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Status Epilepticus

Author: Marcio Sotero de Menezes, MD, Associate Professor, Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Seattle, University of Washington
Coauthor(s): Ednea Simon, MD, Acting Assistant Professor, Department of Neurology, University of Washington
Contributor Information and Disclosures

Updated: Jul 13, 2009

Introduction

Background

Status epilepticus (SE) is defined as seizure activity that lasts more than 30 minutes, constituting a neurological emergency. Seizure activity may be continuous or intermittent without the patient recovering consciousness. Most of the literature deals with the generalized tonic-clonic status epilepticus (GTCSE), but almost as many types of status epilepticus are recognized as types of seizures. This article primarily addresses generalized tonic-clonic seizures but, when appropriate, comments on nonconvulsive status epilepticus (NCSE) are included.

In the past, the common definition of status epilepticus was seizure activity exceeding 60 minutes (as opposed to 30 min). This longer time limit may be one of the reasons for the higher incidence of sequelae in older studies. Other factors accounting for outcome differences include improvement in intensive medical care and the retrospective nature of these older studies, which tended to create a bias toward more severe cases. The rationale for equating intermittent seizures without recovery of consciousness with continuous seizures is 2-fold. First, in animal models, intermittent seizures were quite powerful agents in causing neuropathological changes. Second, in cases of prolonged status epilepticus, outward motor manifestations may become less prominent or intermittent over time without necessarily indicating decreasing intensity of EEG seizure activity.

Types of status epilepticus other than generalized tonic-clonic status epilepticus

Although the terms status epilepticus and generalized tonic-clonic status epilepticus are often used synonymously, status epilepticus includes a few other status types, including the following:

  • Complex partial and absence status epilepticus
    • Many studies combine cases of complex partial and absence status epilepticus under the name nonconvulsive status epilepticus. This is because of the similarity in the seizure semiology, despite of the divergent EEG patterns.
    • In children, about two thirds of nonconvulsive status epilepticus cases have generalized EEG changes suggestive of either typical or atypical absences with or without a myoclonic component.
  • Simple partial status epilepticus
    • Seizures may be quite sustained, especially when associated with focal brain lesions.
    • Simple partial seizures may be tonic (sustained muscle contraction of part of the body) or clonic (alternating muscle contraction and relaxation) without major impairment of consciousness.
    • Simple partial seizures may be accompanied by recurrent subjective feelings, bodily sensations, or visual hallucinations.
    • Prolonged simple partial seizures (often motor and clonic) are frequently termed epilepsia partialis continua.
    • Simple partial seizures are not necessarily associated with diffuse brain damage, unless they become complex partial status epilepticus or are associated with secondary generalization.
  • Complex partial status epilepticus
    • Episodes of complex partial status epilepticus are characterized by major alteration in consciousness, lack of recollection for the event associated with stereotypic automatisms, staring, and, in some cases, vocalization or screaming. Most patients are described as confused (one third of the cases) or unresponsive (one third of the cases).
    • Complex partial status epilepticus episodes have been followed by cognitive deficits in some cases; recognizing the impairment is important.
  • Absence seizures
    • Typical absence seizures are prolonged (hours or even days) episodes of alteration in responsiveness with poor or no recollection for events.
    • Typical absence seizures that exceed 30-minutes duration should be treated because of the risk of secondary generalization. However, prolonged absence status has been described that was not associated with subsequent neurologic deterioration.
    • Alteration of consciousness may not be severe; automatic behavior sometimes occurs, with patients able to perform customary daily activities such as combing their hair, playing video games, and even driving. Preceding behavioral changes have been documented in some cases, which cleared with the use of antiabsence medications. In some cases, the clue for absence status may come from observing myoclonic jerking of the eyelids.
    • Absence seizure status may occur in teenagers and adults who were thought to have outgrown the condition.
  • Myoclonic seizures
    • Myoclonic seizures are characterized by quick, often repetitive, jerks that randomly involve the limbs.
    • Seizures are often repetitive and, in some cases, may be unabated for lengthy periods.
    • Some patients with myoclonic epilepsies may sustain repetitive myoclonus that persists for days with or without altered consciousness.
    • Myoclonic status epilepticus is a term sometimes used to describe these patients' condition.

Classifications of status epilepticus

Most studies of status epilepticus epidemiology and outcome have classified episodes, as follows:

  • Acute symptomatic (26%) - Episodes caused by an acute infection, head trauma, hypoxemia, electrolyte disturbance, hypoglycemia, intoxication or drug withdrawal
  • Progressive encephalopathy (3%) – Status epilepticus occurring with an underlying progressive CNS disorder, such as mitochondrial disorder, CNS lipid storage diseases, aminoacidopathies, or organic acidopathies
  • Remote symptomatic status epilepticus (33%) - A status epilepticus secondary to static conditions (eg, remote cerebral insult in the perinatal period)
  • Remote symptomatic with an acute precipitant (1%) – Status epilepticus that occurs with a chronic encephalopathy but with an acute precipitant such as the same reported in acute symptomatic
  • Febrile (22%) – Status epilepticus that occurs when the only provocation is a febrile illness, after excluding a direct CNS infection
  • Cryptogenic (15%) – Status epilepticus that occurs without identifiable cause

Pathophysiology

Status epilepticus is the result of a failure of the normal factors that serve to terminate a typical seizure, such as changes in GABA receptor composition, loss of benzodiazepines efficacy, excessive glutamate excitation, and activation of drug resistance genes. GABA receptor–mediated inhibition may be responsible for the normal termination of a seizure. In addition, the activation of the N -methyl-D aspartate (NMDA) receptor by the excitatory neurotransmitter glutamate may be required for the propagation of seizure activity. In experimental models, resistance to benzodiazepines and barbiturates may develop during prolonged seizures that may alter the structure and function of GABAa receptors.1

In adolescent baboons, brain damage can be observed after 90 minutes of sustained seizures, with the neocortex, thalamus, and hippocampus most affected.2,3 In the neocortex, small pyramidal cells in layers 3, 5, and 6 were most affected, and resultant lesions tended to be more prominent in the occipital lobe. In this animal model in which seizures were induced by bicuculline or pentylenetetrazol (PTZ), intubation/ventilation and paralyzation did not improve these types of CNS lesions, suggesting that excessive neuronal discharge caused the damage. These studies also established that hyperpyrexia may also contribute to CNS damage observed in prolonged seizures. This observation has been confirmed in studies of adult humans. Cerebellar damage can also be observed; however, because it is more prominent in the border zones of arterial blood supply, this type of damage probably relates to ischemia and/or hyperthermia.

Most definitions of status epilepticus do not distinguish between uninterrupted seizures and intermittent seizures without recovery of consciousness. This concept is supported by the finding that the pattern of brain damage in animals with repetitive seizures induced by allyl glycine (glutamic acid decarboxylase inhibitor) included hippocampal sclerosis (at times asymmetrical or unilateral), cortical gliosis, and ischemic cell-type damage. Lesions in the cortex sometimes were restricted to the occipital cortex or watershed zones, a pattern very similar to that observed in continuous prolonged seizures.

Frequency

United States

The percentage of patients with epilepsy who develop status epilepticus varies from 1.3-16%. The first seizure lasts longer than 30 minutes in 12.6% of cases. Among patients with febrile seizures, duration exceeds 30 minutes in 5% of cases. Almost half (48%) of adults who present with status epilepticus have no prior history of seizures. Among children diagnosed with status epilepticus, a history of prior unprovoked seizures was even less common (32%); pediatric patients who present with febrile status epilepticus rarely have a history of epilepsy.

Although the data are contradictory, status epilepticus incidence may have increased since the advent of modern antiepileptic drugs (AEDs). Data have showed that 43% of patients taking anticonvulsant medications concurrent with a status epilepticus episode had low levels of AEDs. In 19% of cases, some levels were low and other levels were within the therapeutic range. In 38% of cases, all AED levels were in the therapeutic range.

Generalized tonic-clonic status epilepticus may be recurrent in 17-25% of children with status epilepticus. Recurrent status epilepticus primarily occurs in children with neurological abnormalities. Risk of generalized tonic-clonic status epilepticus recurrence also varies among etiologic groups. The idiopathic and remote symptomatic groups have the highest recurrence risk (ie, 28% in prospective studies). The febrile seizure group has a prospective recurrence risk of 3%.

Mortality/Morbidity

Studies of outcomes conducted over the past 15 years report low morbidity and mortality among pediatric patients with status epilepticus. Among children with generalized tonic-clonic status epilepticus, sequelae occurred in 9% of cases. Of these, approximately 58% were only motor sequelae, 29% were motor and cognitive, and 13% were only cognitive.

A striking difference was noted in the respective incidences of sequelae among the etiologic categories.4 Patients classified as having idiopathic febrile seizures and remote symptomatic seizures had a low (1.4%) incidence of sequelae. Patients classified with progressive encephalopathy (chronic progressive) had the highest rate of morbidity at follow-up, reaching 80% on the prospective analysis. Patients classified as having acute symptomatic seizures had an intermediate sequelae rate of 12%. Sequelae rates for patients with generalized tonic-clonic status epilepticus were highest among patients younger than 1 year (29%). Rates declined to 11% for children aged 1-3 years and to 6% for children older than 3 years. Although children younger than 1 year have greater incidence of acute symptomatic generalized tonic-clonic status epilepticus, no difference in the etiologic categories among the other age groups is observed.

Studies show that pediatric patients who die after status epilepticus are almost exclusively included in the acute symptomatic or progressive encephalopathy groups. The mortality rate for both classifications combined was 12%. No patients in the remote symptomatic, idiopathic, and febrile status groups died. Most modern pediatric series report mortality rates of 2% that are directly related to status epilepticus, whereas overall mortality rates, including deaths not directly related to status epilepticus, range from 4-6%. Adults with status epilepticus have a much higher mortality rate. The overall mortality rate for adult patients who die from status epilepticus ranges from 16-35%, with 1-5% of deaths directly related to status epilepticus.  

Refractory generalized tonic-clonic status epilepticus that requires high-dose barbiturate or continuous benzodiazepine infusion is positively associated with long-term cognitive deficits and recurrent seizures even in children who were previously normal. 

Early treatment of seizures with rectal medication (diazepam) is thought to be associated with a better outcome but further testing is required to confirm this statement. 

At least 60% of the patients show some degree of cognitive deterioration after an episode of nonconvulsive status epilepticus.

Clinical

History

Although the sequence of clinical and EEG manifestations during the course of generalized convulsive status epilepticus (SE) in humans and in experimental models has been described in adults, similar patterns are observed in children with partial and generalized seizures, as follows:

  • Phase 1: Initially, discrete partial seizures or, less frequently, generalized seizures can be observed both clinically and on EEG. Blood pressure usually remains within the reference range, but metabolic acidosis may be observed in association with elevated serum lactate and glucose levels.
  • Phase 2: Discrete status epilepticus events fuse, and partial seizures become secondarily generalized. The main outward manifestation of continuous clinical and EEG seizure activity consists of a tonic phase (sustained muscle contraction) followed by clonic jerks (alternating contraction and relaxation of the 4 limbs). Phase II may include altered blood pressure.
  • Phase 3
    • Over time, the patient's EEG findings start to show slow-frequency discharges similar to periodic lateralizing epileptiform discharges (PLEDs). At this stage, clinical seizures may become quite subtle, with brief rhythmic clonic or myoclonic movements often restricted to a single part of the body.
    • Rhythmic activity may be observed as myoclonus that affects only the feet, hands, facial muscles, or eyes as nystagmus.
    • As the episode progresses, a motionless patient's EEG may reveal generalized or PLED-like discharges. This type of activity is thought to represent a burned-out form of status epilepticus. This conclusion is supported by cases in which patients with abnormal mental status and PLED-like discharges as observed on EEG after an episode of status epilepticus revealed hypermetabolism of the mesiotemporal region on positron emission tomography (PET) scanning.
    • Hyperthermia, respiratory compromise, hypotension, and hypoglycemia may be observed. If not promptly treated, these metabolic, cardiovascular, and respiratory complications can exacerbate the patient's clinical condition and neurologic deficit.
  • Nonconvulsive status epilepticus (NCSE): Patients with nonconvulsive status epilepticus are described as appearing forgetful and sleepy, behaving as if deaf and blind (like a zombie), or having the appearance of being drugged. More severe cases are described as unresponsive. Sometimes parents describe the motor component of frequent falls, poor motor control, or abnormal balance.

Physical

During the initial physical examination, seek signs of trauma (eg, bruises, hemotympanum, periorbital hematoma). When the patient's situation stabilizes, look for lymphadenopathy, which suggests catscratch fever.

  • Carefully observe patients who present to the emergency department (ED) after an episode of prolonged seizure for signs of subtle seizures or status epilepticus, such as clonic or myoclonic rhythmic movements involving the limbs or face and eyes. These movements often are easy to recognize in overt generalized tonic-clonic seizures and in status epilepticus. Clonic activity may start focally then spread to the hemibody and finally become generalized. Focal clonic activity may assume the form of rhythmic facial muscle contractions, or it may involve the limbs.
  • Patients with generalized tonic-clonic status epilepticus (GTCSE) usually have bilateral and synchronous movements of the extremities.
  • Although asynchronous alternating movements of the extremities are often thought to be caused by pseudoseizures, a similar pattern can be observed in cases of frontal lobe epilepsy. Epilepsia partialis continua manifests by unilateral and, at times, focal (eg, one hand or even one finger) clonic activity (ie, twitching). Nonetheless, the relationship of seizure-mediated brain damage and duration of simple partial motor seizures is not as clear as in the generalized tonic-clonic status epilepticus studies.
  • Patients with absence seizure status epilepticus present with altered consciousness, with or without clonic movements of the eyelids or upper extremities, and automatisms involving the hands and face. A child may sometimes continue to perform a motor act that he or she was engaged in before onset of the absence (eg, bouncing a basketball). In some cases, the patient may answer simple questions, but detailed examination reveals slowed mentation and poor processing of complex information. Episodes of absence seizure status epilepticus may last 12 hours or longer.

Causes

Most studies that deal with the epidemiology and outcome of status epilepticus have classified the etiology of episodes as (1) acute symptomatic, (2) chronic-progressive neurologic disorders, and (3) remote symptomatic status epilepticus.

  • Acute symptomatic status epilepticus may be caused by an acute infection, head trauma, hypoxemia, hypoglycemia, or drug withdrawal. Acute symptomatic status is the most common etiologic category in children, causing as many as 35% of cases. Idiopathic status is the second most common cause, with a frequency of 30%; febrile status constitutes 25% of the causes. Meningitis is a common cause of convulsive status epilepticus; fever is present in 17% of the cases in children. In patients with febrile convulsive status epilepticus, the classic signs of meningitis may not be present.
    • Always consider the possibility of infections in pediatric patients presenting with generalized tonic-clonic status epilepticus. Sources of infection often, but not always, are obvious (eg, otitis media, pneumonia). Treat these infections appropriately because they contribute to lowering the seizure threshold in predisposed patients.
    • Infections can be the precipitating factor for both generalized tonic-clonic status epilepticus and nonconvulsive status epilepticus. Patients with CNS infections and mental status changes should not be assumed to have infection-related neurologic dysfunction before EEG findings rule out nonconvulsive status epilepticus.
    • Consider catscratch fever (catscratch disease), particularly in a school-aged child with a cat or kitten at home who presents with a history of unexplained mental status changes, status epilepticus of unknown etiology, prolonged seizures, or persistent fatigue. Catscratch fever is an infection acquired from cats (often from kittens) infected with Bartonella henselae via the cat flea.
      • Elevated titers of B henselae are observed in more than 85% of patients, although similar clinical pictures are observed in patients infected by Bartonella quintana and Afipia felis. Confirmation of a catscratch fever diagnosis is based on elevated indirect fluorescent antibody titers to B henselae.
      • The peak incidence of catscratch fever is in children aged 3-12 years. The disease affects teenagers and adults less frequently.
      • In 90-95% of cases, the patient has had contact with a cat, usually a kitten younger than 1 year. Although the disease may be transmitted by any close contact with a cat, scratches or bites cause 75% of cases.
      • Lymphadenopathy in the region draining the primary inoculation site is almost universal, ranging from 95-100% in most series. An inoculation lesion often occurs as well.
      • The possible manifestations of catscratch fever include CNS complications, fever, malaise, anorexia, Parinaud syndrome, sore throat, rash, arthralgia, and conjunctivitis. Neurologic effects of catscratch disease include seizures and status epilepticus, meningoencephalitis, behavioral changes (eg, combativeness), coma, neuroretinitis, myelopathy, radiculitis, cerebral arteritis, and facial nerve palsy.
  • Chronic-progressive neurological disorders represent just 5% of cases.
  • Remote symptomatic status epilepticus, referring to status epilepticus secondary to static conditions (eg, such as a remote cerebral insult on the perinatal period), constitutes 10-15% of cases.
  • More recently, the use of cephalosporin antibiotics (cefepime and ceftazidime) has been associated with the precipitation of status epilepticus. This association is especially important in the setting of impaired renal function.
  • Some anticonvulsants may produce de novo nonconvulsive status epilepticus (both absence and complex partial types). Carbamazepine and tiagabine are commonly mentioned. Patients with Lennox-Gastaut syndrome may develop status epilepticus due to excessive sedation (usually chronic benzodiazepine use). 
  • No precipitant is found in 8-10% of cases of generalized tonic-clonic status epilepticus. Of the many precipitants described in children, infection and fever collectively make up the most common (35.7%). Other common precipitants and their reported frequencies are as follows:
    • Medication changes - 20%
    • Metabolic precipitants - 8%
    • Congenital precipitants - 7%
    • Anoxia - 5%
    • CNS infection - 5%
    • Trauma - 3.5%
  • Generalized tonic-clonic status epilepticus recurrence is as follows:
    • Generalized tonic-clonic status epilepticus may recur in 17-25% of children. Recurrent status epilepticus primarily occurs in children with neurologic abnormalities.
    • The risk of recurrence also varies among the etiologic groups. Idiopathic and remote symptomatic groups have the highest recurrence risk (28% in prospective studies). The febrile seizure group has a prospective recurrence risk of 3%. 
  • Nonconvulsive status epilepticus is commonly associated with a prior diagnosis of the following epileptic syndromes: Lennox-Gastaut syndrome, myoclonic-astatic epilepsy, childhood absence epilepsy, and localization-related epilepsy (partial seizures).

More on Status Epilepticus

Overview: Status Epilepticus
Differential Diagnoses & Workup: Status Epilepticus
Treatment & Medication: Status Epilepticus
Follow-up: Status Epilepticus
Multimedia: Status Epilepticus
References
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Further Reading

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Keywords

status epilepticus, prolonged seizures, SE, generalized tonic-clonic status epilepticus, generalized tonic-clonic SE, GTCSE, nonconvulsive status epilepticus, nonconvulsive SE, NCSE, epilepsia partialis continua, complex partial and absence status epilepticus, simple partial status epilepticus, complex partial status epilepticus, epilepsy, seizures, violent seizures, hypoglycemia, head trauma, progressive encephalopathy, CNS lipid storage diseases, mitochondrial disorder, cerebral insult, electrolyte disturbance, zombie, hyperthermia, hypotension, periodic lateralizing epileptiform discharges, PLEDs, catscratch fever, meningitis, otitis media, pneumonia, lymphadenopathy, carbamazepine, tiagabine, treatment, diagnosis

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Contributor Information and Disclosures

Author

Marcio Sotero de Menezes, MD, Associate Professor, Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Seattle, University of Washington
Marcio Sotero de Menezes, MD is a member of the following medical societies: American Academy of Neurology and American Epilepsy Society
Disclosure: Nothing to disclose.

Coauthor(s)

Ednea Simon, MD, Acting Assistant Professor, Department of Neurology, University of Washington
Ednea Simon, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

G Patricia Cantwell, MD, Associate Clinical Professor, Department of Pediatrics, University of Miami; Director of Pediatric Critical Care Medicine, Miller School of Medicine, Jackson Children's Hospital
G Patricia Cantwell, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Barry J Evans, MD, Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center
Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

CME Editor

Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital; Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services, Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Timothy E Corden, MD, Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin
Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society
Disclosure: Nothing to disclose.

 
 
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