Seizures

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Introduction

• Seizures are paroxysmal changes in cerebral cortex electrical activity that start abruptly, end suddenly and have a tendency to recur.
• Epilepsy is the occurence of recurrent seizures.

Pathophysiology

• Seizures occur when there is imbalance between exitatory and inhibitory processes. This may be due to :
  • Inadequate neuronal inhibition.
    • Major inhibitory neurotransmitters include GABA and glycine.
  • Excessive neuronal excitation.
    • Major excitatory neurotransmitters include aspartate and glutamate.

Proposed Mechanisms

• Defective feed-forward inhibition or feed-back initiation of inhibitory neurons in cortical circuits.
  • Recurrent excitatory collaterals may be formed.
• Changes in membrane properties of neurons.
  • These may include changes at:
    • Potassium, sodium, chloride and calcium ion channels
    • GABA receptors
    • Nicotinic acetyl choline receptors
    • NMDA receptors
      • Activation.
• Changes in the ionic microenvironment.

Seizure Development

1. At the onset of a seizure, abnormal neurons undergo prolonged depolarisations.
   • These depolarisations are associated with the rapid firing of repeated action potentials.
2. Depolarisation of abnormal neurons recruits adjacent neurons with which they are connected.
3. The electrical discharges of the large number of neurons involved become linked together.
4. A storm of electrical activity results, causing a clinical seizure.
5. Seizures may then spread:
   • To adjacent areas of the brain.
   • Through established anatomic pathways to other distant areas.

Nomenclature

• Status epilepticus is the term used to describe
  • A seizure lasting longer than 5 minutes, or
  • A collection of discrete seizures without full recovery of consciousness.
• Cluster seizures occur when 2 or more seizures are experienced in a brief periods, but the patient regains consciousness between them.
• Three classes of seizures are recognised:
  1. Generalised seizures
  2. Focal seizures
  3. Focal generalising seizures

Generalised Seizures

• Generalised seizures may be:
  • Idiopathic
  • Symptomatic
    • Due to intracranial disease e.g. neoplasia, storage diseases etc.
  • Cryptogenic
    • There is probably an underlying cause but it cannot be identified by the diagnostic tests available.
  • Reactive
    • Due to some extracranial disorder, for example a toxin or metabolic disorder.

Clinical Signs

• Initial clinical signs show involvement of both cerebral hemispheres.
• Generalised seizures result in:
  • Change in consciousness
  • Motor activity
    • Tonic-clonic seizures are most common in dogs and cats.
  • Autonomic signs
• The body's energy utilisation can increase to around 250% of the normal value during a generalised seizure.

Stages

1. Prodromal Phase
   • The animal experiences an indication of a forthcoming seizure.
   • This occurs hours to days before the event itself.
2. Aural Phase
   • This is the very start of the seizure.
   • Behaviour changes may be apparent.
3. Ictal Phase
   • The seizure "proper".
4. Postictal phase
   • Consists of transient neurological and behavious changes, which can last from hours to days.

Idiopathic Epilepsy

• Idiopathic epilepsy is a relatively common cause of generalised seizures in the dog.
  • NOT in the cat.
• The onset of seizures is between 1 and 5 years of age.
• The condition presents as recurrent, unprovoked seizures, with no specific cause.
• There are no neurological defects between episodes.
• Seizures tend to start as generalised seizures, with no aura.

Acquired Generalisd Seizures

• Other general seizures may be acquired.
• Seizures can occur at any age, but generally occur in animals younger than 2 years and older than 5 years.
• Causes may include:
  • Intracranial disease
    • Neoplasia
    • Trauma
    • Infection
    • Inflammation
  • Extracranial disease (also known as "reactive epilpsy").
    • Electolyte disorders
    • Metabolic disorders
    • Toxicity

Focal Seizures

• Almost always an acquired disease.
• Active diseases often progress to become more general.
  • Cause generalised seizures.

Simple Focal Seizures

• Onset occurs in a limited area of one cerebral hemisphere.
• No impairment of consciousness.

Complex Focal Seizures

• Arise in a single brain region, but cause impaired consciousness.

Causes of Acquired Seizures

Cause	Examples
Neoplasia	Primary or metastatic
Inflammatory	Distemper, FIP, FeLV/FIV, rabies, cryptococcosis (cats), toxoplasmosis
Traumatic	Immediate or delayed
Vascular	Feline ischaemic encephalopathy, thromboembolism, hypertenstion
Anomalous	Hydrocephalus
Metabolic	Hepatic encephalopathy, uraemia, hyperparathyroidism, hypolycaemia, hyperkalaemia, hypocalcaemia, hypoxia, acid-base disorders, hyperthermia
Toxic	Lead, organophosphates, metaldehyde, strychnine

Investigation of Seizures

• It must first be determined whether seizure activity is in fact a seizure, rather than a non-epileptic paroxysmal event, for example:
  • Syncope
  • Exercise-induced weakness
  • Obsessive-compulsive behaviour
  • Narcolepsy
• Idiopathic epilepsy may be differentiated from secondary or reactive seizures by considering:
  • Age of onset
  • Breed disposition
  • Partial seizures or asymmetrical post-ictal signs
    • These suggest a discrete lesion.
  • Older animals (>5 years) may be more likely to have an acquired aetiology.
  • Younger animals (<6 months) may be more likely to have toxic or metabolic causes.
• Useful tests include:
  • Metabolic screening
  • Haematology
  • Serum biochemistry
  • Urinalysis
  • Serology.
  • Bile acid stimulation test
  • Serum lead
  • MRI and CT scanning, and CSF analysis, help rule out cancer.