PATHOPHYSIOLOGY

The interior of the normal brain cell carries a negative charge with respect to the exterior. This charge (resting membrane potential) is maintained by the sodium-potassium ATPase pump. When the brain cell is excited, the membrane potential becomes more positive until threshold is reached, the cell depolarises, and an action potential is generated. Repolarisation occurs through activation of the ATPase pump.

 

A seizure occurs when brain cells spontaneously depolarise. There are 2 basic pathophysiological processes that can result in the development of seizures. These are:-

 

i) excessive excitation of the cells increasing the likelihood of depolarisation

or  ii) loss of inhibition (disinhibition) of cell depolarisation.

 

For example in hypoglycaemia the ATPase pump is deprived of energy so that the cell resting potential is more positive and depolarisation more likely. In some diseases eg hepatic encephalopathy, the action of some inhibitory transmitters (eg GABA) at their specific receptors is impaired. This lack of inhibition allows depolarisation of cells to be triggered more easily.

 

Abnormal electrical activity in the brain is usually confined to a small area by surrounding inhibition. For a seizure to be propagated, a cell or group of cells must depolarise. When depolarisation is of a sufficient magnitude, the impulse will be conducted to the entire brain producing a generalised seizure. A focal seizure occurs when the electrical discharge does not spread across the brain.

 

In dogs seizures often occur in the middle of the night. During low levels of awareness, drowsiness and dreamless sleep, decreased activity in the reticular formation allows reverberating circuits between the thalamus and the cortex to synchronize. Additionally, some groups of neurons which are only mildly hyperactive when the animal is awake, become more excitable during sleep.

Often seizures arise from the same initial focus each time. Two phenomena may affect seizure focus:

• Mirror focus  - where a seizure focus creates similar activity in a corresponding area of the contralateral hemisphere.

 

•  Kindling  - where occurrence of one seizure can increase the likelihood of further seizures. With time both mirror foci and kindled foci may form a new, independent seizure focus.

 

Why seizures terminate as rapidly as they begin is unknown. Metabolic exhaustion of neurons is not an adequate explanation. There may be specific areas of the brain ie within the cerebellum, the caudate nucleus, parts of the thalamus and reticular formation that inhibit impulse generation and have a role in termination of seizure activity.

References:

Lothman EL (1990) The biochemical basis and pathophysiology of status epilepticus. Neurology 40(suppl 2), 13-23. - PubMed -

 

March PA (1998) Seizures: Classification, etiologies, and pathophysiology. Clin Tech Small Anim Pract 13, 119-131. - PubMed -

 

Platt SR, McDonnell JJ (2000) Status Epilepticus: Clinical Features and Pathophysiology. Compendium on Continuing Education for the Practicing Veterinarian 22; 8, 732+. - Compendium -

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