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What is the Pathophysiology of Seizures?

By Toni Henthorn
Updated Mar 03, 2024
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A seizure occurs when a portion of the brain becomes overly excited or when nerves in the brain begin to fire together in an abnormal fashion. Seizure activity can arise in areas of the brain that are malformed from birth defects or genetic disorders or disrupted from infection, injuries, tumors, strokes, or inadequate oxygenation. The pathophysiology of seizures results from an abrupt imbalance between the forces that excite and inhibit the nerve cells such that the excitatory forces take precedence. This electrical signal then spreads to the surrounding normal brain cells, which begin to fire in concert with the abnormal cells. With prolonged or recurrent seizures over a short period, the risk of future seizures increases as nerve cell death, scar tissue formation, and sprouting of new axons occur.

Nerve cells between discharges normally have a negative charge internally due to the active pumping of positively charged sodium ions out of the cell. Discharge or firing of the nerve cell involves a sudden fluctuation of the negative charge to a positive charge as ions channels into the cell open and positive ions, such as sodium, potassium, and calcium, flow into the cell. Both excitatory and inhibitory control mechanisms act to allow appropriate firing and prevent inappropriate excitation of the cell. The pathophysiology of seizures can occur due to increased excitation of the nerve cell, decreased inhibition of the nerve cell, or a combination of both influences.

Normally after a nerve cell fires, inhibitory influences prevent a second firing of the neuron until the internal charge of the neuron returns to its resting state. Gamma-amino-butyric acid (GABA) is the principal inhibiting chemical in the brain. GABA opens channels for negatively charged chloride ions to flood into the excited neuron, which decreases the internal charge and prevents a second firing of the nerve cell. Most anti-seizure drugs reduce the pathophysiology of seizures by increasing the frequency of the chloride channel openings or increasing the duration during which the channels are open. When there is a disruption in the cells that issue GABA or the receptor sites for GABA, there is a failure of the chloride channels to open and temper the excitability of the nerve cell.

Equally significant to the pathophysiology of seizures are mechanisms that lead to increased excitation of neurons. Glutamate is the main excitatory chemical mediator in the brain, which binds to receptors that open channels for sodium, potassium, and calcium into the cell. Some inherited forms of seizures involve a predilection for excessively frequent or sustained activation of glutamate receptors, increasing the excitability of the brain and the prospect for seizure activity. Furthermore, contiguous spread of the electrical activity along layered parts of the brain may occur from cell to cell, a non-chemical form of propagation that is not subject to regulation by inhibitory mechanisms.

Treatments for the pathophysiology of seizures target not only the molecular abnormalities involving the ion channels in the nerve cells but also the non-chemical spreading of excitation in the brain. Benzodiazepines, such as Valium, and barbiturates, such as Phenobarbital, act to open inhibitory chloride channels. Phenytoin or Dilantin prevents repetitive firing of neurons by shutting down sodium channels into the nerve cells. In situations with poorly managed recurrent seizures, halothane may prevent the non-chemical transmission of nerve impulses. Additionally, insulin and steroids change the function of glutamate receptors, suppressing the excitability of the brain.

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Discussion Comments
By Glasis — On Feb 04, 2014

There are six types of generalized seizures. These seizures produce electrical impulses throughout the brain.

Grand Mal which can results in loss of consciousness, body stiffening, violent jerking and falling.

Absence seizures which can cause a short loss of memory and cause a blank stare by the person having the episode, generally a child.

Myoclonic seizures which cause brief jerks of the body, sometimes described as brief shocks. These happen on either sides of the body.

Clonic seizures which causes body jerks on both sides of the body at once.

Tonic seizures stiffen the muscles.

Atonic seizures give a sudden loss of muscle tone in mainly the arms and legs and can lead to a fall.

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