Seizures

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Classic ptyalism, and facial clonic spasms associated with primary idiopathic seizures in a dog

Seizures are a relatively common neurological disease of dogs, with growing public sympathy, especially for dogs with chronic idiopathic forms of this condition[1].

A seizure is a clinically detectable manifestation of paroxysmal, excessive, and synchronous discharges of a population of hyperexcitable cerebral neurones. They are usually sudden in onset, short in duration and spontaneously resolve. Seizures which occur frequently are categorised as epilepsy.

Seizures are thought to occur through the action of a sudden, large influx of calcium into neurons within the cerebrum. Briefly, the pathological foundation of epilepsy involves a massive neuronal discharge, presumed to be triggered by a violent calcium influx into neuronal cell bodies, followed by cellular depolarization. The trigger for the calcium influx into neurones is thought the presence of excitatory amino acid (EAA) release. These EAAs combine with various neuronal surface receptors, causing calcium channels to suddenly open. This intracellular flush of calcium causes a cascade of neurotransmitter release across the neuron, causing an inadvertent excitation disorder resulting in an epileptic seizure.

In humans, epilepsy diagnosis requires extensive clinical history and ictal clinical signs (semiology) is a key feature for classification of epileptic syndromes.

Causes

Further classification of seizure type relies on appropriate use of the term epilepsy (recurrent seizures). Recurrent seizures are defined more broadly as epilepsy.

Primary epileptic seizures (idiopathic) is the term used if an underlying cause cannot be identified. If seizures result from structural lesion, they are defined as secondary epileptic seizures. The term reactive epileptic seizure is used when the normal brain reacts to transient systemic insult or metabolic disorders; these seizures are not considered recurrent. Secondary epilepsy is common in dogs, and appropriate diagnostic tests are necessary to determine the underlying cause. It can occur secondary to oestrus, organophosphate toxicity and ingestion of numerous toxins.

Primary epilepsy implies recurrent episodes of seizure activity associated with a primary functional cerebral disorder (having a physiological or biochemically related genetic basis). Typically, these seizures are tonic clonic and generalised with no identifiable structural brain lesions. Occasionally these seizures are partial with or without generalization. Partial seizures may be simple and only exhibit motor activity or complex where a component of the seizure involves aberrant behavior. Physical and interictal neurological examinations are normal. Advanced imaging and CSF analysis results are normal. Incidence of primary epilepsy is common in dogs[2].

Secondary epilepsy (also named symptomatic, acquired, or structural) implies recurrent seizure activity caused by acquired brain diseases that occur after traumatic, ischaemic, neoplastic and encephalitic events. According to some authors, the term epilepsy should be restricted to recurrent seizures resulting from nonprogressive intracranial causes of either a structural or functional nature. Others classify secondary epilepsy as recurrent episodes of seizure activity associated with an underlying structural disorder such as inflammation, trauma, ongoing hypoxia or ischaemia, or neoplasia. In cases of secondary epilepsy, partial seizures (simple or complex partial with or without secondary generalisation) are observed more commonly and may be accompanied by an abnormal neurological examination with or without lateralisation. Secondary epilepsy is thought to be less common. Reactive seizures arise as a consequence of extracranial metabolic or toxic insults.

Clinical signs

Seizure type (ictal phase) can be characterised as (1) generalised with major motor activity (i.e., generalised tonic-clonic events) and usually with loss of any evidence of conscious activity, (2) simple partial with subtle motor manifestations [i.e. limb, facial or whisker twitching]), or (3) complex partial, non-motor in which aberrant behavior is exhibited (psychic or autonomic activity [i.e., tail chasing, floor licking, vocalising]).

Generalised and partial seizures occur. Generalised seizures (tonic-clonic or grand mal seizures) manifest as loss of consciousness, recumbency and tonic-clonic motor activity. The major motor activity can consist of generalised tonic movements with the limbs in rigid extension and purposeless limb movements and paddling. Opisthotonus and claw extension in addition to mouth-chomping and pupillary dilation also may be observed. At times, tonic flexion (emprosthotonus) is observed, which may be followed by moderate to severe muscle twitching (clonic phase). The patient may not have loss of consciousness during this type of event. Sometimes generalised seizures can be violent. Autonomic release (urination and defecation) usually accompanies the motor activity in addition to facial twitching, salivation, kicking, piloerection, and chewing. Self-inflicted trauma may be observed to include contusions, excoriations, biting of the tongue, or avulsion of the claws. Dogs also may exhibit mild or non-convulsive seizures, which are manifested by impaired consciousness, pupillary dilation, bilateral facial twitching, muscle spasms of the head and neck, and possibly, autonomic release. The ictus usually lasts from seconds to minutes and sometimes can progress to status epilepticus.

Partial seizures are subdivided into complex partial seizures and simple partial seizures; complex partial seizures are common. Such events often have lateralising signs preceding or during the ictus. Dogs with complex partial (psychomotor) seizures manifest impaired consciousness with stereotypic motor activity (that may lateralise) and abnormal behaviors. These activities include turning of the head to one side, chewing motions, transient staggering, and ventral flexion of the head. These episodes often are preceded by a short, piteous cry, intermittent episodes of aggression or fright, hissing, growling, raising of a single limb (repetitive movements), tail piloerection, and transient periods of uncoordinated, frantic running or bizarre aimless movements. Owners describe their dogs as acting like they are 'possessed', or in a trance as if they were hallucinating. Compulsive activities such as biting, self-excoriation, and circling can be observed. These episodes of bizarre behavior are distinguished from behavioral issues by the presence of facial twitching, salivation or a secondary seizure generalisation.

Simple partial seizures are characterised by near-normal or normal mentation and the appearance of unilateral motor signs involving a part of or all of the body. Dogs with simple partial seizures often twitch the eyelids, whiskers, and/or either in combination or separately. Head-shaking may occur and be accompanied by body jerking. Salivation, urination and pupillary dilation are transient signs. Continuous vocalisation and a brief rise in body temperature can be observed. Hyperthermia ensues as a result of continuous motor activity that can last from minutes to hours. Simple partial motor seizures are variable in clinical presentation and may be difficult to recognise for the untrained eye. Also, partial seizures may progress to clonic-tonic or generalised seizures. Seizures of this type may be more difficult to control because of the prolonged ictus phase.

Up to one third of dogs have seizures that progress to status epilepticus or cluster seizures. Dogs also may have an atypical presentation of non-convulsive seizures that go undetected for prolonged periods. Requesting the pet owner to videotape these episodes is helpful to document the severity and type of seizure.

Seizures in dogs, regardless of cause, manifest themselves in different ways and are more variable in clinical presentation than in dogs. The owner may not notice the ictal phase or actual seizure event readily until the signs are more obvious. The aura or preictal phase may comprise subtle behavioral changes that include aggressiveness, pacing, crying, restlessness, hiding, unusual affection, salivation, frantic running, hissing, growling, and anxiety. The aura may last seconds to days, but usually lasts for several minutes.

The postictal period can last from seconds to days. This period can manifest as confusion, aimless wandering, pacing, blindness, increased hunger, and changes in sleep/awake patterns.

Differential diagnoses

The signalment and history will influence the order of importance of your differential diagnosis. Differential diagnoses for seizure disorders in young dogs (less than 4 years of age) include congenital, infectious inflammatory, toxic and metabolic causes, whereas in older dogs (over 5 years), common differential diagnoses include vascular, neoplastic, and infectious inflammatory causes. Exceptions to this guideline occur; therefore, causes for seizures are assessed on an individual basis.

A patient with seizures requires, at the least, an anatomic diagnosis of a prosencephalic disorder. The differential diagnosis is dependent on the results of your neurologic examination.

  • Normal neurologic examination:
- Primary seizures-idiopathic epilepsy
- Secondary seizures - Structural lesion in a "quiet" area that does not affect the neurologic examination. ie hippocampal neoplasm
- Structural lesions (using the mnemonic 'MIIND'):
- M : malformation - e.g. porencephaly
- I : injury, inflammation (due to infectious agent or immune-mediated disease, e.g. Steroid-responsive meningitis-arteritis
- N : neoplasia (primary or metastatic)
- D : degeneration (vascular compromise, toxicity, storage disorder, thiamine deficiency, metabolic encephalopathies (e.g. hepatic encephalopathy).
- Reactive seizures - systemic metabolic disorders: hypoglycemia, hepatic encephalopathy, electrolyte abnormalities, uremia, hypoxia, hyperlipidemia, hyperthermia, intestinal parasites, post-anesthetic hippocampal necrosis.
  • Abnormal neurologic examination:
- Secondary seizures - Structural lesions: See list above.

In dogs, primary (idiopathic) epilepsy is considered a common differential diagnosis[3].

A differential diagnosis would require an investigation of the following possible causes of epilepsy

  • Neoplasia
- Meningioma
- Lymphoma
- Glial tumours
- Pituitary adenoma / adenocarcinoma
- Choroid plexus adenoma / adenocarcinoma
- Ependymoma
  • Metabolic
severe uremia (end stage renal disease)
hepatic encephalopathy due to portosystemic shunts, cirrhosis/fibrosis, neoplasia, cholangitis/cholangiohepatitis
- hyperthyroidism
- hypocalcemia
- primary hypoparathyroidism
- post-thyroidectomy
- hypoglycaemia
- insulinoma
- insulin overdose
- sepsis
  • infectious agents
- Toxoplasma goondi, Neospora caninum, Cryptococcus spp, Blastomyces spp, Cladosporium spp, Rabies
- parasites - Cuterebra spp, Dirofilaria spp, Otobius spp
- hemoplasmas such as Borrelia spp and Anaplasma spp
  • Toxins such as pyrethrins, lead, organophosphates, ethylene glycol
  • Nutritional - thiamine deficiency
  • Vascular anomalies
- Ischemic encephalopathy
- Hypertension
- Thromboembolism
- Polycythemia (relative versus absolute)
- Hyperviscosity syndrome
  • Degenerative / congenital / anomalous / malformation
- Thromboembolism
- Storage diseases (e.g. amyloidosis)
- Congenital - hydrocephalus, L-2-hydroxyglutaric aciduria
- Vestibular disease

Traumatic

- Immediate
- Delayed (post-traumatic epilepsy)

Treatment

Initial therapy is aimed at controlling epileptic seizures. This can be through the use of benzodiazepam-based medication (e.g. diazepam) or propofol.

Older drugs such as phenytoin are no longer recommended for use in canine patients.

Although ketamine has been shown to lower ictal thresholds at very low doses, it may exacerbate seizures in dogs predisposed to these episodes.

Long term anticonvulsant therapy is based on conventional GABA facilitation, inhibition of sodium channels or modulation of low-voltage-activated calcium currents[4].

Phenobarbital is the most reliable long term therapy and is inexpensive.

References

  1. Preston SM et al (2013) Public perception of epilepsy in dogs is more favorable than in humans. Epilepsy Behav Mar 2
  2. Thomas, WB (2000) Idiopathic epilepsy in dogs. Vet Clin North Am Small Anim Pract 30:183-206
  3. de Lahunta, A. & Glass, E. (2008) Veterinary Neuroanatomy and Clinical Neurology, Elsevier, USA
  4. Lukyanetz, EA Shkryl, VM & Kostyuk, PG (2002) Selective blockade of N-type calcium channels by leviracetam. Epilepsia 43:9