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 months represent an important diagnostic and therapeutic problem for most veterinarians.
Most seizure activity in puppies and kittens are symptomatic seizures and represent the onset or coexistence of significant central nervous system disease. A seizure event in puppies and kittens generally requires immediate medical 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 system is no more vulnerable and possibly more resistant to damage arising from seizure activity than are adults. The immature brain undergoing seizure activity is capable of taking care of its increased energy requirements through an acceleration of glycolytic flux, therefore, avoiding major disruptions in its oxidative metabolism. Puppies are able to maintain their reserves in 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 of cranial malformations are apt to induce seizure activity. A few inborn errors of metabolism involving the cerebral cortex may cause seizure activity. Specifically, lysosomal storage diseases can cause seizures by interference of neuronal function or with accumulation of intracellular byproducts.
Congenital hydrocephalus is a common consideration for seizure activity in a young dog and is associated with fusion of the rostral colliculi causing secondary mesencephalic aqueductal stenosis. Signs of congenital hydrocephalus are typically related to forebrain dysfunction and seizure activity, and the signs vary in severity and onset. An affected animal may have a dome-shaped head and open fontanelles. Typical abnormal mental states are disorientation, obtundation and stupor.
Behavioral abnormalities may include slowness to learn. Diagnostic evaluations used other than case history and physical examination may include magnetic or 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 orally three times daily) - may temporarily reduce the severity of the signs presumably by altering cerebrospinal fluid production. Surgical management creates shunting of cerebrospinal fluid from the ventricles of the brain to another space such as atrium or abdominal cavity. Current shunting procedures may incorporate use of Phoenix Accura Standard Shunt System (www.shunt.com/biomedical/instructions/NS/AccuraShuntSystems.htm). Complications related to such performed shunting procedures include mechanical problems, shunt-related infections and functional problems.
* Hypoxemia in young animals is often from respiratory and cardiovascular compromise. During periods of hypoxia-ischemia and followed by reperfusion, cellular energy failure, excitoxicity, free radical damage and intracellular calcium accumulation may occur. Hypercapnia may also be an important component of the asphyxia.
* Hypoglycemia with blood glucose concentrations less than 40 mg/dl can precipitate seizure activity. Glucose is the predominant energy substrate for the neonatal brain. In newborn puppies during hypoglycemia, lactic acid not only is incorporated into the perinatal brain, but also is consumed to the extent that the metabolite can support up to 60 percent or more of total cerebral energy metabolism.
Although the neonatal brain can readily metabolize ketone bodies, the lack of body fat and prolonged time necessary to produce ketones prevents this activity from protecting the neonatal brain from acute hypoglycemia. Neonates exhibiting neurologic signs should receive glucose parenterally by intravenous or intraosseous route at a dose of 0.25 ml per 25 gram body weight of 10% dextrose solution. Juvenile hypoglycemia can occur because of immature hepatic enzyme systems, lack of glycogen stores and increased requirements for glucose. Fatty liver syndrome may cause hypoglycemia in toy breed puppies at 4 to 16 weeks of age. Glucose replacement therapy involves 1 to 2 ml/kg of a 10% dextrose solution (intravenous or intraosseous) to the animal that is obtunded or having seizure activity.
* Congenital portosystemic shunts are common developmental defects that cause hepatoencephalopathy in puppies and kittens. Signs of hepatoencephalopathy may include ataxia, circling, depression, disorientation, behavior changes and seizures. Although poorly understood, a variety of substances have been implicated in the pathogenesis of the hepatoencephalopathy. Treatment involves management of the hepatic dysfunction and hepatoencephalopathy. After surgical correction, seizures and neurologic sequelae commonly occur following portosystemic shunt attenuation. Such neurologic complications occur more commonly with complete and partial ligation procedures and seem to be less common with the gradual occlusion methods. The reasons for the post-ligational seizures are not understood.
* Central nervous system inflammation: Seizures occur in about 10 percent of all dogs afflicted with this condition. Cats in different parts of the world are diagnosed more often with central nervous system inflammatory disease in these cats suspected to be of viral or immune-mediated origin. In the United States, cats have a similar incidence as in dogs.
* Epilepsy actually means recurrent seizures. Idiopathic epilepsy means there is no identifiable cause for the seizure activity. inherited epilepsy means there is a genetic cause for the seizure activity. Epilepsy that is suspected to have an inherited basis often begins in puppies younger than 1 year of age. Based on pedigree analysis, a genetic basis is strongly suspected in Keeshonds, Belgian Tervuren, Alsatian Shepherd and Labrador and Golden Retrievers. A single recessive gene may contribute to a predisposition of epilepsy in Keeshonds. Epilepsy in the Belgian Tervuren is the result of a complex pattern of inheritance. A polygenic, multifactorial mode of inheritance has been suggested for the Labrador and Golden Retrievers.
* Seizures may occur after a dramatic head injury. Early seizures occur within days of the head injury and may increase the risk of seizure activity later.
* Toxic substances: The central nervous system can be primarily or secondarily involved with a variety of toxic substances. Inquisitive behaviors, lack of discretionary eating habits and physiologic alterations in drug disposition render the puppy and kitten more susceptible to toxicant exposure. Neonates have an increased permeability of the blood-brain barrier that increases the potential for central nervous system exposure to toxins. Skin hydration is highest in neonates and topical exposure to lipid-soluble compounds, such as hexachlorophene and organophosphates, places the puppy or kitten at higher risk of drug absorption. Toxins may induce seizures through increased excitation, decreased inhibition and interference with energy metabolism.
Therapy instituted in puppies and kittens is to minimize the seizure activity with limited drug-related side effects. Drug disposition and pharmacokinetics are different in the younger animal because of lower albumin concentration, larger percentage of total body water and lower amount of body fat. Hepatic metabolism and renal excretion are decreased in the neonate. Dosage reductions or prolonged intervals may be indicated for drugs that are highly protein bound. Hepatic drug metabolizing enzymes of young puppies and kittens are inducible by phenobarbital and other drugs.
Hepatic enzyme activities in puppies are equivalent to the mature dog by 5 to 8 weeks of age. Adult levels of glomerular filtration and tubular function are attained by 2.5 months of age. After these times, dosing regimens can be used as in adults.
If the seizure is severe or multiple, anticonvulsant therapy should be considered after attempts to identify the underlying cause. Rapid elimination of seizure activity is imperative. Alternative routes, other than intravenous for anticonvulsant drug administration, are intranasal and rectal methods.
Serum drug concentrations and body weight are important to monitor in the rapidly growing animal. Anticonvulsant medication should be slowly withdrawn after five to six months if the puppy or kitten has remained completely free of seizure activity.
The preferred anticonvulsant for long-term management of seizures in dogs is either oral phenobarbital or potassium bromide. Their dosages may vary with age and concurrent diseases. The author's therapeutic approach for the initial administration of phenobarbital in young dogs is 0.5 mg/kg once daily for animals younger than 3 months, 1 mg/kg twice daily for animals between 3 and 6 months of age and 2 mg/kg twice daily for animals older than 6 months.
Serum levels should be measured two weeks after initiating therapy. The therapeutic range is 15 to 40 mg/ml; a value between 30 and 40 mg/ml is preferred. However, serum levels in excess of the therapeutic range may be required in some dogs.
Oral potassium bromide may be started in puppies at 12 weeks of age or older, possibly even as young as 8 weeks. Because potassium bromide does not undergo hepatic metabolism, there should be limited problems in starting puppies on potassium bromide at such a young age. Monotherapy with oral potassium 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 usually given once daily, but the total dosage can also be divided and administered twice a day if the puppy is experiencing gastrointestinal upsets. Monitoring serum bromide levels are recommended at four and eight weeks after initiation of the potassium bromide therapy and then every two months. Therapeutic serum 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 be used for chronic seizure control in young cats.
What's your question? Send your pediatric/geriatric related questions to: Pediatric/Geriatric Protocol, DVM Newsmagazine, 7500 Old Oak Blvd., Cleveland, OH 44130. Your questions will be answered by Dr. Hoskins in upcoming columns.