This is the current release of the guideline.

Status epilepticus

Diagnosis
Evaluation

Neurology
Pediatrics

Physicians

To review evidence on the assessment of the child with status epilepticus (SE)

Children and adolescents (age 1 month to 19 years) with status epilepticus

Diagnostic Assessment

1. Blood cultures (considered, but not routinely recommended)
2. Lumbar puncture (considered, but not routinely recommended)
3. Blood antiepileptic drug levels
4. Toxicology testing
5. Testing for inborn errors of metabolism
6. Genetic testing (considered, but not routinely recommended)
7. Electroencephalography
8. Computed tomography
9. Magnetic resonance imaging

Diagnostic yield of the data:

• Incidence of positive blood cultures
• Incidence of central nervous system (CNS) infection
• Antiepileptic drug levels
• Incidence of toxin ingestion
• Incidence of metabolic disorders
• Differential diagnosis of generalized or focal convulsive status epilepticus (SE), nonconvulsive SE, and pseudoseizures
• Incidence of structural CNS lesions found on neuroimaging

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

A literature search was conducted through the library of the University of Minnesota, and MEDLINE, for English-language articles from 1970 to 2005 and yielded 1,609 articles. The search terms were as follows: status epilepticus (SE) and, children and, magnetic resonance imaging (MRI), cranial computed tomography (CT) scan, lumbar puncture, spinal tap, electrolytes, metabolic studies, inborn errors of metabolism, electroencephalogram (EEG), hyponatremia, hypokalemia, hypocalcemia, hypoglycemia, acidosis, alkalosis, azotemia, hypophosphatemia, hypomagnesemia, pleocytosis, toxicology, intoxication. Seizures occurring in neonates less than 1 month of age were excluded, as these are defined as neonatal seizures and are different in cause and prognosis. The upper age limit was 19 years. Only articles reporting studies with more than 20 patients were included in this review. Articles consisting of single patient case reports or small samples of unusual pathologic findings, that would have biased the analysis, or articles that referred specifically to febrile or refractory SE, were excluded. Febrile SE and refractory SE were excluded because each is a selected population. Twenty-five articles were identified and reviewed for preparation of this Parameter. Relevant position papers from professional organizations were also reviewed.

Individual committee members reviewed titles and abstracts for content and relevance. Those papers dealing with diagnostic assessments of SE were selected for further detailed review. Bibliographies of the articles cited were checked for additional pertinent references.

Twenty-five articles were identified and reviewed for preparation of this Parameter. Relevant position papers from professional organizations were also reviewed.

Weighting According to a Rating Scheme (Scheme Given)

Class I. A statistical,¹ population-based² sample of patients studied at a uniform point in time (usually early) during the course of the condition. All patients undergo the intervention of interest. The outcome, if not objective,⁵ is determined in an evaluation that is masked to the patients' clinical presentations.

Class II. A statistical, non-referral-clinic-based³ sample of patients studied at a uniform point in time (usually early) during the course of the condition. Most (>80%) patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation that is masked to the patients' clinical presentations.

Class III. A selected, referral-clinic-based⁴ sample of patients studied during the course of the condition. Some patients undergo the intervention of interest. The outcome, if not objective,⁵ is determined in an evaluation by someone other than the treating physician.

Class IV. Expert opinion, case reports or any study not meeting criteria for class I to III.

Notes: (1) Statistical sample: a complete (consecutive), random or systematic (e.g., every third patient) sample of the available population with the disease; (2) Population-based: The available population for the study consists of all patients within a defined geographic region; (3) Non-referral-clinic-based: The available population for the study consists of all patients presenting to a primary care setting with the condition; (4) Referral-clinic-based: The available population for the study consists of all patients referred to a tertiary care or specialty setting. These patients may have been selected for more severe or unusual forms of the condition and thus may be less representative; (5) Objective: An outcome measure that is very unlikely to be affected by an observer's expectations (e.g., determination of death, the presence of a mass on head computed tomography [CT], serum B12 assays).

Systematic Review with Evidence Tables

Each of the selected articles was reviewed, abstracted, and classified by at least two committee members. Abstracted data included the number of patients, total episodes of status epilepticus (SE) (if given), ages, nature of subject selection, case-finding methods (prospective, retrospective, or referral), inclusion and exclusion criteria, classification, etiology, and the results of laboratory, electroencephalogram (EEG), or neuroimaging tests. A four-tiered classification scheme for determining the validity of studies on yield of established diagnostic and screening tests developed by the Quality Standards Subcommittee was utilized as part of this assessment. Depending on the strength of this evidence, it was decided whether specific recommendations could be made, and if so, the level of strength of these recommendations. Evidence pertinent to each diagnostic test together with the committee's evidence-based recommendations is presented.

Expert Consensus

Recommendations included in this Parameter were based on review of data regarding the following tests for children presenting in status epilepticus (SE): 1) blood culture and lumbar puncture (LP) studies; 2) antiepileptic drug (AED) levels; 3) toxicology screening; 4) metabolic and genetic studies; 5) electroencephalogram (EEG); and 6) neuroimaging including computed tomography (CT) and magnetic resonance imaging (MRI).

Most available literature did not specify whether the diagnostic tests analyzed were uniformly applied during each SE episode. Therefore, where reported data were missing, a minimum diagnostic yield for each test was calculated by dividing the total number of positive diagnostic tests reported by the total number of reported SE episodes from each study (therefore assuming that each diagnostic test was performed for each episode of SE, likely leading to an underestimate of the true diagnostic yield of these tests).

A = Established as effective, ineffective, or harmful for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)

B = Probably effective, ineffective, or harmful for the given condition in the specified population. (Level B rating requires at least one Class I study or at least two consistent Class II studies.)

C = Possibly effective, ineffective, or harmful for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)

U = Data inadequate or conflicting; given current knowledge, test is unproven.

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

Drafts of the guideline have been reviewed by at least three American Academy of Neurology (AAN) committees, a network of neurologists, Neurology peer reviewers, and representatives from related fields.

Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.

Laboratory Studies

Should Blood Cultures and Lumbar Puncture (LP) Be Routinely Done in Children with Status Epilepticus (SE)?

Recommendations

1. There are insufficient data to support or refute whether blood cultures should be done on a routine basis in children in whom there is no clinical suspicion of infection (Level U).
2. There are insufficient data to support or refute whether LP should be done on a routine basis in children in whom there is no clinical suspicion of a central nervous system (CNS) infection (Level U).

Should AED Levels Be Routinely Obtained in Children Taking AEDs Who Develop SE?

Recommendation

1. AED levels should be considered when a child with epilepsy on AED prophylaxis develops SE (Level B, class II and III evidence).

Should Toxicology Testing Be Routinely Ordered in Children with SE?

Recommendation

1. Toxicology testing may be considered in children with SE, when no apparent etiology is immediately identified, as the frequency of ingestion as a diagnosis was at least 3.6% (Level C, class III evidence). To detect a specific ingestion, suspected because of the clinical history, it should be noted that a specific serum toxicology level is required, rather than simply urine toxicology screening.

Metabolic and Genetic Testing

Should Testing for Inborn Errors of Metabolism or Genetic (Chromosomal or Molecular) Studies Be Routinely Ordered in Children with SE?

Recommendations

1. Studies for inborn errors of metabolism may be considered when the initial evaluation reveals no etiology, especially if there is a preceding history suggestive of a metabolic disorder (Level C, class III evidence). The specific studies obtained are dependent on the history and the clinical examination. There is insufficient evidence to support or refute whether such studies should be done routinely (Level U).
2. There are insufficient data to support or refute whether genetic testing (chromosomal or molecular studies) should be done routinely in children with SE (Level U).

Electroencephalography (EEG)

Should an EEG Be Routinely Performed in the Evaluation of a Child with SE?

Recommendations

1. An EEG may be considered in a child presenting with new onset SE as it may determine whether there are focal or generalized abnormalities that may influence diagnostic and treatment decisions (Level C, class III evidence).
2. Although nonconvulsive SE (NCSE) occurs in children who present with SE, there are insufficient data to support or refute recommendations regarding whether an EEG should be obtained to establish this diagnosis (Level U).
3. An EEG may be considered in a child presenting with SE if the diagnosis of pseudostatus epilepticus is suspected (Level C, class III evidence).

Neuroimaging

Should Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) Be Performed in Children with SE?

Recommendations

1. Neuroimaging may be considered for the evaluation of the child with SE if there are clinical indications or if the etiology is unknown (Level C, class III evidence). If neuroimaging is done, it should only be done after the child is appropriately stabilized and the seizure activity controlled.
2. There is insufficient evidence to support or refute recommending routine neuroimaging (Level U).

Definitions:

Classification Scheme for Determining the Yield of Established Diagnostic and Screening Tests

Class I. A statistical,¹ population-based² sample of patients studied at a uniform point in time (usually early) during the course of the condition. All patients undergo the intervention of interest. The outcome, if not objective,⁵ is determined in an evaluation that is masked to the patients' clinical presentations.

Class II. A statistical, non-referral-clinic-based³ sample of patients studied at a uniform point in time (usually early) during the course of the condition. Most (>80%) patients undergo the intervention of interest. The outcome, if not objective, is determined in an evaluation that is masked to the patients' clinical presentations.

Class III. A selected, referral-clinic-based⁴ sample of patients studied during the course of the condition. Some patients undergo the intervention of interest. The outcome, if not objective,⁵ is determined in an evaluation by someone other than the treating physician.

Class IV. Expert opinion, case reports or any study not meeting criteria for class I to III.

Notes: (1) Statistical sample: a complete (consecutive), random or systematic (e.g., every third patient) sample of the available population with the disease; (2) Population-based: The available population for the study consists of all patients within a defined geographic region; (3) Non-referral-clinic-based: The available population for the study consists of all patients presenting to a primary care setting with the condition; (4) Referral-clinic-based: The available population for the study consists of all patients referred to a tertiary care or specialty setting. These patients may have been selected for more severe or unusual forms of the condition and thus may be less representative; (5) Objective: An outcome measure that is very unlikely to be affected by an observer's expectations (e.g., determination of death, the presence of a mass on head computed tomography [CT], serum B12 assays).

Strength of Recommendations

A = Established as effective, ineffective, or harmful for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)

B = Probably effective, ineffective, or harmful for the given condition in the specified population. (Level B rating requires at least one Class I study or at least two consistent Class II studies.)

C = Possibly effective, ineffective, or harmful for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)

U = Data inadequate or conflicting; given current knowledge, test is unproven.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Appropriate diagnostic assessment of children with status epilepticus

Not stated

• This statement is provided as an educational service of the American Academy of Neurology (AAN). It is based on an assessment of current scientific and clinical information. It is not intended to include all possible proper methods of care for a particular neurologic problem or all legitimate criteria for choosing to use a specific procedure. Neither is it intended to exclude any reasonable alternative methodologies. The AAN recognizes that specific patient care decisions are the prerogative of the patient and the physician caring for the patient, based on all of the circumstances involved.
• The classification scheme developed by the Quality Standard Subcommittee (QSS) for studies related to determining the yield of established diagnostic and screening tests or interventions and is appropriate only when the diagnostic accuracy of the test or intervention is known to be good. Additionally, the abnormality potentially identified by the screening intervention should be treatable or, should have important prognostic implications. This classification is different than others currently recommended by the QSS that have been published in recent parameters that relate to diagnostic, prognostic or therapeutic studies.
• It is now common practice to obtain a complete blood count (CBC) and chemistry profiles routinely in children presenting with status epilepticus (SE). Thus, the guideline developers did not develop evidence-based recommendations for these tests but did include in appendix 4 of the original guideline document a summary of previous studies regarding their diagnostic yield. Electrolyte (e.g., Na++ or other electrolytes, Ca++, glucose) abnormalities or basic metabolic disorders were reported in an average of 6% (range 1 to 16%) of children with SE. In most studies these abnormalities were listed as the etiology. However, it was unclear whether these abnormalities were responsible for the episode of SE and if correction resulted in cessation of SE.

An implementation strategy was not provided.

Getting Better
Living with Illness

Effectiveness
Patient-centeredness

Not applicable: The guideline was not adapted from another source.

2006 Nov

American Academy of Neurology - Medical Specialty Society
Child Neurology Society - Medical Specialty Society

American Academy of Neurology (AAN)

Quality Standards Subcommittee
Practice Committee of the Child Neurology Society

Quality Standards Subcommittee Members: Jacqueline French, MD, FAAN (Co-Chair); Gary S. Gronseth, MD (Co-Chair); Charles E. Argoff, MD; Stephen Ashwal, MD, FAAN (ex-officio) (facilitator); Christopher Bever, Jr., MD, MBA, FAAN; John D. England, MD, FAAN; Gary M. Franklin, MD, MPH (ex-officio); Gary H. Friday, MD, MPH, FAAN; Larry B. Goldstein, MD, FAAN; Deborah Hirtz, MD (ex-officio); Robert G. Holloway, MD, MPH, FAAN; Donald J. Iverson, MD, FAAN; Leslie A. Morrison, MD; Clifford J. Schostal, MD; David J. Thurman, MD, MPH; William J. Weiner, MD, FAAN; Samuel Wiebe, MD

CNS Practice Committee Members: Carmela Tardo, MD (Chair); Bruce Cohen, MD (Vice-Chair); Diane K. Donley, MD; Bhuwan P. Garg, MD; Brian Grabert, MD; Michael Goldstein, MD; David Griesemer, MD; Edward Kovnar, MD; Augustin Legido, MD; Leslie Anne Morrison, MD; Ben Renfroe, MD; Shlomo Shinnar, MD; Gerald Silverboard, MD; Russell Snyder, MD; Dean Timmons, MD; William Turk, MD; Greg Yim, MD

American Academy of Pediatrics - Medical Specialty Society
American College of Emergency Physicians - Medical Specialty Society
American Epilepsy Society - Disease Specific Society

This is the current release of the guideline.

This summary was completed by ECRI Institute on May 14, 2007.

This NGC summary is based on the original guideline, which is copyrighted by the American Academy of Neurology.