(p. 1098) Pathophysiology and causes of seizures 

Seizures result from imbalances between excitation and inhibition, and between neuronal synchrony and dyssynchrony. Current models implicate the cerebral cortex in the genesis of seizures, although thalamic mechanisms (particularly the thalamic reticular formation) are involved in the synchronization of cortical neurons. Often, the precipitants of a seizure in the critical care setting are pharmacological. Several mechanisms linked to critical illness can lead to seizures. Failure to remove glutamate and potassium from the extracellular space, functions performed predominantly by astrocytes, occurs in trauma, hypoxia, ischaemia, and hypoglycaemia. Loss of normal inhibition occurs during withdrawal from alcohol and other hypnosedative agents, or in the presence of GABA. Conditions such as cerebral trauma, haemorrhages, abscesses, and neoplasms all produce physical distortions of the adjacent neurons, astrocytes, and the extracellular space. Deposition of iron in the cortex from the breakdown of haemoglobin appears particularly epileptogenic. Although acute metabolic disturbances can commonly produce seizures in critically-ill patients, an underlying and potentially treatable structural lesion must always be considered and excluded.