REVIEW URRENT C OPINION
Pediatric status epilepticus: identification and evaluation Emily R. Freilich, John M. Schreiber, Tesfaye Zelleke, and William D. Gaillard
Purpose of review Status epilepticus is an acute neurologic emergency, the incidence of which is increasing in the United States as the definition evolves and our detection abilities improve. We will present the current definition of status epilepticus, including a recently modified operational definition for use in the clinical setting. We will also provide updates on identifying children in status epilepticus, etiologic considerations, and the rationale for diagnostic testing. Recent findings Recent data reveal the benefits of MRI vs. computed tomography in new-onset status epilepticus, as well as high rates of identification of electrographic seizures in patients with unexplained acute encephalopathy in pediatric ICU settings. Genetic testing should be considered in young children with recurrent status epilepticus. Summary Prompt recognition and diagnostic evaluation of the child in status epilepticus will help identify causes, which may require specific treatment, and help in the management of this life-threatening condition. Laboratory work, neuroimaging, electroencephalogram or continuous video electroencephalogram, lumbar puncture, and genetic testing may be considered in the evaluation of the child in status epilepticus. Keywords diagnostic evaluation, pediatrics, status epilepticus
INTRODUCTION Status epilepticus (SE) is an acute, life-threatening, and neurologic emergency, the incidence of which has risen dramatically over the last 30 years [1 ]. Prompt initiation of treatment can significantly reduce associated morbidity and mortality; therefore, early recognition is critical. In this article, we discuss the evolving definition of status epilepticus, highlighting its various forms and potential etiologies. We outline the diagnostic evaluation of the child who presents with status epilepticus, differentiating between those children with known epilepsy and those with new-onset seizures. &
DEFINITION OF STATUS EPILEPTICUS: AN EVOLUTION In the Classification of Epileptic Seizures in 1981, the International League Against Epilepsy (ILAE) defined status epilepticus as ‘a seizure that persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur’, noticeably lacking a specified duration [2].
Then in 1993, the ILAE altered the definition to ‘a single epileptic seizure of longer than 30 minduration or a series of epileptic seizures during which function is not regained between ictal events in a longer than 30-min period’ [3]. Thirty minutes is long enough to require aggressive treatment, but shorter than the 45–82 min it takes to produce neuronal injury after continuous seizure in animal models [4,5]. Over the last 30 years, however, significant advances in medicine have forced the scientific community to reconsider this rather arbitrary definition. Increased diagnostic capabilities, widespread availability of both electroencephalogram (EEG) and long-term EEG monitoring, and advances in Department of Neuroscience, Children’s National Health System, Washington, District of Columbia, USA Correspondence to William D. Gaillard, MD, Department of Neuroscience, Children’s National Health System, 111 Michigan Ave NW, Washington, DC 20010, USA. Tel: +1 202 476 2120; e-mail: wgaillar @cnmc.org Curr Opin Pediatr 2014, 26:655–661 DOI:10.1097/MOP.0000000000000152
1040-8703 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-pediatrics.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Neurology
KEY POINTS Although status epilepticus is traditionally defined as a continuous seizure activity lasting longer than 30 min, aggressive management of seizures should start after 5–10 min of continuous seizure activity, termed impending status epilepticus. NCSE is increasingly recognized in children admitted to pediatric ICU with acute encephalopathy of various causes, and continuous video EEG monitoring for 24–48 h is recommended. Of patients presenting with first time seizure in status epilepticus, almost one-third will have an acute provoking cause. An MRI is more sensitive than CT in detecting clinically relevant lesions except for blood. Patients with known epilepsy often present with status epilepticus secondary to medication changes or noncompliance, and drug levels of AEDs should be checked on presentation. Genetic testing for Dravet syndrome (SCN1A mutation) is warranted in young patients presenting with recurrent status epilepticus.
treatment both in the hospital and prehospital settings allow for earlier identification and effective treatment of status epilepticus, simultaneously increasing incidence and decreasing morbidity and mortality [1 ]. Thus, debate has ensued regarding shortening the duration of status epilepticus to 20, 10, or even 5 min of continuous seizure activity [4–8]. Adult studies demonstrate that generalized tonic–clonic seizures typically last from seconds to 4 min, with an average of approximately 1 min [9,10]. Most seizures in adults, therefore, should stop spontaneously within 5 min, and those that do not stop within 5 min are less likely to stop on their own without medical intervention [4,11,12]. Similarly, in children, the longer a seizure lasts, the less likely it is to stop spontaneously [13], although it is not uncommon for seizures, especially with fever, to last up to 10 min in children. No consensus has been reached, and different groups have utilized variable definitions of 5–30 min in recent clinical research settings. Prolonged seizures lasting less than 30 min, however, may not carry the same risks as those persisting longer than 30 min, and shortening the definition may impact studies examining treatment and outcomes [12,14]. A proposal, therefore, is that rather than changing the historical definition, modifiers should be added for use in the clinical setting, creating an operational definition, allowing for identification of patients at highest risk for status epilepticus. &
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www.co-pediatrics.com
Patients with a seizure lasting longer than 5 min (or 5–10 min in children) [4,14,15] can be designated threatened or impending status epilepticus, and those that continue for longer than 30 min can be designated as established status epilepticus. Furthermore, patients with ongoing seizure activity after 60 min can be considered refractory status [16]. Refractory status is not limited to this time definition though, as patients are also considered in refractory status epilepticus if they fail to respond to two or three antiepileptic medications (see next article in series by Abend and Loddenkemper) [14,17].
IDENTIFICATION OF STATUS EPILEPTICUS Status epilepticus can take on many different forms that range from easily recognizable to clinically silent. The most easily recognized is convulsive status epilepticus (CSE), which is a combination of tonic (stiffening), clonic (rhythmic), or tonic– clonic movements with alteration of consciousness. Less common is the well-described state of epilepsia partialis continua, a prolonged focal motor seizure without alteration in awareness. There are other types of generalized seizures, that is, myoclonic and atypical absence seizures, which can also become prolonged. Nonconvulsive status epilepticus (NCSE), characterized by persistent alterations in consciousness without overt convulsive movements, requires EEG for diagnosis, and is increasingly recognized in children as EEG monitoring has become more commonplace. NCSE may be seen in children with acute encephalopathy for various reasons, including patients with posttraumatic or postanoxic brain injury, patients with encephalitis, and patients who are not waking up after treatment of CSE, after the convulsions have seemingly ceased [18,19,20 ,21 ]. Electrographic seizures are found in approximately one-third of patients in the pediatric ICU with unexplained altered mental status, with one-third of these being in NCSE [19,20 ,21 ]. NCSE is linked to increased mortality risk and should be aggressively treated [10,21 ]. The majority of electrographic seizures are detected within the first 24 h, thus it is recommended that overnight continuous video EEG monitoring be initiated early and last for 24–48 h [10,14,21 ]. Neonatal status, which is also often difficult to identify without continuous EEG, is unique in terms of presentation, cause, and treatment, and is outside the scope of this article. Although prolonged febrile convulsions are the most common cause of pediatric status epilepticus, children with febrile convulsions follow a unique trajectory for prognosis and outcome, and this will be discussed in the following article. &&
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Volume 26 Number 6 December 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pediatric status epilepticus Freilich et al.
The remainder of this section, therefore, will focus on the child in CSE. CSE in children has historically been divided by seizure etiology according to 1989 ILAE classification [22], as well as underlying cause, which is the main factor in the prognosis and outcome. The terminology of seizure classification is undergoing revision, and proposed changes to etiology include limiting classifications to three categories: genetic, structural/metabolic, and unknown [23]. Table 1 defines and summarizes the classifications using both the old and the new terminology [3,22,23]. In a prospective study, Singh et al. [24] illustrated the various causes of children with new-onset seizures presenting with CSE (Fig. 1). These findings are similar to earlier studies of status epilepticus in children despite slight differences in classification [17,25–28] (Table 2). The younger the child, the higher the likelihood of finding a provoking factor, which means all children deserve an extensive search for any potentially identifiable and treatable cause. The testing that is performed in the emergency room or ICU will be individualized for each patient on the basis of history and physical exam. However, potential testing could include blood chemistries, complete blood count, antiepileptic drug (AED) levels, toxicology screens, lumbar puncture, EEG, and head imaging [computerized tomography (CT) and magnetic resonance imaging (MRI)]. Genetic testing has also become more common in young children, especially those children presenting with recurrent status epilepticus.
THE DIAGNOSTIC EVALUATION The evaluation of a child with CSE is driven primarily by the individual patient’s history and physical examination. CSE is a life-threatening emergency,
and evaluation and management are, therefore, done simultaneously. Not to be overlooked is the critical step of stabilization, along with monitoring of vital signs, including blood pressure, heart rate, and oxygen saturation. It is also important to recognize that much of the diagnostic evaluation can be performed after the child is stabilized, usually in an intensive-care setting, and the seizures have been treated. Table 3 illustrates the similarities and differences between the workup of patients who present in CSE as their first lifetime seizure and those patients with known epilepsy diagnosis [25,27]. Patients with new-onset CSE need a thorough evaluation to search for an underlying and potentially treatable cause. Excluding febrile seizures, systemic and central nervous system (CNS) infections are the most common causes in very young patients (
Pediatric status epilepticus: identification and evaluation Emily R. Freilich, John M. Schreiber, Tesfaye Zelleke, and William D. Gaillard
Purpose of review Status epilepticus is an acute neurologic emergency, the incidence of which is increasing in the United States as the definition evolves and our detection abilities improve. We will present the current definition of status epilepticus, including a recently modified operational definition for use in the clinical setting. We will also provide updates on identifying children in status epilepticus, etiologic considerations, and the rationale for diagnostic testing. Recent findings Recent data reveal the benefits of MRI vs. computed tomography in new-onset status epilepticus, as well as high rates of identification of electrographic seizures in patients with unexplained acute encephalopathy in pediatric ICU settings. Genetic testing should be considered in young children with recurrent status epilepticus. Summary Prompt recognition and diagnostic evaluation of the child in status epilepticus will help identify causes, which may require specific treatment, and help in the management of this life-threatening condition. Laboratory work, neuroimaging, electroencephalogram or continuous video electroencephalogram, lumbar puncture, and genetic testing may be considered in the evaluation of the child in status epilepticus. Keywords diagnostic evaluation, pediatrics, status epilepticus
INTRODUCTION Status epilepticus (SE) is an acute, life-threatening, and neurologic emergency, the incidence of which has risen dramatically over the last 30 years [1 ]. Prompt initiation of treatment can significantly reduce associated morbidity and mortality; therefore, early recognition is critical. In this article, we discuss the evolving definition of status epilepticus, highlighting its various forms and potential etiologies. We outline the diagnostic evaluation of the child who presents with status epilepticus, differentiating between those children with known epilepsy and those with new-onset seizures. &
DEFINITION OF STATUS EPILEPTICUS: AN EVOLUTION In the Classification of Epileptic Seizures in 1981, the International League Against Epilepsy (ILAE) defined status epilepticus as ‘a seizure that persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur’, noticeably lacking a specified duration [2].
Then in 1993, the ILAE altered the definition to ‘a single epileptic seizure of longer than 30 minduration or a series of epileptic seizures during which function is not regained between ictal events in a longer than 30-min period’ [3]. Thirty minutes is long enough to require aggressive treatment, but shorter than the 45–82 min it takes to produce neuronal injury after continuous seizure in animal models [4,5]. Over the last 30 years, however, significant advances in medicine have forced the scientific community to reconsider this rather arbitrary definition. Increased diagnostic capabilities, widespread availability of both electroencephalogram (EEG) and long-term EEG monitoring, and advances in Department of Neuroscience, Children’s National Health System, Washington, District of Columbia, USA Correspondence to William D. Gaillard, MD, Department of Neuroscience, Children’s National Health System, 111 Michigan Ave NW, Washington, DC 20010, USA. Tel: +1 202 476 2120; e-mail: wgaillar @cnmc.org Curr Opin Pediatr 2014, 26:655–661 DOI:10.1097/MOP.0000000000000152
1040-8703 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.co-pediatrics.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Neurology
KEY POINTS Although status epilepticus is traditionally defined as a continuous seizure activity lasting longer than 30 min, aggressive management of seizures should start after 5–10 min of continuous seizure activity, termed impending status epilepticus. NCSE is increasingly recognized in children admitted to pediatric ICU with acute encephalopathy of various causes, and continuous video EEG monitoring for 24–48 h is recommended. Of patients presenting with first time seizure in status epilepticus, almost one-third will have an acute provoking cause. An MRI is more sensitive than CT in detecting clinically relevant lesions except for blood. Patients with known epilepsy often present with status epilepticus secondary to medication changes or noncompliance, and drug levels of AEDs should be checked on presentation. Genetic testing for Dravet syndrome (SCN1A mutation) is warranted in young patients presenting with recurrent status epilepticus.
treatment both in the hospital and prehospital settings allow for earlier identification and effective treatment of status epilepticus, simultaneously increasing incidence and decreasing morbidity and mortality [1 ]. Thus, debate has ensued regarding shortening the duration of status epilepticus to 20, 10, or even 5 min of continuous seizure activity [4–8]. Adult studies demonstrate that generalized tonic–clonic seizures typically last from seconds to 4 min, with an average of approximately 1 min [9,10]. Most seizures in adults, therefore, should stop spontaneously within 5 min, and those that do not stop within 5 min are less likely to stop on their own without medical intervention [4,11,12]. Similarly, in children, the longer a seizure lasts, the less likely it is to stop spontaneously [13], although it is not uncommon for seizures, especially with fever, to last up to 10 min in children. No consensus has been reached, and different groups have utilized variable definitions of 5–30 min in recent clinical research settings. Prolonged seizures lasting less than 30 min, however, may not carry the same risks as those persisting longer than 30 min, and shortening the definition may impact studies examining treatment and outcomes [12,14]. A proposal, therefore, is that rather than changing the historical definition, modifiers should be added for use in the clinical setting, creating an operational definition, allowing for identification of patients at highest risk for status epilepticus. &
656
www.co-pediatrics.com
Patients with a seizure lasting longer than 5 min (or 5–10 min in children) [4,14,15] can be designated threatened or impending status epilepticus, and those that continue for longer than 30 min can be designated as established status epilepticus. Furthermore, patients with ongoing seizure activity after 60 min can be considered refractory status [16]. Refractory status is not limited to this time definition though, as patients are also considered in refractory status epilepticus if they fail to respond to two or three antiepileptic medications (see next article in series by Abend and Loddenkemper) [14,17].
IDENTIFICATION OF STATUS EPILEPTICUS Status epilepticus can take on many different forms that range from easily recognizable to clinically silent. The most easily recognized is convulsive status epilepticus (CSE), which is a combination of tonic (stiffening), clonic (rhythmic), or tonic– clonic movements with alteration of consciousness. Less common is the well-described state of epilepsia partialis continua, a prolonged focal motor seizure without alteration in awareness. There are other types of generalized seizures, that is, myoclonic and atypical absence seizures, which can also become prolonged. Nonconvulsive status epilepticus (NCSE), characterized by persistent alterations in consciousness without overt convulsive movements, requires EEG for diagnosis, and is increasingly recognized in children as EEG monitoring has become more commonplace. NCSE may be seen in children with acute encephalopathy for various reasons, including patients with posttraumatic or postanoxic brain injury, patients with encephalitis, and patients who are not waking up after treatment of CSE, after the convulsions have seemingly ceased [18,19,20 ,21 ]. Electrographic seizures are found in approximately one-third of patients in the pediatric ICU with unexplained altered mental status, with one-third of these being in NCSE [19,20 ,21 ]. NCSE is linked to increased mortality risk and should be aggressively treated [10,21 ]. The majority of electrographic seizures are detected within the first 24 h, thus it is recommended that overnight continuous video EEG monitoring be initiated early and last for 24–48 h [10,14,21 ]. Neonatal status, which is also often difficult to identify without continuous EEG, is unique in terms of presentation, cause, and treatment, and is outside the scope of this article. Although prolonged febrile convulsions are the most common cause of pediatric status epilepticus, children with febrile convulsions follow a unique trajectory for prognosis and outcome, and this will be discussed in the following article. &&
&&
&&
&&
&&
&&
Volume 26 Number 6 December 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pediatric status epilepticus Freilich et al.
The remainder of this section, therefore, will focus on the child in CSE. CSE in children has historically been divided by seizure etiology according to 1989 ILAE classification [22], as well as underlying cause, which is the main factor in the prognosis and outcome. The terminology of seizure classification is undergoing revision, and proposed changes to etiology include limiting classifications to three categories: genetic, structural/metabolic, and unknown [23]. Table 1 defines and summarizes the classifications using both the old and the new terminology [3,22,23]. In a prospective study, Singh et al. [24] illustrated the various causes of children with new-onset seizures presenting with CSE (Fig. 1). These findings are similar to earlier studies of status epilepticus in children despite slight differences in classification [17,25–28] (Table 2). The younger the child, the higher the likelihood of finding a provoking factor, which means all children deserve an extensive search for any potentially identifiable and treatable cause. The testing that is performed in the emergency room or ICU will be individualized for each patient on the basis of history and physical exam. However, potential testing could include blood chemistries, complete blood count, antiepileptic drug (AED) levels, toxicology screens, lumbar puncture, EEG, and head imaging [computerized tomography (CT) and magnetic resonance imaging (MRI)]. Genetic testing has also become more common in young children, especially those children presenting with recurrent status epilepticus.
THE DIAGNOSTIC EVALUATION The evaluation of a child with CSE is driven primarily by the individual patient’s history and physical examination. CSE is a life-threatening emergency,
and evaluation and management are, therefore, done simultaneously. Not to be overlooked is the critical step of stabilization, along with monitoring of vital signs, including blood pressure, heart rate, and oxygen saturation. It is also important to recognize that much of the diagnostic evaluation can be performed after the child is stabilized, usually in an intensive-care setting, and the seizures have been treated. Table 3 illustrates the similarities and differences between the workup of patients who present in CSE as their first lifetime seizure and those patients with known epilepsy diagnosis [25,27]. Patients with new-onset CSE need a thorough evaluation to search for an underlying and potentially treatable cause. Excluding febrile seizures, systemic and central nervous system (CNS) infections are the most common causes in very young patients (
