What is the pathophysiology of status epilepticus (SE)?

Updated: Feb 13, 2018
  • Author: Julie L Roth, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
  • Print

On a neurochemical level, seizures are sustained by excess excitation and reduced inhibition. Glutamate is the most common excitatory neurotransmitter and the NMDA (N-methyl-D-aspartate) receptor subtype is involved. Gamma-aminobutyric acid (GABA) is the most common inhibitory neurotransmitter. Failure of inhibitory processes is increasingly thought to be the major mechanism leading to status epilepticus.

Most seizures terminate spontaneously. Which processes are involved in seizure termination and why or how these processes fail in status epilepticus are active areas of inquiry.

Significant physiologic changes accompany generalized convulsive SE. Many of these systemic responses (eg, tachycardia, cardiac arrhythmias, hyperglycemia) are thought to result from the catecholamine surge that accompanies the seizures.

In the early stages of SE, prominent elevation in systemic arterial pressure is seen. In a study of 21 patients, White et al found a mean elevation of systolic pressure of 85 mm Hg and an elevation of diastolic pressure of 42 mm Hg. [25] As SE continues, blood pressures may decrease to levels below their former baseline.

Body temperature may increase in patients, as a result of the vigorous muscle activity and central sympathetic drive that accompany generalized convulsive SE (but, of course, infectious etiologies also must be considered in febrile patients). In a study by Aminoff and Simon, 75 of 90 patients with SE had hyperthermia, with temperatures reaching 42°C. [26] Hyperthermia has been correlated with poor neurologic outcomes and should be treated aggressively.

Marked acidosis usually occurs. In a study of 70 spontaneously ventilating patients with SE, 23 had a pH of less than 7.0. [26] The acidosis has both a respiratory and a metabolic component. The acidosis usually should not be treated; it does not correlate with the degree of neuronal injury, and acidosis is known to have an anticonvulsant effect. The acidosis resolves with termination of the seizure.

A mild leukocytosis (primarily due to demargination) is common in both blood and cerebrospinal fluid (CSF). In a study of 80 patients, 50 without evidence of infection had WBC count elevations from 12.7-28.8 X 109/L (12,700-28,800 cells/µL). Bands should not be seen. CSF pleocytosis is common but the cell-count elevations are usually modest. In one study, only 4 of 65 patients had greater than 30 cells in the CSF. [26]

Convulsive SE affects not only the mechanical aspects of breathing but also causes pulmonary edema. Many of the medications used to treat SE (specifically, benzodiazepines and barbiturates) inhibit respiratory drive both individually and synergistically when given in combination. A patient with convulsive SE who has already received a full loading dose of benzodiazepines should be electively intubated before being given.

Cerebral metabolic demand increases greatly with generalize convulsive SE. However, cerebral blood flow and oxygenation are thought to be preserved or even elevated early in the course.

Research with paralyzed and artificially ventilated animals concluded that neuronal loss after focal or generalized SE is linked to the abnormal neuronal discharges and not simply to the systemic effects of the seizures. For example, Meldrum and Horton demonstrated that prolonged seizure activity results in pathologic changes after 30 minutes; after 60 minutes, neurons begin to die. [27] The hippocampus seems especially vulnerable to damage by this mechanism.

These observations parallel findings in human clinical studies, which have shown that the duration of SE correlates directly with morbidity and mortality rates. The longer the SE persists, the more likely that neurons will be damaged by excitatory neurotransmitters. Sustained seizure activity also progressively reduces GABA inhibition. On a receptor level, GABAergic mechanisms fail and seizures become pharmacoresistent. [28]

Neuronal death probably results from the inability to handle large increases in intracellular calcium brought about by prolonged exposure to excitatory neurotransmitters. However, changes in gene expression that are induced by SE result in alterations in the number or subunit composition of ion channels, receptors, cell metabolism, and neuronal connectivity. [10, 29]

The observation that prior history of epilepsy is associated with a better prognosis might be related to the fact that brief seizures might result in upregulation of neuroprotective mechanisms. This may serve as a form of adaptive tolerance. [10]

Alterations in the availability of existing receptors during SE might occur relatively quickly. This might contribute to responsiveness to benzodiazepines. [30]

SE in the developing brain seems to have lesser consequences despite a greater susceptibility to seizures. [31] This might be due to better adaptive mechanisms to cope with excitotoxicity.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!