Status Epilepticus

by Michael Wong, MD, PhD

DEFINITION/EPIDEMIOLOGY

Definition of Status Epilepticus (SE)

  1. Historically, the concept of SE was intended to refer to a seizure that had resulted in a fixed, persistent epileptic state with little or no chance of remitting spontaneously (Commission of ILAE 1964).
  2. More recently, the importance of including a specific duration in the definition has been emphasized. The most popular definition of SE is a single seizure or multiple seizures without intervening recovery, lasting 30 minutes or longer. The criteria of 30 minutes is arbitrary, but is loosely based on animal models, which estimate that irreversible cell injury or death may start to occur after 30-60 minutes of seizure activity (Meldrum and Brierly 1973).
  3. From a clinical/operational standpoint, some authors have proposed changing the definition of SE to a shorter duration (Lowenstein et al 1999), based mainly on the natural duration of untreated seizures.
  4. Normal duration of untreated seizures: Overall, there appears to be at least two major groups of seizures based on duration: brief, self-limited seizures lasting less than 5 minutes and prolonged seizures that become progressively less likely to terminate spontaneously.
    1. In patients with refractory complex partial seizures undergoing video EEG monitoring, ~90% of seizures lasted <2 minutes (Theodore et al. 1983).
    2. In a study of first unprovoked seizures, ~50% were <5 min and 50% >5 min with 12.5% in SE (30 min) (Shinnar et al. 1997).
    3. In a study of first febrile seizures, 13% were >10 min, 9% >15 min, and 5% >30 min (Berg and Shinnar 1996).
  5. Stages of SE: Generalized convulsive SE has been described as evolving though several sequential clinical and electrographic stages.
    1. Clinically, overt generalized SE with convulsive motor activitiy evolves into subtle SE with mild motor activity or simply coma, despite continued bilateral ictal EEG discharges (Treiman et al. 1984).
    2. Electrographically, five discrete sequential stages of ictal activity have been identified: discrete electrographic seizures, waxing and waning seizure, continuous ictal discharges, ictal discharges with flat periods, and periodic epileptiform dischanges (Treiman et al. 1990).

Incidence of SE

  1. Cumulative (Lifetime) Incidence: 0.4% by age 75 (Hersdorffer et al. 1998).
  2. First Seizure:
    1. ~10% of first unprovoked seizures are SE (Shinnar et al. 1996, Hauser et al. 1990).
    2. ~ 5% of first febrile seizures are SE (Berg and Shinnar 1996).
  3. Epilepsy
    1. ~ 1% of adult patients with established epilepsy have at least 1 episode of SE annually and ~20% have at least one episode of SE within 5 years after initial diagnosis (Hauser 1990).
    2. ~10% of children with newly-diagnosed epilepsy have already had an episode of SE by the time of diagnosis (Berg et al. 1999).
  4. Age-Distribution: The highest incidence of SE is in infants/young children and the elderly (Hauser 1990, Hersdorffer et al. 1998, Shinnar et al. 1997).

Risk Factors:

  1. Etiology: Acute or remote symptomatic etiology has a higher risk of SE than idiopathic (Berg et al. 1999, Hauser 1990, Hersdorffer et
    al. 1998).
  2. Seizure type: Partial seizures have a higher risk of SE than generalized (Berg et al. 1999, Hersdorffer et al. 1998).
  3. Age: Young children and elderly are at higher risk for SE.
  4. Prior SE: Patients with a prior history of SE are a greater risk for subsequent SE (Berg and Shinnar 1996, Berg et al.1999, Shinnar et al. 1996).

TREATMENT

Treatment protocol: The well-known algorithm for treatment of SE was outlined by a committee of the Epilepsy Foundation of America (Working Group on Status Epilepticus 1993).

Type of Treatment: Four initial treatments (lorazepam, diazepam + phenytoin, phenytoin, phenobarbital) had similar efficacies in terminating overt convulsive SE, with the only significant difference being between the most effective (lorazepam – 65% success) and least effective (phenytoin – 44%). There were no significant differences and overall lower success rate of all treatments for subtle convulsive SE (8-24% success). (Treiman et al. 1998).

Latency to Treatment of Initiation: The latency to initiation of treatment for SE is surprisingly long in most studies.

  1. In a prospective study designed specifically for treatment of SE, median duration to treatment initiation was 2.8 hours for overt convulsive SE and 5.8 hours for subtle convulsive status (Treiman et al. 1998).
  2. In a retrospective review, the mean duration from seizure onset to: EMT arrival – 30 min (15-140 min), arrival at ED – 50 min, and treatment initiation – 85 min (Jordan 1994).

Response to Treatment over Time: Delayed treatment of SE may result in lower efficacy.

  1. In one study, the % of successful response to first-line therapy when treatment was initiated within: 30 min – 80%, 60 min -75%, 90 min -63%, 120 min – 44%, >120 min -37% (Lowenstein and Alldridge 1993).
  2. In another study, the response to initial treatment was greater in overt SE than subtle SE which represents a later stage of SE (Treiman et al. 1998).

Residual Electrographic SE: In a prospective study of 164 patients in convulsive SE, ~15% remained in non-convulsive SE after the convulsive symptoms had stopped, only diagnosable by EEG (DeLorenzo et al. 1998).

PROGNOSIS

Mortality

  1. Overall: Estimates of acute (<1 month) mortality following SE vary widely, ranging from 3-50% (Hauser 1990). The more recent studies report mortality on the lower end of this range (3-20%) (Aminoff and Simon 1980, DeLorenzo et al. 1996, Maytal et al. 1989).
  2. Etiology:
    1. Mortality is usually attributed to the underlying etiology, rather than the seizure itself. Mortality due to the seizure alone is estimated at ~1% or less (Hauser 1990).
    2. Risk of mortality is higher with acute or remote symptomatic etiology compared to idiopathic. In a pediatric study, all patients with SE who died had a symptomatic etiology (12.5% of symptomatic SE), whereas no patients with idiopathic SE died (Maytal et al. 1989).
  3. Age: Children have a lower mortality (~3% overall) from SE than adults, although children with symptomatic “refractory” status had mortality of ~20% (Gilbert et al. 1999). Elderly may have mortality as high as 30-40%, but this may relate primarily to the associated etiology (DeLorenzo et al. 1996, Maytal et al. 1989).

Morbidity: New neurological deficits and other morbidity are commonly reported after SE (Aminoff and Simon 1980, Barnard and Wirrell 1999), which may have a lower incidence in children (9%) (Maytal et al. 1989); again, it is difficult to determine whether this is an effect of the underlying etiology or SE itself.

REFERENCES

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