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.

Polymicrogyria in standard poodles.

BACKGROUND: Polymicrogyria is a disorder of cerebrocortical migration resulting in increased numbers of small, disorganized gyri. This disorder occurs in Standard Poodles and in cattle. OBJECTIVES: To describe the clinical, electroencephalographic, imaging, and histopathologic features in poodles with polymicrogyria. ANIMALS: Five Standard Poodles with histologically confirmed polymicrogyria. METHODS: Retrospective case series. Cases were obtained by personal communication with 1 of 2 authors (TJVW, DPO). RESULTS: All dogs had cortical blindness and other neurologic abnormalities including gait and behavioral changes. Magnetic resonance imaging of 3 dogs showed multiple disorganized gyri, which were especially apparent on T2-weighted dorsal plane images. Electroencephalogram (EEG) of 1 dog revealed epileptiform discharges, including both spike and spike and wave discharges with voltage maximum potentials over the parietal/occipital region. The EEG supported that the repetitive behavior displayed by the dog was a complex partial motor seizure. One dog had concurrent hydrocephalus. All dogs had occipital lobe involvement and 2 dogs had involvement of other lobes. CLINICAL IMPORTANCE: The cases presented here demonstrate a larger age range (7 weeks to 5 years) and a decreased frequency of associated hydrocephalus when compared with the previous report.

Using the World Wide Web to enhance the problem-solving skills of third-year veterinary students.

A Web site was created for the small animal problem-solving elective at Virginia Tech. In addition to signalment, history, physical examination findings, and results of routine laboratory tests, students were able to view images of cytologic and histologic specimens, radiographs, and endoscopic findings and hear examples of breath and cardiac sounds. Students commented that the availability of Web-based case materials allowed them increased opportunities to practice problem-solving skills.

Post-operative computed tomography in two dogs with cerebral meningioma.

Post-operative computed tomography (CT) has been described as a technique for diagnosing incomplete resection or recurrence of cerebral neoplasms in humans. The characteristics of immediate postoperative CT images in dogs with intracranial pathology are unknown. This report describes findings from preoperative, immediate post-operative, and 4 week to 9 month follow-up CT examinations in two dogs with histologically-confirmed cerebral meningiomas. In images of one dog after surgery there was mild contrast enhancement of the tissue surrounding the surgical site. This enhancement had resolved in later images and was probably the result of surgically induced trauma. In post operative images of the other dog there was significant hyperattenuation of the tissues around the surgical site. In post contrast images there was increased enhancement that was evident in later images. These findings, although not supported by necropsy, probably indicate incomplete excision of the tumor.

Subclinical CT abnormalities in the lumbosacral spine of older large-breed dogs.

Computed tomography (CT) of the L5-S3 vertebral levels was performed in six, large-breed dogs presented for problems unrelated to the lumbosacral spine. All dogs were asymptomatic for lumbosacral stenosis on neurologic examination. Breeds included German Shepherd, Golden Retriever, Boxermix and Belgian Malinois. Ages ranged from 5-12 years. Five out of six dogs exhibited CT abnormalities. Among the 18 disc levels examined, the most common findings were idiopathic stenosis, loss of vertebral canal epidural fat, and nerve tissue displacement. Less common abnormalities were vertebral canal or foraminal bone proliferation, loss of intervertebral foramen fat, vertebral canal disc bulging, degenerative articular process joint disease, transitional vertebra, dural ossification, foraminal disc bulging, Schmorl's nodes, calcified extruded disc fragment, and sacroiliac joint osteophytes. Vertebral subluxation was absent in all dogs. Findings indicate that some lumbosacral CT abnormalities may be clinically insignificant, especially in older dogs.

Neuropathologic effects of phenylmethylsulfonyl fluoride (PMSF)-induced promotion and protection in organophosphorus ester-induced delayed neuropathy (OPIDN) in hens.

The serine/cysteine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) has been used both to promote and to protect against neuropathic events of organophosphorus-induced delayed neuropathy (OPIDN) in hens (Veronesi and Padilla, 1985; Pope and Padilla, 1990; Lotti et al., 1991; Pope et al., 1993; Randall et al., 1997). This study is the first to expand upon this work by using high resolution microscopy provided by epoxy resin embedding and thin sectioning to evaluate neuropathological manifestations of promotion and protection, and to correlate them with associated clinical modifications. To evaluate dose-related effects of OPIDN, single phenyl saligenin phosphate (PSP) dosages of 0.5, 1.0, or 2.5 mg/kg were administered to adult hens. PMSF (90 mg/kg) was given either 4 hours after (for promotion) or 12 hours prior to (for protection) PSP administration. Clinical signs and pathologic changes in the biventer cervicis nerve, which is uniquely sensitive to OPIDN (El-Fawal et al., 1988), were monitored. PSP alone, 2.5 mg/kg, caused severe OPIDN (terminal clinical score 7.5 +/- 1.0 [0-8 scale]; neuropathology score 2.7 +/- 0.3 [0-4 scale, based on myelinated fiber degeneration]). PMSF given 12 hours prior to PSP gave complete protection (clinical and neuropathology scores of 0; p<0.0001 compared to PSP alone). Signs and lesions of OPIDN were absent following 0.5 mg/kg PSP alone, but PMSF given 4 hours after PSP potentiated its neurotoxic effects (all hens had clinical scores of 4.0 and the average neuropathology score was 3.5 +/- 0.3; p<0.0001 compared to PSP alone). Although quantitative differences were noted, qualitative differences among nerves from hens with OPIDN were not evident, either with light or electron microscopy. At the time of sacrifice, there was a statistically linear relationship (r2 = 0.76) between the clinical scores on the last day of observation and the neuropathology scores (p<0.0001). This study demonstrates that the degree of peripheral nerve myelinated fiber degeneration correlates with clinical deficits in PMSF-induced potentiation of and protection against OPIDN.

Evaluation of canine lumbosacral stenosis using intravenous contrast-enhanced computed tomography.

The objective of this study was to evaluate intravenous contrast-enhanced computed tomography as a technique for predicting the within-level location(s) of compressive soft tissues in the canine lumbosacral spine. Pre-operative intravenous contrast-enhanced computed tomography of the L5-S3 vertebral levels was performed in 12 consecutive large breed dogs with lumbosacral stenosis. The images were evaluated for enhancement of soft tissues by two radiologists who were unaware of the surgical findings. For each within-level location (dorsal canal, ventral canal, right lateral recess, left lateral recess) enhancement was classified as present, absent or equivocal. The results were compared with the results of surgical exploration and histopathology of excised tissues. The positive predictive values of intravenous contrast-enhanced computed tomography for compressive soft tissues involving the dorsal canal, ventral canal and lateral recesses were 83%, 100%, and 81% respectively. Negative predictive values for compressive soft tissues involving these locations were 29%, 50%, and 40% respectively.

Technique of, and complications attributable to, repeated hyperosmotic blood-brain barrier disruption in dogs.

OBJECTIVE: To design a repeatable technique for reversible, hyperosmotic blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD. ANIMALS: 10 healthy adult dogs. PROCEDURE: Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery of 10 dogs. Blood-brain barrier disruption was achieved in 5 dogs, using intracarotid infusion of mannitol. Five control dogs received only saline solution. After recovery, dogs were monitored for clinical signs of disease before a second, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as well as Evan's blue dye staining on necropsy specimens. RESULTS: Seven dogs completed the entire study. Two treatment dogs were lost after the first infusion because of deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost because of vessel wall damage during catheterization. The remaining dogs had only transient neurologic, ocular, and vasculature injuries. Successful BBBD was documented in all treated dogs by use of CT and Evan's blue dye evaluation. CONCLUSION: Repeated catheterization of the internal carotid artery and disruption of the blood- brain barrier is possible in dogs. CLINICAL RELEVANCE: Refinement of this technique would be useful not only for improved delivery of chemotherapeutic agents in patients with brain tumors, but also would allow further investigation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.