This article includes discussion of generalized tonic-clonic status epilepticus, generalized convulsive status epilepticus, and tonic-clonic status epilepticus. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Status epilepticus is a serious medical condition with annual incidence up to 120,000 cases in the United States alone, of which more than 20% result in death. Generalized tonic-clonic status epilepticus is the most life-threatening form of status epilepticus. Increased awareness of this condition and the evolving treatment paradigms is essential in the management of patients with this condition. This article discusses the definition, clinical presentation, diagnostic workup, and current management of generalized tonic-clonic status epilepticus. A literature review of the epidemiology, etiology, pathophysiology, and treatment of acute status epilepticus and refractory status epilepticus is also reviewed.
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• The new intravenous AEDs now have demonstrated roles in treatment of status epilepticus.
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• The importance of autoimmune causes of status epilepticus is becoming more prominent and relevant.
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• Research indicates changes in synaptic properties, including internalization of receptors; it may complicate treatment of refractory status epilepticus.
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• Continuous video-EEG monitoring has assumed an essential role in management, diagnosis, and treatment of refractory status epilepticus.
Historical note and terminology
Documented description of generalized tonic-clonic status epilepticus as repetitive tonic-clonic seizures without full recovery between seizures goes back to the first millennium BC, in Babylonian cuneiform stone tablets (59). Calmeil, a French physician, was the first in modern time to give a description of generalized tonic-clonic status epilepticus in his published observations of “an etat de mal" (“state of disease”), a term that derived from the slang term used by epileptics at the Salpetriere and Bicetre hospitals in Paris during the 1800s (07). In the beginning of the 20th century, generalized tonic-clonic status epilepticus was described as epilepsy in which seizures are so frequent that "coma and exhaustion are continuous between seizures." In 1964, the International League Against Epilepsy (ILAE) came to a consensus that defined status epilepticus as "a seizure [that] persists for a sufficient length of time, or is repeated frequently enough to produce a fixed and enduring epileptic condition." The definition was broad and nonspecific and could include the full spectrum of seizure types. It was not until the Marseille Conference that generalized tonic-clonic status epilepticus was clearly distinguished from other types of status epilepticus (18). The 1981, ILAE statement removed the term "enduring" and specified "epileptic condition" as "whenever a seizure persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur."
The 30-minute duration for a single episode has been the most common specified time for the diagnosis of status epilepticus. Because most seizures last less than 2 minutes, there is likely a critical threshold beyond which endogenous mechanisms would fail to terminate seizure. In order to treat patients more rapidly, the concept of conceptual and operational definitions of status epilepticus were introduced. In 2015, ILAE proposed a definition of status epilepticus as follows:
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Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
This is the conceptual definition. Generalized convulsive status epilepticus in adults has been operationally defined as 5 or more minutes of continuous seizure or 2 or more discrete seizures between which there is incomplete recovery of consciousness (32). This 5-minute timeframe has been endorsed by the 2012 Neurocritical Care Society Guidelines and the 2016 American Epilepsy Society Guidelines to guide when emergent treatment for convulsive status epilepticus should start.
In the operational definition of status epilepticus, it was proposed that treatment should be instituted for seizure activity that continues beyond 5 minutes as the likelihood of spontaneous cessation decreases (32; 44). For a more detailed review of the history of status epilepticus, see Neligan and Shorvon (37).