Description

• Recently revised definition of SE asserts that SE is a result of failure of the processes responsible for seizure cessation or from the initiation of mechanisms, which lead to abnormally prolonged seizures (T1).
  • T1 defines the time point that is considered “prolonged” and is different depending on the type of SE that is present.
  • T1 determines the earliest time when treatment should be started.
  • For convulsive SE, it is set at 5 minutes; for nonconvulsive SE, it is set at 10 minutes; and for absence SE, it is set at 2 minutes.
• Furthermore, SE is defined as a condition that can cause permanent brain injury and place patients at risk for systemic cardiopulmonary complications, if not terminated within a set time period (T2), leading to neuronal death, neuronal injury, and/or alteration of neuronal networks.
  • T2 defines the time point at which SE should be controlled to prevent long-term consequences.
  • For convulsive SE, it is set at 30 minutes; for nonconvulsive SE, it is set at 30 to 60 minutes; and for absence SE, it is unknown.
• SE presents in various forms and revised classification has divided it into the following:
  • SE with prominent motor symptoms: encompassing convulsive SE, characterized by excessive abnormal muscle contractions, which may be sustained or interrupted; generally tonic–clonic in nature
  • SE without prominent motor symptoms: encompassing nonconvulsive SE, characterized without prominent motor symptoms, comprising continuous or fluctuating states of mentation without tonic–clonic activity
  • Refractory SE: seizure activity persisting despite adequate treatment with initial and secondary pharmacologic treatment

Epidemiology

Incidence

• Overall incidence is 9.9 to 41 cases per 100,000 per year.
  • A recent meta-analysis found the pooled incidence rate to be 12.6/100,000 per year.
• Results of trend studies show an increase in incidence of SE in the past few decades in the United States.
• 760,117 hospital discharges with a diagnosis of SE from 1979 to 2010, with SE accounting for 0.07% of all hospital admissions in the United States over this period
• Predominant sex: male > female (annual relative risk 1.1 in males, P < .0001)
• Racial differences: blacks (13.7/100,000) > other races (7.4/100,000) > whites (6.9/100,000)
• Bimodal age distribution: greatest number in those <1st decade of life (14.3/100,000) and >60 years (28.4/100,000)
  • Other prospective population studies show similar bimodal distribution of SE.
  • Elderly subjects with SE had a higher case fatality rate and crude annual incidence rate.

Prevalence

• 125,000 to 195,000 patients per year present with generalized convulsive SE.
• Mortality rates in the United States range from 19% to 22% based on two large prospective population-based studies.
  • The overall mortality rates do not show a change in trend over the last few decades.
• Cost: Mean hospital costs $18,834 in United States and annual direct costs are projected at $4 billion.

Etiology and Pathophysiology

• Etiologies differ in adults and the pediatric population with anticonvulsant noncompliance being the most common cause of SE in adults and acute symptomatic seizures and remote symptomatic epilepsy being the most common etiology of SE in children.
• Pediatric consideration:
  • Infection with fever not involving CNS (52% of cases) was the major etiology of SE and then remote CNS insult (39%) and low anticonvulsant levels (21%).
• Adult consideration:
  • Three major etiologies include low anticonvulsant levels (34%), remote symptomatic epilepsy (24%), and CVA (22%).
• Geriatric consideration:
  • The most important cause of SE is CVA, followed by acute cardiac, respiratory, or hepatic decompensation, trauma, epilepsy, and dysnatremia.
• Cerebrovascular diseases:
  • Ischemic stroke, bleeding (intracerebral, subarachnoid), hematoma (subdural, epidural), sinus venous thrombosis, vascular dementia, tumors
• CNS infections:
  • Meningitis, encephalitis, PML, toxoplasmosis, TB, prion disease, fungal disease, HIV-related disease
• Neurodegenerative diseases:
  • Alzheimer disease, frontotemporal dementia, etc.
• Head trauma:
  • Closed, open, penetrating head injury
• Intoxications:
  • Alcohol (intoxication, withdrawal, Wernicke), drugs, neurotoxins, heavy metals
• Withdrawal or low antiepileptic drugs levels
• Cerebral hypoxia or anoxia
• Metabolic disturbances:
  • Electrolyte imbalance, glucose imbalance, organ failure, acidosis, renal failure, hepatic encephalopathy
• Autoimmune disorders:
  • Multiple sclerosis (MS), Hashimoto encephalopathy, anti-NMDA encephalopathy, SLE
• Idiopathic, cryptogenic

Risk Factors

Risk factors of SE linked to its etiology above; a previous history of SE (recurrence rate in children, 17%; in those with neurologic abnormality, 50%)

Commonly Associated Conditions

Movement disorders, psychogenic; transient ischemic attack (TIA), CVA, migraines, somatoform disorders, Todd paralysis