Need a Fix for that Fit? Feline Seizures

by James Lavely, DVM, DACViM-Neurology, VCA Animal Care Center of Sonoma County CVMA Spring Seminar in yosemite Speaker

CV66_6.indb 20 11/2/12 11:43 AM eline seizures off er unique challenges treatment may lead to better seizure control. Patients compared to dogs. Both dogs and cats with cluster seizures, status epilepticus or secondary can have generalized or partial seizures. epilepsy should have anticonvulsant therapy started However, cats commonly present with without delay. Patients with an underlying etiology rather bizarre partial seizures. Complex other than idiopathic epilepsy may require medication Need a Fix for that Fit? partial seizures or psychomotor seizures in addition to anticonvulsant therapy. Anticonvulsant Fcan manifest with the cat acting aggressive for therapy is targeted to increase quality of life, decrease several minutes at a time, and may frighten their the frequency and severity of seizures with as few Feline Seizures caretakers. Symptomatic epilepsy or secondary adverse eff ects as possible. epilepsy is more common in cats and accounts for almost half of all seizure disorders in cats. Anticonvulsant therapy for cats is often frustrating Meningiomas are the most common brain tumor in when phenobarbital is unsuccessful. The use of cats, followed by lymphosarcoma. Cryptococcosis, potassium bromide is no longer recommended in FIP and toxoplasmosis are also potential causes of cats due to the potential for asthma secondary to feline seizures. Hypoglycemia should be considered bromide therapy. Signs may resolve once bromide in cats receiving insulin therapy. Idiopathic epilepsy therapy is discontinued. The longer half-life of represents 21% to 59% of feline seizure disorders. diazepam in cats makes them a possible candidate for Interictal neurological examination is normal in cats long term anticonvulsant therapy. However, the use with idiopathic epilepsy, whereas cats with secondary of oral diazepam is limited/not recommended due epilepsy can have a normal or abnormal examination. to the potential risk of severe and potentially fatal Unilateral defi cits identifi ed on examination suggest a hepatopathy in cats. Extensive studies regarding safety structural or vascular cause. and effi cacy of newer anticonvulsants in cats are lacking. Gabapentin 5-10 mg/kg PO BID to TID may Complex partial seizures or psychomotor seizures can manifest with the cat acting aggressive for several minutes at a time, and may frighten their caretakers. Symptomatic epilepsy or secondary epilepsy is more common in cats and accounts for almost half of all seizure disorders in cats.

The increased incidence of secondary epilepsy in be used, however, it has not been highly effi cacious cats warrants further investigation for the cause, for seizures in small animals. Newer anticonvulsants even when the neurological examination is normal such as levetiracetam 20 mg/kg PO TID, zonisamide and signalment is consistent with idiopathic epilepsy. 5-10 mg/kg PO SID and pregabalin 1-2 mg/kg PO BID A thorough evaluation for the underlying cause for in cats appear promising. Due to the limited number seizures should be pursued to optimize anticonvulsant of studies and anecdotal experience (lower incidence therapy. CBC, chemistry, urinalysis, thoracic of seizures in cats compared to dogs) care should be radiographs and abdominal ultrasound should be used when prescribing these medications. Starting at done to rule out extracranial causes for seizures, while the lower end of the dose range may be of benefi t. MRI and CSF should be done to rule out intracranial Serial monitoring of the CBC and serum chemistry is causes. Results of diagnostic testing are normal in recommended when cats are receiving anticonvulsant idiopathic epileptics. Cats with idiopathic epilepsy medication. Therapeutic levels for levetiracetam, typically fi rst seizure between the ages of one and zonisamide and pregabalin are relatively unknown for fi ve. Generalized tonic clonic seizures are typically cats and dogs at this time. seen with idiopathic epilepsy, although focal seizures are also possible. Autosomal recessive inheritance is Phenobarbital most common in dogs, but has not been established Phenobarbital is typically dosed at about 2.5 mg/ in cats. Anticonvulsant therapy is typically started kg PO BID. Most cats are started at 8.1 mg PO BID, when seizure frequency increases, particularly when while small cats are started at four mg PO BID. two or more seizures occur within six months. A Phenobarbital increases the seizure threshold and baseline period is helpful to determine the natural decreases the spread to surrounding neurons. It seizure frequency and can help assess response enhances the inhibitory postsynaptic eff ects of GABA, to anticonvulsant therapy. However this baseline inhibits glutamate activity and decreases calcium fl ux period should not be too long, as earlier antiepileptic across neuronal membranes. Peak levels are achieved

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CV66_6.indb 21 11/2/12 11:43 AM 4-6 hours post oral administration and its T ½ is 34- metabolism in the dog. The T ½ is 3-4 hours in dogs and 50 hours in cats. Phenobarbital metabolism increases about three hours in cats. Cats are given 5-10 mg/kg PO with chronic therapy in dogs, but less commonly in cats. BID to TID. Sedation and ataxia are the most common Adverse eff ects include sedation, ataxia, polyphagia, PU/ adverse eff ects. PD and liver disease. Pregabalin Levetiracetam Pregabalin is a GABA analog structurally similar to Levetiracetam binds synaptic vesicular protein SV2A. gabapentin. Pregabalin has a higher affi nity for the Levetiracetam may prevent hypersynchronization of α2δ subunit of neuronal voltage-gated calcium burst fi ring and seizure propagation. The T ½ is four channels than does gabapentin. The T ½ of pregabalin hours in dogs and three hours in cats. Peak plasma is 7 hours in dogs and 10.4 hours in cats. Pregabalin is concentration occurs two hours post administration administered 2 ‒ 4 mg/kg PO BID to TID in dogs and 1-2 in most cats with approximately 100% bioavailability. mg/kg PO BID in cats. Adverse eff ects include sedation Levetiracetam is started at 20 mg/kg PO TID. Adverse and ataxia and are not uncommon in dogs. Thus, starting eff ects appear minimal, with sedation, ataxia and dose at a lower dose and titrating the dose upward is decreased appetite occurring uncommonly. Food recommended. does not aff ect absorption of levetiracetam. Most of the drug is excreted unchanged through the kidneys. Conclusion The cytochrome P 450 system does not appear to A thorough evaluation is essential for the seizuring cat. be involved. However, concurrent phenobarbital Therapy should be directed at the underlying cause of administration has been shown to decrease seizures, with anticonvulsant therapy to control seizures levetiracetam T ½ and decreases levetiracetam blood and optimize quality of life. Phenobarbital has been the levels in dogs. Thus patients on both phenobarbital and mainstay of anticonvulsant therapy in cats. However, levetiracetam concurrently may require higher dosages when phenobarbital therapy is unsuccessful or if of levetiracetam. adverse eff ects occur the use of newer anticonvulsants can be helpful. Serial monitoring of the CBC and serum Zonisamide chemistry is recommended when cats are receiving Zonisamide is a sulfonamide-based anticonvulsant anticonvulsant medication. drug. Zonisamide blocks voltage-dependent sodium channels and T-type calcium channels. Its T ½ is about Suggested reading: 15 hours in the dog and 35 hours in cats. Zonisamide 1. Cautela MA, Dewey CW, Schwark WS, et al. is metabolized by hepatic microsomal enzymes and Pharmokinetics of oral pregabalin in cats after single is also renally excreted. Its T ½ is reduced with dose administration. In Proceedings ACVIM Forum. concurrent phenobarbital administration. Zonisamide Anaheim, CA: 2010, p 739. is administered 5-10 mg/kg PO BID in dogs, with the 2. Dewey CW, Cerda-Gonzalez S, Levine JM, et al. higher dose range for dogs also receiving phenobarbital. Pregabalin as an adjunct to phenobarbital, potassium Cats are given 5-10 mg/g PO q 24 hours, due to the bromide, or a combination of phenobarbital and longer T ½. Zonisamide is typically well tolerated, with potassium bromide for treatment of dogs with anorexia, sedation and ataxia being the most common suspected idiopathic epilepsy. J Am Vet Med Assoc adverse eff ects. Adverse eff ects are much more common 2009;235:1442‒1449. with increased dosing. About half of cats given 20 mg/ 3. Siao KT, Pypendop BH, Ilkiw JE. Pharmacokinetics of kg had adverse eff ects such as anorexia, vomiting, gabapentin in cats. Am J Vet Res 2010;71(7):817-21. diarrhea, sedation and ataxia. 4. Smith Bailey K, Dewey CW. The seizuring cat. Diagnostic work up and therapy. J Feline Med Surg Gabapentin 2009;11(5):385-94 Gabapentin binds voltage-gated calcium channels and 5. Thomas WB. Idiopathic epilepsy in dogs and cats. Vet decreases intracellular calcium infl ux. It is excreted Clin Small Anim Pract 2010;40:161-179. unchanged by the kidneys with about 30-40% hepatic

Dr. James Lavely leads a team of four neurologists at VCA Animal Care Center of Sonoma. He earned his DVM degree from The Ohio State University in 1999. After completing an internship at Angell Memorial Animal Hospital he underwent his neurology and neurosurgery residency training at UC Davis. Dr. Lavely has published articles on CNS infections, pediatric neurology and seizures. He has also conducted research regarding the diagnosis of myasthenia gravis. Dr. Lavely will be speaking at the CVMA Spring Seminar in Yosemite March 8-10, 2013 (see page 23 ).

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