Pearls from this year’s ACVIM forum include reports on pharmacokinetics of levetiracetam (Keppra), disk herniation, risk factors of meningoencephalitis of unknown origin (MUO), movement disorders, and vertebral osteosarcoma.
Pharmacokinetics of levetiracetam
Veterinary neurologists at the University of Wisconsin reported the pharmacokinetic analysis of single dose extended-release (XR) levetiracetam in cats. The immediate release levetiracetam requires TID dosing to remain within the therapeutic range in cats therefore an alternative was investigated. They gave one 500 mg XR capsule to each cat and analyzed their blood levels over 24 hours. As the therapeutic range of levetiracetam is unknown the human range of 5-45 ug/ml was used. They found that all cats were within the therapeutic range by 90 minutes post-pill and remained within the range for 24 hours. Only one cat had diarrhea and another had sedation. They recommend using 500 mg SID XR levetiracetam in cats.
Dr. Heidi Barnes-Heller evaluated serum levetiracetam concentrations after chronic administration of once daily XR levetiracetam in healthy cats. Eight cats weighing at least 5 kg were given 500 mg XR levetiracetam SID with food at home then admitted for serum chemistry screens and serum levetiracetam levels for 8 hours. Six of 8 cats had serum drug levels above the recommended minimum therapeutic level in humans of 5 ug/ml. There were no serum biochemistry changes and the neurological exam was normal in all cats. These results also suggest that 500 mg XR levetiracetam given SID to cats weighing >5 kg is well tolerated and provides serum concentrations above the minimum therapeutic range in the majority of cats.
Imaging findings and prognosis
Veterinarians at the College of Veterinary Medicine, Texas A &M University reported on the imaging findings and clinical outcome in deep pain negative dogs with intervertebral disc herniation using a 3 Tesla magnet. They evaluated 47 dogs and found that the intramedullary length of T2-weighed hyperintensity did not predict outcome. They then evaluated T2w hypointensity which represents hemorrhage, cellular debris or malacia: a poor prognostic indicator in people. They found 15 dogs with T2w hypointensity and 12 of these dogs had a poor prognosis making this MRI feature a more reliable indicator of outcome.
The effect of post-operative rehabilitation on recovery from acute thoracolumbar intervertebral disc herniations was evaluated by Dr. Natasha Olby et al. Thirty-one non-ambulatory dogs treated surgically for acute IVDH were randomized to a conservative protocol of passive range of motion and sling walking or an intensive staged rehabilitation protocol. Groups were evaluated at 2 weeks and at 42 days. All dogs recovered independent ambulation and intensive rehabilitation was well tolerated with no adverse events recorded. They found no difference in gait or coordination scores at day 14 and day 42 between the two groups. They concluded that early intensive rehabilitation is well tolerated by postoperative dogs, but does not influence the final gait grade or coordination in dogs with incomplete spinal cord injuries.
Risk factors for MUO
Dr. George Moore et al, investigated immune, infectious, and temporal trends in canine MUO. This retrospective study over 3 years found a seasonal trend occurring April-September with 62.4% of cases presenting during this period. They also found that 34.4% of cases had received vaccinations within the 35 days prior to presentation and that multivalent Bordetella (IN) and Leptospira vaccines were most commonly administered. The number of vaccinations administered did not differ between dogs vaccinated. Infectious agents were not found to cause MUO.
Another study by Dr. Heidi Barnes-Heller also evaluated risk factors in the development of inflammatory brain disease in dogs. Her retrospective study of 31 dogs found no association between body condition score, weight, temporal relationship to vaccination, or population density. Females were more likely to develop disease than males. Pursuit of other triggers such as exposure to infectious agents, toxins, and animal crowding could be investigated in future studies.
Dr. Dennis O’Brien spoke on the recognition and treatment of movement disorders. Movement disorders can be either excessive, involuntary movement (hyperkinetic) or difficulty initiating movement (hypokinetic). Focal seizures can mimic movement disorders since they are episodic and do not affect consciousness. Most movement disorders are thought to arise from the basil nuclei whose function is to initiate and plan movement. The best characterized dyskinesias in veterinary medicine are paroxysmal and appear to be hereditary. The episodes can occur infrequently to multiple times per day and they can last minutes to hours. The episodes can vary from simple flexion of one limb while walking to frantic, alternating flexion and extension of multiple limbs. Chinook dogs, Cavalier King Charles Spaniels, Border Terriers, and soft coated Wheaten Terriers have been identified to have a mutation in PIGN. The Wheaten Terriers have a median onset of 2.25 years but some reports have dogs not showing signs until 11 years. The episodes occur when the dog is awake and seem to be triggered by stress/excitement. They show kyphosis and rapid hyperflexion more so in the rear limbs than the front. They also may crabwalk sideways or backwards. Acetazolamide, a carbonic anhydrase inhibitor, has had the most success in treating these patients with some showing complete resolution.
Vertebral osteosarcoma is typically treated with surgery +/- radiation and chemotherapy without consensus on median survival time (MST). Neurologists at Washington State University reported on 21 dogs and divided them into four treatment groups: 1) surgery alone, 2) surgery and carboplatin, 3) surgery and radiation therapy, and 4) surgery, carboplatin, and radiation therapy. The surgery, carboplatin, and radiation group (group 4) had the longest median survival time at 257 days. The surgery alone group (group 1) had only a 42 day MST. The cause of death was regrowth at the original tumor site.Metastasis is very uncommon with osteosarcoma of the vertebra.