You talked and we listened. Many of you told us that as new guidelines for the management of neurologic conditions are published, you would like us to speak with the authors to clarify the recommendations and detail how to deal with murky issues.
We asked Stephen Ashwal, MD, Chief of the Division of Pediatric Neurology at Loma Linda University School of Medicine in Loma Linda, CA, and a member of the Quality Standards Subcommittee of the AAN, to address the updated guidelines for the diagnostic assessment of children with status epilepticus.
In an accompanying sidebar, lead author James J. Riviello Jr., MD, Director of the Epilepsy Program in the Division of Epidemiology and Clinical Neurophysiology and Critical Care Neurology Service in the Department of Neurology at Children's Hospital, and Professor of Neurology at Harvard Medical School, both in Boston, offers a case example exemplifying how a physician might apply the recommendations to a classic patient.
The guidelines, a report of the Quality Standards Subcommittee of the AAN and the Practice Committee of the Child Neurology Society, appear in the Nov. 14 Neurology (2006;67:1542–1550).
SHOULD BLOOD CULTURES AND LUMBAR PUNCTURE BE PERFORMED ROUTINELY IN CHILDREN WITH STATUS EPILEPTICUS (SE)?
As far as evaluating possible sepsis or CNS infection is concerned, data are not sufficient to support routine testing. That doesn't mean an individual patient might not need one or both of the tests. For now, we should keep on doing what we have been doing: Weigh available information to decide if the patient should have the tests or be admitted for observation.
Common clinical practice is that blood cultures should be obtained if there is a clinical suspicion of infection. Likewise, lumbar puncture should be done if clinical features include CNS infection, especially if fever is present.
SHOULD ANTIEPILEPTIC DRUG LEVELS BE OBTAINED ROUTINELY IN CHILDREN TAKING THE DRUGS WHO DEVELOP SE?
We know there are many reasons why pediatric patients taking medication for epilepsy prophylaxis can have low drug levels. Young children may refuse to take medication, for example, or adolescents may stop taking them because of self-image issues.
Additionally, because of their age or developmental status, many infants and children cannot communicate whether or not they are taking medication.
As a result, clinicians should try to obtain antiepileptic drug levels in children with epilepsy to determine if blood concentrations are subtherapeutic.
However, not all hospitals are equipped to measure blood levels within a few hours. In those cases, we have to rely on clinical judgment. Since the recommended dosage is based on a child's body weight, common practice is to calculate the dosage the patient should be taking and reconcile this with the actual amount the child is getting at home.
SHOULD TOXICOLOGY TESTING BE ROUTINELY ORDERED IN CHILDREN WITH SE?
This is a test that most clinicians frequently don't consider, but should.
Ingestion is a surprisingly common cause of SE in children; available data suggest they account for 3.6 percent of cases. Young patients may accidentally take a family member's medications or may be exposed to an environmental substance or live in an environment where parents are prone to substance abuse. As a result, clinicians who can find no apparent etiology should always consider toxicology screening early in the evaluation of childhood SE.
If there is the possibility of a specific toxic ingestion based on the clinical manifestations then specific serum toxicology measures are required, rather than simple urine toxicology screening.
SHOULD TESTING FOR INBORN ERRORS OF METABOLISM BE ROUTINELY ORDERED IN CHILDREN WITH SE?
Although each inborn error of metabolism is relatively rare, they are actually relatively frequent when you consider all of them together, occurring in about 1 in 2,500 births. Of 735 children with SE in nine studies, an inborn error of metabolism was diagnosed in about 4 percent of cases. If no infectious etiology is found and there is no underlying disease such as pneumonia, and toxicology is negative, the next step is to consider testing for these disorders.
A finding of unexplained acidosis on electrolyte testing may offer a clue that testing is needed, and frequently some features of the clinical history or examination should prompt consideration of a metabolic disorder.
SHOULD AN EEG BE PERFORMED ROUTINELY IN THE EVALUATION OF A CHILD WITH SE?
An EEG can be critical and should typically be obtained early to help determine whether seizures are generalized or focal, or whether or not the child is in non-convulsive status epilepticus.
An EEG can also help determine if a child has pseudostatus epilepticus. Sometimes the clinician can tell by examination, but often you need continuous EEG monitoring to confirm this possibility.
EEGs can help neurologists, emergency department physicians, and pediatricians better evaluate the patient and decide on the best approach to controlling the seizures and also to better assess whether prolonged unresponsiveness of the child might be related to subclinical recurrent seizures.
SO WHY DO THE RECOMMENDATIONS STATE THAT THE LEVEL OF EVIDENCE SUPPORTING ROUTINE EEG USE IS WEAK?
Because there have not been robust prospective studies. However, I think that most clinicians appreciate that the EEG is very helpful in evaluating the child with SE.
SHOULD CT OR MRI BE PERFORMED IN CHILDREN WITH SE?
In general, there have not been enough prospective studies of neuroimaging in children in SE. This is another area that requires more research. That said, neuroimaging can be extremely helpful in the evaluation when a serious structural lesion such as subdural hematoma is suspected, especially if there are new-onset focal signs, persistent altered awareness, fever, or recent trauma.
As for which test to perform, MRI can show more subtle abnormalities that might not show up on CT, but MRI is often not available in the emergency department. Also, CT is more sensitive initially in detecting surgically treatable lesions such as intracranial hemorrhage.
If the child is at risk for structural abnormalities that require emergency intervention, then CT should be performed. If CT is not urgent, MRI is better because it is more sensitive and specific.
Neuroimaging should be done only after the child is stabilized and SE has been controlled.
WHAT'S THE NEXT STEP?
The guidelines show a need for additional clinical research so that decisions in the evaluation of SE are based on strong clinical evidence.
Among the specific recommendation for future research are prospective studies to define what factors, or combination of factors, precipitate SE in children; controlled prospective studies to define the role for routine or selective laboratory investigations in the evaluation of children with SE; and controlled prospective blinded studies to define the setting and timing for EEG done in the evaluation of children with SE and to determine if postictal and unexpected ictal EEG findings have prognostic and treatment significance.
THE UPDATED GUIDELINES FOR ASSESSING CHILDREN WITH STATUS EPILEPTICUS
The AAN's and Child Neurology Society's updated evidence-based guidelines for the assessment of the child with status epilepticus (SE):
- Blood Cultures. Data are insufficient to support or refute routine blood cultures in children when there is no clinical suspicion of infection.
- Lumbar Puncture. Data are insufficient to support or refute routine lumbar puncture in children when there is no clinical suspicion of CNS infection.
- Antiepileptic Drug (AED) Levels. There is good evidence that AED levels should be considered when a child with epilepsy on AED prophylaxis develops SE.
- Toxicology Testing. Toxicology testing may be considered in children with SE, when no apparent etiology is immediately identified. This is based on weak evidence.
- Metabolic Testing. Studies for inborn errors of metabolism may be considered when the initial evaluation reveals no etiology, especially if the history suggests a metabolic disorder. This is based on weak evidence.
- Genetic Testing. Data are insufficient to support or refute routine genetic testing (chromosomal or DNA studies).
- Electroencephalography. An EEG may be considered in a child with new-onset SE to help determine if the seizures are focal or generalized, or in a child in whom a diagnosis of pseudo-status epilepticus is suspected. This is based on weak evidence. Data are insufficient to support or refute recommendations regarding whether an EEG should be obtained to establish a diagnosis of non-convulsive status epilepticus.
- Neuroimaging. Evidence is insufficient to support or refute routine neuroimaging. However, weak evidence suggests consideration of CT or MRI if there are clinical indications or if the etiology is unknown.
The full guidelines with detailed findings and supporting evidence can be found at www.aan.com.
APPLYING THE GUIDELINES: A CASE HISTORY
Neurology Today asked lead author James J. Riviello Jr., MD, to share a typical case history exemplifying how a physician might apply the recommendations to a classic patient.
Dr. Riviello is Director of the Epilepsy Program in the Division of Epidemiology and Clinical Neurophysiology and Critical Care Neurology Service in the Department of Neurology at Children's Hospital, and Professor of Neurology at Harvard Medical School, both in Boston.
A 5-year-old boy has a prolonged focal seizure with fever. He has had epilepsy and is being treated with anticonvulsant drugs. He has a one-week history of fever and vomiting.
Since fever with prolonged seizures is present, the first thing you have to be concerned about is whether meningitis is causing the fever. While the guidelines state there was insufficient evidence for routine lumbar puncture (LP) testing, there are special circumstances when you want to consider LP, and this would be one of them.
Since the seizure is focal, you also have to be concerned about whether focal anatomic problems are the cause. So even though the guidelines say neuroimaging is not needed in all cases, you would want to consider it in this case. MRI is always preferred, but is not always available on an emergency basis. If not available, you should get a CT scan.
Additionally, the presence of vomiting leads to measuring electrolyte levels. And since the patient was taking AEDs, blood should be examined to determine if low levels are causing the seizures.
Toxicology testing may also be needed. But that would be done only if no other etiology has been identified. Then, if toxicology also fails to find the cause of the seizures, you might proceed to testing for inborn errors of metabolism and genetic testing.
EEG, on the other hand, would not be helpful because it would be done to tell us whether the seizure is generalized or focal and we already know from the symptoms that it is focal.