Canis ISSN: 2398-2942

Status epilepticus

Synonym(s): Cluster seizures; Fits

Contributor(s): Rodney Bagley, Laurent Garosi, Mark Lowrie

Introduction

  • An epileptic seizure is defined as excessive and/or hypersynchronous abnormal neuronal electrical activity within the cerebral cortex resulting in paroxysmal episodes of abnormal consciousness, motor activity, sensory input, and/or autonomic function.
  • Therefore a seizure represents temporary abnormal forebrain function with the physical manifestation dependent on the location of the abnormality. A seizure is defined as a paroxysmal, transitory disturbance of brain function that has a sudden onset, ceases spontaneously, and has a tendency to recur.
  • Epilepsy is not a specific disease but a chronic condition characterized by recurrent epileptic seizures.
  • Status epilepticus (SE) has been defined as continuous epileptic seizure activity lasting for more than 30 minutes. A clinically more practical definition would be a seizure lasting longer than 5 minutes. Cluster seizures should also be considered and these are defined as 2 or more seizures between which the patient does not completely recover consciousness. In reality, emergency management to stop SE or cluster seizures should begin well before the defining 30 minute period has elapsed.
  • Non-convulsive status epilepticus is recurring electrical seizures within the brain, without associated muscle movements but loss of consciousness.
  • Studies have suggested that SE can be associated with a mortality rate as high as 25%.
  • Cause : intracranial or extracranial disease.
  • Signs :
    • Prolonged seizure (longer than 5 mins).
    • Recurrent seizures without recovery of consciousness between.
  • Diagnosis : signs.
  • Treatment : antiepileptic therapy.
  • Prognosis : guarded - depends on underlying disease process.
Follow the diagnostic tree for Status Epilepticus: Emergency Management Status Epilepticus: Emergency Management.

Pathogenesis

Predisposing factors

General
  • Metabolic derangements.
  • Inflammatory brain injury.

Specific

  • Sudden cessation of antiepileptic medication.

Pathophysiology

  • Epilepsy can be caused by an intracranial (ie congenital or acquired brain damage) or extracranial problem (ie a problem with the content or supply of blood to the brain).
  • The normal brain cell maintains an unevenly distributed electrical charge across the cell membrane. The interior of the cell is negative with respect to the exterior, and this difference is maintained in the resting state primarily via the Na+-K+ ATPase pump that removes three sodium ions in exchange for two potassium ions into the cell.
  • The resting potential of the neuron refers to the difference between the voltage inside and outside the neuron.
  • The resting potential of the average neuron is around -70 millivolts, indicating that the inside of the cell is 70 millivolts less than the outside of the cell.
  • When the cell is excited, the sodium channels open and positive sodium ions surge into the cell. Once the cell reaches a certain threshold (depolarisation), an action potential will fire, sending an electrical signal down the axon.
  • After the neuron has fired, there is a refractory period in which another action potential is not possible.
  • During this time, the potassium channels open and the sodium channels close, gradually returning the neuron to its resting potential. Once the neuron has returned to the resting potential, it is possible for another action potential to occur.
  • There are neurons that are either excitatory or inhibitory.
  • The excitation of neurons is mainly mediated by the glutamate neurotransmitters (also aspartate and acetylcholine) and their receptors – creating excitatory post-synaptic potentials (EPSPs).
  • The inhibition of neurons is mediated by the GABA neurotransmitter (γ-aminobutyric acid; also glycine, taurine and noradrenaline) and their receptors – creating inhibitory post-synaptic potentials (IPSPs).
  • The neuronal membrane potential is determined by the balance of EPSPs and IPSPs – if this balance is compromised, an epileptic seizure will result.
  • The basic pathophysiological processes that result in seizures are excessive excitation or loss of inhibition (disinhibition):
    • Hypoglycemia → loss of energy substrate for the Na+-K+ ATPase pump, failure to extrude Na+, increasing cell positivity resulting in depolarisation (excessive excitation).
    • In a disease process where inhibitory transmitters are unable to function (eg hepatic encephalopathy), the lack of inhibition allows for unregulated depolarisation.
  • Two interesting phenomena that occur due to seizure activity include:
    • Mirror focus - where a seizure focus creates similar activity in a homologous area of the contralateral hemisphere.
    • Kindling - where one seizure increases the likelihood of further seizures. With time both mirror foci and kindled foci may become autonomous and form a new, independent seizure focus.
  • Why seizures terminate as rapidly as they begin is not known. Metabolic exhaustion of neurons is not an adequate explanation. Extracortical inhibitory centers, such as within the cerebellum, may play a role. Ablations of the cerebellum, for example, facilitate seizure activity. Phenytoin, a commonly used antiepileptic medication in humans, dramatically increases the rate of firing of Purkinje neurons. Other areas such as the caudate and parts of the thalamus and reticular formation may also help to terminate seizure activity.
  • In the early stages of SE there is increased autonomic discharge causing tachycardia, hypertension and hypoglycemia. These changes tend to compensate for the increased metabolic demands of the brain.
  • After about 30 mins, decompensation and hypotension, hypoglycemia, hyperthermia and hypoxia develop.
  • Reduced cerebral blood flow results in ischemia and neuronal death.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Hardy B T, Patterson E E, Cloyd J M et al (2012) Double-masked, placebo-controlled study of intravenous levetiracetam for the treatment of status epilepticus and acute repetitive seizures in dogs. JVIM 26 (2), 334-340 PubMed.
  • Monteiro R, Adams V, Keys D et al (2012) Canine idiopathic epilepsy: prevalence, risk factors and outcome associated with cluster seizures and status epilepticus. JSAP 53 (9),  526-530 PubMed.​​
  • Zimmermann R, Hülsmeyer V, Sauter-Louis C et al (2009) Status epilepticus and epileptic seizures in dogs. JVIM 23 (5), 970-976 PubMed.
  • Patterson E E, Mickelson J R, Da Y, Roberts M C, McVey A S, O'Brien D P, Johnson G S, Armstrong P J (2003) Clinical characteristics and inheritance of idiopathic epilepsy in Vizslas. JVIM 17 (3), 319-325 PubMed.
  • Bush W, Bush C S, Darrin E, Shofer F et al (2002) Results of cerebrospinal fluid analysis, neurologicz examination findings, and age at the onset of seizures as predictors for results of magnetic resonance imaging of the brain in dogs examined because of seizures: 115 cases (1992-2000). JAVMA 220 (6), 781-784 PubMed.
  • Platt S R, Haag M (2002) Canine status epilepticus: a retrospective study of 50 cases. JSAP 43 (4), 151-153 PubMed.
  • Saito M, Muñana, K R, Sharp N et al (2001) Risk factors for development of status epilepticus in dogs with idiopathic epilepsy and effects of status epilepticus on outcome and survival time. JAVMA 219 (5), 618-623 PubMed.
  • Levitski R E & Trepanier L A (2000) Effect of timing of blood collection on serum phenobarbital concentrations in dogs with epilepsy. JAVMA 217 (2), 200-204 PubMed.
  • Platt S R, McDonnell J J (2000) Status epilepticus: Managing refractory cases and treating out-of-hospital patients. Comp Contin Educ Pract Vet 22 (8), 732-41 VetMedResource.
  • Platt S R, McDonnell J J (2000) Status epilepticus: Patient management and pharmacologic therapy. Comp Contin Educ Pract Vet 22 (8), 722-729 VetMedResource.
  • Platt S R, McDonnell J J (2000) Status epilepticus: Clinical features and Pathophysiology. Comp Contin Educ Pract Vet 22 (7), 660-9 PubMed.
  • Steffen F, Grasmueck S (2000) Propofol for treatment of refractory seizures in dogs and cats with intracranial disorders. JSAP 41 (11), 496-499 PubMed.
  • Bateman S W, Parent J M (1999) Clinical findings, treatment, and outcome of dogs with status epilepticus or cluster seizures: 156 cases (1990-1995). JAVMA 215 (10), 1463-1468 PubMed.
  • Kathmann I, Jaggy A, Busato A et al (1999) Clinical and genetic investigations of idiopathic epilepsy in the Bernese Mountain Dog. JSAP 40 (7), 319-325 PubMed.
  • Jaggy A, Bernardini M (1998) Idiopathic epilepsy in 125 dogs - a long-term study. Clinical and electroencephalographic findings. JSAP 39 (1), 23-29 PubMed.
  • Knowles K (1998) Idiopathic epilepsyClin Tech Small Anim Pract 13 (3), 144-151 PubMed.
  • March P A (1998) Seizures - classification, etiologies and pathophysiologyClin Tech Small Anim Pract 13 (3), 119-131 PubMed.
  • Podell M (1998) Antiepileptic drug therapy. Clin Tech Small Anim Pract 13 (3), 185-92 PubMed.​
  • Podell M (1995) The use of diazepam per rectum at home for the acute management of cluster seizures in dogs. JVIM (2), 68-74 PubMed.
  • Podell M & Fenner W R (1993) Bromide therapy in refractory canine idiopathic epilepsy. JVIM (5), 318-327 PubMed.
  • Lothman E L (1990) The biochemical basis and pathophysiology of status epilepticus. Neurology 40 (5 Suppl 2), 13-23 PubMed.
  • Bunch S E, Castlemann W L, Hornbuckle W E et al (1982) Hepatic cirrhosis associated with long-term anticonvulsant drug therapy in dogs. JAVMA 181 (4), 357-362 PubMed.
 


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