Treatment Seizuring Cat[1]

REV IEW / The seizuring cat

Primary disordersPrimary seizure disorders are those condi-tions that have no underlying cause. Catsdetermined as having a primary seizure dis -order are referred to as idiopathic epileptics.Idiopathic epilepsy in dogs is usually geneticin origin; however, there is little evidence ofthis in the cat. Historically, idiopathic epilepsyhas been considered rare in cats. However,recent studies have disputed this. While thetrue incidence of idiopathic epilepsy in the catis unknown, it has been suggested thatbetween 21 and 59% of cats with seizures areidiopathic epileptics.68 In a recent study, 25%of cats were classified as having idiopathicepilepsy.7 (This particular study further classi-fied seizures into reactive [22% of cats] andsymptomatic [50% of cats] categories, inwhich the seizure occurred secondarily totoxic and metabolic causes or structural braindisease, respectively; in this present review,these two cat egories are considered under theheading of secondary seizure disorders.)

Typically, cats with idiopathic epilepsyhave tonicclonic and generalized

seizures; however, focal seizuresmay also be a feature of idiopathic

epilepsy. It is estimated that focaland generalized seizures occurwith relatively equal frequen-cy in cats.7 Historically, focalseizures have been associatedwith structural lesions of theforebrain;8 however, in theauthors experience, the pres-ence of focal seizures does not

rule out a diagnosis of idio-pathic epilepsy.

Secondary disorders Secondary seizure disorders are

conditions in which an underlyingstructural lesion or disease is identified.

The major cat egories of secondary seizure dis-orders in cats include vascular events, inflam-matory conditions/encephalitis, infectiousetiologies, toxins, traumatic injuries, metabol-ic derangements, neoplasia, congenital mal-formations and degenerative conditions(Table 1).

Diagnostic work-up for the seizuring cat

HistoryThe first step in determining a diagnosis for a seizuring cat is a thorough history. Seizuresare often confused with syncopal episodes(though rare in cats), vestibular disease, pain/ hyperesthesia or behavioral disorders. Adetailed description or, ideally, a video record-ing of the episode is helpful in ascertaining ifthe patient is truly having a seizure. In situa-tions when an episode is vague and unknown

Cats with idiopathic seizures tend to be younger

than cats with secondary epilepsy.

386 JFMS CLINICAL PRACTICE

Primary or secondary?Differentiating between primary

and secondary seizure disorders is critical both for determining a prognosis and

devising an appropriate treatment plan. Cats withidiopathic seizures tend to have a longer median

survival time compared with cats with secondaryepilepsy.1 The type of seizure (ie, focal versus general-ized) does not appear to be helpful in differentiatingbetween the categories of seizures; however, seizure etiology does appear to be associated with the cats ageat the first seizure.7 Cats with idiopathic seizures tend tobe younger (approximately 3.5 years) than cats with secondary epilepsy (approximately 8 years).

Category Differentials

Vascular Ischemic encephalopathyHypertensionThromboembolic diseasePolycythemia

Inflammatory/infectious

ToxoplasmosisCryptococcosisFeline infectious peritonitisBlastomycosisFeline leukemia virus infectionFeline immunodeficiency virus infectionRabiesBartonellosisAberrant parasitic migration

Cuterebra larvae Adult Dirofilaria immitis

Non-suppurative meningoencephalitis

Toxic LeadOrganophosphateEthylene glycol

Traumatic Traumatic injury

Anomalous HydrocephalusInternal or external

Metabolic Hepatic encephalopathiesPortosystemic shuntHepatic lipidosisHepatic neoplasia

Hypoglycemia Insulin-secreting tumorSevere sepsisIatrogenic insulin overdose

HyperthyroidismHypocalcemiaRenal encephalopathies/uremia

End-stage chronic renal failureAcute renal failure

Thiamine deficiencyHippocampal necrosis

Neoplastic MeningiomaLymphomaGliomaPituitary adenoma/adenocarcinomaChoroid plexus tumorNasal adenocarcinoma (with extensioninto the brain)EpendymomaNeuroblastomaSkull osteosarcomaMetastatic tumors

Degenerative Storage diseases

Differential diagnosis listfor the seizuring cat

TABLE 1

Regardless of the cause of the seizures, antiepileptic medications are needed to treat the seizure activity; additional therapies may benecessary for treating secondary seizure disorders.


(eg, chorioretinitis with feline infectious peri-tonitis [FIP]). The neuroanatomic localizationin all cats with seizures (regardless of thecause) is the forebrain, as seizures are the clin-ical manifestation of hypersynchronousabnormal neuronal activity originating in thecerebral cortex. The neurologic examination(see box below) helps to determine if one sideof the cerebral cortex is more involved or ifother parts of the nervous system, such as thebrainstem or cerebellum, are involved.

Clinical features of forebrain disease in cats(in addition to seizures) include mentationchanges, behavioral changes, visual deficitscontralateral to the lesion, facial/nasal sensa-tion deficits contralateral to the lesion, lipcommissure droop contralateral to the lesion,a head turn towards the side of the lesion,anisocoria, propulsive (wide) circling with anormal gait towards the side of the lesion,general proprioceptive deficits contralateral to

to be a true seizure, electroencephalographymay be undertaken to evaluate brain functionduring the episode, although this is not com-monly performed in a clinical setting.9

Next, additional information must be gath-ered from the owner including the presence ofany behavioral changes prior to the seizures;the cats behavior in between the seizures; eat-ing, drinking, urinating and defecating habits;current medications; environment (indoor oroutdoor cat, exposure to other cats); vaccina-tion status; retrovirus status (if known); travelhistory; and any potential exposure to toxins orhistory of traumatic events.

Physical and neurologic examinations Once a thorough history has been obtained,physical and neurologic examinations are per-formed. Included in the physical examinationis a fundic examination, as abnormalities may be associated with neurologic disease

JFMS CLINICAL PRACTICE 387

Neurological examinat ion checkl ist

Mentation Alert Obtunded Stuporous Comatose

Posture/attitude Head turn Head tilt

Cranial nerve examination Olfactory nerve (CN I)* Optic nerve (CN II)

Menace response, pupillary light response, response to visual cues Oculomotor nerve (CN III)

Pupillary light response, eye position, physiologic nystagmus Trochlear nerve (CN IV)

Eye position, physiologic nystagmus Trigeminal nerve (CN V)

Temporal muscle symmetry, facial sensation, dropped jaw Abducens nerve (CN VI)

Eye position, physiologic nystagmus Facial nerve (CN VII)

Facial paresis/palsy/lip droop, sensation to the inner pinnae Vestibulocochlear nerve (CN VIII)

Head tilt, resting nystagmus, hearing loss* Glossopharyngeal nerve (CN IX)

Gag reflex, swallow reflex Vagus nerve (CN X)

Gag reflex, swallow reflex Accessory nerve (CN XI)

Scapular muscle atrophy Hypoglossal nerve (CN XII)

Tongue symmetry

*Difficult to assess

Gait evaluation Presence of ataxia

Upper motor neuron/general proprioceptiveVestibularCerebellar

CirclingWith normal gaitWith abnormal gait

Spinal reflexes Patellar reflex* Flexor reflexes* Biceps Triceps Gastrocnemius reflex

*These are the only reliableones

Assessment of pain/hyperesthesia Neck Head

Components that should be evaluated in the seizuring cat


the lesion, and possibly head and neck hyper-esthesia evident on palpation.10

The determination of unilateral brain dis-ease is often suggestive of structural diseasesuch as a mass effect (tumor, granulomaor abscess) or a vascular event.Multifocal central nervous systemdisease is often associated withmetabolic, degenerative, toxic,infectious, inflammatory andneoplasic lesions. It must benoted that the neurologic exami-nation is likely to be abnormal ifthe cat is examined shortly aftera seizure has occurred, and is inthe post-ictal phase. In these situ-ations, the examination should berepeated when the patient isbelieved to have fully recovered. It isalso important to note that a normalneurologic examination does not entirelyrule out structural brain disease,especially if the lesion is located ina silent region of the brain.Additionally, cats with large cere-bral masses (often meningiomas)may have increased intracranialpressure, and the cerebellum maypartially herniate through theforamen magnum (Fig 1). Thesecats may present with an acuteonset of cerebellar signs includinga hypermetric/ataxic gait withnormal general proprioception,intention tremors, and a decreasedmenace response with normalvision.

Clinical pathologyBaseline blood work, including a completeblood count (CBC), chemistry profile, thyroidprofile, blood pressure monitoring, and bile

acids as well as urinalysis should be performed in all cats with seizures.

These non-invasive tests may help todiagnose metabolic causes of seizuresand are useful in planning anesthe-sia for any advanced imaging.

Advanced diagnosticsAdvanced diagnostics typicallyinclude magnetic resonance imag-ing (MRI) (Fig 2) or computed

tomography (CT), and potentiallycerebrospinal fluid (CSF) analysis. A

CSF tap is indicated if the imaging isnormal or suggestive of intracranial dis-

ease and the cat is believed to have normalintracranial pressure. If there is a large space-

occupying mass or evidence ofbrain herniation, a CSF tap is con-traindicated. Normal CSF is clearand colorless with fewer than 5cells/l and less than 27 mg/dlprotein (for a cisterna magna tap).Abnormalities in CSF are verysensitive indicators of intracranialdisease, but often are not specific.However, when evaluated in con-junction with MRI/CT, CSF analy-sis can be a helpful diagnostic tool(Table 2). Cultures and infectiousdisease titers (cryptococcosis, tox-oplasmosis and FIP) may also beuseful tests to perform on CSF.1114


Why the need foradvanced diagnostics?

The typical evaluation of a dog with idio-pathic epilepsy reveals normal neurologic and

physical examination findings, a history ofseizures with normal behavior and normal interictal

periods, and normal blood work. These dogs typicallybegin to seizure between 1 and 5 years of age and,therefore, a dog meeting these criteria is presumptivelydiagnosed with idiopathic epilepsy and advanced diag-nostics are often not necessary. Because such typicalguidelines are not available for the feline idiopathicepileptic, advanced diagnostics are usually recom-mended for the seizuring cat, even when idiopathic

epilepsy is suspected.

FIG 2 MRI scans from a cat with intracraniallymphoma. (a) T2-weighted axial image at the level of the interthalamic adhesion. Thehyperintensity noted in the left cerebralhemisphere represents cerebral/peritumoraledema. (b) T1-weighted image at the samelevel acquired after the administration ofgadolinium. A surface-oriented mass isidentified

a b

FIG 1 Cat displaying opisthotonus, which may be a result ofincreased intracranial pressure and herniation of the brain,either under the tentorium cerebelli or through the foramenmagnum. Note the extended neck and thoracic limbs

The neurologic examination is likely to be abnormal if the cat

is examined shortly after a seizure has occurred, and is in the post-ictal phase.

In these situations, the examination should be repeated when the

patient is believed to have fully recovered.


Therapy for feline seizures

Due to the fact that each seizure episode has thepotential to increase the number of epilepticfoci in the brain, and that the response to thera-py, rather than the severity of seizure activity, isan indication of prognosis, aggressive therapyis recommended for cats with seizures.3

PhenobarbitalPhenobarbital is the current drug of choice incats with multiple seizure episodes,4,14 and isavailable in both oral and intravenous formu-lations. The elimination half-life in cats is3450 h and, when given at a dose of 2.5mg/kg body weight PO q 12 h, phenobarbitalis a very effective anti epileptic drug. Sideeffects associated with phenobarbital use incats are minimal and include sedation andataxia, weight gain secondary to polyphagia,and polydipsia and polyurea. Hep ato -toxicosis, a well recognized complication indogs, has not been reported in cats.15,16Occasionally, cats treated with phenobarbitalhave been reported with clinicopathologicabnormalities including leukopenia andthrombocytopenia, as well as immune-

mediated hypersensitivity reactions (severecutaneous eruptions and marked lymph -adenopathy), all of which are reversible withdiscontinuation of the drug.14,17

Serum drug concentrations should be meas-ured 23 weeks after starting phenobarbitaltherapy. Therapeutic levels are similar to thosereported in dogs (2540 g/ml). The idealtherapeutic range in cats is approximately2330 g/ml. In dogs, repeated phenobarbitaladministrations are known to alter estimatedsteady state serum concentration as a conse-quence of enzyme induction. This results inthe need to progressively increase oral dosagewith time in order to maintain steady statetherapeutic levels. This phenomenon ofenzyme induction following repeated admin-istration of phenobarbital is negligible in cats.

Serum drug concentrations should be mon-itored every 6 months, or 23 weeks after anychange in dosage.2,5 In addition, it is recom-mended that CBC, chemistry profiles and bileacids are monitored once to twice yearly incats on maintenance phenobarbital therapy.

DiazepamIn situations where sole phenobarbital thera-py is ineffective, or is contraindicated, addi-tional antiepileptic drugs are needed. Oraldiazepam has a longer elimination half-life incats (1520 h) than dogs (34 h) and is relative-ly effective at controlling seizures in cats.2Additionally, cats do not appear to develop afunctional tolerance to the drug. Therefore,historically, diazepam has been the second-choice drug for treatment of feline epilepsy.18However, oral administration of diazepam incats has been associated with a potentiallyfatal idiosyncratic hepatotoxicosis.19,20Therefore, the use of oral diazepam should belimited; if used, diligent monitoring of clinicalsigns and serum alanine transaminase andaspartate transaminase activity must be per-


CSF finding Description Diseases

Lymphocytic pleocytosis

5 WBC/l> 50% lymphocytesIncreased protein

RabiesCNS lymphoma (lymphoblasts maybe seen)Toxoplasmosis

Albuminocytologicdissociation

Increased protein with normal WBC count

NeoplasiaTrauma

Mixed cell pleocytosis

> 5 WBC/lMix of lymphocytes and largemononuclear phagocytesVariable neutrophilsIncreased protein

Fungal encephalitis (cryptococcosis, blastomycosis)Chronic FIPInfarction (mild)

Neutrophilic pleocytosis

> 5 WBC/lPredominance of neutrophilsIncreased protein

Bacterial encephalitis (neutrophils are often degenerate)Fungal encephalitisFIP (often seen with marked increasesin protein)MeningiomasPost severe seizure/status epilepticus

Eosinophilicpleocytosis

> 5 WBC/lPredominance of eosinophilsIncreased protein

Aberrant parasitic migrationToxoplasmosisCryptococcosisT cell lymphomaRabies (rare)

Presence of intactRBC

IatrogenicSpontaneous subarachnoid hemorrhageInfarction

XanthrochromicCSF

Hemorrhage prior to CSF collection

Primary bleeding disorders/coagulopathies

WBC = white blood cell(s), RBC = red blood cells, FIP = feline infectious peritonitis, CSF = cerebrospinal fluid

Various CSF findings and the diseases associatedmost commonly with them

TABLE 2

Maintenance therapy is specifically recommended when a cat presentswith more than one seizure within 6 months (either generalized or focal),has more than one cluster event (defined as more than one seizure in a24 h period), or experiences status epilepticus (ie, continuous seizureactivity that lasts more than 5 minutes or the presence of multipleseizures without returning to normal in between the seizures).

Therapy with antiepileptic drugs is recommended when seizures occurpost trauma, particularly if they begin within the first week post trauma.

It is strongly advised to treat cats with antiepileptic drugs when there is evidence of structural forebrain disease (obtained via MRI/CT, CSF analysis, etc) such as neoplasia, infectious or non-infectiousencephalitis, or congenital disease. Additional therapy is also warrantedto treat the primary cause of the seizures; however, even after

appropriate therapy (ie, surgery to remove a meningioma),therapy for the seizures is often necessary and is

typically lifelong.

When to treat?


Levetiracetam is considered an idealantiepileptic drug with regard to its pharma-cokinetics.28 It is rapidly absorbed followingoral administration and has an oral bioavail-ability of approximately 100%.29 Peak plasmaconcentrations are achieved at 2 h in the major-ity of cats.30 Food does not affect the extent ofabsorption of levetiracetam, allowing it to besafely administered independent of the feed-ing schedule, which eases the task of givingthe drug three times daily.28,31 The majority oflevetiracetam is excreted unchanged in theurine and approximately 24% is excreted in theurine as an inactive metabolite. Renal elimina-tion occurs primarily by glomerular filtrationand correlates well with creatinine clearance.Therefore, the dose should be decreasedaccordingly in patients with impaired renalfunction. Levetiracetam is not significantlyprotein bound (< 10%) and, therefore, will notdisplace highly protein-bound drugs.25

At a dose of 20 mg/kg PO q 8 h, levetir -acetam is a safe and effective antiepilepticdrug when given as an adjunct to phenobarbi-tal in cats with suspected idiopathic epilepsy.30The half-life is approximately 3 h.29,30 Sideeffects are rare and may include transient inap-petence and lethargy. In addition to treatingsuspected epileptics, the authors have usedlevetiracetam in two cats with intracranialmeningiomas that were surgically removed, inwhich seizure control was not adequate withphenobarbital alone. Both cats showed areduction in seizures and did not experienceany side effects related to the drug.Levetiracetam also shows promise as a choicefor sole antiepileptic drug therapy and hasbeen used by the authors on occasions inwhich phenobarbital was not a viable option.Side effects were not noted in two cats treatedwith sole levetiracetam and the drug appearedto be effective in reducing the seizures.

Although a therapeutic range for levetirac-etam has not been determined specifically forcats, it appears to be similar to that in humans(545 g/ml). Monitoring is recommendedapproximately 1 week after commencing med-ication and then every 612 months. The goalof monitoring is more to aid in adjusting thedrug dose, rather than to avoid side effects, due to levetiracetams high safety margin. Theauthors have found that increasing the dose in20 mg/kg increments is useful when the drugdoes not appear to be effective. In addition,monitoring routine blood work is recommend-ed approximately every 612 months, as in allcats treated with antiepileptic medications.

formed so the drug can be immediately dis-continued should any adverse reactions occur.However, it is strongly recommended thatoral diazepam is not used in feline patients.

The intravenous formulation is not associat-ed with hepatotoxicosis and is discussed laterin the emergency therapy section.

BromideBromide was initially thought to be a safeantiepileptic drug in cats due to its lack ofhepatic metabolism. In addition, bromideslong elimination half-life (approximately 11days), allowing for once-daily dosing, and theavailability of therapeutic drug monitoring,made it a potentially promising antiepilepticdrug in cats.18 However, bromide has beenassociated with an idiosyncratic allergic pneu-monitis, reportedly occurring in 3542% ofcats.21,22 The clinical signs are consistent withbronchial asthma and, although they abatewith discontinuation of the drug, they may belife-threatening. Furthermore, bromide is notparticularly effective as a feline antiepileptic asseizures are only controlled in approximately35% of treated cats.21

LevetiracetamLevetiracetam is a novel antiepileptic drug. Itsmechanism of action is not entirely known butappears to differ substantially from that of themore conventional antiepileptics.2325 In vitroand in vivo recordings of epileptiform activityfrom the hippocampus have shown that leve-tiracetam inhibits burst firing without affect-ing normal neuronal excitability, suggestingthat the drug may selectively prevent hyper-synchronization of epileptiform burst firingand propagation of seizure activity.Levetiracetam appears to have the ability toretard electrical kindling, a property that per-sists even after the drug has been discontin-ued. Therefore, levetiracetam may haveantiepileptogenic properties and may assist inpreventing the progression of epilepsy in at-risk patients.23,24 The synaptic vesicle proteinSV2A is the binding site for levetiracetam.26 Itis present in high concentrations in the synap-tic plasma membranes within the centralnervous system. The molecular action ofSV2A is unknown but it may be involved intransporting calcium or ATP.27


The authors consider oral diazepam use in cats to be contraindicated.

At a dose of 20 mg/kg PO q 8 h, levetiracetam is a safe and effective antiepileptic

when given as an adjunct to phenobarbital in cats with suspected idiopathic epilepsy.



ZonisamideZonisamide is a sulfonamide-based anticon-vulsant drug that has been used successfullyin dogs as an add-on antiepileptic drug.32,33Suspected mechanisms of action includeblockage of T-type calcium and voltage-gated

sodium channels in the brain, facilitation ofdopaminergic and serotonergic neurotrans-mission in the central nervous system, scav-enging free radical species, enhancing GABAin the brain, inhibition of glutamate-mediatedneuronal excitation in the brain, and inhi -

Status epilepticus is considered a true medical emergency,requiring prompt recognition and treatment. If untreated,continuous seizure activity can lead to hyperthermia, hypoxia,hypotension, renal failure, disseminated intravascularcoagulation, aspiration pneumonia and cardiopulmonary failure.A study of dogs with idiopathic epilepsy found that thoseexperiencing episodes of status epilepticus had a significantlyshorter mean survival time.39

First-line emergency therapy Intravenous diazepam, at 0.51.0 mg/kg body weight,

is safe and has a rapid onset of action. If the bolus is successful in ceasing seizure activity, but additionalseizures occur, further boluses or a continuous infusion may be administered. An infusion of diazepam at a rate of 0.52 mg/kg/h is used to maintain a seizure-free state.Careful monitoring of heart rate, blood pressure and respiratory rates, as well as diligent nursing care, are needed while cats are being treated with diazepam infusions. Once seizure-free for approximately 24 h, the infusion should be tapered and discontinued, while carefullymonitoring for additional seizure activity.

Other traditional optionsIf diazepam is unsuccessful in ceasing seizure activity, othertraditional options include pentobarbital, phenobarbital andpropofol. Pentobarbital is a barbiturate that is useful in treating

intractable seizures at a dose of 215 mg/kg IV.14,40 It is notan anticonvulsant drug but rather ceases the motor activitythat is associated with seizures. A complicating factor when using pentobarbital is that animals tend to paddlewhen recovering, which can easily be confused with seizure activity. Pentobarbital takes effect quickly, though not immediately like diazepam. It is potentially a severe respiratory depressant, and also causes hypothermia, so careful monitoring of the patients breathing and temperature is indicated.

Phenobarbital is another viable emergency drug for treatingstatus epilepticus. The bolus dose is 26 mg/kg bodyweight but it must be stressed that the effect is not immediate, but rather can take 1525 minutes, so overdosing needs to be avoided. Use of phenobarbital as anemergency drug is useful when phenobarbital is the chosenmaintenance drug. Phenobarbital can also be administeredas a continuous infusion at a rate of 24 mg/kg/h.14

Propofol is an injectable anesthetic agent that has beenshown to have GABA agonist activity in the central nervoussystem. In addition, it is helpful in lowering intracranial pressure as well as brain metabolic activity.14 The drug mustbe given as a slow bolus (1-6 mg/kg body weight) as apnea

is a common side effect if given too quickly.41

Therefore, precautions must be taken andintubation must be available should thepatient become apneic. Propofol is very successful in ceasing seizure activity and an infusion may be used at a rate of 0.10.6 mg/kg/min (Fig 3).In addition to causing apnea, propofol is also a cardiovascular depressant, so this too requires careful monitoring. Similar to pentobarbital, paddling may be seenwhen the patient is recovering from propofol treatment, and this may be confused with seizure activity. Although apropofol infusion may be expensive for larger dogs, this israrely an issue in cats and, therefore, this is a very usefuldrug to treat status epilepticus.

Where sedation is a risk . . .All of the above drugs, though useful emergency medications,cause sedation of varying degrees, which is undesirable incertain situations such as in post-craniotomy patients, patientswith aspiration pneumonia, or patients in which the neurologicalstatus needs to be continuously monitored. In these situations,intravenous levetiracetam is a viable option. An injectableformulation has been developed for use in humans with partial-onset (focal) seizures and is well tolerated by humans, dogs and cats. The pharmacokinetics for the intravenous formulationare similar to the oral one.29,42 Side effects have not been notedin dogs and cats, though humans report dizziness, somnolence,fatigue and headaches.43

Although additional work is needed, the authors have hadsuccess in ceasing seizure activity with levetiracetamadministered in 20 mg/kg body weight boluses. Theanticonvulsant effect is rapid and is maintained for severalhours (longer than a single diazepam intravenous dose). Moreimportantly, patients do not become sedate and appear torecover from the seizure episode more quickly than withdiazepam administration. The patient can then be maintainedon levetiracetam or transitioned onto phenobarbital dependingon the individual case.

S t a t u s e p i l e p t i c u s a n d e m e r g e n c y t h e r a p y

FIG 3 Cat beingtreated with apropofol infusionfor clusterseizures. Note thatshe is intubatedduring treatmentand kept on a wellpadded surface.She was turnedregularly, keptclean and dry, and had her lungsauscultatedfrequently tomonitor breathsounds and effort


bition of carbonic anhydrase activity.14Zonisamide is metabolized by hepatic micro-somal enzymes and its half-life is significantlyshorter in patients receiving phenobarbital orother drugs that increase the hepatic micro -somal enzyme p450.34

The half-life of zonisamide in cats is 33 h.35Due to this long half-life, once-daily adminis-tration of a 5-10 mg/kg body weight dose islikely to be appropriate in cats, although additional studies are needed to determinethis. Approximately half of cats receiving a 20 mg/kg dose of zonisamide experienceadverse reactions such as anorexia, diarrhea,vomiting, somnolence and ataxia.35 Theauthors have used zonisamide in two cats thatexperienced seizures that were refractory tophenobarbital; one cat developed anorexia,necessitating removal of the drug, and theother cat responded very well, showing a dramatic reduction in seizure frequency.

PregabalinPregabalin is a new anticonvulsant drug thatis considered to be the next generation ofgabapentin. Its mechanism of action appearsto be related to interaction with the 2subunit of neuronal voltage-gated calciumchannels. Reducing calcium influx leads toreduction of the synaptic release of glutamate,an excitatory neurotransmitter. In dogsadministered a 4 mg/kg bodyweight doseorally, pregabalin has a half-life of 6.8 hours;this dose appears to be well tolerated.36 Themajor side effect noted in dogs is sedation andthe dose must be gradually increased from 2 mg/kg to 3 or 4 mg/kg q 812 h as neededfor effectiveness.37


No information is available regarding theuse of pregabalin in cats; however, it is likelyto prove an effective antiepileptic drug in thisspecies. Its predecessor, gabapentin, has beenused with limited success in cats; anecdotally,the dose is 510 mg/kg body weight PO q 12 h.Sedation is the most common side effect notedwith gabapentin therapy, and is likely to be aside effect associated with pregabalin in catsas well. The half-life and therapeutic range forboth gabapentin and pregabalin are currentlyunknown in cats.

Monitoring and assessment of seizure control

All clients should be encour-aged to maintain a seizure

log, detailing the num-ber of seizures as well

as unique features of the seizure (ie, length of ictusperiod, post-ictalperiod, generalizedversus focal versuscluster seizure, andany other events

that may affect thecats life). Regular

physical and neurologicexaminations should be

performed, at a minimum ofevery 6 months. These visits are

often more frequent in the initial stages oftherapy. Monitoring of antiepileptic drug con-centrations and a minimum database (CBC,chemistry profile and urinalysis) is indicatedevery 6 months once the cat is on maintenancetherapy, and more frequently at the beginningof therapy.

When therapy is not effective (ie, the catshows a reduction in seizure frequency of lessthan 50%, or no change, or an increase inseizure frequency), the treatment plan mustbe re-evaluated. Treatment failures are theresult of progressive disease, refractoryseizures, poor client compliance, inadequatedrug dosing or drug interactions. Refractorycases should be treated either by increasingthe dosage of the present drug or by addinganother medication to the treatment regime.This decision is aided by assessing currentantiepileptic drug blood concentrations, gen-eral blood work and side effects related to thedrug. If the drug concentration is within thelownormal range and side effects are notnoted, increasing the initial drug dosage is a viable option. If side effects are present orthe drug concentration is highnormal orhigh, another antiepileptic drug should beadded.

Successful responseto therapy?

Determining how effective anantiepileptic drug is proving should be

based on the individual cats response. A drugis considered to be effective if it results in a reduc-

tion in seizure frequency of 50% or more. For exam-ple, a cat that seizured six times per month prior totherapy, and three or fewer times per month after ther-apy was instituted, is considered to have shown afavorable response to medication. By contrast, a catthat seizured once per month both prior to andafter therapy is considered a treatment failure.

Differentiating between primary and secondary seizure disordersis critical for determining a prognosis as well as devising anappropriate treatment plan.

Cats with idiopathic epilepsy often have tonicclonic andgeneralized seizures. However, focal seizures may also be afeature of idiopathic epilepsy.

Response to therapy, rather than the severity of seizure activity, is an indication of prognosis in cats with seizures; therefore,aggressive therapy with anticonvulsants is recommended.

Phenobarbital is the current drug of choice for cats with multiple seizure episodes.

Levetiracetam is a safe and effective antiepileptic when given as an adjunct to phenobarbital in cats with suspected idiopathic epilepsy, and may be considered a second-line anticonvulsant in cats.

KEY POINTS


C a s e n o t e s

Allison, an 11-year-old female spayed domesticshorthair cat, presented with a recent onset ofgeneralized seizures. She experienced two on the day of presentation and one earlier in the week. According to her owners, she had also beenshowing behavioral changes over the previous few weeks.

Case work-up No major abnormalities were noted onphysical examination. On neurological examination, Allisonwas quiet, alert and responsive. She had a left head turn.Examination of her cranial nerves revealed a negativemenace response in her right eye (OD), and normal palpebraland pupillary light reflexes in both eyes (OU). She haddecreased nasal sensation on the right side of her face and a slight lip droop on the right. She was ambulatory with anormal gait, though she often walked in wide circles to theleft side. Her proprioception was decreased in the rightthoracic and right pelvic limbs, as evidenced by decreasedhopping and decreased extensor postural thrust on the rightside. Her spinal reflexes were all within normal limits.Palpation appeared to elicit head and neck pain.

Allison was presumptively diagnosed with a left forebrainlesion. She had two additional seizures on the day ofadmission and was treated with phenobarbital 2.5 mg/kg IV BID. Prior to anesthesia for advanced imaging, a CBC,chemistry profile and urinalysis were performed and all

results were withinnormal limits. Three view thoracicradiographs wereobtained and were also normal. General anesthesiawas subsequentlyinduced and MRIperformed (see left).

Diagnosis An extra-axial contrast-enhancing mass was identified in the left cerebrum, which was mostconsistent with a meningioma. Allison was taken to surgerythe next day for mass removal via a craniotomy (see right).Histopathology of the mass was consistent with ameningioma. Prednisone 0.5 mg/kg BID was added to the treatment protocol.

Treatment and follow-up Allison initially respondedfavorably to surgery and phenobarbital treatment; herbehavior returned to normal at home and she did not haveany seizures. At her 3-week follow-up examination shecontinued to show a negative menace response OD, but the remainder of her examination was normal. A CBC andchemistry profile were performed and were normal. Herphenobarbital level was measured and the results were in theupper therapeutic range (28 g/ml; ideal range 2330 g/ml).

Shortly after this examination, Allison re-presented followinga cluster of five seizures in a 24 h period. Levetiracetam 20 mg/kg PO TID was added to her treatment protocol.

Six months later, Allison is doing well; she continues tohave a negative menace response OD but is happy at home.She has had one generalized seizure, which occurred about6 weeks after starting levetiracetam treatment. Her serumlevetiracetam level is currently 41 g/ml and serumphenobarbital level is 26 g/ml. No changes to heranticonvulsant therapy have been made.

WHAT THIS CASE DEMONSTRATESDespite therapy for the inciting cause of seizures (surgery, in Allisons case), anticonvulsants are a necessary, and oftenlifelong, component of care for the seizuring cat. In situationswhere phenobarbital is not adequately controlling seizures,and the serum drug concentration is adequate, addition of a second anticonvulsant can be successful. Levetiracetammay be considered the second-line anticonvulsant in cats.


Withdrawal or discontinuation of therapy

Therapy may be extremely successful and catsmay become seizure-free. Although each catrequires an individual approach, a guideline isto consider reducing/eliminating drugs whenthe patient is seizure-free for at least 6 months.Drugs should never be discontinued abruptlyas withdrawal seizures may occur; this is

most commonly seen with phenobarbital dueto the development of physical dependence onthe drug.38 Rather, the cat should be slowlyweaned off over several weeks.

Occasionally, cats will experience a negativereaction or severe side effects to a drug, neces-sitating rapid discontinuation of therapy. Thismay need to be done in a hospital setting, orwith the clients understanding that seizuresmay occur with abrupt drug withdrawal.


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