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Feline Seizure Disorders

by Chelsea Sonius
Fall 2010


Background

Seizures are one of the most common neurological disorders in cats.  A recent study has suggested a prevalence rate of 2.1% of the entire feline population. (1)  Cats of all ages and breeds can be affected by seizures; however, many of the underlying causes of feline seizures are more common amongst the aging feline population.  The clinical appearance, onset, severity of seizure disorders and underlying causes are variable amongst feline patients.  The aim of this paper is to discuss the classification, causes, diagnosis, and treatment of seizure disorders in cats.

Pathophysiology

All seizures originate in a region of the brain called the cerebrum.  The cerebrum is responsible for sensation and perception of stimuli, planning, initiating and controlling movement, and also plays a role in emotion, behavior, and control of autonomic functions.  Due to the dynamic functions of the cerebrum, seizures have a wide range of clinical presentations.  Although the clinical appearance, onset, and severity of seizure disorders are variable amongst feline patients, the pathophysiology at the cellular level is the same.  The onset of a seizure occurs due to an imbalance between excitation and inhibition of neurons in the brain, and is the result of excessive electrical activity in the cerebrum. (2)

Every neuron in the brain has the potential to produce seizures if a "seizure threshold" is overcome; however, not all neurons have the same excitation/seizure threshold.  This threshold is determined by a number of factors, such as neuronal environment and neurotransmitter levels.  As factors favoring excitation of neurons are increased, the threshold is more easily crossed, resulting in predisposition to seizure activity.  Several neurotransmitters and receptors have been shown to play a role in determining the threshold and propagation of seizure activity.  GABA is the primary inhibitory neuron in the brain, and has been postulated to play a role in the propagation of seizures in the brain. (3)  Dysfunction of the GABA receptor and/or a decrease in GABA concentrations within the cerebrum will lead to decreased activation of this receptor complex and ultimately decreased neuronal inhibition.  This can propagate the imbalance of excitation-inhibition within neurons of the brain.  Glutamate is the primary excitatory neurotransmitter in the brain and binds to a receptor called the N-methyl-D-aspartate (NMDA) receptor.  This receptor has also been shown to play a role in promoting increased excitability of neurons within the brain. (4)  The neurons in the brain have intricate connections.  Increased activity in one region of the cerebrum can cause increased activity in other regions of the cerebrum through these connections, a phenomenon termed "hypersynchronous activity".  The brain becomes uncontrollably "hyperexcitable" which leads to seizure activity.

This increased hyperexcitability may occur within specific foci of the brain, termed a focal or partial seizure, or may spread diffusely throughout the cerebrum, termed a generalized seizure.  Further, a seizure that initially presents as a focal seizure may lead to generalized seizure activity. (5)  Focal and generalized seizures are two broad categories of seizures, further classification is discussed below.

Classification – Etiology of Seizures.  There are numerous ways of classifying seizures in the animal population.  As discussed previously, seizures may be described as being partial (focal) or generalized depending on the extent of cerebral involvement.  Seizures may also be classified according to the underlying cause.  A primary seizure disorder is one in which no underlying cause (such as intracranial/brain disease, metabolic disease, etc.) can be found.  This type of seizure disorder is commonly termed "idiopathic epilepsy", and is often associated with a genetic component and breed disposition.  This type of epilepsy is not as common in the cat as it is in the dog, and no feline breed associations have been described.  However, it has recently been reported that in a study of 91 cats presenting for seizure disorders, 25% were suspected to have idiopathic epilepsy. (1)

Conversely, a secondary seizure disorder is one in which an underlying cause of the seizures can be determined.  This classification is further broken down into "symptomatic" and "reactive" categories.  Symptomatic seizures are seizures which occur due to intracranial disease (disease within the brain), whereas reactive seizures occur secondary to disease process occurring outside of the brain.  The same study from above found that of the 91 cats evaluated for seizure disorder, 50% presented with symptomatic seizures, whereas 20% presented with reactive forms. (1)

Generalized seizures may occur due to primary or secondary seizure disorders.  Partial/focal seizures, however, are always due to an underlying acquired disease process, and are therefore always classified as secondary seizure disorders.

Classification – Clinical Signs of Seizures.  Seizures are further classified within the generalized and focal category based upon the clinical presentation of the seizure.  Generalized seizures are seizures in which there is involvement of the entire cerebrum.  These seizures affect the entire body simultaneously and can be characterized as being tonic, tonic-clonic, atonic, myoclonic, or non-convulsant/absence.  Different phases of a seizure exist, and the classification into one of these categories is based on the presentation of these phases.  There are four phases identified in patients with seizure disorders: an aura or prodromal period, ictus, postictus, and interictus period.

The aura/prodromal period is the period of time preceding the seizure activity (minutes to days) and often includes behavioral or mentation changes.  People with seizure disorders often describe this period as alterations in emotion/sensation.  In animals, owners may notice strange behaviors such as snarling, dilation of pupils, fur standing up on end, or other abnormal behavior.  Ictus is the time in which seizure activity is occurring, generally lasting no more than a few minutes.  The ictus or ictal period varies amongst patients, and seizures are classified based on the character of this ictal period.  Postictus is the period of time following seizure activity (minutes to days), and is often accompanied by neurological and behavioral abnormalities.  Animals often appear confused and disoriented.  They may pace around and appear blind for a short period of time.  Interictus is the time period of normalcy in between seizure episodes. (2)

Tonic Seizures-Generalized.  Patients having tonic seizures often show an aura immediately preceding the seizure.  Behaviors such as restlessness, wandering, hiding, licking, and vocalization may be noted during this time.  During the ictus phase the cat loses consciousness, falls to the ground, demonstrates increased rigidity of all four limbs, and may show extension of the neck, a condition termed opisthotonos.  The cat often stops breathing during this time.  Urination, defecation, and salivation may also occur.  This form of seizure generally lasts less than 1 minute, and a postictus of a few minutes is generally noted.  The postictus often includes disorientation, wandering, vocalizing, inability to recognize the owner, and temporary blindness. (2)

Tonic-Clonic Seizures-Generalized.  These seizures start out with a presentation that is identical to tonic seizures, however, they also have a ?clonic? phase associated with them.  The clonic phase in cats is characterized by flailing of the limbs; the cat may even propel themselves into the air.  Because these seizures can be violent in nature, the cat may sustain injuries during this time.  The postictus is similar to that of tonic seizures.

Atonic Seizures-Generalized.  Atonic seizures are rare.  These seizures are characterized by complete lack of tone in the muscles.  The animal collapses and remains flaccid throughout the ictal period.

Myotonic Seizures-Generalized.  Myotonic seizures are also very uncommon.  They are characterized by major jerking of a muscle or group of muscles, and have a clinical presentation much different than that of tonic-clonic seizures.

Nonconvulsive or Absence-Generalized.  In humans, these seizures are characterized as a brief loss of consciousness with absent motor activity.  These forms of seizures are difficult to diagnose in an animal, as we are not able to tell that the animal has lost consciousness simply by looking at them.

Partial Motor-Focal.  Partial motor seizures arise near the motor cortex of the cerebrum, which is responsible for muscle contraction and movement.  These seizures are characterized by increased muscle activity and movement of one part of the body.  Often, this motor activity is increased in one limb only, or is confined to muscles of the face.

Psychomotor or Complex Partial-Focal.  Complex partial seizures are associated with behavior and mood changes, and are thought to arise in areas of the brain such as the hippocampus, amygdala, and temporal pyriform lobe.  In the cat, these seizures are often classified by non-responsiveness to external stimuli and a "trance-like" stare.  The cat may be found staring at a wall, and will often have facial twitching.  Behaviors such as growling, hissing, and circling during seizure activity are also common. (11)

Status Epilecticus.  Status epilecticus is a state in which generalized seizures occur uninterrupted for an extended period of time.  It is a life-threatening medical emergency, as prolonged seizure activity can lead to hyperthermia, permanent neurological consequences, cardiovascular and respiratory disturbances, disturbances in blood flow, and ultimately death.  Status epilecticus may occur following acute brain injury, toxic/metabolic insults to the brain, withdrawal from medications to control seizures, or when the patient fails to respond to anticonvulsant medication.  Emergency efforts should aim to stop seizure activity, cardiovascular and respiratory stability, and decrease hyperthermia.  A thorough investigation regarding the underlying cause is critical, and treatment options should address both the seizure activity and the cause.  The prognosis for patients with status epilecticus depends on the inciting disease process.  The longer the patient remains in status epilecticus, and the more difficult it is to stop the status, the worse the prognosis becomes for the patient. (19)

Etiology

Any disease process that alters brain function has the ability to produce seizures.  As described earlier, "Symptomatic" seizures are seizures that are caused by diseases that are intracranial in nature, such as neoplasia (brain tumors), cerebral vascular disease, or cerebral inflammation.  Seizures can also be caused by primary disease process occurring outside of the brain, such as metabolic disorders or toxicities, that lead to secondary brain involvement.  These seizures are termed "reactive" seizure disorders.  Intracranial diseases are far more common in the feline patient.  However, especially as the cat ages, metabolic causes of seizure disorders must be considered.

Symptomatic Seizure Disorders.

Neoplasia.  Meningiomas, lymphoma, and glial cell tumors are the most common intracranial cancers of cats.  A recent study investigating tumor types in 160 cats found 58% to be meningiomas, 14% to be lymphoma, and 8% to be glial cell tumors. (8)

Meningioma.  Meningiomas are the most common cause of intracranial neoplasia in cats.  They are slow growing, space occupying, compressive tumors that arise from cells on the exterior surface of the meningeal layers that envelope the brain.  As this is a slow-growing tumor, signs generally occur progressively over several months.  Clinical signs may include behavioral changes, changes in gait that are commonly localized to one side of the body, weakness that is often localized to one side of the body, and other neurological deficits that are often most easily noted by the attending veterinarian.  Not all patients with meningiomas present with seizure disorders, and seizure disorders may be either generalized or focal in nature.  The mean age for feline patients diagnosed with meningiomas in one study was 12.1 years of age, and males appear to be more affected than females. (8)

Lymphoma.  Lymphoma is also a leading cause of intracranial tumors in cats.  Lymphoma is a form of cancer that is caused by inappropriate growth and proliferation of lymphoid tissue.  Lymphoid tissue is found in numerous areas throughout the body, and consequently, lymphoma can affect many different tissues and organ systems.  Presentation is variable, depending on the tissues that are affected, and may include signs similar to that of a meningioma.  However, cats with lymphoma often have concurrent spinal cord involvement and signs such as weakness and alteration in gait may be more prevalent than in patients with mengioma.  Further, depending on the extent of other organ system involvement, there may be a variety of other clinical signs not associated with CNS dysfunction. (11)  Some common clinical signs that may be seen in patients with lymphoma are weight loss, anorexia, vomiting, increased drinking, increased urination, and increased respiratory effort.  The median age for cats diagnosed with intracranial lymphoma was younger than those diagnosed with meningioma (10.5 years) and there does not appear to be a sex predilection. (8)

Glioma.  Glial cell tumors are the third most common form of intracranial neoplasia in cats, with astrocytomas most commonly represented. (9)  Gliomas are tumors that arise due to proliferation of the cells within the brain that play a support role for the neurons that carry out brain activity.  Astrocytomas are a specific type of tumor that arises from support cells called astrocytes.  Clinical signs depend on the exact region of the brain affected and are similar to those found for patients with mengioma.  The median age for presentation has been estimated to be 12.9 years, and in one study, 5 males to 1 female was affected. (8)

The prognosis for feline patients with intracranial neoplasia is variable, depending on the tumor type and extent of tissue involvement.  Cats with meningiomas often carry a better prognosis than those with glial cell tumors or lymphoma, as meningiomas are often able to be removed surgically.

Vascular Diseases.  Any disease condition affecting the delivery of blood to the brain parenchyma also has the propensity to produce CNS dysfunction and seizure disorders.  Common vascular disturbances in the feline patient include Feline Ischemic Encephalopathy (FIE), polycythemia, and hypertension.

Feline Ischemic Encephalopathy (FIE).  Feline Ischemic Encephalopathy is a disease characterized by vasculitis and subsequent thrombosis (clotting) of the vasculature in the brain.  As this disease affects the cerebrum, seizures are a common clinical finding.  Other common clinical findings include behavioral changes and unilateral neurological signs such as head-tilt (head tilted toward one side or the other), ataxia (gait changes), and unilateral blindness.  The pathogenesis of this disease is not well understood; however, cardiac disease, feline infectious peritonitis, and intracranial migration of the Cuterebra parasite have been hypothesized to play a role. (9)  Cats are not the typical Cuterebra host; however, aberrant migration in the feline host can occur.  Young to middle aged outdoor cats appear to be the most susceptible, and it is believed that the Cuterebra parasites gain access to the brain through the nose or middle ear.  A few case studies report that cats with cuterebriasis displayed respiratory signs such as sneezing and nasal discharge within 1 week prior to neurological signs. (12)

Polycythemia.  Polycythemia is a term used to describe an increase in circulating red blood cells that may occur secondary to disease conditions that cause hypoxia (low tissue oxygen) such as cardiovascular disease or pulmonary disease, and diseases that result in increased endocrine stimulation to produce new red blood cells via the hormone erythropoietin (such as inappropriate renal erythropoietin secreting tumors).  Elevations in red blood cell mass may also be due to a primary dysfunction of the bone marrow, and is termed polycythemia vera.  In the feline patient, bone marrow disorders are the most common cause of polycythemia.  Increased red blood cell mass and volume leads to "sludging" of the blood and decreased blood flow, which causes damage to the brain tissue, and subsequent neurological dysfunction.  Seizures, behavioral changes, blindness, and muscle disturbances are common clinical findings. (8)  Other clinical signs that may be present depend on the primary cause of polycthemia.  For example there may be evidence of cardiopulmonary disease (exercise intolerance, weakeness, etc.) pulmonary disease (increased respiratory effort, etc.) or renal impairment (increased water consumption, increased urination, etc.).

Hypertension.  Hypertension in the cat is defined as a systolic blood pressure exceeding 160-170 mmHg, and is a common systemic disease amongst the feline population.  It occurs secondary to diseases such as renal disease, hyperthyroidism, and diabetes mellitus, all of which are common diseases of the feline patient.  Systemic hypertension most commonly affects the eye, kidney, heart, and brain.  By complicated mechanisms, elevations in systemic blood pressure can cause elevations in intracranial pressure.  This increase in intracranial pressure can lead to neurologic dysfunction.  Neurologic signs are similar to those discussed previously, with the most common presenting neurologic signs being seizures and vestibular disease. (15)  Vestibular disease in animals is a condition similar to vertigo in humans, wherein the animal has an altered sense of balance and visual perception of its surroundings.  Patients with vestibular disease will often have a head-tilt, will show evidence of alternating eye movements (a term called nystagmus), and may show signs of altered gait and circling.  Other clinical signs depend on the degree of involvement of other organs such as the eye (retinopathy, choroidopathy), kidney (renal disease), and heart (cardiomyopathy).  The underlying cause for hypertension should be determined and treated.

Inflammatory/Infectious.  Any inflammatory or infectious disease that is able to reach the cerebral cortex has the potential to induce seizures in the affected patient.  In the cat, some of the more common inflammatory and infectious diseases include Feline Infectious Peritonitis, Toxoplasmosis, and Cryptococcus.  FeLV and FIV positive cats are at greater risk of developing these diseases due the immunosuppressive effects of these viruses.

Feline Infectious Peritonitis (FIP).  Feline infectious peritonitis virus is thought to be acquired via a mutation in a common, much more benign, feline virus, called the feline enteric corona virus.  Feline enteric corona virus does not normally cause disease in cats, but when a mutation occurs in this virus, eline infectious peritonitis virus results and causes devastating disease in the cats that it affects.  FIP can cause vasculitis and inflammation in many different organ systems, most commonly involving the abdomen, kidney, and brain.  There are two forms of the disease that are generally encountered, and are commonly termed "wet" and "dry" forms.  The "wet" form is more commonly seen in young cats, and is characterized by effusions (accumulation of fluid) of the thoracic and abdominal cavities.  The non-effusive, or "dry" form, is common in older cats, and does not tend to cause fluid accumulations/effusions as is seen in the "wet" form.  Both the "wet" and "dry" forms can cause inflammatory lesions in the brain that lead to clinical neurologic symptoms, including seizures.  However, a recent study indicated that it is more typically seen in older cats with non-effusive form. (6)  The most common signs of neurologic disease that have been described in patients with FIP include behavioral changes, dementia, and central vestibular disease (as described above in the hyperthyroid section).  This study reported a 34% incidence of seizures in cats showing neurological disease.  Along with CNS disease, FIP can affect many other organ systems, and concurrent clinical signs will depend on the organ systems involved. (6)  The prognosis for patients with FIP is grave. (14) 

Toxoplasmosis.  Toxoplasmosis is caused by the intracellular parasite Toxoplasma gondii.  T. gondii is an intracellular protozoa that is acquired after ingestion of infective T. gondii eggs or after ingestion of meat from infected animals.  In the cat it is most commonly acquired by hunting of rodents.  It is a zoonotic disease that may also affect humans.  In humans it is most commonly acquired via ingestion of undercooked meat.  Following infection, T. gondii infects the intestinal cells and can invade other tissues by way of blood or lymphatic flow.  Cats will commonly show gastrointestinal signs during infection, but other tissues and organ systems may be involved, as well.  One paper indicated that of cats with extra-intestinal signs of toxoplasmosis, approximately 7% showed neurologic involvement. (17)  Neurological signs such as seizure, uncoordination, paresis (weakness of the limbs), and blindness may be seen.  Patients exhibiting neurologic signs associated with Toxoplasma have a grave prognosis. (14)

Cryptococcosis.  Cryptococcus is the most common systemic fungal infection of cats, and is caused by the organism Cryptococcus neoformans.  Along with neurologic disease, cats with Cryptococcus infections often also show evidence of skin lesions on the face, respiratory disease, and/or ocular disease.  The neurologic signs seen will depend on the region of the brain that is affected. (11)  Patients with cryptococcosus involving the CNS may require life-long treatment with antifungals; as with all infectious diseases, patients with FeLV or FIV have a poorer prognosis. (13)

Reactive Seizure Disorders.  A variety of diseases originating from extracranial sources may also cause seizure disorders in cats, which are especially important to consider in the aging feline patient.  Some of the more common metabolic abnormalities causing seizures in cats include hepatic encephalopathy, renal encephalopathy, hypoglycemia, and hyperthyroidism.

Hepatic Encephalopathy.  Hepatic encephalopathy may occur in cats with liver dysfunction (such as a portosystemic shunt or following hepatic lipidosis).  Both of these disease processes lead to an elevation in circulating ammonia, as the liver is responsible for converting ammonia to less noxious byproducts.  Excess ammonia leads to elevations in the neurotransmitter glutamate, which causes excitation of the NMDA receptors in the brain.  Increased activity of the NMDA receptors causes an increase in excitatory transmission in the brain, which, in essence, lowers the seizure threshold in the brain. (18) Patients with hepatic encephalopathy will often appear mentally dull, may show signs of visual deficits and circling, and may walk into corners or press their head against the wall, especially following meals.  The feline patient with hepatic encephalopathy induced seizure disorders will also often show other non-specific signs of illness such as weight loss, vomiting, anorexia, or a yellow tinge to the skin, due to liver dysfunction.  If the shunt can be repaired and the lipidosis corrected, prognosis is good. (14)

Renal Encephalopathy.  Seizures may also be precipitated by kidney dysfunction.  Renal encephalopathy or uremic encephalopathy may occur in patients with kidney failure, or patients who have recently undergone kidney transplantation or dialysis.  Several mechanisms are thought to induce seizures in these patients including increased circulating hormones that act as neurotoxins, vasculitis secondary to increased circulating urea, hypercalcemia leading to mineralization of neurons, and neuronal dehydration. (5)  Patients with renal encephalopathy will show signs consistent with renal failure such as increased drinking, increased urination, weight loss, anorexia, and lethargy.

Hypoglycemia.  Hypoglycemia in adult cats is most commonly caused by an insulin overdose, sepsis, or an insulin-secreting tumor (less common).  In kittens, due to a lesser degree of glucose storage pools, it can be caused by inadequate intake, as well.  The brain depends entirely on glucose for energy, and a certain blood glucose level must be maintained for the brain cells to function properly.  Patients suffering from hypoglycemia induced seizure disorders will often present weak and with mentation changes (irritibiliity, obtundation, coma).  It is important to correct the hypoglycemia ASAP in order to prevent further brain damage from occurring. (5)

Hyperthyroidism.  Hyperthyroidism is a common disorder of the feline patient and can be a cause of metabolic-induced seizures.  It is believed that elevated thyroid hormones may play a role in decreasing the seizure threshold in the brain by altering the level of neurotransmitters, as well as by directly increasing neuronal excitability.  Elevations in thyroid hormones also increase oxygen and glucose demand to the brain, creating a potential for hypoxic and hypoglycemic induced seizures.  Patients will present with signs consistent with hyperthyroidism, such as increased appetite, weight loss, increased drinking and urination, and increased activity levels. (11)

Toxins.  A variety of toxins can cause seizures in the cat.  Toxins such as permethrin (an insecticide found in flea collars), organophosphates, lead, rodenticides, and many more can cause neurological signs and seizure disorders by a variety of very different mechanisms.  Other clinical signs induced by different toxins vary, as well; the history, clinical signs, and characteristics of the seizure will be helpful to the clinician in determining the likely toxins involved.

Diagnostic Evaluation

A thorough history, physical examination, and diagnostic work up is essential in determining the underlying cause of seizures in the cat.  An extensive history should be taken regarding the character the seizure activity, frequency of seizure activity, and length of time since the seizure activity has been occurring.  The clinician should take care in ruling out other conditions that may mimic seizures.  If possible, a video recording of the seizure activity can be extremely helpful in evaluating and characterizing the type of seizure that is occurring.

A thorough behavioral and medical history should also be taken.  Since seizures arise in the cerebrum, which is responsible for behavior in animals, almost all cats will have behavioral changes.  However, these changes might be subtle, and not all owners will recognize them.  Often, many owners will attribute these changes to old age in the geriatric patient, and not consider these behavioral changes to be significant.  For this reason, if a seizure disorder is suspected, it is very important for the clinician to ask specific questions regarding the cat?s behavior in order to gain a full appreciation of the extent of behavioral alteration that has occurred.  As with every exam, a medical history should be taken, as well.  A detailed medical history will often reveal clues to the etiology that the owner may not have considered to be related to the seizure disorder. (7,10)

A complete physical examination should be performed, with particular attention paid to the musculoskeletal, cardiovascular, and ophthalmic systems; as well as, of course, an in-depth neurological examination.  Specific attention to the musculoskeletal system can reveal abnormalities associated with neurologic disease, such as muscle weakness and atrophy.  The location of these abnormalities can aid the clinician in determining an anatomic location and diagnosis for the lesion.  The cardiovascular examination can help to differentiate syncope (fainting) from seizure activity, as well as provide evidence to help rule-out or rule-in diseases such as hypertension and vascular causes of cerebral disease.  The ophthalmic exam should also be thorough, as many diseases that commonly effect brain structures also affect structures of the eye, for example both FIP and Toxoplasma can cause chorioretinitis (inflammation of the retina and vascular supply to the eye).

The neurological examination can be difficult in feline patients, as they often oppose many of the examination maneuvers that are performed; however, the clinician should be diligent in trying to obtain the most thorough neuro examination possible. (10)  As discussed earlier, a patient with intracranial disease that is having seizures necessarily has involvement of the cerebrum.  However, the extent of cortical involvement and/or the extent of involvement of other structures within the brain will vary amongst cats, even amongst cats in which the same disease process is occurring.  Even very slight abnormalities in the neurological examination can be useful in helping to localize the area of brain involvement.

Before beginning any part of the physical examination the clinician should take note of the behavior and gait of the cat.  There are often slight changes in mentation and gait that can be missed when the patient is under the stress of a physical examination.  The cerebrum is responsible for producing behavior, and affected patients will often exhibit some degree of depression or peculiar behaviors While behaviors are not necessarily helpful in determining the exact location of the lesion within the brain, they can be helpful in determining that there is, indeed, cerebral involvement; solidifying evidence for seizures vs. some other clinical condition (such as syncope or muscle tremors).

Disorders in gait are of value in determining laterality and extent of the lesion.  For example, involvement of the right motor cortex may be expected to be involved in a patient exhibiting left- sided hemiparesis (muscle weakness lateralized to the fore and hind limb of one side of the body).  In addition to giving clues regarding the localization of the brain lesions, this can also be of useful in ranking a differential list.  A left-sided hemiparesis (left-sided weakness) would be less likely in a cat with a disease process that causes diffuse cerebral dysfunction (for example, hypertension), and would be more likely in a cat with a more localized lesion, such as a meningioma.  If the patient has had a seizure within the last 1 to 2 days, the neurological examination should be withheld for 24-48 hrs, as the postictal period can often cause difficulty in interpreting the neuro exam accurately. (20)

A complete neurological examination should include an examination of all cranial nerves.  The majority of cats with seizure disorders do not present with cranial nerve deficits.  However, if cranial nerve deficits are present, they can be useful in determining laterality, as well as extent of involvement of other structures of the brain.  Any part of the cranial nerve exam that requires a reaction to a stimulus (versus a simple reflex) involves some degree of cerebral involvement, and absence/inappropriateness of these reactions can be extremely valuable to the clinician in determining the location of an intracranial lesion. (20)

Finally, the clinician should look for evidence of other neurological deficits that could indicate involvement of structures outside of the cerebrum.  For example, a patient with a disease affecting the brainstem will often present obtunded with much more severe paresis and proprioceptive deficits (abnormal placement and correcting of limbs).  A patient with a head tilt or circling would likely indicate involvement of the vestibular system, where as a patient with hypermetria (exaggerated limb movements) and intention tremors (exaggerated movements associated with the onset of a planned motor activity) may indicate involvement of the cerebellum, etc. (20)  Clinical neurological signs taken together with other physical examination findings will allow the clinician to make and rank a differential list, which is imperative for determining which further diagnostics and treatment avenues to pursue.

A complete blood count (CBC), biochemical profile (including BUN, ALT, ALP, glucose, and calcium), urinalysis, and fasting bile acids should be performed for all patients with a history of seizures.  These tests will not only help to rule-out metabolic causes of seizures, but can also be useful in providing a baseline for monitoring treatment strategies down the road.  Phenobarbital, a drug very commonly used to treat seizures, can cause liver dysfunction; comparison of liver enzymes and bile acids pre and post treatment with this drug is very important in determining whether liver dysfunction is occurring.  Details regarding this are further discussed in the treatment section.

Finally, advanced diagnostics such as an MRI, CT, or CSF (cerebrospinal fluid) analysis can be performed to further characterize the extent and nature of intracranial disease.  MRI and CT can be extremely helpful in localizing regions of the brain that are affected.  If possible, MRI and CT should be performed before a CSF analysis.  CSF is contraindicated in patients with increased intracranial pressure due to masses or brain herniation, by performing the MRI/CT first, the clinician can first visualize if one of these processes is occurring.

These initial waves of diagnostics may provide the clinician with all the information that is needed to come up with a diagnosis.  Many times, however, additional tests (such as antigen testing for infectious disease, flow cytometry for characterization of lymphoma, ultrasonography for evidence of portosystemic shunt, etc.) are necessitated to further characterize the disease.  If an underlying disease cannot be found, the cat may be diagnosed with a primary or idiopathic seizure disorder. (21)

Treatment

If an underlying cause of seizures is determined, it should be addressed and treated accordingly.  Treatment of the underlying disease in some cases may lead to complete cessation of seizure activity, such as correction of hepatic encephalopathy following hepatic lipidosis or correction of hypoglycemia following an accidental insulin overdose.  Some disease processes are not as easily treatable/curable, however, and if seizures occur in great enough frequency, the cat will likely be placed on a long term anticonvulsant.  Further, even if the primary underlying cause is treated successfully, some seizure disorders may persist well after the inciting disease is gone.

Phenobarbital is the first line drug of choice for cats with seizure disorders.  The exact mechanism of seizure control produced by Phenobarbital is not entirely understood; however, it is thought to decrease glutamate release, increase activity in the GABA receptor complex, and inhibit the uptake of calcium. (5)  The primary side effects of Phenobarbital administration in cats include sedation, ataxia (abnormal gait), polyuria (increased urination), polydypsia (increased drinking), and polyphagia (increased food consumption).  In dogs, Phenobarbital has been found to cause liver dysfunction, but this has yet to be reported in cats.  Serum Phenobarbital levels should be monitored 2-3 weeks following initiation of therapy, to evaluate whether serum levels fall within the therapeutic range.  Levels should also be measured every 2-3 weeks following any dosage changes, and every 6 months during periods in which no drug administration changes have taken place.  Although cats have not been shown to develop liver toxicity while on Phenobarbital, it is still recommended that liver enzymes and bile acids be measured every 6 months to monitor for any liver changes. (21)

Potassium bromide is not considered a drug of choice for seizure control in the cat, as it is in the dog.  It has been shown to cause an allergic respiratory disease in 35 to 42% of cats receiving Potassium bromide therapy. (22,23)  Further, in comparison to Phenobarbital it is much less effective in controlling seizure activity in cats.

Cats in which Phenobarbital either fails to control seizures or causes excessive side effects may be placed on one of several adjunctive anticonvulsive drugs.  Leviteracetam appears to be a drug that is well tolerated in cats, and is thought to inhibit seizures by modifying neurotransmission.  Compared to other drug options, Leviteracetam has a lower incidence of side-effects, but can still cause sedation.  A recent study of 12 cats with idiopathic seizure disorders found that 70% of the cats showed decreased seizure activity following treatment with Levetiracetam. (24)  Several other alternative drugs are available for adjunct therapy if the cat does not respond well to Leviteraceteam, including Gabapentin, Zonisamide, Felbamate, and Topiramate.  The current health status of the animal, the nature of seizures, response to previous therapy, and financial constraints of the owner should all be considered when determining which drugs to use for adjunctive therapy.

As stated previously, cats should be monitored every 6 months for bile acids and Phenobarbital levels to maximize safety and effectiveness of treatment.  At this time, the patient should also receive a physical examination, and a detailed history should be obtained regarding the seizures and/or any other changes.  In some instances, cats are able to be taken off anticonvulsant therapy.  One paper recommends 6 months seizure-free as a guideline to start with. (22)  The patient should be weaned off of their anticonvulsant over the course of several weeks, as withdrawal seizures can occur with abrupt termination of drug.  With ongoing neurology and pharmacology research, our knowledge of feline seizure disorders and treatment strategies is ever-increasing.  Hopefully with continued medical improvements we will be able to more effectively diagnose and manage seizure disorders of cats in the future.

Bibliography

1.  Schriefl S, Steinberg T, Kasper M, et al.  Etiologic classification of seizures, signalment, clinical signs, and outcome in cats with seizure disorders: 91 cases (2000-2004).  J Am Vet Med Assoc, 2008; 233: 1591-1597.

2.  Lorenz MD, Kornegay JN:  Seizures, Narcolepsy, and Cataplexy, p.323-344.  In Handbook of Veterinary Neurology, 4th ed.  St. Louis, MO, 2004.  Saunders.

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