Epilepsy
Robert J. MacKay
According to guidelines put forth in 2015 by the International Veterinary Epilepsy Task Force, epilepsy is defined as a disease of the brain characterized by a persistent predisposition to generate epileptic seizures.1 In practice, this usually means at least two unprovoked epileptic seizures more than 30 days apart.
A systemic condition or chemical/drug may cause a normal brain to generate reactive seizures; however, these are not classified as epilepsy. Epilepsy may be idiopathic or structural. Idiopatbic epilepsy connotes either genetic predisposition (known or suspected) or epilepsy of unknown cause in which there is no indication of a structural cause. Genetic epilepsies are rare in large animals, but a few heritable epilepsy syndromes have been described in horses, such as juvenile idiopathic epilepsy of Arabian foals of Egyptian lineage,2 Arabian lavender foal syndrome,3 and suspected familial epilepsy in cattle of various breeds.4,5 Structural epilepsy occurs as a result of known or suspected intracranial/cerebral disorders, including vascular, inflammatory/infectious, traumatic, anomalous/ developmental, neoplastic, or degenerative diseases. Polioen- cephalomalacia is the most commonly reported diagnosis in ruminants with seizures caused by structural brain disease: In one report, 14 of 19 sheep and goats and 8 of 13 cattle with structural-origin seizures had polioencephalomalacia.6,7 In 42 horses older than 3 weeks with structural-origin seizures, the causes listed were skull fractures, cerebral hemorrhage, cerebral edema, neoplasia, cholesterinic granuloma, vasculitis, meningoencephalitis, abscesses, intracranial vascular events, leuko- encephalomalacia, congenital abnormalities, and EPM.8Epileptic seizures result from abnormal, synchronous, electrical discharges in the neurons of the forebrain that spread to the somatic and visceral motor areas to initiate spontaneous, paroxysmal, involuntary movements that may begin and end spontaneously.1 Each seizure (ictus) may be generalized, involving neural networks of both cerebral hemispheres and resulting in generalized bilateral motor activity over the whole body, or focal, involving one side of the forebrain and lateralized motor signs or sensations.
Generalized seizures usually begin with tonic muscle contractions of the muscles of the neck and limbs but progress to rhythmic clonic limb thrashing, often accompanied by abnormal eye positions and movements. Affected animals often fall and display various autonomic signs, such as salivation, urination, and defecation. The oroalimentary form of generalized seizures occurs particularly in neonatal foals and is characterized by lip smacking, lip pursing, chewing, licking, odontoprisis, or swallowing.1 Focal seizures begin as involuntary tonic or clonic contractions of groups of facial, jaw, or body muscles. These signs may stop spontaneously without progression, but more typically they spread from the initial focus to involve the whole body. In rare cases, seizures may be preceded by a prodrome of up to several hours' duration, usually characterized by signs of restlessness or disorientation, and are usually followed by a period of stupor, restlessness, and central blindness that is usually short-lived but can last several days in foals.In large animals, the best characterized genetic epilepsy syndrome is juvenile idiopathic epilepsy in Arabian horses of Egyptian lineage.2 Seizures usually begin in affected foals by 2 months of age (range, 2 days to 6 months), but onset as late as 18 months has been described. Seizures are usually symmetric and generalized, often with no prodrome. After a brief period of whole-body myotonus and collapse into lateral recumbency, the animal exhibits clonic (“galloping”) limb movements, opisthotonos, sweating, retracted lips, and staring, unblinking eyes. Each seizure can last up to 5 minutes but typically is less than a minute. Postictal signs are usually profound and persistent and are often the first abnormality detected by the owner: obtundation, cortical blindness, loss of maternal bond and interest in suckling, and other variable behavioral signs. Blindness, the last sign to resolve, typically lasts several days (range, hours to 2 weeks).
Injuries, especially to the skull, may occur during seizures or as a result of collisions during the period of blindness. Juvenile idiopathic epilepsy responds well to anticonvulsant therapy and does not usually recur (see Treatment section). Untreated foals also may grow out of the condition by a year of age but are subject to cumulative seizure-associated injury, and there are anecdotal reports of permanent behavioral abnormalities in untreated horses.A diagnosis of epilepsy is supported by the finding of epileptiform discharges on interictal EEG, although this test does not appear to be highly sensitive.9 Epileptiform discharges were identified on EEG of only 9 of 13 foals with juvenile idiopathic epilepsy.2 Artifacts induced by patient movement or sedative drugs limit the usefulness of traditional electroencephalography in large animals. Ambulatory electroencephalographic recording, as is routinely used in human neurology, may be a more sensitive and reliable method for investigating suspected seizures in large animal patients.9
Specific protocols for antiepileptic drugs have not been established for most large animal species. However, most seizures are controlled in the acute phase with diazepam (0.05 to 0.2 mg/kg IV) and over the long term with oral or IV phenobarbital. A simple approach to treatment of epileptic horses has been described and can be followed in other species10: oral phenobarbital, 5 mg/kg twice daily, begun without a loading dose. Treatment at this dosage is continued for at least 2 weeks. If signs are insufficiently controlled, the dosage is increased by 1 mg/kg and continued for another 2 weeks. This cycle of incremental dosage increase is continued until adequate control is achieved or side effects prevent further increase. Potassium bromide (90 mg/kg once daily PO, which may be preceded by an optional loading course of 120 mg/kg/day for 1 week) can be added to phenobarbital in these cases to provide additional anticonvulsant effect.
The therapeutic trough concentration of phenobarbital is 15 to 40 μg7mL. After 6 months of seizure-free therapy, the dosage of phenobarbital can be tapered over several weeks. If the horse remains free of seizures for 6 months after anticonvulsants have been discontinued, the horse is considered by some authorities to be no longer epileptic; however, it is prudent to continue to advise owners that such horses should never be ridden or used for sporting purposes. Foals with juvenile idiopathic epilepsy are usually treated for 3 months with phenobarbital, which is then tapered. Basic pharmacokinetic studies have been used to rationalize antiepileptic dosages of phenytoin (10 to 15 mg/kg PO once daily) and levetiracetam (32 mg/kg), although these drugs have not been field tested for efficacy.11 All ruminants experiencing seizures should also immediately be treated with thiamine (10 to 20 mg/kg IV, IM, or subcutaneously [SC]).