Large Animal Neurology. Joe Mayhew

nasal sensation, anisocoria, a head deviation with or without blindfold applied, facial paresis and facial hypertonia, and asymmetry in hopping on the forelimbs. If an epileptic horse is essentially healthy with minimal or no neurologic signs evident between seizures, then most possible causes of forebrain disease that include viral encephalitis, hepatoencephalopathy, leukoencephalomalacia (Fusarium sp. mycotoxicosis), and other toxicities are exceedingly unlikely to be the cause of the epilepsy. Three diseases at least should however be given consideration as underlying specific causes in such situations. In horses that have been on the American continents, equine protozoal myeloencephalitis caused by Sarcocystis neurona or Neospora hughesi must be considered.²⁷ Serum and cerebrospinal fluid immunoassay tests can be performed so that appropriate treatment can be initiated and continued if the tests are positive. In most countries, consideration should be given to treatment for thromboembolic and migratory verminous encephalitis at the beginning of an epileptic syndrome using larvicidal doses of anthelmintics and short‐term nonsteroidal anti‐inflammatory or glucocorticosteroid therapy. And third, cases with bacterial granulomatous ependymitis and choroiditis, true brain abscesses, and cholinisteric granuloma can be insidious in their clinical progression, and one or more seizures may be the initial overt sign. Indeed, in an aged horse with epilepsy that may be responsive to glucocorticosteroid drugs for quite some time, cholinisteric granuloma must be given strong consideration.²⁸ Various surgical and antibacterial therapeutic regimens are feasible, but heroic approaches in such cases. Rare occurrences of ear tick infestation, hypoglycemia associated with pancreatic neoplasia, intracranial neoplasia, and vascular dysplasia might be considered.^29–31

      Guidelines aimed at assisting in the handling of large animal epileptic patients and in advising owners are not available, thus recommendations are rather empiric. To begin with, it must at least be reported to the owner that a patient with epilepsy is unsafe to ride until seizure free and not on anticonvulsant medication for at least 6 months. Also, if the horse injures itself to require veterinary attention, and thus documentation of the injury for the record, then euthanasia must be considered (Figure 6.1). With respect to this decision, and in reporting to an insurance company, it is reassuring to have a video of one of the seizures and to have some, albeit subtle, interictal sign to corroborate the horse having epilepsy associated with an acquired intracranial morbid disease process. On the other hand, a sensible owner can be advised that the vast majority of seizures will occur at quiet times and not while working; however, the written report must state that the horse is unsafe to ride.

      The following points are a guide to maintenance anticonvulsant therapy to help control seizures in epileptic adult horses:

       Have the owner keep a diary of seizure activity and all medication given.

       All anticonvulsant drugs are not licensed for use in large animals.

       Begin phenobarbital at 5 mg/kg BID, PO.

       Increase the dose about 20% every 2 weeks until persistent sleepiness occurs or seizures are not controlled.

       Reduce dose say by 20% and add KBr at 25–90 mg/kg SID, PO, with or without loading doses of 120–200 mg/kg SID, PO for 1–5 days.⁴¹

       Consideration then can be given to incorporating phenytoin, carbamazepine, gabapentin or levetiracetam, etc., to the regimen if further control required and/or side effects are unacceptable.

       After control, monitor serum concentrations and aim to keep them in the therapeutic ranges (e.g., phenobarbital, 15–40 μg/mL; bromide, 1000–4000 μg/mL).

       Seizure threshold may be lowered with estrogen, therefore anticonvulsant dosage may be increased prior to onset of and during estrus activity.

       If the patient is completely seizure free for 6 months. then slowly wean the patient off one drug at a time over 3 months. If seizures begin, raise the dose again.

       Interactions must be considered when other drugs are to be administered to an animal already on anticonvulsant therapy.

      These guidelines may be extrapolated to other species. Metabolic disorders especially hypocalcemia and hypomagnesemia must be considered in ruminants. All ruminants that have seizures of uncertain cause should receive gram doses of thiamin immediately after any diagnostic samples have been drawn for red cell transketolase activity.

      The client should be encouraged to keep an accurate diary of known and suspected seizure episodes particularly noting preictal signs, site on the body where the motor disturbance begins, and the severity and timed duration of each seizure. This will allow a best prediction as to whether the epilepsy is stable, resolving or progressing, to be made. Should individual seizures be occurring say fewer than one every month and the patient does not injure itself to require veterinary attention, then medication is probably not indicated. If there are cluster seizures, status epilepticus or more than one seizure a month, or if the patient injures itself to require veterinary attention and the client does not accept euthanasia as an option, then anticonvulsant therapy must be considered.

For acute control of seizures in adult horses, IV glucose should be administered if hypoglycemia is suspected. Then, 50 mg IV doses of diazepam or midazolam can be used.^{32, 33} Benzodiazepine drugs should not be left in a plastic container or syringe for more than a few minutes as they may become inactivated. If diazepam or an alternative benzodiazepine drug is not available, then standard doses of alpha‐2 agonist drugs, or IV levetiracetam can be used. If these are ineffective, then general anesthesia is indicated and at this stage euthanasia must be strongly considered. Midazolam can also be considered as first line therapy for neonatal seizures in foals,^32,34 and intranasal equivalent doses may expedite seizure control.³⁵

      Pharmacokinetic and related drug disposition studies on phenobarbital,^36–39 potassium bromide^40,41 and phenytoin in horses,^42–44 potassium bromide in sheep,⁴⁵ and phenobarbital⁴⁶ and levetiracetam ^{in foals have been published. Gabapentin,48 pregabalin,49 and imepitoin50 may need to be considered if the starting drugs are ineffective at giving some seizure control. Several other human anticonvulsant drugs may be worth considering if control of seizures is unsatisfactory. Two drugs that have been tried in foals with unsubstantiated anticonvulsant results are carbamazepine (a sodium channel stabilizer) at 250–500 mg doses and triazoline (an excitatory amino acid antagonist) at 1 g doses. Discussions on the use of antiseizure medication in small animals51 and in humans52 are useful resources to consult.}

References

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      6 5bMiller, S. M. (2020). Putative Otobius megnini‐associated clinical signs in horses in South Africa (2012–2018). J S Afr Vet Assoc, 91(0), e1–e6. 10.4102/jsava.v91i0.1983

      7 6 Mayhew IG, Jolly RD, Burnham D, et al. Familial episodic ataxia in lambs. N Z Vet J 2013; 61(2): 107–110.

      8 7 Dittmer KE, Jolly RD, Mayhew IG, et al. Familial episodic ataxia in lambs is potentially associated with a mutation in the fibroblast growth factor 14 (FGF14) gene. PLoS ONE 2017; 12(12): e0190030.

      9 8 Wong M. Advances in the pathophysiology of developmental epilepsies. Semin Pediatr Neurol 2005; 12(2): 72–87.

      10 9 Blumenfeld H. Impaired consciousness in epilepsy.