cats utilizing morphometry, compare this to dogs and cats with caudal transtentorial herniation (CTH), foramen magnum herniation (FMH) or both identified on MRI, and investigate associations between herniation severity, clinical signs, and 24‐hour outcome. Animals Ninety‐two controls (66 dogs, 26 cats), 119 cases with herniation (88 dogs, 31 cats). Methods Retrospective case series. The MRI database was searched for controls with normal brain anatomy and cases with brain herniation. Morphometry in controls established TTX (transtentorial to rostroventral cerebellum) to quantify CTH and FMX (caudoventral cerebellum to foramen magnum) to quantify FMH. Measurements were compared between cases and controls. Correlations with specific clinical variables and outcome were investigated. Results Measurements in medium/large control dogs versus small dog and cat controls were significantly different (P < .001, TTX: −0.46, −0.305, −0.3, FMX: 0.695, 0.27, 0.25, respectively). 119/1564 (7.6%) cases that underwent brain imaging had brain herniation. TTX and FMX were significantly different between controls and cases with CTH or FMH (P < .001). 67/89 (75%) cases with supratentorial lesions had no signs directly attributable to herniation. 71/119 (60%) had a normal anesthetic recovery. TTX was significantly associated with 24‐hour survival (P < .001). Conclusions and clinical importance Brain herniation can be quantified on MRI. Clinical signs directly attributable to brain herniation commonly are absent, and more severe CTH based on TTX is associated with a worse short‐term outcome.

The effect of electromagnetic fields on postoperative pain and locomotor recovery in dogs with acute, severe thoracolumbar intervertebral disc extrusion: a randomized placebo-controlled, prospective clinical trial.

Spinal cord injury (SCI) attributed to acute intervertebral disc extrusions (IVDEs) is common in dogs and is treated by surgical decompression. Dogs with sensorimotor complete injuries have an incomplete recovery. Pulsed electromagnetic fields (PEMFs) reduce post-operative pain through anti-inflammatory effects and there is growing evidence for neuroprotective effects. This randomized, controlled clinical trial evaluated the effect of PEMF on post-operative pain and neurological recovery in dogs with surgically treated sensorimotor complete SCI attributed to acute IVDE. Sixteen dogs with surgically treated complete thoracolumbar SCI were randomized to receive PEMF (15 min every 2 h for 2 weeks then twice-daily for 4 weeks) or placebo starting immediately after diagnosis. The primary outcome was gait score at 2 weeks. Secondary measures of gait, pain perception, and proprioceptive function were evaluated at 2 and 6 weeks. Plasma glial fibrillary acidic protein (GFAP) concentration was measured as an SCI biomarker. Post-operative pain was quantified by measuring mechanical sensory thresholds (MSTs) at control and surgical sites. There was no significant difference in demographics or GFAP concentration between the two groups at trial entry. There was no difference in primary outcome or in secondary measures of gait, but proprioceptive placing was significantly better at 6 weeks and GFAP concentrations were significantly lower at 2 weeks in the PEMF group. MSTs were significantly higher in the PEMF-treated group. We conclude that PEMF reduced incision-associated pain in dogs post-surgery for IVDE and may reduce extent of SCI and enhance proprioceptive placing. Larger clinical trials are warranted.