Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine), 4th Ed.

CHAPTER 52. Seizures

George T. Koburov

HIGH-YIELD FACTS

• Seizures are the most common neurologic disorder in children in the United States.

• Epilepsy is defined as two or more unprovoked (absence of fever, acute trauma, etc.) seizures.

• Although 1 in 10 individuals will experience a seizure in their lifetimes, seizures are still poorly understood in regards to etiology and optimal treatment.

Seizures are the most common neurologic disorder in children in the United States.1 A seizure is defined as abnormal, excessive, transient paroxysmal electrical discharge of neurons within the brain. Epilepsy is defined as two or more unprovoked (absence of fever, acute trauma, etc.) seizures. Although 1 in 10 individuals will experience a seizure in their lifetimes, seizures are still poorly understood in regards to etiology and optimal treatment. As such, seizures can be a vexing and anxiety-provoking event for emergency medicine physicians, staff, and the families of affected children.

CLASSIFICATION

The etiology and pathophysiology of seizures is poorly understood and manifestations of this process are quite variable. These manifestations may include changes in behavior, consciousness, sensation, motor activity, or autonomic function. Some seizures are very subtle, described as daydreaming to the opposite extreme of generalized convulsing of the body with loss of consciousness. An international classification of epilepsies and seizures disorders was developed in 1989 and continues to serve to classify seizures (Table 52-1).1 A revised terminology for seizures and epilepsies was released by the International League Against Epilepsy (ILAE) Commission in 2009.2 Neither classification is particularly useful or prescriptive for guiding acute management in the emergency department (ED), but can be useful in communicating with neurologists when determining the need for ongoing anticonvulsive therapies.

TABLE 52-1

International Classification of Seizures

Partial Seizures

• Simple partial seizures (consciousness not impaired)

• with motor symptoms

• with sensory symptoms

• with autonomic symptoms

• with psychic symptoms

• Complex partial seizures (with impaired consciousness)

• simple partial seizures followed by impairment of consciousness

• with impairment of consciousness at seizure onset

• Partial seizures evolving to secondary generalized seizures

• simple partial secondarily generalized

• complex partial secondarily generalized

• simple partial evolving to complex partial evolving to generalized


Generalized Seizures

• Absence seizures (formerly called petit mal)

• Myoclonic seizures

• Clonic seizures

• Tonic seizures

• Tonic clonic seizures (formerly called grand mal)

• Atonic seizures (drop attacks)

There are a few seizure types that are unique to pediatrics. These include benign Rolandic seizures, juvenile myoclonic epilepsy, and infantile spasms. These can often be diagnosed based on their unique presentations and may obviate the need for some diagnostic evaluations.

Infantile spasms (West syndrome) typically present between 4 and 18 months of age with males more commonly affected. The vast majority has mental retardation and the mortality rate is quite high. These seizures are characterized by clusters of sudden jerking contractions of the head, trunk, and extremities. The electroencephalogram (EEG) shows a characteristic hypsarrhythmia pattern. Optimal treatment is high-dose ACTH.3

Benign Rolandic epilepsy occurs in children aged 3 to 13 years and is most prevalent in 5- 10-year age range. It is inherited as an autosomal dominant trait. These patients have brief seizures as they fall asleep. Features of a typical attack involve twitching, numbness, or tingling of the child’s face, tongue, and shoulders which often interferes with speech and may cause drooling. These seizures last no more than 2 minutes and the child may remain fully conscious or sometimes the child also may have tonic–clonic seizures, usually during sleep. The seizures are usually infrequent, but they may occur in widely spaced clusters. Avoiding sleep deprivation may significantly reduce the frequency of these seizures. These seizures resolve at the time of puberty and unless they are frequent, treatment is not required. In a few patients, cognitive/academic dysfunction may occur and further care may be warranted.4 An EEG in concert with the history is generally diagnostic. Patients with typical clinical and EEG features do not need a CT or MRI.

Juvenile myoclonic epilepsy is an inherited autosomal dominant trait and presents in early adolescence, typically 12 to 18 years of age. Generally patients are reported as having jerking episodes on awakening. These can be generalized as well. Typically, these are provoked by lack of sleep, stress, hormonal changes, or other factors. EEG is helpful in the diagnosis and these cases almost always require treatment because of their recurrent nature. Valproate is the drug of choice with levetiracetam and zonisamide as alternates.5

image MANAGEMENT OF THE PATIENT WITH AN ACUTE SEIZURE

Most patients who present for evaluation of an acute seizure are no longer seizing on arrival in the ED. Initial evaluation consists of a brief and directed history and physical examination. Based on this, a determination as to whether the patient has had a seizure is made. If the seizure is ongoing, our prime objectives are supporting ABC’s and cessation of any seizure activity.

There are several paroxysmal events that may be challenging to differentiate from a true seizure. Seizure-like symptoms can be seen with breath-holding spells, pseudo-seizures, syncope, G-E reflux, tics, and sleep-related movements. Differentiating these is largely contingent on a thorough and detailed history. Blurred vision or seeing black spots, dizziness/light-headedness, and pallor usually precede syncopal episodes. Gastroesophageal reflux usually results in arched back positioning with crying, no loss of consciousness, and is temporally related to feeding. Cyanotic breath-holding spells usually occur after an intense crying episode, followed by holding one’s breath, and then loss of consciousness and the child becomes limp. The child often turns bluish and may sweat. With a pallid breath-holding spell, the infant often sustains minor head trauma, loses consciousness, stops breathing, and becomes pale and limp. They may develop a generalized increase in muscle tone with incontinence and have a postictal period. During a pseudo-seizure, the patient keeps their eyes tightly closed and resists eye opening, avoids painful stimuli, and lacks a postictal phase. Daydreamers can immediately be “brought back to earth” with verbal or physical stimuli. The absence of motor movements may also help to distinguish it from absence seizures.

image HISTOR

The history should include any previous history of neurologic abnormalities, developmental delays, mental illness, or seizures including any known triggers. The events (immediately) (temporally related) prior to the onset of seizures may also elicit clues. For example, the onset of a febrile illness, recent trauma, or the child was being baby-sat by grandma who is known to take a variety of prescription medications. Prodromal symptoms should be noted such as an aura or dizziness that may indicate migraines or a syncopal event. An accurate description of the seizure including motor activity (focality), level of consciousness, incontinence, length of seizure, and a postictal state are useful. In patients with a history of seizure, any variance from a “typical seizure” should be noted. It is important to point out that some patients will present simply with altered mental status and may be in “nonconvulsive status.” In addition, some motor movements may be very subtle, and in a moment of crisis, go unrecognized by caretakers. Practitioners on their examination often miss these subtleties as well.

image PHYSICAL EXAMINATIO

The brief directed initial examination should ensure that the ABC’s are addressed and a full set of vital signs obtained. Often, following an acute seizure, patients will have a period of respiratory depression that can be managed with supplemental oxygen. Occasionally, respirations may need to be supported with bag-valve-mask ventilation. The likelihood of this transient respiratory depression increases if family members or prehospital personnel administered an anticonvulsant medication. Securing the airway needs to be determined on a case-by-case basis. Subsequently, a neurologic survey is done where a determination of ongoing seizure activity versus postictal state should be made. The family, particularly with recurrent seizures, can be instrumental in helping the practitioner make this distinction. A more systematic head-to-toe examination should ensue looking for signs of trauma, toxidromes, CNS infection (meningismus), dysmorphic features, or a focal neurologic deficit. New focal deficits would be concerning for an acute intracranial process that should prompt emergent neuroimaging. Certain cutaneous manifestations may prompt one to consider neurofibromatosis, tuberous sclerosis, or other neurocutaneous disorder. If on presentation the patient has not returned to his/her baseline, it is imperative to ensure that serial reevaluations are performed. Patients who have not returned to their baseline during an observation period may benefit from further evaluation or inpatient observation. The caregiver’s input may reveal that “Johnny typically sleeps for 8 hours postseizure” and they manage this at home. In patients without previous seizures no such assumptions should be made and if a patient has not returned to his or her baseline within 1 hour, an extended evaluation and observation period/admission should ensue. If there is any question of persistent seizure activity or nonconvulsive status epilepticus (NCSE), a stat EEG should be obtained and further treatment pursued.

image LABORATORY EVALUATION

A bedside glucose evaluation is indicated for virtually all patients if not obtained in the prehospital arena. For patients who are taking antiseizure medication, obtaining a drug level, if available, is generally warranted. If a history of drug ingestion or substance abuse is suspected, a toxicology screen should be obtained. Patients with a first-time seizure who have returned to baseline and have no discernable risk factors generally do not require emergent laboratory studies.

Unlike children >6 months of age, where idiopathic and febrile seizures tend to dominate, younger children often have significant underlying pathology. A more liberal approach to laboratory evaluation is generally employed in children younger than 6 months of age as well as any child presenting in status epilepticus (SE) or with prolonged altered mental status.6 Generally, these labs include an electrolyte profile including calcium, magnesium, liver function tests, ammonia level, complete blood count, and possibly a venous or arterial blood gas sample. Additional tests that may be considered include organic and amino acids, lead levels, inborn errors of metabolism, etc. These additional tests do little to contribute to the care of the patient in the ED setting and may be best reserved for the neurologist. The laboratory yield for this cohort of patients is potentially useful, with abnormalities of sodium and calcium being the most common findings.7 In contrast, cerebrospinal fluid studies in well-appearing afebrile children even under 6 months of age appears to have little diagnostic value.8,9

For patients who present with a febrile seizure (see later section), the etiology of the fever should be sought. If this is not clear from the physical examination, further laboratory studies may be warranted. Any child who presents with meningeal signs or other evidence of a CNS infection should undergo lumbar puncture (LP). This should be done once it is determined that it is safe to do so. The recommendations for “routine” LP have recently been revised. In children presenting with a simple febrile seizure, aged 6 months to 1 year, the recommendation had been to strongly consider LP.10 The newer data and practice parameter now makes this an option in children who have not received their scheduled Hib or Pneumococcal vaccines.1012 In addition, there are data that suggest the yield from LP is low among children who present with their first complex febrile seizure and LP should be done judiciously.13

image IMAGING EVALUATION

Emergent neuroimaging studies for new-onset seizures are of little (limited) value in most cases in the ED.14 These tests should be reserved for patients with a history of trauma/concern of nonaccidental trauma, who have focal neurologic signs or had a focal seizure, persistent altered mental status, severe preceding headache, bleeding disorder, malignancy, hydrocephalus, or age <6 months.15,16 A subset of patients who are at risk for stroke (e.g., sickle cell disease) may also benefit. An exception to this is children <6 months of age where clinically relevant imaging findings are common.

Practitioners often feel compelled or pressured to provide an imaging study for patients with new-onset seizures. However, in a child with a normal examination and without other risk factors, the inherent value of this test is low. These patients are generally better served with an outpatient elective MRI17 at the discretion of a pediatric neurologist or their primary care physician. MRI is a much more sensitive test for elucidating anatomical abnormalities that may predispose to seizure activity. This also eliminates the additional risk that radiation poses from CT scanning.18 In addition, 9% of CT scans will uncover incidental congenital anomalies, such as arachnoid cysts, that further and unnecessarily increase the anxiety of families and require follow-up MRIs.19

image ELECTROENCEPHALOGRAM

An EEG is a valuable tool in evaluating patients who have had their first afebrile seizure, offering significant diagnostic value. An acute EEG should be employed emergently if there is a concern for possible ongoing seizure activity. A high level of suspicion should be maintained for nonconvulsive status in patients with persistent altered level of consciousness.20 If there is a question of malingering or pseudo-seizures, a stat EEG can be of value as well.

image TREATMENT

Patients with persistent acute seizure activity should be treated promptly. Attention to the patient’s ABC’s is an initial step with simultaneous plan for administering antiepileptic drugs (AEDs). Oxygen should be administered and the airway positioned. Securing the airway is decided on a case-by-case basis. Use of a nasal airway can help improve patency of the airway. Intravenous access should be obtained and if this proves difficult, placement of an intraosseous (IO) needle should be pursued. If the patient is hypoglycemic, IV glucose should be administered or if no access is available, IM glucagon. Naloxone, or other appropriate antidotes, should be administered if an overdose is suspected. Pyridoxine (vitamin B6) should be considered in neonates and infants with unremitting seizure activity.

It is quite common for patients to have received AED treatment in the prehospital setting. AEDs can be given via various routes: intravenous, intramuscular, intranasal, buccal, and per rectum.21,22

There are various AEDs available for long-term therapy. In a neurologically normal child without a history of mental illness it would be unusual to initiate treatment following a first unprovoked seizure. If the patient’s seizure is a recurrence or there are other factors that raise the concern that the patient is at increased risk for recurrence (e.g., juvenile myoclonic epilepsy), a consultation with a pediatric neurologist should ensue. There is currently no one optimal AED for initial monotherapy for new-onset seizures.23 A variety of medications are available, the choice of which may depend on the type of seizure, patient’s age, other medications, etc. Most of these medications will require ongoing laboratory evaluation for therapeutic range and for potential side effects.

image DISPOSITION

The majority of patients who present with their first unprovoked seizure are candidates for discharge. Most of them require minimal or no diagnostic evaluation and generally no antiepileptic treatment. Discussion with the family’s primary care physician or a pediatric neurologist should ensue prior to discharge to ensure follow-up. Consideration for admission should be given if there is a concern for appropriate outpatient care.

Parents may be skeptical and frightened to take their child home following a first-time unprovoked seizure. Although the risk of seizure recurrence within 12 months is about 24%, there is no evidence that failure to institute immediate treatment increases the risk of the child developing epilepsy. In fact, treating children following a first unprovoked seizure would result in overtreatment of over 50%. The medications used are also not without risk. Families can be reminded that it has been so many years before he/she had a seizure and there is no reason to believe that he/she would have another before a follow-up evaluation. If the seizure persisted for >5 minutes, a prescription for rectal diazepam (Diastat) should be considered. It is important to give the parents safety instructions for their children on discharge. This would include no bathing or swimming independently, no rock-climbing or similar activities, and if the patient drives they should not do so until instructed it is safe and legal to do so. In addition, in some states physicians are mandated reporters of seizures in adolescents of driving age.

A nice resource for families is epilepsy.com and the epilepsy foundation (epilepsyfoundation.org).

Factors that would lead one to consider admission of a child with an unprovoked first-time seizure include

Failure to return to baseline

New neurologic abnormalities

Severe parental/caretaker anxiety

Prolonged seizure

Worrisome social situation

Age <6 months

Delayed access to EMS services

Patients with seizures as a result of trauma, ingestion, or other abnormality uncovered during the ED evaluation are best managed as inpatients.

image FEBRILE SEIZURES

Fever-induced seizures are the most common seizure type in children. By definition, a febrile seizure is a seizure accompanied by a fever >38°C in the absence of CNS infection, in children aged 6 to 60 months. Approximately 2% to 5% of children will experience a febrile convulsion. The greatest risk for manifesting a febrile seizure occurs in the first 2 years of life, with fever >39°C and on the first day of a febrile illness.24 Febrile seizures are more likely if there is a family history of fever seizures. Some estimates place the risk as high as 80% if both parents have a history.25 The recurrence risk is also increased with a family history as well as initial febrile seizure in infancy. The overall recurrence risk is roughly 30%.26

Febrile seizures are further divided into simple and complex. A simple febrile seizure is defined as primary generalized seizure that lasts for less than 15 minutes without recurrence in a 24-hour time frame. Complex febrile seizures have one or more of the following characteristics: they are prolonged, focal, or recurrent.11 Other than this distinction, complex febrile seizures do not appear to be associated with significantly higher pathology with the exception of a higher recurrence risk.

Most cases of febrile seizures do not require a diagnostic evaluation aside from a bedside glucose. Unless there is a concern of a concurrent metabolic or traumatic cause, the evaluation should be focused on the cause of the fever. For the vast majority of children, the etiology appears to be viral or no identifiable cause. Reactions to immunizations are not uncommon with DPT vaccine–related seizures generally occurring within 24 hours and MMR reactions 7–10 days postimmunization. The indications for LP have been modified and should be done if a CNS infection is suspected and is an option in children 6 to 12 months of age who are deficient in their immunizations, or have been pretreated with antibiotics as this may mask signs and symptoms of meningitis.11 In contrast to afebrile seizures, an EEG is NOT recommended. Although focal seizures are indications for neuroimaging in an unprovoked seizure, complex febrile seizures with focality do not appear to have a significant risk of intracranial pathology.27,28Therefore, neuroimaging should not be obtained routinely for either simple or complex febrile seizures.19,27,28

The treatment of febrile seizures is generally supportive. If the patient’s seizure duration persists beyond 5 minutes, treatment with benzodiazepines should be initiated. (This is discussed in the Status Epilepticus section.) Otherwise, antipyretics and comfort measures should be administered if not already initiated. If a bacterial source is identified, appropriate antibiotic therapy should be initiated. Unfortunately, antipyretic agents do not appear to reliably prevent recurrences of febrile seizures.29,30 In patients with recurrent febrile seizures, both continuous and intermittent AEDs have been shown to reduce recurrence during a febrile illness. However, the risk of side effects does not warrant their routine use. Intermittent treatment during a febrile illness may be warranted for a selected few as determined by their primary care physician/neurologist.26,31

As with all seizures, a major challenge is often allaying the parents’ concerns. Parental reassurance and education regarding the benign nature of febrile seizures, the low risk of recurrence and morbidity should be emphasized. A focus on making their child comfortable with antipyretics and hydration should be stressed.

image NEONATAL SEIZURES

These are seizures that occur during the first 28 days of life, the majority of these occurring shortly after birth. Most of these occur in the NICU/hospital setting and are a result of perinatal asphyxia, neurologic insult (infection, trauma, infarction, congenital abnormalities), or metabolic abnormality (electrolyte imbalance, inborn errors of metabolism, hypoglycemia, pyridoxine deficiency, acidosis, etc.). Neonatal seizures differ from those of older children and adults. The most frequent neonatal seizures are described as subtle because the clinical manifestations are frequently overlooked.

Benign neonatal convulsions and familial neonatal convulsions may also present within the first 5 days of life. Although the outcome is favorable, up to 15% will develop epilepsy.

A history should include prenatal/pregnancy history (known problems, maternal substance use), delivery history (Apgar scores, sexually transmitted diseases, including herpes), and the postnatal period. A thorough evaluation is warranted in these children including laboratory and imaging studies. This should include glucose, electrolytes, magnesium, liver function tests, calcium, toxicology evaluation, complete blood count, urinalysis, TORCH titers, CSF studies, and pan-cultures of blood, urine, and CSF. Metabolic error studies include serum amino acids, ammonia, lactate, and pyruvate with urine for organic acids.

Management principles are consistent with other seizures. Evaluate and stabilize the ABC’s. Identify and treat reversible etiologies such as hypoglycemia. If infection is suspected, empiric antibiotics should be started with ampicillin and cefotaxime or ampicillin and gentamicin. Acyclovir should be considered especially if the history or CSF findings are suggestive of herpes infection. Initiate anticonvulsive therapy. The first-line treatment is phenobarbital (20 mg/kg) and the second choice is phenytoin (20 mg/kg). For refractory seizures, benzodiazepines and pyridoxine should be considered. Midazolam showed good efficacy in neonates who failed phenobarbital/phenytoin treatment.32 Midazolam was given as a bolus of 0.15 mg/kg followed by continuous infusion beginning at 1 μg/kg/min and increasing by 0.5 to 1 μg/kg/min every 2 minutes to electrographic seizure control or to a maximum of 18 μg/kg/min.

image STATUS EPILEPTICU

The traditional definition of SE has been an unremitting seizure or series of seizures without full return of consciousness lasting >30 minutes. This definition has been evolving to where some would now consider seizures persisting beyond 5 minutes as defining SE. This may also be called “impending status epilepticus,” but nonetheless is a threshold to implement aggressive antiepileptic treatment. (The term impending is intended to convey a sense of urgency and danger on the horizon.) The premise for this change is twofold: (1) the recognition that seizures persisting for 5 minutes are increasingly unlikely to cease spontaneously; and (2) the recognition that neuronal injury has likely started (ensued) by 15–30 minutes.31,33 So, the obvious conclusion from a treatment standpoint would be to initiate appropriate measures to abort the seizure before the damage is done.

Anticonvulsant strategies have been variable between institutions. The singular (principal) goal of treatment is to stop both clinical and electrographic seizure activity. While simultaneously assessing and managing the ABC’s, one should consider reversible causes for the seizure (hypoglycemia, administer antibiotics if CNS infection is suspected, etc.) and initiate prompt treatment. Anticonvulsant therapy should be initiated promptly with a clear plan and with attention to side effects such as hypoventilation or apnea.

The first-line treatment for SE is benzodiazepines. With initiation of care in the ED, consideration of any prehospital treatment should be taken into account. There is recent prehospital evidence to support the use of IM midazolam over IV lorazepam in terminating seizures more quickly. This is not a reflection of the medication itself but rather the delays often inherent with establishing IV access in the acutely seizing child.34 As a result, more seizure patients presenting may not have IV access. There is evidence that IV administered agents abort seizure activity more rapidly.28,34 Intraosseous access can be obtained quickly if IV access is difficult. Lorazepam is the first drug of choice29because of its long half-life and safety profile. A recent study suggests that an initial dose of 0.1 mg/kg with a 4 mg maximum is better than 0.05 mg/kg. If a second dose were required, then the 0.05 mg/kg dose would be appropriate to avoid excessive sedation.35 If no access is available, IM midazolam is the drug of choice dosed at 0.2 mg/kg with a 10 mg maximum. Rectal diazepam may be given if there is no IV access and IM midazolam is contraindicated or unavailable. Furthermore, after two appropriate doses of benzodiazepines it is unlikely to expect additional doses to terminate the seizures. This is likely a result of “receptor fatigue.”31,35 The risk of respiratory depression is also increased with more than two doses,27 so one should move on to other therapies at this time.29

If benzodiazepines have failed to terminate seizures, most sources advocate use of Fosphenytoin/phenytoin or Valproic acid as the next step.30 Fosphenytoin has some advantages with safety and speed of administration that would favor it over phenytoin. In addition, Fosphenytoin may be given IM. The dosing for Fosphenytoin is 20 mg phenytoin equivalents (PE) per kilogram IV/IO/IM and phenytoin is 20 mg/kg IV.

One can expect onset of action within 5 minutes. Valproic acid is dosed at 20–40 mg/kg IV. Onset of action is rapid with minimal respiratory depressant effects.

Phenobarbital is also commonly used at this stage of care and remains the drug of choice for neonatal seizures. The loading dose is 20 mg/kg with more substantial respiratory and cardio-depressant effects. These side effects are additive with benzodiazepines.

Refractory SE is when the patient has received two doses of benzodiazepines as well as an additional AED. Additional measures should be taken. There is little consensus on optimal pharmacologic treatment at this juncture. If the airway has not been secured, it should be done so as these medications have increased respiratory and cardiac effects such as hypoventilation and hypotension. Commonly employed options are pentobarbital with the possibility of inducing a “pentobarb coma.” Propofol, ketamine, levetiracetam, diazepam, and midazolam and others are also employed. Should these fail, general anesthetics are required. Pyridoxine should also be considered, especially in children less than 1 year of age, as a possible reversal agent for B6 deficiency.

It is imperative that institutions and practitioners have a clear understanding of what their protocol for termination of SE is. This is best done in partnership with a pediatric neurologist whether it is at your institution or potentially the final destination in case of transfer. This should include knowledge of the prehospital algorithm and potential plans for transfer to a higher level of care. Treatment should be initiated early, aggressively, and in a stepwise fashion with an end goal of cessation of both clinical and electrical seizure activity.

REFERENCES

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2. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51(4):676.

3. Arya R, Shinnar S, Glauser TA. Corticosteroids for the treatment of infantile spasms: a systematic review. J Child Neurol. 2012;27(10):1284.

4. Northcott E, Connolly AM, Berroya A, et al. The neuropsychological and language profile of children with benign Rolandic epilepsy. Epilepsia. 2005;46(6):924.

5. Noachtar S, Andermann E, Meyvisch P, et al. Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. Neurology. 2008;70(8):607.

6. Riviello JJ, Ashwal S, Hirtz D, et al. Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review). Neurology. 2006;67:1542.

7. Bui TT, Delgado CA, Simon HK. Infant seizures not so infantile: first-time seizures in children under six months of age presenting to the ED. Am J Emerg Med. 2002;20(6):518.

8. Lateef TM, Tsuchida TN, Chang T, et al. Diagnostic value of lumbar puncture in afebrile infants with suspected new-onset seizures. J Pediatr. 2008;153:140.

9. Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in children. Neurology. 2000;55:616.

10. American Academy of Pediatrics. Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. Pediatrics. 1996;97(5):769.

11. Duffner PK, Berman, PH, Baumann RJ, et al. Febrile seizures: guideline for the neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011;127:389.

12. Kimia AA, Capraro AJ, Hummel D, et al. Utility of lumbar puncture for first simple febrile seizure among children 6 to 18 months of age. Pediatrics. 2009;123(1):6.

13. Kimia A, Ben-Joseph EP, Rudloe T, et al. Yield of lumbar puncture among children who present with their first complex febrile seizure. Pediatrics. 2010;126:62.

14. Maytal J, Krauss JM, Novak G, et al. The role of brain computed tomography in evaluating children with new onset of seizures in the emergency department. Epilepsia. 2000;41(8):950.

15. Joffe A, McCormick M, DeAngelis C. Which children with febrile seizures need lumbar puncture? A decision analysis approach. Arch Pediatr Adolesc Med. 1983;137(12):1153.

16. Dayan PS, Lillis K, Bennett J, et al. Interobserver agreement in the assessment of clinical findings in children with first unprovoked seizures. Pediatrics. 2011;127(5):e1266.

17. Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in children. Neurology. 2000;55:616.

18. Brenner DJ, Hall EJ. Computed tomography – an increased source of radiation exposure. N Engl J Med. 2007;357:2277.

19. Sharma S, Riviello JJ, Harper MB, et al. The role of emergent neuroimaging in children with new-onset afebrile seizures. Pediatrics. 2003;111(1):1.

20. Saengpattrachai M, Sharma R, Hunjan A, et al. Nonconvulsive seizures in the pediatric intensive care unit: etiology, EEG, and brain imaging findings. Epilepsia. 2006;47(9):1510.

21. Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy & Behavior. 2004;5(2):253.

22. Mpimbaza A, Ndeezi G, Staedke S, et al. Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial. Pediatrics.2008;121:e58.

23. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia.2006;47(7):1094.

24. Waruiru C, Appleton R. Febrile seizures: an update. Arch Dis Child. 2004;89:751.

25. Kira R, Ishizaki Y, Torisu H, et al. Genetic susceptibility to febrile seizures: case-control association studies. Brain Dev. 2010;32(1):57–63.

26. Hodgson ES, Glade GB, Harbuagh N, et al. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121(6):1281.

27. Wilfong A. Management of status epilepticus in children. http://www.uptodate.com/contents/management-of-status-epilepticus-in-children?source=search_result&search=clinical+features+and+complications+of+status+epilepticus&selectedTitle=10%7E113. Accessed September, 2012.

28. Chin RFM, Neville BGR, Peckham C, et al. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol. 2008;7(8):696.

29. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3.

30. Agarwal P, Kumar N, Gupta G, et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16(6):527.

31. Chen JWY, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006;5:246.

32. Castro Conde JR, Hernandez Borges AA, Domenech Martinez E, et al. Midazolam in neonatal seizures with no response to phenobarbital. Neurology. 2005;64(5):876.

33. Wilfong A. Clinical features and complications of status epilecticus in children. http://www.uptodate.com/contents/clinical-features-and-complications-of-status-epilepticus-in-children?source≥search_result&search=clinical+features+and+complications+of+status+epilepticus&selectedTitle=1%7E113. Accessed September, 2012.

34. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591.

35. Chamberlain JM, Capparelli EV, Brown KM, et al. Pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus. J Pediatr. 2012;160(4):667.