Proceedings- feline seizures.docx

PRACTICAL MANAGEMENT OF SEIZURES IN CATS
Daniel G. Hicks, DVM, MS, DACVIM (Neurology) Puget Sound Veterinary Referral Center, PLLC
Introduction
Seizures are a common clinical problem representing 2-3% of all feline cases presenting to the
veterinary practitioner. As with any other clinical problem it is important to clarify certain
clinical features in order to determine the underlying etiology, prognosis, and appropriate
treatment plan. Management of cats with seizures involves treatment of the underlying etiology
when known and medication to control seizures.
Effective management of seizures in cats includes client communication. Often, clinical
decisions are made based on historical information from the owner. Therefore, specific
questioning is required to help differentiate seizures from seizure-like syndromes such as
syncope, vestibular disease, or movement related paroxysmal problems. Differentiating these is
not always possible. Having owners videotape an episode may help understand the problem.
Other situations mandate broad diagnostic work-up. Also discussions should include ongoing
management of cats with seizures including therapeutic drug monitoring, routine blood work,
frequent drug adjustments, and the possibility of break-through seizures. They should also be
prepared for emergency visits to their veterinarian in the event of status epilepticus.
Pathophysiology
The pathogenesis of a seizure is multifactorial. Conceptually, appropriate balance between
neuronal excitation and inhibition normally prevents hypersynchronus abnormal electrical
activity. When the balance is shifted towards excitation seizures can result. If focal neuronal
excitation occurs in a discrete region of the brain partial seizures result. Depending on the
location of this activity (frontal, parietal, occipital, limbic system) various manifestations of
seizures could be seen. For example, motor seizure activity occurs when motor areas of the brain
are affected. Less clear in veterinary medicine is the incidence of limbic seizures. These could
manifest as behavior changes, episodes of absence, altered arousal, changes in appetite, and
nausea. Because these are more difficult to observe in veterinary medicine, this type of seizure
may be underreported. At times, focal seizure activity will secondarily generalize. Surrounding
neurons and neuronal networks become involved in the hypersynchronus activity due to an
upswing in excitatory neurotransmitters. What started as a focal (partial) seizure may become a
generalized tonic colonic seizure. If seizure activity begins in or near the thalamus (a centralized
switching station with diffuse neuronal networks) generalization may occur immediately or very
quickly after onset. Likely, the incidence of partial seizure activity with secondary
generalization is underreported since the initial partial seizures may go unrecognized by the
evaluator.

Seizures can be generalized (whole body tonic and/or clonic) or partial (movement of face,
single limb, ear, head, etc). As previously mentioned, some partial seizures may secondarily
generalize. One report found that about half of the cats evaluated had generalized seizures while
the remaining half had partial seizures with or without secondary generalization. Importantly,
type of seizure is not a predictor of underlying etiology and should not be used to determine
prognosis. Generally, it’s been reported that cats with symptomatic or reactive seizures tended to
have shorter survival times, while cats with no identifiable cause (idiopathic) had significantly
longer survival. Cats with idiopathic seizures typically are younger than cats with other seizure
types.
A universal system for classifying seizure etiology in cats has not been developed. However,
one commonly used system classifies them into 3 distinct categories: reactive, symptomatic, and
idiopathic. Reactive seizures are those caused by metabolic disease or toxin exposure. Renal
and liver encephalopathy, electrolyte and glucose abnormalities, and CNS intoxication are
examples of conditions that could cause reactive seizures. (Table 1) Symptomatic seizures are
those caused by organic brain disease such as neoplasia, meningoencephalitis, cerebrovascular
disease, and traumatic lesions. Symptomatic seizures are reportedly more common than reactive
seizures in cats (50 – 60% vs. 20-30%, respectively). In cats, unlike dogs, a genetic basis for
seizures has not been established. Therefore, the term “idiopathic” does not denote an inherited
form of epilepsy, but rather implies that no underlying disease can be detected.
While symptomatic epilepsy is reportedly more common than reactive or idiopathic, the true
incidence of various causes of seizures is not well known since most reports come from referral
institutions where selection bias is unavoidable.
Hepatic encephalopathy Severe uremia Hypoglycemia Common metabolic causes of seizures in Severe hyperthyroidism Severe anemia Hypocalcemia Hypertriglcyeridemia Table 1. Common metabolic causes of reactive seizures in cats.
Clinical examination
Clinical examination can help prioritize a list of differential diagnoses. It is important to note
that any cat, despite the underlying cause of seizure, may have neurological abnormalities during
the period following the seizure (post-ictus). Post-ictal intervals are variable, lasting hours to
days. Up to 50% of cats have post-ictal deficits including: central blindness (absent menace with
normal PLR’s), decreased postural reactions, altered mentation, anisocoria, and ataxia.
Therefore, repeated neurological evaluations should be performed. Many cats with seizure
disorders have unremarkable neurological evaluations during the inter-ictal period.
Unfortunately, this is not a good predictor of underlying etiology and consideration of
symptomatic, reactive, and idiopathic causes should still remain on the list of rule-outs.

In cats with persistent asymmetric neurological abnormalities, especially during the inter-ictal
period, symptomatic epilepsy should be suspected. Examples of neurological abnormalities of
the prosencephalon are listed in Table 2. Differential diagnoses for cats with structural disease
causing symptomatic epilepsy include neoplastic, inflammatory, vascular, and traumatic
diseases. Neoplasia may be primary (originating from tissue within the brain) or metastatic.
Inflammatory disease may be infectious (viral, bacterial, protozoal, or fungal) or non-infectious
(meningoencephalitis of unknown etiology). Vascular disease (ischemic or hemorrhagic infarct)
could be the result of a systemic problem such as hypertension, hypoproteinemia, systemic
inflammatory disease, endocarditis, endocrine disease, or toxic disease. Occasionally, adherent
parasite migration (cuterebra, etc) has been reported.
Circling Head pressing Contralateral hemiparesis Contralateral menace deficit Blindness Altered mentation Delayed or absent knuckling Hyper or hyporexia Aggression Table 2. Common signs suggestive of structural prosencephalic brain disease
Various metabolic diseases can lead to reactive seizures. The most common include diseases of
the liver and kidney, and diseases that cause electrolyte or glucose abnormalities. Reported
clinical features of cats with portosystemic vascular anomalies include copper colored irises and
ptyalism, however these clinical findings are neither senisitive nor specific. Myriad toxic insults
should also be considered. A complete list of CNS toxins can be found in several texts.
Diagnostic evaluation
Diagnostic work-up is highly dependent on individual clinical situations including age of cat,
other medical history, and the financial situation of the client. Ideally, a complete diagnostic
evaluation would include tests to screen for metabolic and structural disease. Magnetic
resonance imaging (MRI) is currently the gold-standard in evaluating the structure of the brain.
Management of cats with seizures varies considerably based on owner philosophy and
expectations, underlying cause of the seizure, concomitant illness, and financial constraints. It is
important to remember that ongoing cost and time commitments are often necessary to properly
monitor drug levels and organ function and to make emergency visits to a veterinarian in the case
of break-through seizures. Prior to initiating an extensive diagnostic plan, the owner should be
aware of the future commitments.
Treatment of the primary underlying disease should occur whenever possible. Each of these
conditions carries its own prognosis, treatment plan, and financial consideration. Simultaneous
treatment of the seizures is also important.
Antiepileptic drugs
The decision to initiate pharmacologic therapy for seizures balances many factors including,
severity and frequency of seizures, underlying disease process, and type of seizure (partial vs.
generalized). In general, it should be the goal to minimize or stop all seizure activity. Criteria
for deciding when to begin drug treatment can be found in Table 3.
Antiepileptic drugs (AED) should ideally control seizures with no or minimal side-effects and be
affordable to clients. Unfortunately, no single AED fits all of these criteria. Currently, a handful
of AED’s are commonly used in cats. These drugs are summarized in Table 4.
Phenobarbital is still commonly used and remains the drug of choice in many situations. With
serum drug monitoring and vigilant patient management successful long-term seizure control is
possible with minimal side-effects. Hepatotoxicity is uncommon when appropriate serum drug
levels are maintained. Increased eating, drinking, urinating, and lethargy are usually short-term
side-effects, but raise concern in many owners.
Short and long acting benzodiazepines are also useful in cats. Diazepam is generally safe, but
has been associated with idiosyncratic hepatic necrosis (rarely). Clonazepam is also safe, longer
acting, and has not been associated with hepatic necrosis.
Criteria for starting anticonvulsant drug therapy Symptomatic epilepsy is diagnosed per imaging or CSF analysis Status epilepticus event >2 isolated seizure events within a 6-9 month period >2 isolated cluster seizure events (cluster = two or more seizures within a 24-hour period) Seizures develop after severe exogenous trauma Post-ictal deficits are severe or prolonged Table 3. Criteria for deciding when to begin anticonvulsant drug therapy in cats.
A couple of novel AED’s developed for use in humans, levetiracetam (Keppra®) and zonisamide
have been used more frequently over the last few years. Levetiracetam has a poorly understood
mechanism of action, but it is thought to work on different ion channels than standard AED’s.
Studies in cats demonstrate that it is well absorbed orally and excreted by the kidneys relatively unchanged. Cats with renal disease may theoretically require dose reductions. Since there is no hepatic metabolism it could be used in cats with hepatic disease. Additionally, it appears to have a large safety margin with only inappetance and lethargy noted at high doses. While it has been evaluated as an add-on medication with phenobarbital, many have used it as a sole agent. Serum levels approximating those reported as therapeutic in people were achieved with doses of approximately 20 mg/kg orally every 8 hours. Lacking are randomized placebo controlled prospective studies to determine short and long-term efficacy in cats. Zonisamide was effective in a laboratory setting at stopping convulsions in cats with various types of induced seizures. It also appears to be safe in cats. At this time, zonisamide has been used with success in cats with refractory epilepsy. Again, controlled studies are lacking. As more cats are treated with this medication, information will become available regarding side-effects and efficacy. Generally, it may be a drug used in cases that are refractory to other treatment. Gabapentin can also be used in cats. It is excreted by the kidneys and has a relatively high safety margin. The most common reported side effect is sedation. Some authors recommend gradually increasing dosing over a period of a couple of weeks to mitigate this side-effect. Gabapentin has been used most commonly as an add-on drug, but it has also been used as a sole agent. Starting dose
Monitoring
Side Effects
mcg/ml; monitor liver polyphagia, function hepatotoxicity, blood dyscrasia, dermatitis, altered behavior. Therapeutic levels not GI related, ataxia, well established Therapeutic levels not Lethargy inappetance well established Table 4. Commonly used antiepileptic drugs (AED) for managing seizures in cats.
Practical Summary
Let’s now take the above information and boil it down to a practical approach to the seizuring
cat. A couple of scenarios may highlight some important “take home” points. Scenario 1. You
are presented with a cat that the owners claim has had a seizure. Questions characterize the
event as one that sounds like seizure activity and not a “seizure-like” episode. If this is not clear
diagnostics may also evaluate the cardiovascular system, musculoskeletal system, and screen for
non-seizure neurological dysfunction. Naturally, the first goal is to determine the underlying
etiology of seizures. Consideration of reactive, symptomatic, and idiopathic causes should be
done. Typically, ruling out metabolic causes (reactive) first allows you to move from least costly
and least invasive tests to more costly/invasive. Routine laboratory data will answer most
questions regarding metabolic status. Adding a liver function test like bile acids (fasted and 2-
hour post prandial) would, in most circumstances, cover all bases for metabolic disease. If, upon
questioning or examination, you are suspicion of toxin exposure than appropriate treatment and
diagnostics could be carried out. Typically, you’ll need to target a very specific toxin in order to
get any valuable information or select an effective treatment. General non-specific treatment
could be carried out if a toxin exposure is suspected.
In those cases that are normal metabolically, then consider a structural problem (i.e.,
symptomatic epilepsy) next. Gold-standard work-up for these cats would include a MRI and
cerebrospinal fluid analysis. Computed tomography can demonstrate some lesions, but is less
sensitive than MRI. Typically, CSF is collected after imaging, this allows the clinician to have
knowledge prior to the tap about the primary lesion or brain herniation. Cases in which the MRI
is very characteristic of a specific diagnosis or in those suspected of having high intracranial
pressure, a tap may be avoided. CSF can allow characterization of certain inflammatory or
neoplastic conditions, however, a specific diagnosis is rarely determined. CSF allows the
clinician a minimally invasive method for sampling the CNS and allows that sample to undergo
culture, titer testing, or other biochemical analysis.
Scenario 2. You are presented with a cat that is actively seizuring. In this case immediate action
should be taken to halt the seizure. This can usually be done with rectal diazepam. Most cats
require 1 – 2 ml to stop the seizure. In other cases, the dose will have to be repeated. Don’t be
bashful about using diazepam. You can repeat several times in most cases without risk of major
side effects. In cats with a portosystemic vascular anomaly, diazepam could make them severely
sedated due to altered hepatic metabolism of the drug. If this occurs ventilatory assistance may
be required. Flumazonil can be used to reverse the effects of diazepam. In those cases that do
not responds to diazepam try using levetiracetam (Keppra; 20 mg/kd IV). This has been shown
to be effective at stopping seizures acutely. Propofol, pentobarbital, and inhalant gases have all
been used to stop seizures as well.
After stopping the seizure, assessment of body temperature, respiration, blood pressure and heart
rate should be done. This is a good time to place a catheter (saving a sample of blood while
placing a catheter is a good idea). For longer term management of the convulsions a diazepam
CRI may be necessary in addition to starting the cat on another AED. As a starting point for
diazepam, use the same dose per hour as the amount of diazepam required to stop the seizure.
For example, if you gave two 1 ml rectal doses to stop the seizure, then start the CRI at a rate of
2 ml/h. This rate is easily adjusted as necessary. Remember that diazepam binds to plastic and
will breakdown in light. (Running a small amount of diazepam through a line saturates the
benzodiazepine receptors.) Loading with phenobarbital or starting a drug like Keppra could also
be initiated at this time.
After stabilization of the patient proceed with the plan described in scenario 1.
In reality, many clients will be unable or unwilling to pursue all of the available diagnostics,
especially imaging. At a minimum a metabolic workup should be done (this may be an easier
sell after quoting an approximate cost for a MRI - $1500 to 1800). Ultimately, you may have to
manage the seizures without knowing the underlying etiology. Generally, phenobarbital is still
the drug of choice unless there is a specific contraindication (hepatic disease). If so, I generally
choose levetiracetam as a good front line sole agent. Remember to warn the clients about
ongoing serum monitoring, break-through seizures, constant drug adjustments in the early phase
of treatments, and the fact that the underlying etiology may make seizure control difficult.
Conclusion
Overall, a standard approach to cats with seizures should be used since it is difficult to predict
the underlying etiology based on clinical features alone. Working them up in a logical step wise
fashion insures that the client incurs the least cost and the patient only undergoes what is
absolutely necessary. Management of seizures can be frustrating for many because there is
frequently ongoing cost and time commitments. However, depending on the nature of the
underlying disease, managing the seizures themselves can lead to an improved quality of life.
SUGGESTED READING:
Barnes HL, Chrisman CL, Mariani CL, et al. Clinical signs, underlying cause, and outcome in
cats with seizures: 17 cases (1997 – 2002). J Am Vet Med Assoc 2004;225:1723-1726.
Schriefl S, Steinberg TA, Matiasek K, 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.
Podell M. Seizures. In: BSAVA Manuel of Canine and Feline Neurology, ed Platt SR, Olby NJ.
BSAVA 2004. Pp 97-112.
Hasegawa D, Kobayashi M, Kuwabara T, et al. Pharmacokinetics and toxicity of zonisamide in cats. J Feline Med and Surg 2008;10:418-421. Bailey KS, Dewey CW, Boothe DM, et al. Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy. J Am Vet Med Assoc 2008;232:867-872. Falzone C, Baroni M, De Lorenzi D, et al. Toxoplasma gondii brin granuloma in a cat: diagnosis using cytology from an intraoperative sample and sequential magnetic resonance imaging. J Sm Anim Pract 2008;49:95-99. Lipscomb VJ, Jones HJ, Brockman DJ. Complications and long-term outcomes of the ligation of congenital portosystmeic shunts in 49 cats. Vet Record 2007;160:465-470. Timmann D, Cizinauskas S, Tomek A, et al. Retrospective analysis of seizures associated with feline infectious peritonitis in cats. J Fel Med and Surg 2007;10:9-15.

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