Introduction

• Cause: multiple potential extracranial and intracranial causes. Seizures in ferrets are often caused by hypoglycemia secondary to insulinoma. However, many other differential diagnoses are possible such as metabolic disease, head trauma, intracranial lesions and CNS infections. Intoxication is possible, but relatively uncommon in ferrets, as is idiopathic epilepsy.
• Signs: vary depending on underlying cause.
• Diagnosis: aim to identify underlying cause where possible. Full physical examination. CBC, serum chemistries (particularly blood glucose in emergency situations) and blood electrolytes. Further investigations will depend on the particular case but may include serology (eg toxoplasmosis), toxin identification, ultrasonography, radiography, CT, MRI and CSF analysis. EEGs are rarely performed in ferrets.
• Treatment: check first for hypoglycemia and address if present. If ongoing seizing when normoglycemic, control active seizures with benzodiazepines. Some may require the addition of phenobarbital, levetiracetam or even general anesthesia. For long-term management some may need phenobarbital and/or potassium bromide, or levetiracetam. General supportive care, including fluid therapy and nutritional support. Other treatments dependent on etiology, but can include administration of dextrose, mannitol, hypertonic saline or systemic antibiotics. Steroids may be used if there is cerebral edema.
• Prognosis: depends on etiology and response to treatment of the seizures. Seizures can reoccur even if underlying cause is resolved as a ‘seizure focus’ (scar tissue?) in the brain may have developed. Status epilepticus gives a poor to grave prognosis, particularly if it cannot be medically controlled. Grave prognosis if agonal.

Pathogenesis

Etiology

• Metabolic imbalances (most common etiology): hypoglycemia (eg secondary to insulinoma), hypocalcemia, severe uremia, electrolyte imbalances, hepatic disease.
• Toxins Toxicosis overview: ibuprofen Ibuprofen toxicity, organophosphate, permethrin, clostridium botulinum endotoxin, lead, overdosing of metronidazole.
• Infectious:
  • Viral: aleutian disease Aleutian disease, coronavirus Ferret systemic coronavirus, distemper Canine distemper, rabies Rabies, or (experimentally) rift valley fever virus.
  • Parasitic: toxoplasmosis, sarcocystosis.
  • Bacterial: Stretococcus zooepidemicus.
  • Fungal: cryptococcosis Cryptococcosis, blastomycosis.
  • Otitis media/interna Otitis: rare.
• Immune-mediated: meningoencephalitis, eosinophilic syndrome Eosinophilic gastroenteritis.
• Trauma: head injury.
• Neoplastic: CNS lymphosarcoma Lymphoma overview, or any CNS primary or metastatic neoplasm. Osteoma Musculoskeletal neoplasia, granular cell tumor and lymphoma Lymphoma overview all reported in ferrets. Insulinoma Insulinoma may lead to hypoglycemia Hypoglycemia.
• Congenital: skull/brain defect.
• Degenerative: neuronal vacuolation.
• Vascular: infarct in the brain secondary to cardiac disease:
  • May be difficult to detect antemortem.
  • Cardiac evaluation Heart examination, including echocardiogram and ECG, may be indicated.
• Idiopathic: epilepsy - this is usually the diagnosis after all other causes ruled out (appears to be rare in ferrets).

Predisposing factors

General

• Insulinoma Insulinoma may lead to secondary hypoglycemia Hypoglycemia.
• Cardiac disease Heart disease can be involved in precipitation of clots and emboli, that may cause infarcts in CNS.
• Distemper Canine distemper and rabies Rabies are more likely in unvaccinated ferrets.

Specific

• Access to toxins.

Pathophysiology

• Seizures are due to brain dysfunction in the cerebrum.
• A seizure is defined as a sudden, uncontrolled, transient increase in electrical discharge in the brain:
  • This results in an alteration or loss of consciousness.
  • Altered muscle tone including twitching.
  • There may be jaw movements like chewing.
  • There may be urination, defecation, salivation.
• Grand-mal seizures (generalized) are tonic-clonic:
  • Muscle tone extremely increased (tonus), usually alternating quickly with relaxation (clonus).
  • Paddling of the limbs with the ferret lying on its side.
• Partial motor seizures are characterized by asymmetrical signs, focal twitching, isolated tonic-clonic movements of just the facial muscles or limbs.
  • There are classically 3 phases to a seizure, however it may be difficult to identify or recognize these in some ferrets:
    • Pre-ictal (aura):
      • Restlessness, anxious, hyperexcitable (jump at small sounds), appears to look at non-existent things, may vocalize with sounds associated with nervousness.
      • May not have been noticed or may last for several minutes.
    • Ictal:
      • Usually only lasts for 1-2 min.
      • Owner usually perceives it as much longer.
      • Loss of consciousness.
      • Fall over, may paddle, twitch, make chewing/jaw movements.
      • May urinate, defecate.
      • Some may vocalize.
  • Post-ictal:
    • Period following the seizure.
    • Seems disoriented, stuporous.
    • May not recognize owner or surroundings.
    • Can have vision defects, circle, head press or other behavior changes.
    • May last for minutes to hours.
• Excessive discharges in aggregates of neurons occur from an area of the brain that is designated as a 'seizure focus', this is the origin of the seizure:
  • Abnormal electrical impulses from this spread to other parts of the brain which cause the activity associated with the seizure.
  • There can be a single focus or multiple foci in the brain. They can fire separately or simultaneously.
  • A seizure event changes the electrical charges within the brain - lowering the threshold for nerves to depolarize. This makes it easier for additional seizures to start in close proximity to the original source.
  • Localization of these foci can be found using electroencephalogram (EEG), although this is rarely done in pet ferrets.

Timecourse

• Depends on etiology.
• A seizure itself is a peracute event.

Diagnosis

Treatment

Prevention

Outcomes