Seizures in puppies, kittens difficult diagnostic and therapeutic problem

Q: What are potential causes of seizure activity in puppies and kittens, and the possible management?

A: Seizure activity in puppies and kittens younger than 6 monthsrepresent an important diagnostic and therapeutic problem for most veterinarians.

Most seizure activity in puppies and kittens are symptomatic seizuresand represent the onset or coexistence of significant central nervous systemdisease. A seizure event in puppies and kittens generally requires immediatemedical attention and special considerations for its management.

Q: Can seizures cause brain damage to the immature brain?

A: In humans, reports have shown that the immature nervous systemis no more vulnerable and possibly more resistant to damage arising fromseizure activity than are adults. The immature brain undergoing seizureactivity is capable of taking care of its increased energy requirementsthrough an acceleration of glycolytic flux, therefore, avoiding major disruptionsin its oxidative metabolism. Puppies are able to maintain their reservesin cerebral high-energy phosphates. Prolonged seizure activity will, however,eventually lead to cerebral edema and laminar necrosis of cortical neurons.Chronic seizure activity may also alter the expected pattern of brain development.

Causes and management

Congenital disorders related to neuronal migration and some forms ofcranial malformations are apt to induce seizure activity. A few inborn errorsof metabolism involving the cerebral cortex may cause seizure activity.Specifically, lysosomal storage diseases can cause seizures by interferenceof neuronal function or with accumulation of intracellular byproducts.

Congenital hydrocephalus is a common consideration for seizure activityin a young dog and is associated with fusion of the rostral colliculi causingsecondary mesencephalic aqueductal stenosis. Signs of congenital hydrocephalusare typically related to forebrain dysfunction and seizure activity, andthe signs vary in severity and onset. An affected animal may have a dome-shapedhead and open fontanelles. Typical abnormal mental states are disorientation,obtundation and stupor.

Behavioral abnormalities may include slowness to learn. Diagnostic evaluationsused other than case history and physical examination may include magneticor computed tomographic imaging, ultrasonography and/or electroencephalography.Medical therapy - prednisone (0.25 to 0.5 mg/kg daily to twice daily), furosemide(0.5 to 2.0 mg/kg daily to twice daily) or acetazolamide (0.1 mg/kg orallythree times daily) - may temporarily reduce the severity of the signs presumablyby altering cerebrospinal fluid production. Surgical management createsshunting of cerebrospinal fluid from the ventricles of the brain to anotherspace such as atrium or abdominal cavity. Current shunting procedures mayincorporate use of Phoenix Accura Standard Shunt System (www.shunt.com/biomedical/instructions/NS/AccuraShuntSystems.htm).Complications related to such performed shunting procedures include mechanicalproblems, shunt-related infections and functional problems.

* Hypoxemia in young animals is often from respiratory and cardiovascularcompromise. During periods of hypoxia-ischemia and followed by reperfusion,cellular energy failure, excitoxicity, free radical damage and intracellularcalcium accumulation may occur. Hypercapnia may also be an important componentof the asphyxia.

* Hypoglycemia with blood glucose concentrations less than 40mg/dl can precipitate seizure activity. Glucose is the predominant energysubstrate for the neonatal brain. In newborn puppies during hypoglycemia,lactic acid not only is incorporated into the perinatal brain, but alsois consumed to the extent that the metabolite can support up to 60 percentor more of total cerebral energy metabolism.

Although the neonatal brain can readily metabolize ketone bodies, thelack of body fat and prolonged time necessary to produce ketones preventsthis activity from protecting the neonatal brain from acute hypoglycemia.Neonates exhibiting neurologic signs should receive glucose parenterallyby intravenous or intraosseous route at a dose of 0.25 ml per 25 gram bodyweight of 10% dextrose solution. Juvenile hypoglycemia can occur becauseof immature hepatic enzyme systems, lack of glycogen stores and increasedrequirements for glucose. Fatty liver syndrome may cause hypoglycemia intoy breed puppies at 4 to 16 weeks of age. Glucose replacement therapy involves1 to 2 ml/kg of a 10% dextrose solution (intravenous or intraosseous) tothe animal that is obtunded or having seizure activity.

* Congenital portosystemic shunts are common developmental defectsthat cause hepatoencephalopathy in puppies and kittens. Signs of hepatoencephalopathymay include ataxia, circling, depression, disorientation, behavior changesand seizures. Although poorly understood, a variety of substances have beenimplicated in the pathogenesis of the hepatoencephalopathy. Treatment involvesmanagement of the hepatic dysfunction and hepatoencephalopathy. After surgicalcorrection, seizures and neurologic sequelae commonly occur following portosystemicshunt attenuation. Such neurologic complications occur more commonly withcomplete and partial ligation procedures and seem to be less common withthe gradual occlusion methods. The reasons for the post-ligational seizuresare not understood.

* Central nervous system inflammation: Seizures occur in about10 percent of all dogs afflicted with this condition. Cats in differentparts of the world are diagnosed more often with central nervous systeminflammatory disease ­ in these cats suspected to be of viral or immune-mediatedorigin. In the United States, cats have a similar incidence as in dogs.

* Epilepsy actually means recurrent seizures. Idiopathic epilepsymeans there is no identifiable cause for the seizure activity. inheritedepilepsy means there is a genetic cause for the seizure activity. Epilepsythat is suspected to have an inherited basis often begins in puppies youngerthan 1 year of age. Based on pedigree analysis, a genetic basis is stronglysuspected in Keeshonds, Belgian Tervuren, Alsatian Shepherd and Labradorand Golden Retrievers. A single recessive gene may contribute to a predispositionof epilepsy in Keeshonds. Epilepsy in the Belgian Tervuren is the resultof a complex pattern of inheritance. A polygenic, multifactorial mode ofinheritance has been suggested for the Labrador and Golden Retrievers.

* Seizures may occur after a dramatic head injury. Early seizuresoccur within days of the head injury and may increase the risk of seizureactivity later.

* Toxic substances: The central nervous system can be primarilyor secondarily involved with a variety of toxic substances. Inquisitivebehaviors, lack of discretionary eating habits and physiologic alterationsin drug disposition render the puppy and kitten more susceptible to toxicantexposure. Neonates have an increased permeability of the blood-brain barrierthat increases the potential for central nervous system exposure to toxins.Skin hydration is highest in neonates and topical exposure to lipid-solublecompounds, such as hexachlorophene and organophosphates, places the puppyor kitten at higher risk of drug absorption. Toxins may induce seizuresthrough increased excitation, decreased inhibition and interference withenergy metabolism.

Therapeutic thoughts

Therapy instituted in puppies and kittens is to minimize the seizureactivity with limited drug-related side effects. Drug disposition and pharmacokineticsare different in the younger animal because of lower albumin concentration,larger percentage of total body water and lower amount of body fat. Hepaticmetabolism and renal excretion are decreased in the neonate. Dosage reductionsor prolonged intervals may be indicated for drugs that are highly proteinbound. Hepatic drug metabolizing enzymes of young puppies and kittens areinducible by phenobarbital and other drugs.

Hepatic enzyme activities in puppies are equivalent to the mature dogby 5 to 8 weeks of age. Adult levels of glomerular filtration and tubularfunction are attained by 2.5 months of age. After these times, dosing regimenscan be used as in adults.

Anticonvulsant medication

If the seizure is severe or multiple, anticonvulsant therapy should beconsidered after attempts to identify the underlying cause. Rapid eliminationof seizure activity is imperative. Alternative routes, other than intravenousfor anticonvulsant drug administration, are intranasal and rectal methods.

Serum drug concentrations and body weight are important to monitor inthe rapidly growing animal. Anticonvulsant medication should be slowly withdrawnafter five to six months if the puppy or kitten has remained completelyfree of seizure activity.

The preferred anticonvulsant for long-term management of seizures indogs is either oral phenobarbital or potassium bromide. Their dosages mayvary with age and concurrent diseases. The author's therapeutic approachfor the initial administration of phenobarbital in young dogs is 0.5 mg/kgonce daily for animals younger than 3 months, 1 mg/kg twice daily for animalsbetween 3 and 6 months of age and 2 mg/kg twice daily for animals olderthan 6 months.

Serum levels should be measured two weeks after initiating therapy. Thetherapeutic range is 15 to 40 mg/ml; a value between 30 and 40 mg/ml ispreferred. However, serum levels in excess of the therapeutic range maybe required in some dogs.

Oral potassium bromide may be started in puppies at 12 weeks of age orolder, possibly even as young as 8 weeks. Because potassium bromide doesnot undergo hepatic metabolism, there should be limited problems in startingpuppies on potassium bromide at such a young age. Monotherapy with oralpotassium bromide is recommended at 40 to 80 mg/kg/day as a starting dose,may have to increase to 120 mg/kg/day in some dogs. The dosage is usuallygiven once daily, but the total dosage can also be divided and administeredtwice a day if the puppy is experiencing gastrointestinal upsets. Monitoringserum bromide levels are recommended at four and eight weeks after initiationof the potassium bromide therapy and then every two months. Therapeuticserum bromide levels should range within 1.5 to 3.5 mg/ml.

Either phenobarbital (similar regimen to that for young dogs) or diazepam(0.5 to 1.0 mg/kg orally daily, divided into two or three doses) may beused for chronic seizure control in young cats.

What's your question? Send your pediatric/geriatricrelated questions to: Pediatric/Geriatric Protocol, DVM Newsmagazine, 7500Old Oak Blvd., Cleveland, OH 44130. Your questions will be answered by Dr.Hoskins in upcoming columns.