Article #4

CE

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

Joan R. Coates, DVM, MS, DACVIM (Neurology)
University of Missouri, Columbia

Robert L. Bergman, DVM, MS, DACVIM (Neurology)

Carolina Veterinary Specialists Charlotte, North Carolina

ABSTRACT:

Seizures in young dogs and cats have received little attention because of the ambiguous clinical nature of seizures. In human medicine, certain aspects of brain development are now thought to have a role in childhood seizures. Epileptogenesis (i.e., generation of seizures) in an immature brain is influenced by inhibitory and excitatory systems, ionic microenvironment, and degree of myelination. Developing neurons appear to be less vulnerable to damage and loss after seizure activity. Dogs and cats younger than 1 year of age are more likely to have symptomatic epilepsy. Early recognition of potential causes of seizures in young dogs and cats is important for appropriate diagnostic considerations and timely therapeutic interventions.

lthough the prevalence of seizures in pediatric dogs and cats is unknown, the overall incidence in the pet population is reportedly 2% to 3%.1,2 Seizures in young dogs and cats are a diagnostic dilemma for practitioners. In young animals, seizures usually signal the onset or coexistence of significant central nervous system (CNS) disease. A seizure in puppies and kittens often requires prompt medical attention with special considerations for medical management. For the purpose of this discussion, immature or young animals are defined as those younger than 6 months of age. Categorically, Send comments/questions via email the neonatal period is 0 to 2 editor@CompendiumVet.com weeks of age, the socialization or fax 800-556-3288. period is 3 to 12 weeks of age, and the juvenile period is 12 Visit CompendiumVet.com for weeks of age to adult (i.e., 3 to 6 full-text articles, CE testing, and CE months of age).3 test answers.
June 2005

PATHOPHYSIOLOGY An immature brain is more prone to seizures than is a mature brain because of multiple changes that occur during development. Epileptogenesis (i.e., generation of seizures) in an immature brain is influenced by the inhibitor y and excitator y systems, ionic microenvironment, and degree of myelination. Much of the outlined information on this has been extrapolated from laboratory animal model studies.4 In immature animals, windows of either decreased or increased susceptibility to seizures depend on the maturation of several factors within the CNS. 5,6 Maturity of inhibitory systems is crucial for cessation of seizure activity in an immature brain. -Amino butyric acid (GABA) is the predominant inhibitory neurotransmitter in the brain. The GABA receptor may select for chloride conCOMPENDIUM

447

448

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

ductance (GABA A ) or potassium conductance (GABAB).7 Ultrastructural studies comparing immature with adult rat brains show that GABA terminals in immature brains are smaller and contain fewer synaptic vesicles.8 Likewise, there are fewer synapses and lower concentrations of GABA receptors. 9,10 The rate of GABA formation and catabolism changes during maturation.1113 Differences lie not in receptor composition but rather in maturational changes to the chloride ion gradient that govern the equilibrium potential for

ated with loss of kindling antagonisms.4 Kindling is defined as local, repeated, and initially subconvulsive stimulation of neurons that progresses to alter the excitability of other nearby neurons and to develop into a seizure focus. The threshold of kindling varies with age, and spontaneous seizures occur more readily in developing animals than in adults.6 The lower epinephrine level in the immature brain may be a factor responsible for facilitating kindling.4 Incomplete myelination contributes to seizure expres-

Developmental changes in the brain may increase or decrease the window of susceptibility for seizures in young dogs and cats.
GABA A channels. 14 Consequently, in the immature brain, GABAA responses result in depolarization with subsequent activation of sodium ion (Na+) and calcium ion (Ca+2) channels.6 In contrast to the inhibitory system, the excitatory system is overdeveloped. Glutamate is the major excitatory neurotransmitter in the brain, and several subtypes for the glutamate receptor exist, including N-methyl-Daspartate (NMDA), kainate, and -amino-3-hydroxy-5methyl-4-isoxazoleproprionate (AMPA). 15,16 The hippocampus of the prenatal brain has an excess number of recurrent excitatory synapses and an overabundance of NMDA receptors. 17 As the brain continues to develop, these excitatory synapses are modulated or pruned to adult levels. Expression of glutamate transporters that play a role in glutamate uptake is also developmentally regulated. Decreased expression of glutamate transporters and variation of subtypes can lead to increased seizure susceptibility and to a lower seizure threshold.5,18 Differences in the ionic microenvironment that surrounds neurons and glial cells also contribute to epileptogenicity of the immature brain. The potassium concentration is increased in the extracellular fluid of immature brains.5 Glial function immaturity may allow the extracellular potassium concentration to increase, causing excitability.4 Thus the action potentials in immature neurons last longer because of altered potassium channel conductance, thereby causing a lower resting membrane potential and increased neuronal excitability.19 Catecholamines, especially norepinephrine, play a role in the generalization of epileptic activity during kindling. Lower levels of norepinephrine have been associCOMPENDIUM

sion in young animals. Myelination of the CNS begins in the last stage of gestation and continues more rapidly after birth. It occurs first in phylogenetically older regions of the brain and brain stem and later in the corpus callosum and neocortex.20 It is speculated that this may have a role in poor interhemispheric synchrony of seizure discharges.4 Can seizures cause brain damage to the immature brain? In humans, the neonatal CNS is particularly susceptible to seizures.21 However, the immature nervous system is no more vulnerable and possibly more resistant to damage arising from seizures.22 The immature brain undergoing convulsive activity is capable of taking care of increased energy requirements through acceleration of glycolytic flux, thus avoiding major disruptions in oxidative metabolism. 22 Cerebral high-energy phosphates (i.e., ATP and ADP) have been preserved in puppies with seizures.23 Nuclear magnetic resonance spectroscopy studies of the brains of puppies with seizures receiving supplemental oxygen have also shown sufficient preservation of energy balance even after prolonged status epilepticus.24 Developing neurons are less vulnerable to neuronal damage and cell loss.6 Thus the immature brain appears to be more resistant to the toxic effects of glutamate than does the mature brain.25 NMDA receptor expression in neonatal rat pups shows a decreased response to glutamate associated with differences in receptor subtypes, thus indicating that the degree of calcium entry into the neurons is directly related to age.26 This may be partly due to the lower density of active synapses, lower use of energy substrates, and immaturity of biochemical cascades that subsequently cause cell death.26,27 HowJune 2005

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis CE

449

ever, there is increasing evidence that recurrent seizures affect neuronal development by mechanisms that alter synaptogenesis and neurogenesis.6,28 The long-term effects of continued seizure activity are unknown. Neonatal seizures can increase the susceptibility of the developing brain to subsequent seizureinduced injury.29,30 Experimental studies of immature rats showed that various pathologic changes developed after 50 short seizures.31 Histopathologic studies of epileptic beagles have shown evidence of astrocytic swellings and ischemic changes in cerebral cortical neurons.32 Magnetic resonance imaging (MRI) of the brain has shown reduced myelination in children who have had neonatal convulsions.21,33 However, a recent analysis of humans with recurrent seizures concluded that the risk to developing individuals was low.34

CLASSIFICATION Classifying seizures is useful in identifying the type and determining an underlying cause. In humans, controversy exists over defining a solitary classification scheme for clinically describing seizures in neonates. The scheme used in adults established by the International League Against Epilepsy35 has been unreliable and difficult to apply to infants.36 Important differences exist in the clinical expression of seizures in adults and neonates.37 Adults more commonly present with partial seizures, whereas neonates have postural abnormalities. Neonatal seizures are often described as subtle and fragmentary, and some neonatal behaviors can mimic the phenomenology of true seizures.38 These seizure-like behaviors have been referred to as reflex or release phe-

tal seizures with further categorization according to clinical features (i.e., focal clonic, focal tonic, or myoclonic seizures; spasms).40,41 A classification scheme for seizures according to their clinical appearance in domestic animals has not been thoroughly defined, and currently used schemes are extrapolated from the human literature.42,43 In veterinary medicine, seizure types are classified into two major categories: generalized and focal.44 A generalized seizure often reflects a widespread seizure focus, producing loss of consciousness, autonomic activity, and whole body movements with alternating tonic and clonic phases of movements. A focal seizure reflects the activity of a local seizure focus in an area producing motor activity. It has been believed that generalized motor seizures are the most common seizure type in dogs. 42,45,46 This has recently been brought into question by Berendt and Gram47 who applied a human classification scheme for epilepsies to dogs. Results showed that focal seizures with and without generalization were most common and further emphasized reevaluation of currently used terminology for epilepsy in veterinary medicine. In puppies, generalized tonic seizures have been observed as early as 4 weeks of age.48 Immaturity of the brain and neurotransmission processes may prevent more accurate recognition of seizures in younger animals.

CAUSE Recurrent seizures are more broadly defined as epilepsies. Podell et al42 adopted a nomenclature scheme from human epilepsies based on identifiable cause. Primary epileptic seizure (i.e., idiopathic) is the term used if an

Seizures in young dogs and cats often reflect a symptomatic or an acquired cause; however, idiopathic epilepsy is being recognized more frequently as a diagnostic differential in younger animals.
nomena and must be distinguished from true seizures. Neonatal seizures are currently classified using electroencephalography and simultaneous video monitoring. Neonatal seizures have been described as seizures with a close correlation to electroencephalogram (EEG) seizure discharges, seizures with an inconsistent or no relationship to EEG ictal discharges, infantile spasms, and EEG seizures without clinical seizures.39 This has led to classification of epileptic and nonepileptic neonaJune 2005

underlying cause cannot be identified. If seizures result from a structural lesion, they are defined as secondary epileptic seizures. The term reactive epileptic seizure is used when there is a reaction of the normal brain to transient systemic insult or physiologic stresses; these seizures are not considered recurrent. Epilepsies are also described as asymptomatic (i.e., primary, idiopathic) and symptomatic (i.e., secondary).49 This article uses the terminology of asymptomatic and symptomatic epilepsies.
COMPENDIUM

450

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

Table 1. Causes of Seizures in Young Dogs and Catsa

Disorder/Category Affected Breeds/Specific Diseases

Developmental Anomalies Hydrocephalus Hydranencephaly, porencephaly Lissencephaly Polymicrogyria Agenesis of corpus callosum Dandy-Walker syndrome Chiari malformation Intracranial arachnoid cyst Degenerative Leukodystrophy Dalmatian, Labrador retriever, Shetland sheepdog, Samoyed, silky terrier Alexanders disease (Scottish terrier, miniature poodle, Burmese Mountain dog, Labrador retriever) Metachromatic leukodystrophy Subacute necrotizing encephalomyelopathy (mitochondrial encephalopathy) Spongiform encephalopathy Glycogen storage disease Lysosomal storage disease Saluki, Labrador retriever, silky terrier, Egyptian Mau cat Type 1 (silky terrier dog, domestic shorthaired cat, toy breeds), type 2 (domestic shorthaired cat), type 4 (Norwegian forest cat) GME1 gangliosidosis (German shorthaired pointer, Portugese water dog, beagle, Alaskan husky, Siamese cat [type 2], domestic shorthaired cat [types 1 and 2], Korat cat [type 2]) GME2 gangliosidosis (Siamese cat, domestic short-haired cat, Korat cat) Fucosidosis (English springer spaniel) Glycoproteinosis (Laforas disease; Basset hound, miniature poodle, beagle) Ceroid lipofuscinosis (infantile, juvenile) Multisystemic neuronal degeneration Hereditary quadriplegia and amblyopia Metabolic Portosystemic shunting Hepatic microvascular dysplasia Hypoglycemia Hypoxemia Hypocalcemia Yorkshire terrier, Maltese, schnauzer, Irish wolfhound, Old English sheepdog Poodle, schnauzer, dachshund, Yorkshire terrier, shih tzu, cocker spaniel Toy and miniature breeds Neonatal asphyxia Primary hypoparathyroidism Chihuahua, Dalmatian, English setter, dachshund, saluki, Australian blue heeler, Australian cattle dog, Border collie, Siamese cat Cocker spaniel, Rhodesian ridgeback Irish setter Domestic shorthaired cat Australian cattle dog, Alaskan husky, Maltese Boston terrier, Chihuahua, English bulldog, Maltese, Lhasa apso, Pomeranian, toy poodle, Cairn terrier, pug, Pekingese, Siamese cat Secondary to infection Lhasa apso, Irish setter, wire fox terrier, domestic shorthaired cat, Korat cat Poodle Domestic shorthaired cat, Labrador retriever Not breed specific in dogs and cats Cavalier King Charles spaniel, other small-breed dogs Not breed specific

COMPENDIUM

June 2005

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis CE

451

Table 1. Causes of Seizures in Young Dogs and Catsa (continued)

Disorder/Category Affected Breeds/Specific Diseases

Nutritional Thiamine deficiency Inflammatory Viral Fungal Bacterial Protozoal Parasitic Rickettsial Noninfectious inflammatory Idiopathic Epilepsy Traumatic Acute and chronic Toxicosis Posttraumatic epilepsy Pesticides (organophosphates, carbamates, pyrethrins, metaldehyde), rodenticides (bromethalin, strychnine, rotenone, zinc phosphate, vacor), herbicides, heavy metals (lead, triethyltin, thallium), drugs, poisonous plants, mycotoxins (amanita mushrooms, penitrems A), antifreeze (ethylene glycol), disinfectants (hexachlorophene), methylxanthines, street drugs Beagle, Belgian Tervuren, keeshond, British Alsatian, Labrador retriever, golden retriever, collie, dachshund, vizsla CDV, FIP, feline panleukopenia, FIV, nonsuppurative meningoencephalomyelitis in cats Cryptococcus spp infection Infection with aerobes or anaerobes, abscessation Toxoplasmosis, encephalitozoonosis Cuterebra spp larval myiasis Ehrlichiosis, Rocky Mountain spotted fever Eosinophilic meningoencephalitis, encephalitis (pug, Maltese, Yorkshire terrier), GME, periventricular encephalitis Seizures in dogs fed diets mainly of meat and fish

aLists

only breeds and diseases in which seizures have been clinically documented in young dogs and cats. CDV = canine distemper virus; GME = granulomatous meningoencephalomyelitis.

Specific seizure types have been associated with specific disease processes in humans; however, this still needs further evaluation in veterinary medicine. Podell et al 42 found a higher probability of symptomatic epilepsy in dogs with a short interictal interval and focal seizures, supporting the belief that focal seizures are an indication of a structural cerebral lesion. Similar results were reported in later studies by Berendt and Gram47 as well as Patterson et al.50 In contrast, these results additionally documented that dogs considered idiopathic epileptics also exhibited focal seizures. A more recent study of vizslas with inherited idiopathic epilepsy showed that focal seizures of variable frequency were the predominant seizure type.50 Age is also a significant predictor of symptomatic epileptic seizures in young dogs (i.e., <1 year of age).42 In Table 1, the DAMNIT-V clasJune 2005

sification scheme is used to summarize disorders associated with or that cause seizures in immature animals.5153

Symptomatic Epilepsies Degenerative/Anomalous Disorders related to neuronal migration and some forms of cranial malformations are apt to induce seizures. Brain malformations associated with seizure activity include hydrocephalus, Dandy-Walker syndrome, hydranencephaly, lissencephaly (Figure 1), Chiari-like malformation, intracranial intraarachnoid cyst, polymicrogyria, and agenesis of the corpus callosum.44,53 Congenital or acquired hydrocephalus is a common diagnostic differential for seizures in young dogs and cats.54 Hydrocephalus was found to be the most common cause of secondary epileptic seizures in dogs younger
COMPENDIUM

452

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

Figure 2. Gross necropsy image of severe internal

hydrocephalus from a 4-month-old party (multicolored) poodle. Note the enlarged lateral ventricles and collapsed cerebrocortical tissue. (Courtesy of Dr. Gayle C. Johnson, University of Missouri)

Figure 1. Gross necropsy image of a lissencephalic brain from a young Lhasa apso with a history of seizures. Note the lack of gyri and sulci in the cerebral cortex. (Courtesy of Dr. Gerald R. Bratton,Texas A & M University)

than 1 year of age.42 Internal (Figure 2) and external hydrocephalus refer to increased fluid accumulation within the ventricular and subarachnoid spaces, respectively. Noncommunicating (i.e., obstructive) hydrocephalus refers to increased cerebrospinal fluid (CSF) only within the ventricular system, and communicating refers to increased CSF within the ventricular system and subarachnoid space. Congenital hydrocephalus often represents a secondary manifestation of a developmental (e.g., Chiari type 1like malformation)55 or an acquired (e.g., perinatal exposure to toxins or infectious disease) disorder.5658 Congenital hydrocephalus is associated with fusion of the rostral colliculi, causing secondary mesencephalic aqueductal stenosis. Head conformation often involves a dome shape and an open bregmatic fontanelle. Clinical signs of hydrocephalus vary in severity and typically manifest with seizure activity and forebrain dysCOMPENDIUM

function. Forebrain signs include mentation changes such as disorientation, obtundation, and stupor as well as behavioral abnormalities that can consist of an inability to learn skills such as housebreaking.59 Hydrocephalus can be diagnosed using MRI or computed tomography (CT), ultrasonography, and electroencephalography.5961 Medical therapies can reduce the severity of clinical signs, presumably by altering CSF production. The goal of surgical management is shunting CSF from the ventricles to another space (e.g., atrium, abdominal cavity). Shunting procedures are the mainstay of therapy for hydrocephalus in human medicine and are now advocated in veterinary medicine.62,63 Only a few inborn errors of metabolism (e.g., organic/mitochondrial encephalopathies) involving the cerebral cortical tissue can cause clinical signs of seizure in dogs.6466 Neuronal metabolism is directly affected when the enzyme defect is located in a major metabolic pathway. Clinical descriptions for some of the organic/mitochondrial encephalopathies include episodic extensor rigidity, myoclonus, and epileptiformlike seizures. 6466 Lysosomal storage diseases cause seizures by interference of neuronal metabolism or accumulation of intracellular by-products. Seizure events that occur with some storage disorders usually manifest at the end stage of the disease process. Storage disorders for which seizure activity is a predominant clinical feaJune 2005

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis CE

453

ture include ceroid lipofuscinosis, glycoproteinoses, and leukodystrophies.67

Metabolic Hypoxemia in young animals is often suspected after severe respiratory and cardiovascular compromise. In addition, hypoxemia may increase the anesthetic risk in patients undergoing early spay and neuter procedures. Brain injury in newborn fetuses may be associated with hypotensive effects instead of hypoxia or acidosis.68 During the period of hypoxiaischemia and reperfusion injury, various cytotoxic processes include cellular energy failure, excitoxicity, free radical damage, and intracellular calcium accumulation.69 Hypercapnia may also be an important component of neonatal asphyxia. Fourteenday-old neonatal dogs had increased seizure susceptibility during the recovery phase of experimentally induced hypercapnia (i.e., partial pressure of carbon dioxide values: 50 to 100 mm Hg).70

of gluconeogenic substrates. Fatty liver syndrome causes hypoglycemia in toy breed puppies at 4 to 16 weeks of age.74 Persistent juvenile hypoglycemia is often related to a glycogen storage disorder.75 Extrinsic factors that cause hypoglycemia include stress, hypothermia, parasitism, and low birth weight. In addition, hypoglycemia combined with hypoxiaischemia is more deleterious to the immature brain than either condition alone.76 Portosystemic shunts (PSSs) are common congenital defects causing hepatoencephalopathy in dogs and cats.77,78 Common clinical signs of hepatoencephalopathy include ataxia, circling, depression, behavior changes, and seizures. A variety of compounds have been implicated in the pathogenesis of hepatic encephalopathy, although this process is poorly understood. Postulated causes include elevated ammonia, altered ratios of neurotransmitters, and increased brain concentrations of benzodiazepine-like neurotransmitters.79 Recent studies found higher concentrations of glutamine, tryptophan, and

An immature brain is more prone to seizures than is a mature brain because of multiple changes that occur during development.
Hypoglycemia at glucose concentrations less than 40 mg/dl can precipitate neuroglycopenia. Neuroglycopenia is manifested by depression, hypothermia, weakness, seizures, and coma. Factors responsible for clinical signs of neuroglycopenia include rate of decrease, level of hypoglycemia, and duration of hypoglycemia.71 Glucose is the predominant energy substrate for the adult and neonatal brain. Although the receptor numbers for glucose transport protein are low in the immature brain, the transport protein for ketone bodies as well as lactate and pyruvate is high. Studies of newborn dogs have shown that during hypoglycemia, lactic acid is not only incorporated into the perinatal brain but also consumed to the extent that the metabolite can support up to 60% or more of total cerebral energy metabolism.72 Although the neonatal brain can readily metabolize ketone bodies, lack of body fat and prolonged time necessary to produce ketones prevent this mechanism from protecting neonates from acute hypoglycemia. 73 Juvenile-onset hypoglycemia occurs because of immature hepatic enzyme systems, deficiency of glucagon, and deficiency
June 2005

quinolinate, a metabolite of tryptophan, in the CSF of dogs with PSS. 80 Quinolinate is an agonist of the NMDA receptor, and the developing brain is more sensitive to NMDA activation.81 This may play a role in development of seizure activity in young dogs with PSSs. Pathologic lesions are characterized by protoplasmic astrocytic proliferation (as in Alzheimer type 2 reactions) and spongiform changes in the brains of dogs with PSSs.82 Treatment involves managing the hepatic dysfunction and encephalopathy. Seizures and neurologic sequelae following PSS attenuation have been well documented.8385 Neurologic complications have been associated with all of the occlusion methods.86 Potential risk factors for neurologic complications include older dogs and dogs with single extrahepatic and portoazygous shunts.86 The pathophysiologic mechanisms of postligational seizures are poorly understood.87

Inflammatory Seizures occur in about 13% of dogs with CNS inflammatory diseases.88 Cats with seizures were frequently
COMPENDIUM

454

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

diagnosed with inflammatory disease (47% [14 of 30] of cats) of suspected viral or immune-mediated origin. 89 Canine distemper virus (CDV) encephalitis is the most common infectious inflammatory cause of seizures in dogs younger than 1 year of age.42 Specifically, CDV causes acute polioencephalitis in young dogs.90 Seizures often are focal, which is characterized by chewing gum seizures, or consist of generalized motor activity.88,90 Similarly, seizures have been reported with postvaccinal CDV encephalitis in puppies.91 These seizures are often pro-

senting sign. The diagnosis is based on CSF analysis.101 Recovery or remission of clinical signs can occur with glucocorticoid therapy.

Trauma Seizures that occur after traumatic head injury can have an early or delayed onset. Early onset of seizures occurs within days of the injury and may pose an increased risk of seizure activity later. Controversy exists in human and veterinary medicine regarding the role of prophylactic

An abnormal neurologic examination between seizures lends support for a symptomatic cause.
gressive and refractory to antiepileptic drug therapy. Identifying the underlying inflammatory disease process is important because the disease continues to progress without appropriate treatment. Dogs with noninfectious inflammatory disorders with cerebral cortical involvement clinically manifest seizure activity. Granulomatous meningoencephalomyelitis (GME) rarely affects young dogs92 and is an inflammatory disease of the white matter of the brain.9395 The disseminated form is usually acute and rapidly progressive, whereas the focal form progresses more slowly. About 20% of affected dogs have seizures along with other neurologic deficits.96 Breed-specific meningoencephalitis occurs in pugs,97 Yorkshire terriers,98 and Malteses.99 Pathologic features consist of nonsuppurative necrotizing meningoencephalitis, with a predilection for the cerebrum in pugs and Malteses. Seizures have also been reported in Yorkshire terriers, but brain-stem signs are more commonly manifested. Young dogs are predisposed and are usually 6 months of age or older. Dogs with the chronic form more often have clinical signs of generalized or focal seizures. Definitive diagnosis of the noninfectious inflammatory meningoencephalitides is based on a histopathologic diagnosis.95 A diagnosis can be suspected based on patient signalment as well as findings from advanced imaging and CSF analysis.100 Serology can assist in ruling out infectious causes. Eosinophilic meningoencephalitis is characterized by eosinophilic pleocytosis of the CSF in dogs and a cat.101103 Neurotoxic substances are released from the granules of eosinophils, causing secondary neurologic signs. This disease has been reported in young dogs. Neurologic signs are variable, but seizures can be a preCOMPENDIUM

antiepileptic drug therapy for patients with head injuries. Current management involves waiting to begin antiepileptic drug therapy until seizures actually occur. Electrical shock resulting from curious behaviors in young animals may induce seizures and potentially lifethreatening noncardiogenic pulmonary edema.104

Toxicosis The CNS is primarily or secondarily involved with a variety of toxic substances. Dorman105 reported that seizures occurred in 8.2% of all cases of suspected toxicosis. Inquisitive behaviors, lack of discretionary eating habits, and physiologic alterations in drug disposition render pediatric patients more susceptible to toxicant exposure.106 Neonates have a more permeable blood brain barrier than do adults, thus increasing the potential for CNS exposure to toxins.107 Skin hydration is highest in neonates, and topical exposure to lipid-soluble compounds (e.g., hexachlorophene, organophosphates) places pediatric patients at higher risk of significant absorption.106 Toxins induce seizures through a number of different mechanisms: increased excitation, decreased inhibition, and interference with energy metabolism.108 Asymptomatic Epilepsy Idiopathic Epilepsy Epilepsy is characterized by recurrent seizures.49 The term idiopathic epilepsy, also known as primary or asymptomatic epilepsy, is used when there is no identifiable cause of seizures. The term inherited epilepsy is used when there is a genetic cause of seizures. Epilepsy suspected of having an inherited basis frequently occurs in dogs
June 2005

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis CE

455

younger than 1 year of age. Although most dogs with idiopathic epilepsy have their first seizure at 1 to 5 years of age, seizures have been reported in Labrador retrievers as young as 2 months of age.42,109 An inherited basis, familial transmission, or a higher incidence has been recognized in many breeds. Based on pedigree analysis, a genetic basis is strongly suspected in keeshonds,110 Belgian Tervurens,111 Alsatian shepherds,112 Labrador and golden retrievers,113,114 vizslas,50 and a colony of laboratory-raised beagles.115 The mode of inheritance has been suggested in some breeds. Hall and Wallace116 found evidence of a single recessive gene contributing to a predisposition of epilepsy in keeshonds. Statistics suggest that seizures in Belgian Tervurens result from a complex pattern of inheritance.117,118 A polygenic multifactorial mode of inheritance is suggested in golden and Labrador retrievers.113,114 An autosomal recessive pattern of inheritance is suspected in vizslas with idiopathic epilepsy.50 In humans, genes have been identified for ion channel defects in some epilepsies.119

DIAGNOSTIC CONSIDERATIONS The appropriate diagnostic procedures for seizures in young animals are variable and depend on the most likely differentials.44,53 Tests may be subdivided into procedures that do and do not require anesthesia (Figure 3). The minimum database should include patient signalment, history, physical and neurologic examinations, and clinical pathology. The patients history plays an important role, especially if toxin exposure is a consideration. The history can also help identify vaccination status, pedigree information, environmental factors, and seizure

(CBC), serum chemistry profile, and urinalysis. Abnormal findings may further support a metabolic or toxic cause of seizures. Screening tests in a serum biochemical profile should include blood urea nitrogen, alkaline phosphatase, alanine transaminase, calcium, and blood glucose levels. Interpretation of results should also take into account an animals age because adult and immature animals have different serum values. Based on clinicopathologic abnormalities, additional diagnostic testing is indicated when specific organ pathology is suspected. Liver function tests, such as pre- and postprandial bile acid concentrations and blood ammonia levels, can provide evidence of hepatic dysfunction. Scintigraphy and ultrasonographic studies can further aid in identifying a PSS.120 Profiles for metabolic screening of blood, urine, and CSF are useful when storage disorders or inborn errors of metabolism are suspected.121,122 Serology and immunologic testing may indirectly lend further support to infectious causes. 123 Overall, viral causes are difficult to definitively diagnose with less invasive diagnostic testing. Results of serologic testing are also difficult to interpret because of the presence of circulating antibodies from maternal immunity, vaccination, or environmental exposure. Immunofluorescent antibody staining of epithelial cells from the conjunctiva has reportedly identified about 54% of dogs with CDV infection.90,124 Additional neurodiagnostic testing can further determine the type and extent of intracranial pathology. Ultrasonography is useful in animals with an open bregmatic fontanelle or intracranial arachnoid cysts.125,126 Findings of only mild hydrocephalus should be carefully interpreted because this may not be the inciting cause.

It is important to identify the underlying inflammatory or metabolic disease because clinical signs continue to progress without appropriate treatment.
patterns. Abnormal findings on physical and neurologic examinations lend support for symptomatic causes of seizures and more extensive diagnostic testing. Neuroanatomic localization for seizure activity is in the forebrain. Neurologic examination findings may reveal forebrain dysfunction or evidence of a multifocal or diffuse disease process. A funduscopic examination may show active or previous signs of chorioretinitis. Clinical pathology testing should include a complete blood count
June 2005

Advanced imaging such as CT or MRI can aid in diagnosing structural abnormalities related to cranial and intracranial malformations, inflammatory disorders, and neoplasms. MRI is more ideal for identifying soft tissue abnormalities. In human medicine, the efficacy of using CT in children after the first nonfebrile seizure has been questioned based on lack of abnormal findings.127 Electroencephalography in animals may show characteristic patterns in disease, such as hydrocephalus and
COMPENDIUM

456

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

Figure 3. Algorithm of diagnostic considerations regarding seizures in young dogs and cats.

SEIZURE ACTIVITY

Signalment and history

Physical and interictal neurologic examination

Fundic examination

Clinical pathology (CBC, serum chemistry, urinalysis; blood urea nitrogen, alkaline phosphatase, alanine transaminase, calcium, and glucose levels)

Serology

Electrolyte monitoring

Glucose evaluation

Liver function testing

Metabolic screening for inborn errors of metabolism

EEG

Ultrasonography/ scintigraphy

Ultrasonography of the cranium

Diagnostic procedures above the dashed line do not require anesthesia; those below the dashed line do.

Advanced imaging (CT, MRI)

CSF analysis

encephalitis.61,128 However, an animals age should be carefully considered because EEG patterns in young animals can mimic patterns associated with disease. An electroencephalograph can develop the pattern of an adult dog by approximately 5 months of age.129 In our experience, continual electroencephalography is also useful in monitoring persistent seizure activity and adequate response to therapy. CSF analysis is particularly useful in identifying the presence of inflammatory disease.88 Because inflammatory disCOMPENDIUM

ease is a more likely differential than neoplasia in younger animals, CSF analysis may more often provide a greater diagnostic yield than imaging procedures alone. CSF can be collected by puncturing the cerebellomedullary cistern. Analysis should include a nucleated cell count, protein concentration, and cytologic evaluation within 30 minutes of sample collection. Unfortunately, results of CSF analysis tend to be nonspecific for some disease processes. Intrathecal antibody production can be determined to further assist in diagnosing some infectious diseases.123
June 2005

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis CE

457

CONCLUSION Early recognition of the cause of seizures in young dogs and cats is important for appropriate therapeutic intervention. Inappropriate therapy can delay cessation of seizures and increase patient morbidity and mortality.

19. Hablitz JJ, Heinemann U: Extracellular K+ and Ca2+ changes during epileptiform discharges in the immature rat neocortex. Brain Res 433:299303, 1987. 20. Eayrs JT, Goodhead B: Postnatal development of the cerebral cortex in the rat. J Anat 93:385402, 1959. 21. Rennie JM: Neonatal seizures. Eur J Pediatr 156:8387, 1997. 22. Vannucci RC, Fujikawa DG: Energy balance of the immature brain during status epilepticus, in Wasterlain CG, Vert P (eds): Neonatal Seizures. New York, Raven Press, 1990, pp 99112. 23. Sacktor B, Wilson JE, Tiekert CG: Regulation of glycolysis in brain, in situ, during convulsions. J Biol Chem 241:50715075, 1966. 24. Young RS, Osbakken MD, Briggs RW, et al: 31P NMR study of cerebral metabolism during prolonged seizures in the neonatal dog. Ann Neurol 18:1420, 1985. 25. Marks JD, Bindokas VP, Zhang XM: Maturation of vulnerability to excitotoxicity: Intracellular mechanisms in cultured postnatal hippocampal neurons. Brain Res Dev Brain Res 124:101116, 2000. 26. Marks JD, Friedman JE, Haddad GG: Vulnerability of CA1 neurons to glutamate is developmentally regulated. Brain Res Dev Brain Res 97:194206, 1996. 27. Liu Z, Stafstrom CE, Sarkisian M, et al: Age-dependent effects of glutamate toxicity in the hippocampus. Brain Res Dev Brain Res 97:178184, 1996. 28. McCabe BK, Silveira DC, Cilio MR, et al: Reduced neurogenesis after neonatal seizures. J Neurosci 21:20942103, 2001. 29. Moshe SL, Albala BJ: Kindling in developing rats: Persistence of seizures into adulthood. Brain Res 256:6771, 1982. 30. Schmid R, Tandon P, Stafstrom CE, Holmes GL: Effects of neonatal seizures on subsequent seizure-induced brain injury. Neurology 53:17541761, 1999. 31. Liu Z, Yang Y, Silveira DC, et al: Consequences of recurrent seizures during early brain development. Neuroscience 92:14431454, 1999. 32. Montgomery DL, Lee AC: Brain damage in the epileptic beagle dog. Vet Pathol 20:160169, 1983. 33. Martin E, Boesch C, Zuerrer M, et al: MR imaging of brain maturation in normal and developmentally handicapped children. J Comput Assist Tomogr 14:685692, 1990. 34. Verity CM: Do seizures damage the brain? The epidemiological evidence. Arch Dis Child 78:7884, 1998. 35. Commission on classification and terminology of the international league against epilepsy: Proposal for classification of epilepsies and epileptic syndromes. Epilepsia 26:268278, 1985. 36. Jayakar P, Chiappa KH: Clinical correlations of photoparoxysmal responses. Electroencephalogr Clin Neurophysiol 75:251254, 1990. 37. Nordli Jr DR, Kuroda MM, Hirsch LJ: The ontogeny of partial seizures in infants and young children. Epilepsia 42:986990, 2001. 38. Volpe JJ: Neonatal seizures: Current concepts and revised classification. Pediatrics 84:422428, 1989. 39. Tharp BR: Neonatal seizures and syndromes. Epilepsia 43(suppl 3):210, 2002. 40. Mizrahi EM, Kellaway P: Characterization and classification of neonatal seizures. Neurology 37:18371844, 1975. 41. Mizrahi EM: Neonatal seizures and neonatal epileptic syndromes. Neurologic Clinics 19:427463, 2001. 42. Podell M, Fenner WR, Powers JD: Seizure classification in dogs from a nonreferral-based population. JAVMA 206:17211728, 1995. 43. March PA: Seizures: Classification, etiologies, and pathophysiology. Clin Tech Small Anim Pract 13:119131, 1998. 44. Lorenz MD, Kornegay JN: Seizures, narcolepsy, and cataplexy, in Lorenz MD, Kornegay JN (eds): Handbook of Veterinary Neurology. St. Louis, Elsevier Science, 2004, pp 323344.

Watch for an upcoming article on managing seizures in young dogs and cats.
REFERENCES
1. Bunch SE: Anticonvulsant drug therapy in companion animals, in Kirk RW (ed): Current Veterinary Therapy IX. Philadelphia, WB Saunders, 1986, pp 836844. 2. Cunningham JG, Farnbach GC: Inheritance and idiopathic canine epilepsy. JAAHA 24:421424, 1988. 3. OBrien D: Neurological examination and development of the neonatal dog. Semin Vet Med Surg Small Anim 9:6267, 1994. 4. Kubova H, Moshe SL: Experimental models of epilepsy in young animals. J Child Neurol 9(suppl 1):S3S11, 1994. 5. Sanchez RM, Jensen FE: Maturational aspects of epilepsy mechanisms and consequences for the immature brain. Epilepsia 42:577585, 2001. 6. Holmes GL, Khazipov R, Ben Ari Y: New concepts in neonatal seizures. Neuroreport 13:A3A8, 2002. 7. Hevers W, Luddens H: The diversity of GABAA receptors: Pharmacological and electrophysiological properties of GABAA channel subtypes. Mol Neurobiol 18:3586, 1998. 8. Seress L, Frotscher M, Ribak CE: Local circuit neurons in both the dentate gyrus and Ammons horn establish synaptic connections with principal neurons in five-day-old rats: A morphological basis for inhibition in early development. Exp Brain Res 78:19, 1989. 9. Seress L, Ribak CE: The development of GABAergic neurons in the rat hippocampal formation: An immunocytochemical study. Brain Res Dev Brain Res 44:197209, 1988. 10. Kunkel DD, Hendrickson AE, Wu JY, Schwartzkroin PA: Glutamic acid decarboxylase (GAD) immunocytochemistry of developing rabbit hippocampus. J Neurosci 6:541552, 1986. 11. Roberts E, Kuriyama K: Biochemical-physiological correlations in studies of the gamma-aminobutyric acid system. Brain Res 8:135, 1968. 12. Fritschy JM, Paysan J, Enna A, Mohler H: Switch in the expression of rat GABAA-receptor subtypes during postnatal development: An immunohistochemical study. J Neurosci 14:53025324, 1994. 13. Gaiarsa JL, McLean H, Congar P, et al: Postnatal maturation of gammaaminobutyric acid A and B-mediated inhibition in the CA3 hippocampal region of the rat. J Neurobiol 26:339349, 1995. 14. Staley KJ, Soldo BL, Proctor WR: Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors. Science 269:977981, 1995. 15. Platt SR, McDonnell JJ: Status epilepticus: Patient management and pharmacologic therapy. Compend Contin Educ Pract Vet 22:722729, 2000. 16. Young AB, Fagg GE: Excitatory amino acid receptors in the brain: Membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci 11:126133, 1990. 17. Insel TR, Miller LP, Gelhard RE: The ontogeny of excitatory amino acid receptors in rat forebrainI. N-methyl-D-aspartate and quisqualate receptors. Neuroscience 35:3143, 1990. 18. Furuta A, Rothstein JD, Martin LJ: Glutamate transporter protein subtypes are expressed differentially during rat CNS development. J Neurosci 17:83638375, 1997.

June 2005

COMPENDIUM

458

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

45. Farnbach GC: Seizures in the dog. Part I: Basis, classification, and predilection. Compend Contin Educ Pract Vet 6:569576, 1984. 46. Heynold Y, Faissler D, Steffen F, Jaggy A: Clinical, epidemiological and treatment results of idiopathic epilepsy in 54 Labrador retrievers: A longterm study. J Small Anim Pract 38:714, 1997. 47. Berendt M, Gram L: Epilepsy and seizure classification in 63 dogs: A reappraisal of veterinary epilepsy terminology. J Vet Intern Med 13:1420, 1999. 48. Knowles K: Seizure disorders in the pediatric animal patient. Semin Vet Med Surg Small Anim 9:108115, 1994. 49. Thomas WB: Idiopathic epilepsy in dogs. Vet Clin North Am Small Anim Pract 30:183206, vii, 2000. 50. Patterson EE, Mickelson JR, Da Y, et al: Clinical characteristics and inheritance of idiopathic epilepsy in Vizslas. J Vet Intern Med 17:319325, 2003. 51. Oliver JE, Lorenz MD, Kornegay JN: Handbook of Veterinary Neurology. Philadelphia, WB Saunders, 1997. 52. Podell M: Seizures in dogs. Vet Clin North Am Small Anim Pract 26:779809, 1996. 53. Dewey CW: Encephalopathies: Disorders of the brain, in Dewey CW (ed): A Practical Guide to Canine and Feline Neurology. Ames, Iowa State University Press, 2003, pp 99178. 54. Becker SV, Selby LA: Canine hydrocephalus. Compend Contin Educ Pract Vet 2:647652, 1980. 55. Lu D, Lamb CR, Pfeiffer NE, Targett MP: Neurological signs and results of magnetic resonance imaging in 40 cavalier King Charles spaniels with Chiari type I-like malformations. Vet Rec 153:260263, 2003. 56. Csiza CK, Scott FW, de Lahunta A, Gillespie JH: Pathogenesis of feline panleukopenia virus in susceptible newborn kittens. I: Clinical signs, hematology, serology, virology. Infect Immun 3:833837, 1971. 57. Scott FW, de Lahunta A, Schultz RD, et al: Teratogenesis in cats associated with griseofulvin therapy. Teratology 11:7986, 1975. 58. Summers BA, Cummings JF, de Lahunta A: Malformations of the central nervous system, in Summers BA, Cummings JF, de Lahunta A (eds): Veterinary Neuropathology. St. Louis, Mosby, 2000, pp 6894. 59. Simpson ST: Hydrocephalus, in Kirk RW, Bonagura JD (eds): Current Veterinary Therapy X: Small Animal Practice. Philadelphia, WB Saunders, 1989, pp 842847. 60. Hudson JA, Simpson ST, Buxton DF, et al: Ultrasonographic diagnosis of canine hydrocephalus. Vet Radiol 31:5058, 1990. 61. Klemm WR, Hall CL: Electroencephalograms of anesthetized dogs with hydrocephalus. Am J Vet Res 32:18591864, 1971. 62. Levesque DC, Plummer SB: Ventriculoperitoneal shunting as a treatment for hydrocephalus. Proc 12th ACVIM Forum:891893, 1994. 63. Gage ED, Hoerlein BF: Surgical treatment of canine hydrocephalus by verticuloatrial shunting. JAVMA 153:14181431, 1968. 64. Podell M, Shelton GD, Nyhan WL, et al: Methylmalonic and malonic aciduria in a dog with progressive encephalomyelopathy. Metab Brain Dis 11:239247, 1996. 65. Brenner O, de Lahunta A, Summers BA, et al: Hereditary polioencephalomyelopathy of the Australian cattle dog. Acta Neuropathol (Berl) 94:5466, 1997. 66. Brenner O, Wakshlag JJ, Summers BA, de Lahunta A: Alaskan Husky encephalopathy: A canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome). Acta Neuropathol (Berl) 100:5062, 2000. 67. Skelly BJ, Franklin RJM: Recognition and diagnosis of lysosomal storage diseases in the cat and dog. J Vet Intern Med 16:133141, 2002. 68. Williams CE, Mallard C, Tan W, Gluckman PD: Pathophysiology of perinatal asphyxia. Clin Perinatol 20:305325, 1993.

69. Gluckman PD, Pinal CS, Gunn AJ: Hypoxic-ischemic brain injury in the newborn: Pathophysiology and potential strategies for intervention. Semin Neonatol 6:109120, 2001. 70. Yoshioka H, Nioka S, Miyake H, et al: Seizure susceptibility during recovery from hypercapnia in neonatal dogs. Pediatr Neurol 15:3640, 1996. 71. Howerton TL, Shell LG: Neurologic manifestations of altered serum glucose. Prog Vet Neurol 3:5764, 1992. 72. Hellmann J, Vannucci RC, Nardis EE: Bloodbrain barrier permeability to lactic acid in the newborn dog: Lactate as a cerebral metabolic fuel. Pediatr Res 16:4044, 1982. 73. Atkins CE: Disorders of glucose homeostasis in neonatal and juvenile dogs: Hypoglycemia (Part I). Compend Contin Educ Pract Vet 6:197206, 1984. 74. van der Linde-Sipman JS, van den Ingh TS, van Toor AJ: Fatty liver syndrome in puppies. JAAHA 26:912, 1990. 75. Atkins CE: Disorders of glucose homeostasis in neonatal and juvenile dogs: Hypoglycemia (Part II). Compend Contin Educ Pract Vet 6:353364, 1984. 76. Vannucci RC, Vannucci SJ: Hypoglycemic brain injury. Semin Neonatol 6:147155, 2001. 77. Center SA, Magne ML: Historical, physical examination, and clinicopathologic features of portosystemic vascular anomalies in the dog and cat. Semin Vet Med Surg Small Anim 5:8393, 1990. 78. Butler LM, Fossum TW, Boothe HW: Surgical management of extrahepatic portosystemic shunts in the dog and cat. Semin Vet Med Surg Small Anim 5:127133, 1990. 79. Maddison JE: Hepatic encephalopathy: Current concepts of the pathogenesis. J Vet Intern Med 6:341353, 1992. 80. Holt DE, Washabau RJ, Djali S, et al: Cerebrospinal fluid glutamine, tryptophan, and tryptophan metabolite concentrations in dogs with portosystemic shunts. Am J Vet Res 63:11671171, 2002. 81. McDonald JW, Silverstein FS, Johnston MV: Neurotoxicity of N-methyl-Daspartate is markedly enhanced in developing rat central nervous system. Brain Res 459:200203, 1988. 82. Rothuizen J, van den Ingh TS, Voorhout G: Congenital portosystemic shunts in sixteen dogs and three cats. J Small Anim Pract 23:6781, 1982. 83. Mathews K, Gofton N: Congenital extrahepatic portosystemic shunt occlusion in the dog: Gross observations during surgical correction. JAAHA 24:387394, 1988. 84. Matushek KJ, Bjorling D, Mathews K: Generalized motor seizures after portosystemic shunt ligation in dogs: Five cases (19811988). JAVMA 196:20142017, 1990. 85. Hardie EM, Kornegay JN, Cullen JM: Status epilepticus after ligation of portosystemic shunts. Vet Surg 19:412417, 1990. 86. Tisdall PL, Hunt GB, Youmans KR, Malik R: Neurological dysfunction in dogs following attenuation of congenital extrahepatic portosystemic shunts. J Small Anim Pract 41:539546, 2000. 87. Aronson LR, Gacad RC, Kaminsky-Russ K, et al: Endogenous benzodiazepine activity in the peripheral and portal blood of dogs with congenital portosystemic shunts. Vet Surg 26:189194, 1997. 88. Tipold A: Diagnosis of inflammatory and infectious diseases of the central nervous system in dogs: A retrospective study. J Vet Intern Med 9:304314, 1995. 89. Quesnel AD, Parent JM, McDonell W, et al: Diagnostic evaluation of cats with seizure disorders: 30 cases (19911993). JAVMA 210:6571, 1997. 90. Thomas WB, Sorjonen DC, Steiss JE: A retrospective evaluation of 38 cases of canine distemper encephalomyelitis. JAAHA 29:129133, 1993. 91. Cornwell HJ, Thompson H, McCandlish IA, et al: Encephalitis in dogs associated with a batch of canine distemper (Rockborn) vaccine. Vet Rec 122:5459, 1988. 92. Murtaugh RJ, Fenner WR, Johnson GC: Focal granulomatous meningoencephalomyelitis in a pup. JAVMA 187:835836, 1985.

COMPENDIUM

June 2005

Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis CE

459

93. Braund KG: Granulomatous meningoencephalomyelitis. JAVMA 186:138141, 1985. 94. Cordy DR: Canine granulomatous meningoencephalomyelitis. Vet Pathol 16:325333, 1979. 95. Ryan K, Marks SL, Kerwin SC: Granulomatous meningoencephalomyelitis in dogs. Compend Contin Educ Pract Vet 23:644650, 2001. 96. Sorjonen DC: Clinical and histopathological features of granulomatous meningoencephalomyelitis in dogs. JAAHA 26:141147, 1990. 97. Cordy DR, Holliday TA: A necrotizing meningoencephalitis of pug dogs. Vet Pathol 26:191194, 1989. 98. Tipold A, Fatzer R, Jaggy A, et al: Necrotizing encephalitis in Yorkshire terriers. J Small Anim Pract 34:623628, 1993. 99. Stalis IH, Chadwick B, Dayrell-Hart B, et al: Necrotizing meningoencephalitis of Maltese dogs. Vet Pathol 32:230235, 1995. 100. Plummer SB, Wheeler SJ, Thrall DE, Kornegay JN: Computed tomography of primary inflammatory brain disorders in dogs and cats. Vet Radiol Ultrasound 33:307312, 1992. 101. Smith-Maxie LL, Parent JP, Rand J, et al: Cerebrospinal fluid analysis and clinical outcome of eight dogs with eosinophilic meningoencephalomyelitis. J Vet Intern Med 3:167174, 1989. 102. Bennett PF, Allan FJ, Guilford WG, et al: Idiopathic eosinophilic meningoencephalitis in rottweiler dogs: Three cases (19921997). Aust Vet J 75:786789, 1997. 103. Schultze AE, Cribb AE, Tvedten HW: Eosinophilic meningoencephalitis in a cat. JAAHA 22:627, 1986. 104. Drobatz KJ, Concannon K: Noncardiogenic pulmonary edema. Compend Contin Educ Pract Vet 16:333346, 1994. 105. Dorman DC: Toxins that induce seizures in small animals. Proc 8th ACVIM Forum:361364, 1990. 106. Boothe D, Peterson ME: Considerations in pediatric and geriatric poisoned patients, in Peterson ME, Talcott P (eds): Small Animal Toxicology. Philadelphia, WB Saunders, 2001, pp 114127. 107. Hellmann J, Vannucci RC, Nardis EE: Bloodbrain barrier permeability to lactic acid in the newborn dog: Lactate as a cerebral metabolic fuel. Pediatr Res 16:4044, 1982. 108. OBrien DP: Toxic and metabolic causes of seizures. Clin Tech Small Anim Pract 13:159166, 1998. 109. Gerard VA, Conarck CN: Identifying the cause of an early onset of seizures in puppies with epileptic parents. Vet Med 10601061, 1991. 110. Wallace ME: Keeshonds: A genetic study of epilepsy and EEG readings. J Small Anim Pract 16:110, 1975. 111. Van der Velden NA: Fits in Tervueren shepherd dogs: A presumed hereditary trait. J Small Anim Pract 9:6370, 1968. 112. Falco MJ, Barker J, Wallace ME: The genetics of epilepsy in the British Alsatian. J Small Anim Pract 15:685692, 1974. 113. Jaggy A, Faissler D, Gaillard C, et al: Genetic aspects of idiopathic epilepsy in Labrador retrievers. J Small Anim Pract 39:275280, 1998. 114. Srenk P, Jaggy A: Interictal electroencephalographic findings in a family of golden retrievers with idiopathic epilepsy. J Small Anim Pract 37:317321, 1996. 115. Bielfelt SW, Redman HC, McClellan RO: Sire- and sex-related differences in rates of epileptiform seizures in a purebred beagle dog colony. Am J Vet Res 32:20392048, 1971. 116. Hall SJ, Wallace ME: Canine epilepsy: A genetic counselling programme for keeshonds. Vet Rec 138:358360, 1996. 117. Famula TR, Oberbauer AM, Brown KN: Heritability of epileptic seizures in the Belgian Tervueren. J Small Anim Pract 38:349352, 1997.

118. Famula TR, Oberbauer AM: Segregation analysis of epilepsy in the Belgian tervueren dog. Vet Rec 147:218221, 2000. 119. Berkovic SF, Scheffer IE: Genetics of the epilepsies. Epilepsia 42(suppl 5):1623, 2001. 120. Winkler JT, Bohling MW, Tillson DM, et al: Portosystemic shunts: Diagnosis, prognosis, and treatment of 64 cases (19932001). JAAHA 39:169185, 2003. 121. Ozand PT, Gascon GG: Organic acidurias: A review. Part 1. J Child Neurol 6:196219, 1991. 122. Ozand PT, Gascon GG: Organic acidurias: A review. Part 2. J Child Neurol 6:288303, 1991. 123. Fenner WR: Central nervous system infections, in Greene CE (ed). Infectious Diseases of the Dog and Cat. Philadelphia, WB Saunders, 1998, pp 647657. 124. Palmer DG, Huxtable CR, Thomas JB: Immunohistochemical demonstration of canine distemper virus antigen as an aid in the diagnosis of canine distemper encephalomyelitis. Res Vet Sci 49:177181, 1990. 125. Rivers WJ, Walter PA: Hydrocephalus in the dog: Utility of ultrasonography as an alternate diagnostic imaging technique. JAAHA 28:333343, 1992. 126. Saito M, Olby NJ, Spaulding KA: Identification of arachnoid cysts in the quadrigeminal cistern using ultrasonography. Vet Radiol Ultrasound 42:435439, 2001. 127. Maytal J, Krauss JM, Novak G, et al: The role of brain computed tomography in evaluating children with new onset of seizures in the emergency department. Epilepsia 41:950954, 2000. 128. Redding RW, Prynn RB, Wagner JL: Clinical use of the electroencephalogram in canine encephalitis. JAVMA 148:141149, 1966. 129. Fox MW: Postnatal development of the EEG in the dog (part III). J Small Anim Pract 8:109112, 1967.

ARTICLE #4 CE TEST

This article qualifies for 2 contact hours of continuing education credit from the Auburn University College of Veterinary Medicine. Subscribers may purchase individual CE tests or sign up for our annual CE program. Those who wish to apply this credit to fulfill state relicensure requirements should consult their respective state authorities regarding the applicability of this program. To participate, fill out the test form inserted at the end of this issue or take CE tests online and get real-time scores at CompendiumVet.com.

CE

1. Which statement regarding inhibitory and excitatory synapses in the immature brain is correct? a. The GABA terminals are smaller, and the synapses are fewer. b. The excitatory synapses are underdeveloped. c. The rate of GABA metabolism remains the same during CNS maturation. d. Stimulation of the GABAA receptor results in repolarization of the immature neuron. e. Expression of NMDA receptors is increased in the prenatal brain.

June 2005

COMPENDIUM

460

CE Seizures in Young Dogs and Cats: Pathophysiology and Diagnosis

2. Which of the following occurs within the ionic microenvironment of the immature brain? a. The resting membrane potential is increased. b. The potassium concentration is increased in the extracellular fluid of immature brains. c. The action potentials for immature neurons are of short duration because of prolonged potassium channel conductance. d. Glial function immaturity results in a decreased extracellular potassium concentration. e. An increased extracellular potassium concentration results in neuronal hyperpolarization. 3. An area within the brain in which myelination is completed last is the a. cerebrum. b. brain stem. c. olfactory region. d. hippocampus. e. pyriform lobe. 4. _________________ is the most common cause of secondary epilepsy in young dogs. a. Lissencephaly b. Hepatic encephalopathy c. Hydranencephaly d. Hypoglycemia e. Hydrocephalus 5. Which statement regarding glucose use in the immature brain is correct? a. Receptor numbers for the glucose transport protein are high. b. Lactic acid can support 60% of cerebral energy metabolism. c. Receptor numbers for the ketone body transport protein are low. d. Receptor numbers for the lactic acid transport protein are low. e. The neonatal brain has a readily available source of ketones to prevent acute hypoglycemia. 6. Which statement regarding CDV encephalomyelitis is correct? a. CDV encephalomyelitis is the most common inflammatory cause of seizures in dogs younger than 1 year of age.

b. CDV causes acute leukoencephalomyelitis in young dogs. c. Seizure activity is characterized only by chewing gum seizures. d. Seizures are often controlled well with antiepileptic drug therapy. e. Seizure activity has not been associated with postvaccinal CDV encephalitis. 7. Which noninfectious inflammatory disorder is least likely to occur in young dogs with seizure activity? a. pug encephalitis b. Yorkshire terrier encephalitis c. Maltese encephalitis d. steroid-responsive meningoencephalomyelitis e. GME 8. Which factor is likely to predispose young dogs and cats to toxin exposure? a. increased bloodbrain barrier permeability b. increased skin hydration c. inquisitive behavior d. alterations in drug disposition e. all of the above 9. Which statement regarding primary epilepsy is correct? a. Inherited epilepsy can manifest with seizures in dogs younger than 1 year of age. b. Inherited epilepsy is a rare form of idiopathic epilepsy. c. Epilepsy does not occur in Labrador retrievers. d. All inherited epilepsies have an autosomal recessive mode of inheritance. e. Inherited epilepsy is a form of symptomatic epilepsy. 10. Which diagnostic method can provide a greater diagnostic yield if an inflammatory disorder is suspected of causing seizures in young animals? a. serology b. CBC c. CSF analysis d. funduscopic examination e. CT or MRI

June 2005

Test answers now available at CompendiumVet.com

COMPENDIUM