A Rational Approach to Pediatric Seizures
A Rational Approach to Pediatric Seizures
Authors: Claudia R. Gold, MD, FACEP, Chair, Department of Emergency Medicine, Children’s Hospital of Orange County, Orange, CA.; Jessica Pierog, EMT, St. Joseph Hospital, Orange, CA.
Peer Reviewer: Martha S. Wright, MD, Associate Professor of Pediatrics, Case Western Reserve University School of Medicine; Associate Director, Pediatric Emergency Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH.
Children with seizures, shaking spells, and other convulsive activity commonly are seen in the emergency department (ED). As many as 10% of all ambulance calls for children are for seizure activity, and approximately 1-2% of total ED visits by children are for seizure-related complaints.1,2
Children who experience seizures are a heterogeneous group with a wide range of associated problems. While many children with seizures are otherwise healthy, many also have significant primary and secondary diagnoses, and the initial seizure may be the presenting symptom of serious underlying disease.
Most children who arrive with a complaint of seizure activity can be grouped into one of five categories for emergency evaluation and management: 1) febrile seizure; 2) new onset nonfebrile seizure; 3) established seizure disorder with recurrence; 4) status epilepticus; or 5) neonatal seizure.
Of these, the management of children with new onset, nonfebrile seizures is the most challenging and controversial. However, the focus in the ED should be the same for patients in all categories: Stabilize the child, identify and manage any life-threatening condition, and arrange appropriate disposition and follow-up. This article will provide a rational approach to seizures.
— The Editor
Definitions and Classification
A seizure is defined as a paroxysmal electrical discharge of neurons in the brain resulting in alteration of function or behavior. Seizures may occur in both normal and abnormal brain tissue. The clinical manifestations of a seizure will vary with the number, location, and duration of the electrical discharges involved. Epilepsy is defined as two or more seizures not immediately provoked by a specific event such as fever, trauma, infection, or chemical changes. Neonatal seizures are those that occur during the first 28 days of life (most commonly in the first few days of life), but that do not indicate epilepsy.3 A febrile seizure is an event in infancy or childhood that usually occurs between 3 months and 5 years of age and is associated with fever but has no evidence of intracranial infection or a definable cause.4
Historically, the most widely used terms to describe seizures were grand mal, petit mal, and psychomotor. This language has since been replaced by a classification system introduced by the International League Against Epilepsy. This classification separates seizures into three major categories: partial, generalized, and unclassified.5 (See Table 1.)
|
Table 1. Seizure Classification |
| PARTIAL SEIZURES (FOCAL, LOCAL) |
| Simple Partial Seizures (consciousness not impaired) • With motor signs • With somatosensory or special sensory symptoms • With autonomic signs or symptoms • With psychic symptoms Complex Partial Seizures (consciousness impaired) • Simple partial onset followed by impaired consciousness (with or without automatisms) • Onset with impaired consciousness (with or without automatisms) Partial Seizures Evolving into Generalized Seizures • Simple partial evolving to generalized • Complex partial evolving to generalized • Simple partial evolving to complex partial evolving to generalized |
| GENERALIZED
SEIZURES (CONVULSIVE OR NONCONVULSIVE) |
|
Absence Seizures • Typical absence (brief stare, lapse in awareness, no movement) • Atypical absence (may have tonic, mild clonic, atonic, automatism, or autonomic features) • Myoclonic seizures (brief, repetitive, symmetrical contractions) Clonic Seizures (rhythmic jerking) Tonic Seizures (sustained muscle contraction) Tonic-Clonic Seizures (usually begins with tonic phase) Atonic Seizures (abrupt loss of muscle tone) |
| UNCLASSIFIED EPILEPTIC SEIZURES |
| Adapted from: Commission on Classifications and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22:489-501. |
While a definitive diagnosis of a particular seizure type is often deferred in the ED, it is important to be familiar with current terminology to accurately describe seizure activity and effectively communicate with consulting physicians.
A generalized seizure implies that the entire cerebral cortex demonstrates simultaneous, synchronous electrical discharges that result in one of several clinical manifestations: tonic, clonic, tonic-clonic, myoclonic, atonic, or absence seizures. Tonic activity is a continuous muscle contraction resulting in rigidity, whereas clonic seizures are manifested by rhythmic jerking of flexor muscles. Tonic-clonic seizures are a combination of both, usually beginning with the tonic phase. Myoclonic seizures manifest as brief jerks or contractions of a specific muscle or muscle group. Myoclonus is a component of several epilepsy syndromes, and commonly is symmetrical. Atonic seizures result in a sudden loss of postural muscle tone and may result in falling (drop attacks). Absence seizures are characterized by brief staring spells, or loss of awareness, typically lasting less than 10 seconds, and with no post-ictal effects. Patients also may have atypical absence events that differ from simple absence seizures in that the onset occurs at an earlier age, and the electroencephalogram (EEG) findings do not demonstrate the typical absence generalized spike and wave discharges at three per second.6
In contrast, partial seizures have a focal onset. A simple partial seizure causes no alteration in consciousness, whereas complex partial seizures are accompanied by a change in consciousness. A partial seizure, both simple and complex, also may secondarily generalize to tonic-clonic activity. It is important to distinguish partial from generalized seizures, as they may respond differently to anticonvulsant medications. In addition, partial seizures more often are associated with a focal area of intracranial pathology that might be amenable to surgical treatment.
Epidemiology
Epilepsy is a common medical condition affecting 0.5-1% of all children. Each year, approximately 150,000 children in the United States will have a newly occurring, single seizure, and one-fifth subsequently will be diagnosed with epilepsy.7 The incidence of seizures is highest in early childhood, and reaches 4.1 per 1000 in children younger than 11 years of age.2,8 Febrile seizures occur at least once in approximately 2-5% of children, and account for 30% of all childhood seizures.8 They are the most common type of seizures in children between 6 months and 5 years of age. In children ages 5-15 years, central nervous system (CNS) infections and head trauma are identified almost equally as the precipitating causes.9 In the early neonatal period, the most common seizure etiology is hypoxic-ischemic encephalopathy. Other causes include congenital CNS anomalies, pyridoxine deficiency, drug withdrawal, and electrolyte disturbances. In the later neonatal period (after 4 days of age), infections become the most common etiology.10 (See Table 2.)
|
Table 2. Etiology of Seizures in Childhood |
||
| INFECTIOUS | TOXIC | |
|
• Meningitis • Encephalitis • Cerebral abscess • Shigella • Roseola |
• Drug intoxication • Drug withdrawal |
|
| NEOPLASTIC | ||
|
• Primary CNS tumor • Metastatic lesions |
||
| METABOLIC | ||
|
• Hypoglycemia • Hyponatremia • Hypocalcemia • Hypomagnesemia • Hypernatremia • Pyridoxine deficiency • Hypoxia • Inborn error of metabolism |
EPILEPTIC | |
|
• Inadequacy of anticonvulsant • Noncompliance |
||
| MISCELLANEOUS | ||
|
• Idiopathic • Febrile seizures • Postimmunization • Ventriculoperitoneal shunt malfunction • Neurocutaneous syndromes • Familial • Cerebral degenerative disease • Pregnancy (eclampsia) |
||
| TRAUMATIC | ||
|
• Epidural or subdural hematoma • Subarachnoid hemorrhage • Cerebral contusion |
||
Clinical Approach to the Child with a Seizure
The emergency evaluation of seizures in children clearly depends on the circumstances of the presentation. During an active seizure, evaluation and treatment must occur simultaneously. In the majority of cases, however, the seizure will have stopped in the prehospital phase, and the evaluation is then guided by whether or not the child has returned to a normal baseline. Frequently, a child will be brought in by his or her parents after a significant amount of time has elapsed since the "event" occurred. The diagnosis then will have to be based primarily on the history, which often is unreliable.
History. It is imperative to determine if a seizure actually occurred. While parents, bystanders, and even medical personnel may report witnessing a seizure, it is important to remember that children manifest a large repertoire of conditions that may be misconstrued as seizure activity. An accurate history may be hampered by the emotional state of the witnesses, and is often subject to interpretation. Bystanders often embellish the motor activity or grossly overestimate the duration of the event. Older pediatric patients may be able to contribute to their own history, especially regarding the circumstances prior to the seizure. However, they frequently have little or no recall of their attacks.
When gathering the history, speak to all available witnesses and attempt to distinguish actual observations from opinions and interpretations of what happened. The patient’s personal physician, if available, should be contacted for pertinent medical information.
Important questions should include:
• What was the child doing when the attack occurred?
• Did anything seem to precipitate the attack?
• Was there an aura?
• How long did the event last?
• Was there a loss of or change in consciousness?
• What abnormal movements occurred?
• Were there abnormal eye movements or automatisms?
• Was there a change in breathing or color or frothing at the mouth?
• Was there urinary or fecal incontinence?
• Did any injury occur during the event?
• What was the postictal behavior?
• Are there any underlying medical conditions?
• Is there a history of recent fever, head injury, poisoning, or drug use? (See Table 3.)
• Is there a possibility of pregnancy?
• Is there a family history of seizures?
|
Table 3. Drug-Related Seizures |
• Amphetamines
• PCP
• Phenothiazines
• Tricyclic antidepressants
• Hypoglycemics
• Methylxanthines
• Salicylates
• Meperidine
• Propoxyphene
• Antihistamines
• Isoniazid
• Haloperidol
• Beta blockers
• Lead
• Carbon monoxide WITHDRAWAL
• Alcohol
• Narcotics
• Anticonvulsants
Fortunately, many features of true seizures help to distinguish them from other paroxysmal attacks. While some seizures are precipitated by auras or other nonspecific prodromal symptoms, the actual seizure activity begins abruptly. Any attack that develops gradually over many minutes should be considered suspect. The duration of most seizures is brief, usually lasting fewer than two minutes, although prolonged seizures may occur. With the exception of simple partial seizures, all seizures result in some impairment of consciousness. Accordingly, the patient usually has impaired memory of the event. Any attack in which there is significant alteration in consciousness, yet is recalled by the patient in significant detail, is unlikely to be a true seizure. Motor activity during a seizure is usually simple, synchronous, and purposeless (automatisms). Violent thrusting, or movements that change in response to the environment should be considered suspect. True seizures only rarely are provoked by specific stimuli such as sudden emotion or fright. Finally, most seizures, with the exception of simple absence or simple partial types, are followed by a postictal period of lethargy or confusion. Any dramatic convulsive activity followed by a rapid return to normal mental status should prompt a search for an alternative diagnosis.11
There are numerous isolated and recurrent events that may be mistaken for seizures. (See Table 4.)
|
Table 4. Conditions that Mimic Seizures |
|
| SYNCOPE • Vasovagal syncope • Orthostatic hypotension • Micturitional syncope • Cough syncope |
SLEEP DISORDERS • Nightmares • Night terrors • Sleepwalking • Somniloquy • Narcolepsy |
| BREATH-HOLDING SPELLS | |
| • Pallid spells • Cyanotic spells |
MIGRAINE HEADACHES • Classic migraine • Complicated (basilar) migraine |
| MOVEMENT DISORDERS • Tics • Tremors • Tourette’s syndrome • Shudder attacks • Spasmus mutans • Paroxysmal kinesigenic choreoathetosis • Sandifer’s syndrome |
PSYCHOLOGICAL • Pseudoseizures • Hyperventilation syndrome • Hysteria and rages • Panic attack • Attention deficit disorder |
Syncope. Syncope is one of the most common events mistaken for seizures. Syncope usually is accompanied by warning signs such as nausea, pallor, lightheadedness, and diaphoresis; however, true sensory auras do not occur. Some convulsive activity as well as incontinence may be seen, however, which adds to the confusion. Recovery is usually immediate with no distinct period of postictal confusion.
Breath-Holding Spells. Breath-holding is common in early childhood, occurring in approximately 5% of children younger than 2 years. These attacks follow a precipitating event such as fright, pain, or anger. The child will appear either pale or cyanotic, become limp, and then often stiffen in an apparent tonic seizure. There may be some clonic activity as well. Apnea and severe bradycardia may accompany the spell, though intervention is rarely necessary.12,13
Sleep Disorders. Sleep disorders (night terrors, nightmares, narcolepsy, nocturnal enuresis, sleepwalking, and sleeptalking) are common childhood conditions. Night terrors may result in a child suddenly sitting up panic stricken, screaming, sweating, and unresponsive to calming efforts. These episodes are usually followed by a return to sleep, with no memory of the event the next day. Sleep disorders can result in excessive daytime sleepiness due to nighttime disturbances. Narcoleptic behaviors may be misinterpreted as absence seizures. Sleepwalking and nocturnal enuresis are reported in up to 15% of children.13,14
Paroxysmal Movement Disorders. Tics and tremors are rapid, brief, and repetitive involuntary movements that occur intermittently, and often in response to stress. There is no change in consciousness with these motor activities. Shudder attacks consist of periods of shivering motion, also with no altered consciousness. Spasms mutans is a disorder seen in children between 4 and 12 months of age that causes head tilt, nodding, and asymmetric nystagmus. Paroxysmal kinesigenic choreoathetosis is a rare movement disorder precipitated by the onset of movement after a period of rest (such as getting out of a chair at the end of a class).12-14 Sandifers syndrome refers to the infantile tonic posturing, arching of the back, and torticollis, associated with gastroesophageal reflux.13
Migraines. Migraines are relatively common in children, and may be associated with only a mild headache. The symptoms may resemble the auras reported by patients with complex partial seizures. Complicated migraines may involve a loss of consciousness, although generally no motor activity occurs. A family history commonly is found.13
Psychogenic Seizures. Psychogenic seizures (pseudoseizures) are not rare in children, and may be difficult to distinguish from true seizures. Unfortunately, they often are seen in patients who also have epilepsy. Psychogenic seizures usually are precipitated by stress, and often are more violent in nature, though rarely lead to injury or incontinence, and do not occur during sleep. A test for elevated serum prolactin may be useful if performed within 30 minutes of the event. If positive, it suggests true seizure activity.11,13,15
Physical Examination
The physical examination should be directed toward determining any underlying cause of the seizure, as well as any injury resulting from the event. Particular attention should be paid to signs of underlying systemic disease, infection, toxic exposure, or any focal neurological finding. The level of consciousness is most important. Patients found to have impaired consciousness require frequent serial examinations to determine whether a cause other than a simple postictal state is responsible. Vital signs, including pulse oximetry, should be checked initially, and re-evaluated as indicated by clinical condition. The child must be undressed completely to evaluate any dysmorphic features or cutaneous stigmata of underlying systemic disease (café au lait spots, neurofibromas), or infection (rashes). A careful evaluation for trauma is required. Palpation of the head may reveal a skull fracture, hematoma, or bulging fontanelle. Examination of the musculoskeletal system may suggest fractures or dislocations. Oral mucosa lacerations are particularly common. The eye examination should include pupil size, symmetry, and reactivity, as well as assessment of conjugate or disconjugate gaze. A fundal assessment should search for papilledema and retinal hemorrhages. Any signs of meningeal irritation such as photophobia or neck stiffness should be noted. Cardiac assessment should note any significant ectopy or murmurs. Further neurological examination should search for any focal abnormalities and include assessment of motor strength, coordination, sensation, and reflexes. Hyperreflexia and bilateral Babinski signs may occur following a seizure, but should resolve in the postictal period.9,16 Transient focal findings lasting several hours or more (Todd’s paralysis) may be seen after an apparent generalized seizure and suggest a focal etiology.11 It is helpful to document the patient’s mental and physical capacities in descriptive operational terms, rather than vague words such as weak, lethargic, or confused.
Diagnostic Studies
Laboratory. Decisions regarding which laboratory tests to order in patients with seizures should be guided and individualized by the clinical scenario. Although there is little evidence of utility, it is unfortunately still common practice to order routine or baseline lab studies in patients who present with a first, or even a recurrent, seizure.
Known epilepsy patients who present with a typical seizure while on their medications but who have returned to normal, should only require a measurement of their anticonvulsant levels (if the test is available). This assumes, however, there is no comorbidity that would suggest a metabolic derangement.16-19
The management of patients presenting to the ED after a first seizure who are alert, oriented, and without clinical findings is controversial. Most authors agree with routinely obtaining a blood glucose, though as a general rule hypoglycemia that is significant enough to result in a seizure will not be associated with a normal clinical exam.17 The incidence of new onset seizures due to electrolyte abnormalities in neurologically normal patients is extremely low. Therefore, routine measurements should be reserved for those children with an abnormal mental status,with significant underlying medical conditions such as diabetes or renal disease, taking medications such as diuretics, and with significant signs of dehydration or malnourishment. An exception to these guidelines should be made in the case of neonatal seizures, where routine glucose, electrolytes, calcium, and magnesium levels result in a much higher yield.8
The complete blood count (CBC) in clinically well patients has shown to be minimally helpful, if at all. Although many studies have demonstrated an abnormal white blood cell (WBC) count in a significant percentage of new onset, as well as recurrent, seizure patients, the values did not affect their management.8,17
There are no prospective studies supporting the performance of a lumbar puncture in the diagnostic evaluation of children with a first-time seizure who are alert, oriented, asymptomatic, and immunocompetent. A lumbar puncture should be performed without delay if meningitis or a subarachnoid hemorrhage is suspected. It also should be considered strongly in children with an abnormally prolonged postictal state, fever, a positive HIV history, or those who are otherwise immunocompromised.16
In some cases, laboratory studies may be useful in determining if the patient actually had a seizure as opposed to another paroxysmal event. Creatine phosphokinase levels (CPK) may be elevated after a seizure, and metabolic acidemia may be present. Rhabdomyolysis may be detected if the urine tests positive for blood in the absence of red blood cells on microscopic examination. A more specific finding is an elevated blood prolactin level drawn within 30 minutes of the attack; however, a normal prolactin level cannot exclude a true seizure.11,16 The need for any general or specific toxicology studies should be determined by the history and examination findings.
Neuroimaging. Considerable disagreement exists about the need for neuroimaging in the evaluation of patients presenting with a first seizure. Similarly, controversy exists over the specific study to be done (computed tomography [CT] vs magnetic resonance imaging [MRI]), as well as the urgency with which it should be obtained.
Neuroimaging studies should be considered strongly in the ED in patients with a history of head trauma, persistent alteration in consciousness or other abnormal neurological findings, severe headache, malignancy, immunocompromise, anticoagulation, cerebrospinal fluid (CSF) shunt, or a geographic risk of cystercercosis.11,13,20 However, in patients who are neurologically normal on exam, the indications for neuroimaging are much less clear.
The most recent clinical policy from the American College of Emergency Physicians (that applies to patients age 6 and older) advises non-contrast CT scanning in the evaluation of all patients with first-time seizures without known cause. It also recommends non-contrast CT scanning as a rule in all previously diagnosed seizure patients with a change in seizure pattern without attributable cause.17 However, patients who have recovered completely from their seizures, with nonfocal examinations, and have no significant risk factors for intracranial abnormalities may have neuroimaging studies performed electively at a later time, assuming reliable follow-up is planned.17,20,21
MRI, though not as readily available, is superior to CT imaging when evaluating children for epileptic lesions. Small tumors in the temporal lobe or close to bony structures may be masked on CT scans.8,9 Follow-up MRI scans are used to exclude subtle lesions in patients with normal, emergency CT scans, as well as to better characterize lesions previously detected by a CT scan. An argument can be made, then, to defer neuroimaging in low-risk patients until a subsequent MRI can be arranged.11
Electroencephalography. An EEG is an extremely important diagnostic tool in the evaluation of seizure patients, though it is rarely available on an emergency basis. An emergent EEG is recommended, however, in patients with persistent altered mental status following the apparent termination of the seizure. This would allow the diagnosis of subtle convulsive, or nonconvulsive status epilepticus (SE). It also may be helpful in making the diagnosis of epilepsy in patients who present with new onset altered level of consciousness of uncertain cause. Another emergent indication for an EEG is monitoring the adequacy of treatment in patients with SE whose convulsions have been suppressed either by muscle paralysis to facilitate intubation, or by barbiturate coma.22
Treatment Decisions
The appropriate management of a patient with a first seizure involves controlling any ongoing seizure activity, treatment of any known precipitating cause, and the prevention of seizure recurrence.
A child who has not made a full recovery from the initial seizure, or who has recurrent seizures, requires admission for further observation, evaluation, and treatment. Any underlying disease that may have precipitated the attack must be identified, as it usually will pose a greater risk to the child than the seizure itself. Examples include CNS infections, drug intoxications, severe electrolyte derangements, and mass lesions. Treatment of the underlying disorder may obviate the need for anti-epileptic medication. Moreover, anticonvulsant therapy, if started, may not be effective unless the causative problem is corrected.
The more controversial issue involves the decision to begin anticonvulsant therapy in a child who has fully recovered from an initial seizure and does not require admission to the hospital. It is generally considered reasonable in these patients to allow discharge from the ED, with follow-up neuroimaging and EEG studies as an out-patient. Whether or not to begin antiepileptic medication should be decided by the predicted risk of recurrence. These statistics vary considerably, however, especially if the EEG and neuroimaging results are unknown at the time of discharge.
If the child had an idiopathic seizure, and the EEG is subsequently normal, the risk of recurrence is about 25%. However, if the EEG is abnormal, the risk of recurrence is almost 60%. The majority of seizure recurrences will happen within the first three months, and if there is a second seizure, the likelihood of further seizures rises to approximately 75%.13 In children, the sleep state of the first seizure is also predictive, with the risk of recurrence being twice as great if the initial seizure occurred while sleeping.14
Treatment decisions also must consider the risks and consequences of beginning antiepileptic medication. (See Table 5.) No anticonvulsant drug offers 100% protection against future seizures, and all medications have potential side effects ranging from minor problems (i.e., gastrointestinal upset and sedation) to severe complications (i.e., liver failure, aplastic anemia, agranulocytosis, Lupus-like disease, and Stevens-Johnson syndrome, among others).6 Additional treatment considerations must include compliance issues, the cost of the medication, and its monitoring requirements.
|
Table 5. Common Seizure Prophylactic Drugs |
||||
| DRUG | TRADE NAME | MAINTENANCE
DOSE (MG/KG/DAY) |
THERAPEUTIC LEVEL | SIDE EFFECTS |
| Phenytoin | Dilantin | 4-8 bid, tid, or qhs | 10 - 20 | Gingival hyperplasia, hirsutism, rashes, Stevens- Johnson syndrome, megaloblastic anemia, lymphoma |
| Phenobarbital | Luminol | 2-6 bid | 15-40 | Sedation, behavioral problems |
| Carbamazepine | Tegretol | 10-40 bid | 4-12 | Rashes, liver disease, leukopenia, dizziness, rare aplastic anemia |
| Valproate | Depakene | 10-60 tid or qid | 50-100 |
GI upset, weight gain, alopecia, tremor, hepatitis, pancreatitis |
| Ethosuximide | Zarontin | 20-40 bid or qd | 40 - 100 | GI upset, headaches, rashes, hiccups, blurred vision, lethargy, SLE |
| Primidone | Mysoline | 10-25 bid or tid | 5-12 | Behavioral problems, sedation, rashes, ataxia |
| Clonazepam | Klonopin | 0.05-0.2 bid | 0.02-0.08 | Fatigue, behavioral problems, increased salivation |
| Gabapentin | Neurontin | 20-70 tid | Unknown | Fatigue, dizziness, ataxia, diarrhea |
| Lamotrigine | Lamictal |
3-15, depending on concurrent drugs, qd x 14 d, then bid |
1-3 | Sedation, dizziness, headaches, nausea |
If medical treatment is initiated in the ED, it should be in consultation with the primary care physician or pediatric neurologist who will be following the child. The drug chosen should be the most appropriate for the seizure type, taking into account the above issues of side effects, cost, and compliance. (See Table 6.)
|
Table 6. Anticonvulsant Therapy
in Common |
||
| SEIZURE TYPE | PREFERRED DRUG | ALTERNATE(S) |
| Generalized tonic-clonic | Carbamazepine Phenytoin |
Valproate Phenobarbital |
| Absence | Ethosuximide | Valproate |
| Atypical Absence | Valproate | Lamotrigine |
| Myoclonic | Valproate | Clonazepam Lamotrigine |
| Atonic | Valproate Clonazepam |
Lamotrigine Ethosuximide |
| Partial, simple and complex |
Carbamazepine Phenytoin |
Valproate Phenobarbital Primidone Gabapentin Lamotrigine Tiagabine Topiramate |
| Lennox-Gastaut syndrome |
Adjunctive treatment with felbamate Lamotrigine |
|
| Infantile Spasms | ACTH (corticotropin) | Prednisone Vigabatrin |
Generalized tonic-clonic seizures may be controlled with phenytoin, phenobarbital, carbamazepine, valproic acid, and primidone. The drugs of choice for partial seizures are phenytoin and carbamazepine. Phenobarbital and primidone also are effective against partial seizures but have a much higher incidence of adverse effects. Absence seizures are typically treated with ethosuximide, but if absence seizures are associated with other seizure types as well, valproic acid is the better choice. Valproic acid also is used in the management of myoclonic and atonic seizure disorders. Clonazepam also has been used to manage myoclonic and atonic epilepsy; however, most patients develop tolerance to its antiepileptic effect.6
Over the past decade, several new antiepileptic drugs have been introduced. These include felbamate, gabapentin, lamotrigine, topiramate, tiagabine, and vigabatrine. These newer agents should not be considered as first-line therapy, and they should be used under the direction of a pediatric neurologist.23-25
Seizures Unique to Childhood
Febrile Seizures. As defined by the National Institutes of Health (NIH) Consensus Development Conference of Febrile Seizures in 1980, "A febrile seizure is an event in infancy or childhood, usually occurring between 3 months and 5 years of age, associated with fever but without evidence of intracranial infection or defined cause." Seizures associated with fever in children who have suffered a prior nonfebrile seizure are excluded.26,27 Approximately 2-5% of all children experience at least one febrile seizure before age 5. The peak incidence is from 9-20 months of age.26,28
A simple febrile seizure typically occurs early in the course of illness, is brief (fewer than 15 minutes), and does not have focal features. It does not occur more than once in a 24-hour period. Approximately 20% of first febrile seizures are classified as complex. These are defined as being longer than 15 minutes and focal in nature or occurring in a series during a 24-hour period. Febrile epilepticus is defined as any febrile seizure lasting more than 30 minutes, or recurrent seizures lasting a total of more than 30 minutes without regaining consciousness.26
Most febrile seizures are associated with viral illnesses such as upper respiratory infections or gastroenteritis, though they also may be associated with bacterial infections. Seizures in children with shigella gastroenteritis are not uncommon, and may occur before the diarrhea stage begins. Classic viral illnesses associated with rashes such as roseola may be the precipitating cause; however, the diagnosis may be missed, as the seizure usually occurs before the rash appears. The height of the fever and the intensity of the illness are thought to affect the seizure threshold, though a direct correlation is unknown. There is a higher risk of febrile seizures in children with a positive family history of this condition.12,26,29
As simple febrile seizures are typically very brief, the child usually will not be actively seizing on arrival to the ED, and may have recovered completely from the postictal period. Many parents will not realize their child had a fever until the temperature is taken either by paramedics or in the ED. The evaluation then should focus on finding the cause of the fever by a thorough history and physical examination. Immunization status must be ascertained, and any recent history of antibiotic use is particularly important, as it may lead to the consideration of partially treated meningitis.
There is general agreement that routine laboratory and radiographic studies are not indicated in uncomplicated first or repeat febrile seizures. Appropriate diagnostic studies should be based on the search for the fever source and will vary in individual patients. The greatest controversy arises over the necessity of performing a lumbar puncture. Many protocols advise an age cut-off between 12 and 18 months, based on the general experience that meningeal signs are difficult to appreciate in this age group. However, many also argue that the decision should be based on the clinical characteristics of each case, as well as physician experience and judgment.26,30,31 (See Critical Pathway in the full PDF of this issue.) Almost all children with meningitis or encephalitis will present with other signs and symptoms in addition to fever and seizures. In one widely cited study of 503 consecutive children with meningitis, none were found to have meningitis manifesting solely as a simple febrile seizure.30
Neuroimaging studies are not helpful in the evaluation of febrile seizures unless the history or physical exam suggests intracranial pathology. An EEG is not indicated as it does not reliably predict the risk of recurrence or the future development of epilepsy.26,27
The treatment of febrile seizures is based on the underlying cause of the fever, and also is directed toward control of the fever itself. The actual seizure activity rarely requires anticonvulsant medication.
The risk of recurrence is estimated at 25-50%. One-half of the children who have a second febrile seizure also will have a third. Most recurrences happen within 6-12 months of the initial episode, and in approximately 20% the recurrence is within the same febrile illness.26,29 Routine prophylaxis with antiepileptic medication is not indicated, although both phenobarbital and diazepam historically have been recommended for this purpose in cases of recurrent or complex febrile seizures.
Parents and other caregivers must be counseled regarding the possibility of seizure recurrence. A common fear is that the child has or will suffer brain damage as a result of the seizure. Reassurance should be given that there is no increased risk of neurological damage, learning disorders, or death as a result of a simple febrile seizure alone. Education in the management of an actively seizing child should be provided, as well as instruction on when to seek immediate medical attention.
Neonatal Seizures. Seizures occur more commonly during infancy than at any other time during childhood.33 Even though the threshold for seizures is high in the neonatal period, the overall incidence is 1 in 200 live births.10 Neonatal seizures tend to be brief and commonly are quite subtle. Clinical signs may vary from eye blinking and mouth and tongue movements to repetitive "bicycling" motion of the extremities. Autonomic changes in heart rate, blood pressure, and respirations may occur, including apnea, though apnea as a sole manifestation of a seizure is rare in the newborn.12 Unlike epilepsy in older children, many events thought to be seizure activity do not have concurrent electrical abnormality on the EEG. Likewise, many epileptic discharges in the newborn EEG are not associated with any clinical signs and are thus of questionable significance.12
The most common cause of neonatal seizures is hypoxic-ischemic encephalopathy, with an onset usually in the first day of life. Other conditions precipitating early seizures include congenital CNS anomalies, intracranial hemorrhage, electrolyte derangements, infections, drug withdrawal, and pyridoxine deficiency. Hypoglycemia and hypocalcemia commonly are seen in association with infants of diabetic mothers. Infections are the most common cause of neonatal seizures in the second week of life. Intracranial hemorrhage is observed more frequently in premature infants when seizure activity may be particularly difficult to recognize.10
Several features of neonatal seizures may help distinguish them from nonseizure events such as "jitters." Nonepileptic spells usually can be both provoked, and inhibited by sensory stimulation, whereas seizures occur independently of such stimuli. Nonepileptic events usually are not associated with the autonomic changes frequently seen in true seizures. Drug withdrawal seizures usually include general tremulousness, tachypnea, vomiting, diarrhea, and sometimes fever.
The management of neonatal seizures must initially focus on maintaining an adequate airway, ventilation, and cardiovascular support. In the presence of acceptable vital signs and oxygenation, aggressive intervention to terminate brief seizure activity is unwarranted as it is not associated with permanent deficits.10 Blood glucose should be checked immediately and hypoglycemia corrected if found. Other laboratory studies should include electrolytes, calcium, and magnesium. A CBC, blood and urine cultures, and a lumbar puncture for CSF evaluation also should be obtained. TORCH antibody titers will provide information regarding in utero infections with toxoplasmosis, rubella, cytomegalovirus, and herpes. Other appropriate studies will vary with individual cases and may include an arterial blood gas, ammonia level, blood and urine amino acids, liver enzymes, cranial ultrasound, and head CT.10
While most neonatal seizures do not require anticonvulsant medication, those that are prolonged or more compromising should be treated with phenobarbital (15 to 30 mg/kg loading dose). Peak concentration is reached within 90 minutes-6 hours. Pyridoxine deficiency should be considered in the case of intractable seizures, as they will not resolve until pyridoxine is replaced.12
Lennox-Gastaut Syndrome. This syndrome refers to a mixed seizure disorder, with the usual onset in children younger than 8 years, in which patients have frequent tonic, absence, myoclonic, and atonic seizures.12,13 These children often are seen in the ED for evaluation of injuries due to falls associated with their seizures. These children almost always are mentally retarded, although they may not be at the disease onset. They also may have severe behavioral disorders. SE occurs frequently in these children, and they also are prone to nonconvulsive status in which they appear to be in a continuous daze. This condition is characterized by its frequent lack of response to usual anti-epileptic medications. Newer drugs, such as felbamate and lamotrigine, have been used with some success. The ketogenic diet also may be used to manage these children, which is especially important to consider in the ED, because the use of glucose-containing solutions can break the induced ketosis state and, subsequently, increase seizure frequency.
Infantile Spasms (West’s Syndrome). This syndrome is characterized by the onset of spasms consisting of sudden single jerks of one or more muscle groups resulting in a sudden flexion or extension of the body. Although each spasm is very brief, they usually occur in clusters and may be associated with a short crying sound. They can be misinterpreted as colic.13 The typical age at onset is between 4 and 12 months. Therapy traditionally involves the use of adrenocorticotropic hormone (ACTH) or corticosteroids, which may help in the early phase, but the overall prognosis is poor. The vast majority of these children become severely disabled, and usually require institutional care.13
Benign Rolandic Epilepsy. This is one of the most common childhood epilepsy syndromes, manifesting as simple partial seizures affecting otherwise normal children between 3 and 13 years of age. These seizures almost always occur at night, waking the child, and may secondarily generalize. The child is unable to speak during the episode. This syndrome may be initially difficult to distinguish from other less benign causes of partial seizures, and the definitive diagnosis requires an EEG. The seizures are benign, resolve during the teenage years, and rarely require treatment. However if they are occurring so frequently as to interrupt sleep, they can be managed with carbamazepine.12,13
Juvenile Myoclonic Epilepsy. This syndrome generally occurs in normal patients with a peak onset in the early teenage years, and the etiology appears to be genetic. The hallmark of this disorder is myoclonic seizures, typically on awakening, although tonic, tonic-clonic, and absence seizures also may occur. Frequently, the myoclonic events are not recognized, and the syndrome is not discovered until the onset of a tonic-clonic seizure. Often, these seizures are precipitated by stress, lack of sleep, or excessive alcohol consumption. An EEG is required for definitive diagnosis. The treatment of choice is valproic acid, and usually is required indefinitely.
Status Epilepticus
SE is one of the most common life-threatening emergencies in childhood. It is defined as continuous seizure activity lasting more than 30 minutes, or the occurrence of two or more seizures without full recovery of consciousness in between.34 Of the approximately 150,000 cases of SE reported each year, the greatest proportion occurs in young children and those older than 60 years. As many as 70% of children younger than 1 year with epilepsy experience at least one episode of SE.35,36
Significant hemodynamic and metabolic abnormalities may occur with prolonged seizures and can lead to permanent neurological impairment or even death. The repetitive muscle contractions of SE place a great strain on the patient’s cardiovascular, respiratory, and renal systems. Tachycardia and other arrhythmias may occur. Acidosis and hyperkalemia develop from the accumulation of lactate, and the development of rhabdomyolysis. Respiratory acidosis and hypoxia also may be seen. Moreover, the medications used to control SE may contribute to these findings. Nevertheless, the mortality rate is determined primarily by the etiology and severity of the underlying disease.35,36 Although any type of seizure can progress to SE, generalized tonic-clonic seizures are the most common presentation and will be the focus of discussion.
Management of Status Epilepticus. Most seizures in children stop spontaneously in the prehospital phase, without any anticonvulsant medication. Therefore, it is safe to assume that if a child is actively seizing on arrival to the ED, the seizure will continue unless treated. It is important to ascertain if any anti-epileptic medication has been given prior to arrival. It has been shown that the prehospital administration of diazepam can shorten the duration of SE and reduce the risk of recurrence.37,38
In an actively seizing child, the initial supportive, therapeutic, and diagnostic measures must occur simultaneously. (See Table 7.) Cardiorespiratory support must take precedence over the ultimate goal of ending the convulsions. Several studies have determined that SE is much less dangerous when not associated with hypoxia.36 Vital signs, pulse oximetry, and cardiac rhythm must be closely monitored. A bedside blood glucose level should be immediately determined, and any hypoglycemia corrected. The initial stabilization phase, which should not delay the administration of anticonvulsants, should be accomplished within the first 10 minutes. This includes establishing either intravenous (IV) or intraosseous (IO) access, obtaining blood for laboratory studies, and a directed history and physical examination. Specific attention should be given to any history or signs of trauma, poisoning or substance abuse, pre-existing epilepsy, and focal neurological findings.
|
Table 7. Management of Convulsive |
| STABILIZATION |
|
• Protect the patient • Check airway, breathing, and circulation (ABCs) • Monitor vital signs with pulse oximetry • Intubate, if indicated, to secure the airway • Establish IV or IO access with normal saline • Draw blood for laboratory tests • Check for hypoglycemia |
| INITIAL INTERVENTION |
|
• Give glucose if hypoglycemic • Give antibiotics if meningitis is suspected • Cooling measures and antipyretics, if indicated • First-line IV anticonvulsant medication - Lorazepam, 0.1 mg/kg at 2,mg/min, or - Diazepam, 0.2 mg/kg at 5 mg/min, or - Midazolam, 0.2 mg/kg - Consider the use of rectal diazepam, or IM, IN, or buccal Midazolam if there is no IV access • Add long-acting IV anticonvulsant medication - Phenytoin, 20 mg/kg at 1 mg/kg/min, or - Fosphenytoin, 20 mg PE/kg at 3 mg/kg/min |
| IF SEIZURES PERSIST |
|
• IV load with second long-acting anticonvulsant - Phenobarbital, 20 mg/kg at 100 mg/min • If seizures continue, add Phenobarbital, 5-10 mg/kg until a maximum of 40 mg/kg or 1 gm |
| REFRACTORY STATUS EPILEPTICUS |
|
• If not given previously, IV bolus with midazolam 0.2 mg/kg, |
Laboratory tests should be guided by the available history, and may include CBC, chemistry studies, arterial blood gas, toxicology screens, and medication levels as indicated. A lumbar puncture should be performed when the seizures are controlled and the child is hemodynamically stable. However, if meningitis or encephalitis is suspected, antibiotic or antiviral therapy should not be delayed until the lumbar puncture is done. A head CT should be ordered prior to the lumbar puncture whenever intracranial hypertension, hydrocephalus, or a mass lesion is suspected. MRI may be more helpful in a known seizure patient who has had prior CT scans.34,51
SE in patients with a tricyclic antidepressant overdose poses a special challenge, as the treatment requires that bicarbonate be given to raise the arterial pH above 7.5.11 Otherwise, all patients with prolonged convulsions will show a metabolic acidosis, which should not be corrected with bicarbonate as it will resolve once seizure control is achieved.35 Particular attention also should be paid to preventing hyperthermia, which is another common complication and may contribute to future neurological impairment.35
Traditionally, IV benzodiazepines have been the first-line anticonvulsants of choice. Both diazepam (0.1-0.5 mg/kg) and lorazepam (0.05-0.2 mg/kg) administered either IV or IO have proven to be potent, rapidly acting, and effective in terminating seizure activity approximately 75% to 90% of the time.34,36,39 Lorazepam is currently preferred due to its longer duration of action and its slightly safer profile of adverse effects. Both lorazepam and diazepam have been used rectally with good results, however rectal diazepam has been studied more extensively.11,34,40 Lorazepam needs to be kept refrigerated, which limits its usefulness outside the hospital.36 A rectal gel has been formulated containing 5 mg/mL of diazepam packaged in pre-filled syringes.39 This has been particularly useful in the prehospital phase when no IV or IO access is available. It also has been well received and used extensively by families in many European countries and the United Kingdom. The recommended dosages for rectal diazepam are: ages 2-5 years, 0.5 mg/kg; ages 6-11 years, 0.3 mg/kg; and ages 12 and older, 0.02 mg/kg. Regardless of the method given, both lorazepam and diazepam share the potential for hypotension, respiratory depression, impairment of consciousness, and short-term duration of seizure control.34,35,39
Another benzodiazepine, midazolam, rapidly is emerging as an alternative treatment for SE, both as the initial anticonvulsant given and in cases refractory to more traditional therapy.35,39-46 The water solubility, rapid onset of action, and short elimination half life of midazolam offer clear advantages over other benzodiazepines. The short elimination half life and the relative inactivity of its metabolites allow for a better post seizure neurological evaluation.
Midazolam also offers significant advantages with its versatility of use, including IV, IM, rectal, intranasal, and buccal routes of administration. Recent reports of the successful use of intranasal and buccal midazolam in halting SE may lead to it becoming the treatment of choice, especially in the prehospital phase.42,43 Midazolam has also been shown to have a good safety profile with low rates of cardiovascular and respiratory depression.34,35,41
The majority of seizures will stop following adequate doses of benzodiazepines; however, a longer-acting agent also should be given to prevent recurrence. A second-line drug also will be required in those cases unresponsive to initial therapy. IV phenytoin generally is considered the drug of choice for this purpose. Phenytoin is very effective in both acute and chronic seizure management. When administered as an IV loading dose of 20 mg/kg, peak brain levels are reached in 10-30 minutes.39 Phenytoin has the advantages of a long duration of action, an easy transition to oral maintenance, and the lack of significant cardiac, respiratory, or CNS depression. The drawbacks of phenytoin use include the necessity of IV use, the association with cardiac arrhythmias requiring continuous cardiac monitoring, and administration at a rate no faster than 50 mg/min. In addition, IV phenytoin must be given in normal saline as any glucose containing IV fluid will cause precipitation. This may require that a second IV line be accessed. Moreover, severe tissue necrosis may result if there is any extravasation.
Fosphenytoin has been approved for use since 1996, and is gaining acceptance as a phenytoin substitute. Fosphenytoin offers significant administration and several safety advantages over phenytoin. It can be given much more quickly by the IV route, and is compatible with glucose-containing solutions. It is much less of a tissue irritant, and the availability of an IM form allows treatment when vascular access is difficult.39 Fosphenytoin has a peak serum level within 30 minutes after IM use, and at six minutes following IV loading. The dose of fosphenytoin is expressed as phenytoin equivalents (PE) and is 15-20 mgPE/kg. If given IV, the maximum infusion rate is 150 mg /min (3 mg/kg/min).35,39 The current roadblocks to widespread fosphenytoin acceptance seem mainly related to its high cost and the lack of significant experience in the pediatric population.
Phenobarbital is the next anticonvulsant treatment recommended for those patients who continue to seize even after first-and second- line therapy. The recommended IV dose is 20 mg/kg, given at an infusion rate of 100 mg/min.34,36 The infusion rate should be slowed if seizures abate prior to completing the dose. Although phenobarbital has a long history of successful use as an antiepileptic agent, it is generally considered second to phenytoin for long-term seizure control due to its marked sedative effects. It is however preferred over phenytoin for the management of SE in neonates.47 The average time from phenobarbital administration to control of SE is 15-30 minutes. However, due to its long elimination half-life (approximately 100 hours), its effective duration of action is about 48 hours.34,36 The patient’s respiratory status must be closely guarded with phenobarbital use, and intubation may be required. The risk of respiratory depression is significantly increased when phenobarbital is given to a patient who has already received a benzodiazepine. If SE continues after the initial phenobarbital loading, additional doses of 5-10 mg/kg may be given up to a total of 40 mg/kg, or a maximum dose of 1 gm.47
SE that persists even after the above treatment is considered refractory, and may require general anesthesia. As previously mentioned, however, recent studies with midazolam have shown promise in terminating SE and would be a good choice in refractory cases prior to consideration of the more traditional barbiturate coma. Several studies report success with midazolam when the prior use of diazepam, lorazepam, phenytoin, and phenobarbital have failed.41,48-50 The IV dose advised is a bolus of 0.2 mg/kg, followed by a continuous IV drip in a range of 1-10 mcg/kg/min.51
Pentobarbital remains the barbiturate of choice for the induction of coma. It penetrates the brain rapidly and is in turn more quickly eliminated than phenobarbital or thiopental. It has no active metabolites, and may also exert a protective effect in cerebral hypoxia, as well as lower intracranial pressure.34,44,51 Pentobarbital is administered as an IV loading dose of 5-15 mg/kg, followed by a maintenance infusion of 0.5-5.0 mg/kg/hr.51 All patients with a pentobarbital-induced coma require intubation and ventilatory support. A barbiturate coma suppresses all brainstem function, thus requiring extensive hemodynamic and EEG monitoring. Pentobarbital use is adjusted to produce a burst suppression on continuous EEG monitoring.
Other drugs that have been used in the management of refractory SE include IV lidocaine, IV propofol, IV and rectal valproic acid, rectal paraldehyde, rectal chloral hydrate, and inhalational anesthesia with halothane and isoflurane gases.36,39,51 However, with the better known pentobarbital coma, and the encouraging use of midazolam, these alternative agents should rarely be required.
Summary
Children with both new onset and established seizure disorders commonly seek care in the ED. The evaluation of each child will vary with the circumstances of presentation. The management of a child with an apparent first seizure is particularly challenging. A patient with active convulsions must be immediately stabilized. In an already stable patient, the approach begins with a careful assessment of the details of the event, with consideration given to various disorders that may mimic seizure activity. The history and physical and diagnostic tests are directed at determining the etiology of the seizure, and guide management. The necessity and appropriateness for both immediate and future anticonvulsant therapy must be determined, and should be coordinated with the child’s primary care physician or pediatric neurologist. Disposition must take the child’s social situation, compliance issues, and available resources into account. Family education regarding home management is essential, as well as the need for close follow-up.
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