Seizure Refresher

By Lisa Murphy DACVECC

Seizures are one of the most common neurological emergencies seen by small animal vets both in general practice and in emergency clinics. What follows is a brief discussion of seizures and some of the more commonly used anticonvulsive medications for management of these cases.

Idiopathic Epilepsy:

  • Most dogs suffering from idiopathic epilepsy are between 1-5 years old with genetic predilection in the beagles, the Keeshond, the dachshund, the Irish wolfhound, Labrador and Golden Retrievers and the English springer spaniel.
  • They can have any type of seizure (generalized/tonic-clonic, focal) but generalised is more common.
  • Predisposing factors are not known in animals but in people include stress, sleep deprivation, missed medications and concurrent illness.
  • Idiopathic epilepsy is less common in cats although also usually occurs around 1-5 years old.
  • In studies evaluating dogs > 5 years old, 35% had no identifiable cause of epilepsy, while the remainder were divided into those with neoplasia (52%) and those with other aetiologies (inflammatory, vascular, congenital). All dogs in the 8-10 year old group and in the over 15-years old group, and 80% of dogs in the 11-13 years old group, had neoplasia as the underlying cause.
  • When comparing the neurological exam to MRI findings, of those who had an abnormal neurological exam 79% went on to have a lesion on MRI. A properly performed neurological exam is considered to have 74% sensitivity and 62% specificity for diagnosing secondary epilepsy. 

Metabolic and Toxic Causes:

Among the lesser studied causes of seizures in our patients are metabolic and toxin associated seizures, of which there are a number of potential culprits.

A retrospective study was performed on almost 100 dogs and found some very interesting findings. Intoxications were the most common cause with metaldehyde most likely (although this likely depends on geographic location). When evaluating metabolic causes alone, hypoglycaemia was most common. Interestingly, reactive seizures secondary to metabolic disorders or toxins had a 1.57x higher risk of a status epilepticus presentation as compared to idiopathic epilepsy.

Secondary Intracranial Hypertension: 

While most seizures do not tend to be life-threatening, animals which have multiple seizures in a short period may be at risk for developing intracranial hypertension (ICH). Typically, intracranial pressure (ICP) is maintained within a narrow range secondary to several physiological processes. These can be disrupted as a result of seizure activity. 

If left untreated, significant intracranial hypertension may lead to the Cushings response which is often fatal. Clinically it should be suspected in a seizuring patient with systemic hypertension and bradycardia. 

Anticonvulsive Medications

Common first line anticonvulsive medications:

Thankfully, most patients presenting with seizures do not go on to develop such life-threatening complications and typically just require acute control of their seizures.

Benzodiazepines:

  • The most common medications employed to stop seizures are benzodiazepines. Diazepam and midazolam are typically given intravenously (0.5 mg/kg) or rectally (1 mg/kg) for rapid seizure control.
  • It is important to note however that they have a very short duration of action and animals may start having seizures again within 10 minutes of their administration.
  • These drugs also need to be used cautiously in patients with seizures due to hepatic encephalopathy as the drug’s metabolism will be reduced resulting in more significant sedation.
  • In some cases, a continuous infusion or repeated bolus administration must be used while waiting for the patient to respond to medications used for longer-term seizure control. Midazolam is recommended for this as it is water soluble and causes less thrombophlebitis; however, neither drug is superior to the other for seizure control.

Ketamine/Dexmedetomidine:

  • Some patients are refractory to acute control with benzodiazepines and will continue to seizure. Recent case reports in veterinary patients have shown that ketamine and dexmedetomidine may be able to offer short-term seizure control in such cases.
  • In both cases, high doses are typically needed and patients require continuous monitoring for significant side effects.
  • Patients typically remain on an infusion until they are seizure free for at least 6-12 hours. The drug then needs to be slowly weaned over the next 6-12 hours.
  •  While the dog is on these infusions, a second medication for chronic seizure control must be started.  

Common long-term anticonvulsive medications:

Phenobarbital:

  • The most commonly used drug in veterinary patients.
  • Benefits include relatively low cost and, for most animals, being well tolerated long term.
  • Major disadvantages include the need to ‘load’ the drug as therapeutic levels can take several days to be attained during which time the animal would be at continued risk of further seizures. This involves the administration of a larger dose for the first 24 hours followed by a much lower maintenance dose. At high loading doses, most dogs will be very sedated. Their carers need to be warned that they can continue to be very sedated, and potentially ataxic, for the first few days of treatment.
  • Cats tend to show fewer side effects.
  • Phenobarbital also needs to be used cautiously in animals with an underlying hepatic disease as the drug will increase hepatic enzymes over time. 

Potassium Bromide (KBr):

  • Can also be employed in dogs
  • It requires loading to attain therapeutic levels during which time the dog can be very sedated.
  • While it can offer excellent seizure control, some dogs develop significant side-effects (e.g. gastrointestinal, megaoesophagus, dysphagia) and treatment needs to be discontinued.
  • It is important to note that bromide competes with chloride ions in the renal tubule. Vets treating animals that are on chronic KBr treatment with intravenous fluids need to recognize that concurrent use of 0.9% sodium chloride will speed up renal clearance of KBr. 

Levetiracetam:

  • Has become more widely used in recent times
  • The exact mechanism of action is unknown
  • Major benefits of this drug include minimal side effects and that it attains therapeutic levels within 60 minutes of administration
  • While levetiracetam has excellent short-term effects, its use as long-term monotherapy for seizure control is controversial. It has been used in this was for idiopathic epilepsy but, after a ‘honeymoon’ period, an additional anticonvulsive medication may be needed.

Zonisamide:

  • A synthetic sulfonamide based drug
  • Takes a few days to achieve therapeutic levels
  • Tends to be well tolerated by most dogs
  • Advantages include generic drugs now available (so less cost) and the need for only twice daily dosing (so better compliance)
  • There are sparse case reports of dogs developing immune-mediated thrombocytopenia secondary to the sulpha component within the drug so this risk, while low, should be discussed with carers.
  • One caveat to its use is that concurrent use of phenobarbital increases the renal clearance of zonisamide so the dose may need to be increased. 

Pregabalin:

There is not as much data available for the use of this drug in dogs. Studies that have been performed show that it can reduce seizure frequency by fifty per cent when used in dogs on chronic phenobarbital or potassium bromide therapy.