Seizures are the most common neurological problem encountered in small animal practice. It has been estimated that up to 5 percent of dogs in the general population will seizure during their lifetime. The management of seizure disorders can be quite challenging; there are numerous causes and diverse manifestations of seizures, and response to treatment is often variable. However, by adopting a systematic approach to the evaluation of seizures, the practitioner can manage even the most difficult cases more effectively.
• Step 1: Confirm that the episodes are seizures. Seizures are episodic events and are frequently not observed by the practitioner. Because of this, it is necessary to obtain an accurate description of the episode from the owner to determine whether or not a seizure disorder is considered likely. Disorders that can be confused with seizures include syncope, narcolepsy/cataplexy, transient vestibular dysfunction and behavioral disorders. Narcolepsy/cataplexy, vestibular dysfunction and behavioral disorders typically are not associated with the alterations in consciousness seen with most seizures. Syncope does cause loss of consciousness, but the episodes manifest with muscle flaccidity rather than rigidity or movement that is typical of seizures, and animals are usually normal immediately after the syncopal event in contrast to the abnormalities frequently observed in a postictal period. If the episode proves difficult to characterize based on the description alone, it can be helpful to have the owner videotape an episode for review.
• Step 2: Characterize the seizure type. Generalized seizures typically involve alterations in consciousness with rhythmic involuntary motor activity of the limbs and face, and variable degrees of salivation, urination and defecation. In contrast, partial seizures manifest as isolated head turning, licking, jaw snapping, movement of a single limb or behavioral changes. It has long been accepted that primary generalized seizures are the most frequently recognized type of seizure in dogs. However, some recent studies suggest that partial onset seizures may be more common than previously believed. Partial seizures are caused by an underlying abnormality in a focal area of the brain. Accordingly, characterizing the seizure type will help in the development of a differential diagnosis list and the diagnostic plan.
•Step 3: Obtain a thorough history. Historical information can be useful in formulating a differential diagnosis. Questions should be asked regarding the age at the onset of seizures, any events that seem to precipitate the seizures, any past history of trauma (which usually has to be severe enough to render the dog unconscious), potential exposure to toxins, vaccination history, any family history of seizures and any past illnesses.
•Step 4: Perform a complete physical and neurological examination. The majority of dogs that are evaluated for seizures are normal between episodes. Nonetheless, it is imperative to perform a complete examination to look for evidence of concurrent disease or subtle neurological signs that might be present. With respect to the latter, animals should be evaluated for any change in mentation or behavior, visual deficits, gait abnormalities or postural reaction deficits. In addition, a fundoscopic examination should be performed to evaluate for the presence of retinal lesions, as inflammatory conditions affecting the central nervous system frequently also involve the retina.
•Step 5: Formulate a list of differentials and a diagnostic plan. The causes of seizures can be divided into extracranial and intracranial categories. Extracranial causes include metabolic or toxic disturbances that secondarily effect brain function, such as hepatic disease, renal disease, electrolyte disturbances, hypoglycemia, polycythemia and toxicity due to exposure to various compounds including lead and other heavy metals, organophosphates, strychnine, metaldehyde and ethylene glycol. Intracranial causes refer to structural or functional abnormalities of the brain that incite seizures. This category includes anomalous disorders, such as hydrocephalus, neoplastic conditions, either primary brain tumors or metastatic disease, infectious agents, inflammatory (non-infectious) disease such as granulomatous meningoencephalomyelitis, trauma, vascular disease, and primary or idiopathic epilepsy. Primary epilepsy is caused by a functional defect of the brain, and no structural abnormalities can be found in these dogs to account for the seizures. The disorder is heritable in several breeds of dogs and has a typical age of onset between 1 year and 5 years.
Historical information and examination findings are useful in directing the clinician to likely causes for the seizures. It is helpful to rank differential diagnoses based on the age of onset of seizures. Typically, extracranial causes are explored first, and if none are identified, then intracranial causes are pursued.
In an animal less than 1 year of age, metabolic conditions, such as In formulating a differential diagnosis, historical information can be useful. Ask questions about the age and onset of seizures, and any events that precipitate seizures. hypoglycemia and portosystemic shunts. As well, toxic causes of seizures are considered likely.Within the intracranial category, anomalous conditions and infectious etiologies are most commonly identified.
Initial diagnostic evaluation of an animal with seizures of onset less than 1 year of age should be directed at potential extracranial causes, with a hemogram, chemistry profile, urinalysis and bile acid tolerance.
Lead levels should also be performed if lead exposure is a possibility. If these test results are normal, further diagnostic tests, such as brain imaging (CT or MR) and cerebrospinal fluid analysis, should be recommended. In puppies, ultrasound of the brain through an open fontanelle can provide adequate imaging to look for evidence of hydrocephalus. Cerebrospinal fluid analysis is necessary to exclude infectious causes.
The most likely diagnosis in a dog with onset of seizures between 1 year and 5 years of age is primary epilepsy. However, toxic and metabolic causes are still possible, and a hemogram, chemistry profile, urinalysis and bile acid tolerance is indicated. If these tests are normal and the signalment, history and physical examination suggest that primary epilepsy is likely, then further diagnostics are not necessary and a presumptive diagnosis can be made.
However, if the owner desires a more definitive diagnosis, then brain imaging and cerebrospinal fluid analysis is indicated. In addition, animals in this age group with partial seizures or seizures that prove refractory to treatment should undergo further diagnostic testing to evaluate for structural brain abnormalities.
In dogs with an onset of seizures greater than 5 years of age, metabolic causes of seizures again assume a greater importance due to an increased incidence of organ failure and neoplastic disease. Initial diagnostic workup is identical to that discussed for the other two age groups — hemogram, chemistry profile, urinalysis and bile acid tolerance. If no abnormalities are identified, intracranial causes should be explored. Brain neoplasia and vascular diseases are more prevalent in older animals. Blood pressure should be measured, and if normal, brain imaging and possible cerebrospinal fluid analysis should be recommended.
•Step 6: Decide when to start treatment. Treatment should be directed at any underlying cause identified in the diagnostic workup. This is especially true for metabolic causes, as seizures due to conditions, such as hypoglycemia or hypocalcemia, tend to respond poorly to antiepileptic drug (AED) therapy alone.
When deciding whether to initiate AED therapy for a seizure disorder, the general health of the animal must be considered as well as the owner's ability to comply with the proposed therapeutic regimen and the financial impact. In general, the author will recommend initiation of treatment based on the following factors:
However, the final decision to initiate treatment must be made on a case-by-case basis, with all factors in mind.
Client education is extremely important in the successful management of an epileptic dog. Owners should be made aware that once therapy is initiated, in most instances it is lifelong, and that it is imperative that the AED be administered on a regular basis at established treatment intervals. Owners need to realize that the goal of treatment is control of the seizures, and that many animals do not become seizure free. Dogs with epilepsy require continuous care, and drug dosage most likely will need to be adjusted over time.
Finally, side effects of the medications are common, and an effort should be made to maximize seizure control while minimizing adverse effects.
•Step 7: Decide on a treatment regimen. It is generally agreed that monotherapy is preferred in medical seizure management. A second drug should not be added until treatment with the first has been proven unsuccessful — either due to continued seizures despite therapeutic serum drug concentrations or the presence of unacceptable side effects.
Phenobarbital is still considered by many the first line drug in treating canine seizures. It is effective in controlling seizures in the majority of epileptic dogs when serum concentrations are maintained within the therapeutic range of 20-45 µg/ml. Additional advantages include the relatively low cost, ease of administration and relatively short time to reach steady state concentrations.
Common side effects of phenobarbital include polydipsia, polyphagia, polyuria and sedation. Less common, but more serious, side effects include hepatotoxicity and bone marrow suppression. The risk of hepatotoxicity is in part correlated with serum phenobarbital concentrations and the duration of treatment. Liver pathology can be reversible if identified early in the course of disease and the medication discontinued.
It is important to recognize that increases in liver enzymes are common in dogs on phenobarbital, and this in itself is not an indicator of liver dysfunction. However, dramatic increases or decreases in liver enzymes from one evaluation to the next, or increases in serum phenobarbital levels without a concomitant dosage increase, might suggest liver dysfunction and necessitate further evaluation.
It is recommended that serum phenobarbital concentrations be measured two weeks after initiating therapy or any dosage adjustment, and patients on phenobarbital be monitored at six- to 12-month intervals with a hemogram, serum chemistry profile and serum phenobarbital level. Although many practitioners routinely will measure trough drug concentrations, the timing of blood collection for measurement of serum concentrations is probably not important is most dogs.
Bromide has been used as an AED in dogs since the mid 1980s. It is effective when used in combination with phenobarbital and more recently has been recommended as a sole AED. Bromide does not undergo hepatic metabolism, being eliminated unchanged by the kidneys. Bromide is not available as an approved drug, but rather is compounded from either the potassium or sodium derived analytic grade chemical. The therapeutic range is 1-2 mg/ml when used in conjunction with phenobarbital and 2-3 mg/ml when used alone. The elimination half-life of bromide is quite long, such that it takes at least two to four months to reach steady-state concentrations. A loading dose of bromide can be given at the initiation of treatment in order to achieve therapeutic drug concentrations more rapidly. A common misconception is that administering a loading dose will shorten the time required to reach steady-state concentrations. Although therapeutic serum levels can be obtained quicker, the time to reach steady state concentrations is not altered.
Vomiting is a side effect with bromide, presumably due to gastric irritation. Administering the drug with food can minimize this. Other side effects include polyphagia, polyuria, polydipsia, sedation and ataxia. In addition, a possible association between potassium bromide and pancreatitis exists.
Changes in salt intake can alter the elimination rate of bromide and change serum concentrations. Because of this, the diet should remain constant while on bromide therapy. If a diet change is necessary, the bromide level should be monitored closely for several months after the transition.
•Step 8: Regularly reassess treatment plan. The management of an epileptic dog is an ongoing task. It is recommended that dogs with epilepsy be evaluated at a minimum of once each year, to assess for treatment efficacy and screen for potential side effects of the medication.
If a dog does not achieve satisfactory seizure control with phenobarbital and bromide, treatment with one of the newer human AEDS, such as gabapentin, felbamate, zonisamide, levetiracetam or topiramate, can be attempted.
With regular care to ensure that problems are identified early and addressed as needed, most epileptic dogs can be expected to have a normal lifespan and an overall positive quality of life.
Dr. Muñana is associate professor of neurology at North Carolina State University College of Veterinary Medicine. A diplomate of the American College of Veterinary Internal Medicine (Neurology), she completed a residency in neurology and neurosurgery at Colorado State University. Her research area includes inflammatory disorder of the central nervous system in dogs and cats and epilepsy in dogs with a focus on alternative treatments of seizure control in patients that respond poorly to available medications. Dr. Muñana received her DVM from the University of California-Davis.