We searched PubMed and article references for papers in English published between Jan 1, 1969, and Jan 31, 2015, with the terms “status epilepticus”, “status epilepticus mortality”, “refractory status epilepticus”, “status epilepticus and EEG monitoring”, “status epilepticus radiographic findings”, “status epilepticus and MRI”, and “status epilepticus treatment”. The final set of publications was selected based on the quality of each study and its relevance to this Review.
ReviewStatus epilepticus in adults
Introduction
Most seizures are brief and self-limited. Status epilepticus is broadly defined as a prolonged seizure or multiple seizures with incomplete return to baseline and remains a common neurological emergency with an annual incidence of 10–41 per 100 000 population.1, 2, 3, 4, 5 The overall mortality associated with status epilepticus approaches 20%,6, 7 with generalised convulsive status epilepticus representing about 45–74% of all cases.1, 2 In view of the incidence of status epilepticus and its substantial morbidity and mortality, annual direct inpatient costs are estimated at more than €83 million in Germany8 and US$4 billion in the USA.9
Several advances in the study of status epilepticus have been made, and the increased use of extended electroencephalography (EEG) monitoring has shown a high prevalence of seizures and status epilepticus in the hospital setting. An improved understanding of the pathophysiological mechanisms underlying status epilepticus highlights the need for a more practical definition of the disorder and underscores the importance of early seizure cessation to avoid pharmaco-resistance as seizure duration increases. These concepts have contributed to the design of treatment trials in status epilepticus during the past decade.
In this Review, we discuss the current knowledge about status epilepticus and refractory status epilepticus in adults and focus mainly on the definitions, pathophysiology, epidemiology, outcomes, and treatment of generalised convulsive status epilepticus. We then summarise the data on the utility of extended EEG monitoring and emphasise the importance of early termination of status epilepticus, examine the use of new anti-epileptic rescue drugs, and review the major pre-hospital treatment trials for status epilepticus. We also propose an updated, practical treatment algorithm for generalised convulsive status epilepticus, describe plans for upcoming treatment trials, and highlight areas in need of further research.
Section snippets
Definitions
The 1981 International League Against Epilepsy (ILAE) definition of status epilepticus describes a seizure that “persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur”.10 The absence of a definitive timeframe of seizure duration creates ambiguity, which makes it difficult to accurately define and treat status epilepticus. Accordingly, status epilepticus was redefined as a seizure lasting 60 min, then further refined by the
Epidemiology, aetiology, and outcomes
Status epilepticus is relatively common, with estimates of 50 000–60 000 new cases annually in the USA.2, 16 The incidence of status epilepticus in Europe is somewhat lower (10–16 per 100 000 population)4, 5, 17 compared with the USA (18–41 per 100 000 population). Notably, American ethnic minorities have a substantially higher incidence (57 per 100 000) than whites (20 per 100 000).1 Results of trend studies3, 18 show an increase in incidence of status epilepticus in the past few decades in
Pathophysiology and neuronal injury
Much of the pathophysiology of status epilepticus is still poorly understood, but studies using animal models have led to substantial advances in the understanding of the basic mechanisms underlying status epilepticus. Although numerous molecular and cellular processes are almost certainly involved in the development of status epilepticus, the fundamental principle involves a failure of endogenous mechanisms to terminate a seizure. This failure can occur because of excessive abnormal excitation
Diagnostic yield of extended EEG monitoring
Status epilepticus can present in several forms: convulsive, non-convulsive, and electrographic. The initial presentation of convulsive status epilepticus is typically not subtle, and is characterised by unresponsiveness and tonic, clonic, or tonic-clonic movements of the extremities. Non-convulsive status epilepticus has not been precisely defined, but is characterised by prolonged seizure activity evidenced by epileptiform discharges on EEG. There are various subtypes of non-convulsive status
Pre-hospital management of status epilepticus
In a retrospective review of adults presenting with status epilepticus,79 first-line therapy (typically diazepam followed by phenytoin) effectively aborted status epilepticus in 92 (60%) of 154 patients treated within 30 min of seizure onset. However, the efficacy of first-line treatment decreased as seizure duration increased. Owing to our knowledge of pharmaco-resistance and neuronal injury as status epilepticus duration increases, clinical research has focused on early treatment of status
Hospital management of status epilepticus
Generalised convulsive status epilepticus is managed as a true medical emergency, in which the patient is stabilised, airway and vital signs are assessed and controlled, and intravenous access is obtained. Tonic-clonic seizures can be associated with periods of apnoea, cyanosis, and metabolic acidosis. The metabolic acidosis almost always self-corrects once seizures are adequately controlled. Most patients are able to breathe adequately during a seizure as long as their airway remains patent.
Refractory status epilepticus
A comprehensive review of refractory status epilepticus is beyond the scope of this Review but can be found in reviews by Rossetti and Lowenstein105 and Ferlisi and Shorvon.106 Refractory status epilepticus is commonly defined as status epilepticus that does not terminate with a first-line agent (benzodiazepines) or a second-line anti-epileptic drug (phenytoin, valproic acid, levetiracetam, or phenobarbital).107 The diagnosis of refractory status epilepticus is clinical and often involves the
Conclusion and future directions
Substantial progress has been made in the identification and treatment of status epilepticus, yet the disorder remains a common neurological emergency with substantial morbidity and mortality. Knowledge regarding the process of epileptogenesis and the transition from a single seizure to self-sustaining status epilepticus has improved through basic research largely with animal models. This research has also led to increased recognition that persistent seizures cause further neurological injury,
Search strategy and selection criteria
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