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May/June 2014 Today's Veterinary Practice 33 THe CanIne SeIzuRe PaTIenT: FouR IMPoRTanT QueSTIonS | tvpjournal.com dogs with brain tumors such that, in certain breeds (eg, golden retriever, boxer, Boston terrier, French bulldog), even 1 seizure at 4 years or older should be cause for con- cern. 12 In young (1–5 years of age), small breed dogs (eg, pug, Chihuahua, Maltese, poodle) that have 3 or more seizures within a few months, meningoencephalitis of unknown etiology (MUE) should be considered a likely cause for the seizures. Behavior Even subtle behavior changes around the time of the first seizure indicate that a patient is likely to have symptomatic epilepsy (Table 2). Examination Findings If a neurologic examination performed between seizures has abnormal results, there is a high probability that a structural brain lesion is the cause of the seizure. Howev- er, 30% of brain tumor patients will have a normal exami- nation, and 18% of idiopathic epileptics can have a tran- siently abnormal examination. 10 It is useful to observe a seizure patient in the examination room to evaluate gait and behavior, coupled with an exami- nation of the postural reactions and menace response. As a guideline, the following findings suggest structural dis- ease, although other causes are possible: • Confusion • Circling to one side • Postural reaction • Menace deficits on one side. 3 SHOULD AN AED BE ADMINISTERED? AED drug therapy is recommended if any of the fol- lowing are present/occur: • Structural cause for the seizure • Severe first seizure or post-ictal period • Owner preference to reduce chances of another seizure. For IE, I recommend AED therapy after 1 or 2 seizures in a 6- to 12-month period for several reasons: 1. Although rarely life-threatening, seizures are very up- setting to owners, and a recent owner survey showed that most owners felt the only acceptable seizure con- trol is no seizure. 13 2. AED therapy likely reduces the chance of a life-threat- ening seizure/status epilepticus. 3. Although controversial, there is both bench-top and clinical data that demonstrates every seizure a patient experiences increases the chance for another seizure, independent of the seizure cause. In other words, sei- zure begets seizure. 14,15 4. Newer generation AEDs do not have as many side effects or organ toxicities compared to older AEDs, and are now available in generic or cost-effective formulations (Table 3, page 34). 16 -18 4 WHICH AED SHOULD BE CHOSEN FOR THERAPY? Maintenance Therapy When and which AED to apply in the clinical setting remains uncertain and controversial (see Studies Evalu- ating AED Efficacy & Safety). Some reasonable guide- lines for seizure management are to: • Use one medication at a time • Choose medications with best efficacy, lowest cost/dosing interval, fewest side effects, and lowest risk of toxicity. Table 3 lists AEDs in the order they are used by most neurologists in our clinic. 11,19 When to Change. Side effects or lack of efficacy can prompt the need to change AEDs. Studies show that only about 70% of dogs are well controlled on an AED, 17 and fewer than half the dogs on phenobarbital and/or bro- mide are seizure-free without adverse medication-related side effects. 20 Treating with multiple AEDs may be beneficial because Table 2. Common behavior Changes in Dogs with Structural brain Disease • aggression • Inappropriate elimination • Irritability • lethargy/head pressing • not greeting owners • Restless at night • Sleeping more during the day Studies Evaluating AED Efficacy & Safety In veterinary medicine, placebo-controlled or cross- over studies to determine the effectiveness or side effects of a sole aeD (monotherapy) are lacking. Multiple studies have evaluated the addition of a newer generation aeD (ie, pregabalin, levetiracetam, zonisamide) to phenobarbital ± bromide therapy, re- sulting in at least a 50% reduction in seizure frequen- cy. 21-23 However, placebo has been shown to reduce the number of seizures in dogs 79% of the time, and also reduces seizure frequency by 50% in 29% of pa- tients. 24 one explanation for the placebo effect is re- gression to the mean—a term used to describe fluc- tuations in biological variables that occur over time, and take the form of a sine wave around the mean. 24 When levetiracetam was evaluated as an add-on in a placebo-controlled, randomized, crossover study, a significant reduction in seizure frequency was not observed; however, quality of life was considered better on levetiracetam relative to placebo. 25 Read The Neurologic Examination in Companion Animals — Part 1: The Exami- nation (January/February 2013) and Part 2: Interpreting Findings (March/april 2013)—at tvpjournal.com (enter "neurology" in the search bar in the upper right-hand corner of the homepage). TVP_2014-0506_Seizure Patient.indd 33 5/24/2014 10:44:52 AM