2nd Annual Veterinary Neurology Symposium, University of California, Davis - USA 2005 Close Window to return ______________________________________________________________________________________ to IVIS

Approach to the Seizure Patient

Richard A. LeCouteur, BVSc, PhD, Diplomate ACVIM (Neurology), Diplomate ECVN

A comprehensive case history, complete physical and neurological examinations, and a minimum data base consisting of results of hematological and serum chemistry analyses should be obtained for all animals suspected of having a seizure disorder, even if only one seizure has been observed. On the basis of this information a list of dierential diagnoses should be made. Further clinical laboratory, toxicological, or radiographic procedures may be indicated after the results of these initial tests are known.

HISTORY
The environment, nutritional status, immunizations, birth complications, previous illnesses or injuries, age at onset of seizures, type and frequency of seizures, possible occurrence of localizing signs before or during the ictus, and inter-ictal signs, may provide important diagnostic information. Of particular interest are a description of the seizures and the age, breed and gender of the animal.

Description of Seizures
A description of an animals seizures, their frequency and duration, and the animals behavior between seizures (inter-ictal period) may be helpful in determining the cause of a seizure disorder. It is important to determine whether a seizure has occurred and to distinguish it from a syncopal episode (resulting from cardiac and/or pulmonary disease), narcolepsy or cataplexy, or episodic weakness (resulting from myasthenia gravis, polymyopathy, polyneuropathy or metabolic abnormality). Any involuntary phenomenon that is episodic and recurrent should be evaluated as a seizure. Tonic and clonic muscle movements, with or without loss of consciousness, accompanied by signs of autonomic disturbance such as urination, defecation, or salivation are highly suggestive of a seizure. Loss of consciousness accompanied by muscle accidity is more often associated with narcolepsy or syncopal episodes. Collapse and muscle accidity without loss of consciousness are more consistent with episodic weakness resulting from a motor unit disease or metabolic dysfunction. Partial seizures are characterized by a localizing sign that is indicative of the part of the brain acting as the epileptogenic focus (Table 1). The localizing sign may be motor, sensory, or behavioral in nature, depending on the area of the brain aected. Animals may turn their head to one side, show tonus and/or clonus in one limb or ipsilateral thoracic and pelvic limbs, or adopt abnormal postures. Sensory disturbances probably occur in animals but rarely are recognized. Animals may or may not appear to lose consciousness. If seizures originate from portions of the limbic system, they may appear as behavioral changes. These seizures have been termed psychomotor seizures and may be referred to as partial seizures with complex symptomatology. The clinical signs include somnolence, aggression, appetite changes, aimless running, screaming or barking, attacking inanimate objects, and chewing or licking movements. Autonomic signs (salivation, urination) may predominate. Behavioral disorders such as y biting, tail chasing, or ank sucking may reect partial seizure activity. A partial seizure may progress to a generalized seizure within seconds or minutes and localizing signs may be present only briey before the onset of a tonic-clonic seizure. Jacksonian seizures, which are characterized by a slowly spreading tonic spasm in one limb that may extend along one side of the body and then to the other side, rarely occur in dogs and cats. These seizures arise from the sensorimotor cortex in carnivores.

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Table 1. International classication of epileptic seizures in people.

Seizures that are generalized from the time of onset appear to be synchronous and symmetrical throughout the entire body (Table 1). Clinical signs include loss of consciousness, a tonic phase characterized by extension of the limbs, opisthotonus, and apnea that may last several seconds to several minutes followed by a clonic phase characterized by alternating contraction and relaxation of muscles of similar duration. The clonic phase is followed by a period of walking or running (paddling) movements. Urination, defecation, and/or salivation commonly occur during a seizure. Chewing movements of lips, jaws, and tongue may occur during a generalized seizure and may be seen at the onset of a seizure. Many animals do not exhibit pre-ictal signs, but some owners report a change in an animals behavior or expression. In addition, some animals search for their owners, hide from them, or cry out before the onset of a seizure. After the animal has regained consciousness it may appear normal immediately or may be depressed, confused, appear blind, bump into objects, or in some cases become aggressive for minutes to several hours after a seizure. This post-ictal phase may be longer (hours or days) in animals that have had multiple seizures in a short period of time. The type of seizure seen in dogs or cats may be useful in determining the nature of the underlying cause. Generalized seizures are characteristic of most metabolic and toxic causes of seizures, and of inherited or idiopathic epilepsy. Partial seizures usually are seen in animals with an acquired focal or multifocal cerebral abnormality that may be progressive or nonprogressive (eg, congenital cerebral abnormalities, neoplasia, encephalitis, or a previous episode of cerebral hypoxia, ischemia, trauma, or infection). However, partial seizures may be seen in animals with a metabolic encephalopathy that would be expected to cause generalized seizures, and partial seizures with or without secondary generalization may be seen in animals with inherited epilepsy (eg, beagle and Horaks laboratory dogs) and also in animals with idiopathic epilepsy that do not have pathological evidence of concurrent or prior intracranial disease. Psychomotor seizures may be seen in animals with lead poisoning. Similarly, animals with focal intracranial disease such as neoplasia may exhibit generalized seizures without localizing signs. The frequency and duration of seizures also are of importance in determining further diagnostic

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procedures that may be necessary and in deciding therapy. An increase in the frequency of seizures, especially in older animals, may be an indication of a progressive intracranial disease such as neoplasia, and investigation of possible intracranial causes of seizures is then warranted. It is important to determine if seizures occur at a certain time of the day or if they are related to exercise or feeding. Certain metabolic encephalopathies such as hypoglycemia or hepatic encephalopathy result in seizures at times related to feeding. The frequency of seizures in animals may be dicult to establish, and an owner should be questioned about both known seizure episodes and any suspected seizures (eg, evidence of urination and/ or defecation in inappropriate places or abnormal behavior such as that seen in the post-ictal phase of a seizure). Owners often overestimate the duration of an animals seizure. Usually seizures last from several seconds to minutes. If an animal has seizures that last longer than several minutes or seizures that occur in clusters (in which more than one seizure occurs within a 24-hour period) or episodes of status epilepticus (in which an animal has repeated seizures without regaining consciousness), anticonvulsant therapy usually is indicated regardless of the frequency of the seizure episodes. Age, Breed and Gender The cause of seizures often is related to the age of an animal. Therefore, the age of onset of seizures is important in forming a diagnostic plan for an animal with a history of recurrent seizures. Generally, animals with idiopathic epilepsy or a suspected inherited predisposition to seizures have their rst seizure between 6 months and 5 years of age, although seizures may not be recognized until an animal is older than 5 years of age. In some cases, however, epilepsy may be recognized in dogs younger than 6 months of age. Seizures may occur at an earlier age in ospring of epileptic dogs, and with increased inbreeding. Acquired epilepsy may result in onset of seizures at any age, and seizures may not occur for as long as 4 years after the initial cerebral insult that resulted in development of a seizure focus. Epilepsy inheritance has been proven in beagles and Horaks laboratory dogs. Data suggest epilepsy may be genetically determined in breeds such as Belgian (Tervuren) shepherd dogs, German shepherd dogs (Britain), keeshonden, and Collie dogs. Several breeds of dogs have been reported to have a high incidence of idiopathic epilepsy. These include golden retriever dogs, Irish setters, Saint Bernard dogs, German shepherd dogs, American cocker spaniels, Wire-haired fox terriers, Alaskan malamutes, Siberian huskies, and miniature poodles. Epilepsy may have an inherited basis in these breeds, although genetic studies have not been performed. Idiopathic epilepsy may occur in dogs of any breed, including mixedbreed dogs. In one study, the incidence of seizure disorders appeared to be constant across breeds and mixed-breed boundaries. In the same report, the high frequency of seizure disorders in certain breeds was shown to reect the popularity of these breeds. Idiopathic epilepsy also occurs in cats and may be the cause of seizures in as many as 28% of cats with seizures. Acquired epilepsy may occur in any breed of dog or cat. Seizure disorders in dogs and cats generally do not appear to have a sex predilection. Nevertheless, inherited epilepsy in beagles more frequently aects males than females (5:1). A higher incidence of epilepsy also has been reported in male German shepherd dogs in Britain and keeshonden. An increased frequency or severity of seizures may be seen in female dogs during estrus or pregnancy. Miscellaneous Considerations Other factors are important in determining the possible causes of seizures. For example, does the animal have a known history of head trauma (especially if accompanied by loss of consciousness), meningitis, encephalitis, systemic infection, hypoxic episode or dicult birth, toxin exposure, or access to possible toxins such as lead-containing paint or linoleum in old houses? Is there a history of seizures in a related animal? Has the animal been vaccinated for canine distemper and is the vaccination current? What is the animals diet?

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Physical Examination
A thorough physical examination is important in all animals with a seizure disorder. Cardiac or respiratory abnormalities may result in syncope or episodic weakness that the owners may interpret as seizures. Tumors outside the calvaria may have metastasized to the skull, meninges or brain, resulting in seizures. Nasal discharge or epistaxis may be associated with nasal tumor or infection that may also extend intracranially. Systemic illness or endocrine abnormalities also may result in seizures. Palpation of the skull may detect abnormalities associated with trauma, tumors, or congenital defects. Ophthalmoscopic examination may detect chorioretinitis associated with viral, fungal, or protozoal CNS infection. Papilledema resulting from increased intracranial pressure may be present in animals with congenital or acquired hydrocephalus, neoplasia, or CNS infection.

Neurological Examination
A thorough neurological examination is also important in animals with a history of seizures. Animals with epilepsy usually are neurologically normal between seizures, whereas animals with seizure disorders as a result of toxic, metabolic, congenital, neoplastic, or inammatory disease often have neurological abnormalities between seizures. However, animals with acquired epilepsy may have other neurological decits in addition to seizures, and seizures may be the only abnormality in some animals with CNS neoplasia or metabolic abnormalities such as hypoglycemia or lead poisoning. When possible, it is important to examine animals between seizures and when the animal is not in a postictal state. Many animals show temporary neurological abnormalities (blindness, weakness, behavior change) for minutes to hours after a seizure. Animals that have had an episode of status epilepticus or a cluster of seizures may require several days to one week without further seizures before a reliable neurological examination may be performed. Neurological examination ndings may also be aected by CNS depressant drugs such as anticonvulsant or anesthetic agents.

Minimum Data Base

A complete blood count, serum chemistry prole, including a fasting blood glucose, calcium, BUN, albumin, total protein, cholesterol, triglycerides, ALT, and alkaline phosphotase determinations, and urinalysis should all be done for animals that have had one or more seizures to detect any metabolic or toxic cause of the seizure disorder or evidence of systemic infection. Blood samples should be collected after at least a 12-hour fast, because lipemia seen after feeding may invalidate some results but, if present after fasting, lipemia may be abnormal. Hypoglycemia resulting from anorexia, illness, or metabolic dysfunction frequently causes seizures in dogs younger than 6 months of age. In older dogs (usually more than 5 years of age) hypoglycemia may result from the presence of an insulinsecreting tumor (insulinoma). In these animals, fasting for more than 24 hours may be necessary to induce hypoglycemia. Blood lead quantication should be done in an animal with possible exposure to lead-containing materials, in all animals from areas where the incidence of lead poisoning is high (big cities, areas with old houses, etc) and in animals that are less than 1 year of age (as these animals have a higher incidence of lead poisoning). Blood lead quantication is the most reliable way of detecting lead poisoning, because hematological abnormalities are not always present and aected animals may or may not show abnormal behavior between seizures. Radiographs of the thorax or abdomen may be indicated as part of the minimum data base, particularly in animals older than 5 years of age or in animals in which results of a physical examination suggest abnormal pulmonary or cardiac function. Fecal examination should be done in puppies with a seizure disorder. A heavy intestinal parasite burden may be associated with seizures, probably as a result of induced metabolic abnormalities such as anemia or hypoproteinemia. However the specic cause of seizures in these cases is usually undetermined.

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CAUSES OF SEIZURES
The normal brain is capable of convulsing in response to a variety of stimuli within the central nervous system and to many external inuences. Consequently, the causes of seizures are numerous. Disorders that induce seizures may arise either outside the nervous system (extracranial causes) or within the nervous system (intracranial causes) (Table 2). Each of these groups of causes may be divided in turn into two categories. Extracranial causes are divided into those that originate outside the body (eg, toxic agents) and those that arise within the body but outside the nervous system (eg, hypoglycemia). Intracranial causes of seizure disorders may be divided into progressive and nonprogressive diseases. Progressive causes of seizure disorders include those diseases that, in time, may aect an increasing volume of brain tissue (eg, neoplasia), and may produce clinical signs other than seizures. Nonprogressive intracranial causes of seizures include inherited, acquired, and idiopathic true epilepsy.

Table 2. Causes of seizures in dogs and cats.

Clinically, it is essential to distinguish between progressive and nonprogressive brain diseases that produce seizures. Therapy for progressive diseases requires not only control of seizures but also specic therapy for the underlying disease. If therapy of the underlying disease is not possible, the veterinarian should at least provide an accurate diagnosis and prognosis. On the other hand, it is seldom possible to make a precise etiologic or anatomic diagnosis in nonprogressive seizure disorders of intracranial origin (ie, epilepsy). Once the nonprogressive nature of the cause of a seizure disorder is established, therapy with an anticonvulsant medication is indicated.

Extracranial Disorders
Extracranial disorders may alter brain metabolism and electrophysiology, leading to paroxysmal discharges and seizures. Because the disorders aect both hemispheres, primary generalized seizures usually occur, although other clinical signs may be superimposed on them. Extracranial disorders frequently result from various metabolic conditions, such as hypoglycemia, liver disease, hyperlipoproteinemia, renal disease, hypocalcaemia, and hypothyroidism. Toxicoses, including lead or organophosphate poisoning, caeine or theobromine toxicosis (from excessive chocolate consumption) may also result in seizures. Intestinal parasitism and hyperthermia are other extracranial causes of seizures.

Intracranial Disorders
Intracranial causes of seizures include malformations (eg, hydrocephalus), inammatory disorders (eg, canine distemper encephalitis), nutritional disorders (eg, thiamine deciency), neoplasia, cranial trauma, degenerative conditions (eg, storage diseases), and cerebral infarction (Schwartz-Porsche, 1994). Aected

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animals typically present with progressive neurological disease. In some animals, such as animals with a previous history of cranial trauma, morphological brain lesions may have occurred long before the rst seizures occur, and may be inactive but leave the brain in a seizure-prone state. In other animals, seizures may be an early sign of progressive brain disease, such as cerebral neoplasia, and may be the sole clinical sign for a prolonged period. With intracranial disease, secondary or primary generalized seizures occur in a wide variety of clinical manifestations, depending on the location and extent of the underlying lesion(s). The frequency of seizures may vary considerably, and the association with rest and sleep seems to be less pronounced than in idiopathic epilepsy (see later). Most intracranial diseases lead to other neurological or clinical signs during the interictal period, and these diseases may have a progressive or nonprogressive clinical course.

True Epilepsy
The seizures seen in association with idiopathic epilepsy are caused by functional disorders of the brain in which both hemispheres are aected by paroxysmal neuronal discharges. Epileptic seizures are generalized and symmetrical from the onset. Morphological lesions are not observed in the cerebrum of animals with true epilepsy, with the exception of animals with microdysgenesis (a condition where subtle alterations of embryofoetal development, such as increased neuron density, may result in a lowered seizure threshold). However, lesions such as gliosis, atrophy, or laminar cortical necrosis, may occur secondary to severe seizures, clusters of seizures, or status epilepticus. These lesions may evolve into a secondary epileptic focus. Idiopathic epilepsy of dogs or cats usually begins with a single seizure. The seizures most often occur during or following a period of sleep or rest, and rarely occur during periods of activity. Seizure frequency is variable (days to months between seizures), however the time between seizures usually decreases as the disorder becomes more chronic. Intervals between seizures may be uniform, or highly variable. Clusters of seizures may occur over hours or days in some breeds of dog (eg, German shepherd dogs, Saint Bernard dogs, Irish setters).

DIFFERENTIAL DIAGNOSIS
Information obtained from the history, physical, and neurological examinations and the results of a minimum data base may be used to form a list of dierential diagnoses. Idiopathic epilepsy may occur at any age, but it occurs most frequently in dogs or cats between 6 months and 5 years of age. Using idiopathic epilepsy as a reference point, a list of dierential diagnoses for seizure disorders may be formed for each of three age groups: <6 months of age, 6 months to 5 years of age, and >5 years of age. A list of the most common diseases other than epilepsy that may occur in association with seizures in each of these age categories is included in Table 3.

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Table 3. Most frequently occurring causes of seizures in dogs and cats other than true epilepsy.

ADDITIONAL DIAGNOSTIC TESTS

Selection of additional tests should be based on results of physical and neurological examinations and on the results of tests that comprise a minimum data base (Table 4). The dogs or cats age should also be considered because certain disorders that may result in seizures are more frequently associated with younger dogs and cats (Table 3).

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Table 4. Diagnostic approach for a dog or cat with a seizure disorder.

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An extracranial cause of seizures is most likely associated with an abnormal minimum data base (Table 4). Additional tests may be selected to investigate such extracranial causes. For example, in animals with serum chemistry abnormalities that are consistent with liver disease (eg, low BUN, elevated ALT and /or alkaline phosphotase, low glucose, low total protein, etc) further tests may be needed to assess liver function. Quantication of serum bile acids after a 12-hour fast, and 2 hours postprandially, provides a reliable indicator of liver function. After conrmation of an extracranial cause for seizures, specic therapy may be indicated. In certain instances, anticonvulsant medication may be instituted in addition to specic therapy of an extracranial disorder to control seizure activity during such therapy. Depending on the nature of the underlying extracranial disease, such anticonvulsant therapy may or may not be discontinued at some later date. It should be remembered that in rare instances both an extracranial and an intracranial disorder may be present, and yet the extracranial disorder may not be related to the cause of the seizures. For example, it is possible that a dog with seizures may have hepatic cirrhosis and a primary intracranial neoplasm. For this reason, it is essential to monitor closely the response of an animal to therapy for an extracranial cause of seizures. Should the seizures continue or worsen in the face of a response to therapy of the extracranial disease, then further diagnostic tests may be indicated. An intracranial cause of seizures is most likely associated with normal results of a minimum data base (Table 4). An intracranial cause should also be considered if the results of additional tests completed to fully investigate abnormalities seen on a minimum data base prove to be normal. Cerebrospinal uid (CSF) analysis is essential for any dog or cat in which an intracranial cause for seizures is suspected. In addition to submission of CSF for cytological examination and protein quantication, aerobic and anaerobic bacterial and/or mycotic culture and sensitivity testing may be done, and titers for infectious agents may be completed (eg, cryptococcosis, canine distemper, etc). Radiographs of the skull may be useful for detecting calvarial tumors, mineralized intracranial neoplasms, or fractures of the skull associated with head trauma. Electroencephalography (EEG) is helpful in the diagnosis of congenital malformations such as hydrocephalus or lissencephaly. The EEG can also be useful to evaluate electrical events associated with a seizure that may occur during recording and in the identication of paroxysmal electrical events that occasionally occur inter-ictally in the recordings of some epileptic animals. Advanced imaging modalities, such as x-ray computed tomography or magnetic resonance imaging, may provide specic information regarding the location and extent of intracranial lesions such as neoplasms, granulomas, infarcts, or hemorrhages. Animals more than 6 months and less than 5 years of age that have a history of a seizure or of recurrent seizures, that have normal physical and neurological examinations, and that have normal results on a minimum data base most likely have a non-progressive intracranial disorder. Ideally, additional diagnostic procedures should be done in such animals, however, consideration of costs involved and potential for morbidity and mortality associated with anesthesia may result in a decision to delay further tests pending assessment of response to anticonvulsant medication. If a response to therapy is not seen, if seizure frequency or severity increase, or if additional clinical signs develop, then further diagnostic tests to investigate progressive intracranial causes of seizures should be done.

______________________________________________________________________________ This syllabus is reproduced in the IVIS website with the permission of the Organizing Committee