Am Fam Physician. 2000;62(5):1109-1116
Uncomplicated seizures and epilepsy are common in infants and children. Family physicians should be aware of certain epilepsy syndromes that occur in children, such as febrile seizures, benign focal epilepsy of childhood, complex partial epilepsy, juvenile myoclonic epilepsy and video game–related epilepsy. Not all uncomplicated childhood seizures require neuroimaging or treatment. Febrile seizures, rolandic seizures and video game–related seizures are childhood epileptic syndromes that are typically not associated with brain structural lesions on computed tomography or magnetic resonance imaging, and are often not treated with anticonvulsant drugs. Juvenile myoclonic epilepsy does not require neuroimaging but does require treatment because of a high rate of recurrent seizures. Complex partial epilepsy often requires both neuroimaging and treatment. Although seizures are diagnosed primarily on clinical grounds, all children with a possible seizure (except febrile seizures) should have an electroencephalogram. Interictal EEGs may be normal. Computed tomography has demonstrated abnormalities in 7 to 19 percent of children with new-onset seizures. The yield of magnetic resonance imaging for specific childhood seizure types is not known, but it is the preferred modality of neuroimaging for many clinical presentations. Most children's seizures treated with anticonvulsants are controlled by the first drug selected. The value of “therapeutic” serum drug levels is questionable in the management of uncomplicated childhood seizures.
Seizures are a common childhood neurologic disorder. Approximately 4 to 10 percent of children have an unprovoked seizure without recurrence. Each year, about 150,000 children and adolescents have their first seizure and 30,000 of them are found to have epilepsy.1
Seizure Type vs. Epilepsy Syndrome
Determining the type of seizure, and whether it constitutes part of a specific epilepsy syndrome, is important for purposes of work-up, treatment and prognosis. The approach to a child with a new-onset seizure has two components. First, the physician should attempt to identify the specific type of seizure (i.e., tonicclonic or complex partial). Second, the physician should determine if the specific type of seizure is a component of an epilepsy syndrome.
An epilepsy syndrome, which is defined by seizure type(s), clinical findings and electroencephalographic (EEG) abnormalities, may require specific anticonvulsant drug treatment and is often associated with a predictable prognosis. This article discusses five epilepsy syndromes with which family physicians should be familiar (Table 1).
| Type | Age of onset | EEG findings | Treatment |
|---|---|---|---|
| Febrile seizure | 6 months to 6 years | Usually normal | Supportive measures Antipyretics |
| Benign focal (rolandic seizures) | 3 to 13 years | Abnormal | Carbamazepine (Tegretol), valproic acid (Depakene) |
| Complex partial | Any age | Abnormal | Various anticonvulsants |
| Juvenile myoclonic epilepsy | 12 to 18 years | Abnormal | Valproic acid |
| Video game–related epilepsy | Any age, although more typical in adolescents | About 50 percent abnormal | Abstinence from video games |
Specific Epilepsy Syndromes
FEBRILE SEIZURES
Febrile seizures are benign seizure episodes that occur in approximately 3 percent of children between the ages of six months and six years (peak age: 18 to 24 months). Most are “simple”—i.e., single, brief (less than 15 minutes in duration) and generalized. Approximately one third are “complex”—i.e., multiple occurences within 24 hours, prolonged or focal. Neuroimaging tests are invariably normal, and EEGs are usually not helpful in predicting the need for treatment or the risk of recurrent febrile seizures or future epilepsy.2 Lumbar puncture should be considered in children with onset of febrile seizures before 18 months, because clinical meningeal signs may be absent at this age.2
The recurrence rate of simple febrile seizures is 30 percent, with a higher rate (50 percent) in those whose first seizure occurs before 12 months of age. There is no consistent evidence that simple febrile seizures cause brain injury or cognitive deficits, but they may be associated with subsequent epilepsy. Risk of epilepsy is approximately 2 to 4 percent in children with simple febrile seizures. The highest risk exists in children with prior abnormal neurodevelopmental status, family history of afebrile seizures and a complex feature.3 A careful history is essential to determining a complex feature, which is present in approximately one third of initial and recurrent febrile seizures.4
Treatment may reduce recurrences, but no study has demonstrated that treatment prevents later development of epilepsy. Most children with febrile seizures do not require anticonvulsant drugs5; however, counseling is needed to reassure parents about the absence of associated mortality and the low morbidity (primarily later epilepsy), as well as to educate them about methods to reduce possible harm during a seizure.
Effective treatments for reducing recurrences include oral diazepam (Valium) at the time of fever, daily phenobarbital or valproic acid (Depakene).5 Rectal diazepam (Diastat) also plays an important role in treatment, especially in stopping acute, prolonged seizures.6 If an anticonvulsant drug is used (e.g., multiple recurrences), the typical duration of therapy is one year, which represents the period with the highest risk of recurrence. It is prudent to recommend the use of antipyretics at the time of fever, but parents should be aware that these agents may not prevent seizure recurrences.5
BENIGN FOCAL EPILEPSY
Benign focal epilepsy of childhood (rolandic, centrotemporal spikes, sylvian) has its onset between three and 13 years of age and is one of the most common focal epilepsies in childhood.7 It is genetically inherited as an autosomal dominant trait with an age-dependant penetrance. The typical “focal” seizure lasts seconds to minutes and involves the mouth in sensory symptoms or focal twitching. A sudden inability to speak and drooling may occur. Children must be queried about these focal episodes because they are not associated with loss or alteration of consciousness, have no postictal phase and may be remembered by a child who may not have complained to a parent about previous episodes. Often, these children present for medical attention because of the high association (50 percent) with generalized seizures, which tend to be nocturnal or early-morning episodes.
EEGs can be helpful in diagnosis by demonstrating a specific pattern of high-amplitude spikes and waves in one or both centrotemporal areas. This epileptic syndrome is important to identify because it is “age-dependent;” seizures stop recurring by 14 to 16 years of age.7 If anticonvulsant therapy is used, these seizures can be effectively treated with carbamazepine (Tegretol). One bedtime dose may be all that is needed to control recurrences.
COMPLEX PARTIAL EPILEPSY
Complex partial (temporal lobe, psychomotor) epilepsy is a common type that occurs at any age. The frequency of seizures is highly variable. Alteration of consciousness typically occurs. Symptoms are myriad but tend to localize around the eyes (glassy-eyed, “drugged”, dazed, far-away look), the mouth (lip-smacking, drooling, gurgling) and the abdomen (nausea, vomiting, epigastric sensation).8 Most seizures last for several minutes and are associated with a postictal phase of confusion, sleep or headache. Secondary generalization can occur in up to one third of children. Thus, a witness to a child's generalized tonicclonic seizure should be queried about initial symptoms that suggest that the seizure's onset was complex partial in nature.
EEGs should include a study performed during sleep to maximize abnormalities. Magnetic resonance imaging (MRI) should be strongly considered to detect temporal lobe abnormalities, such as mesial temporal sclerosis, which might predict that the epilepsy may become refractory to medication.8 Complex partial epilepsy usually requires anticonvulsant drug therapy.
JUVENILE MYOCLONIC EPILEPSY
Juvenile myocolonic epilepsy, with onset between 12 and 18 years, consists of a “seizure triad”: generalized, absence and myoclonic, the latter occurring primarily in the morning.9 This epilepsy syndrome is postulated to be genetically inherited as an autosomal dominant trait with incomplete penetrance. The symptom of early-morning myoclonus, unassociated with alteration of consciousness, is often not mentioned by patients unless they are specifically questioned about it. The myoclonus may cause objects to “fly out of their hands,” cause repetitive flexion of the neck and shoulders or result in a fall.
Absence episodes mimic “petit mal” seizures. Generalized seizures are common and often occur on awakening; usually, however, it is only after questioning patients about myoclonus or absence episodes that the diagnosis of juvenile myoclonic epilepsy is suspected. In some patients, only two of the three “seizure types” are present.
Sleep deprivation easily provokes the seizures. EEG is helpful in diagnosis, demonstrating a generalized spike-polyspike and wave pattern in many patients, and a photo-convulsive effect in one third. It is important to diagnose this epileptic syndrome because up to one half of the patients have lifelong seizures and require prolonged anticonvulsant therapy. The drug of choice is valproicacid or divalproex (Depakote), which can be effective in reducing all three phenomena of the seizure triad.
VIDEO GAME–RELATED EPILEPSY
The precipitation of seizures by the flicker frequency of video games, although uncommon, is a frequent concern of parents. These seizures can occur with both full-screen and hand-held monitors.10 The seizure types vary and include generalized, simple or complex partial, or absence. One half of the patients have abnormal EEGs, often with a photoconvulsive effect. The most effective treatment is to abstain from playing video games, but anticonvulsant medical therapy should be strongly considered in those who have had other unprovoked seizures. Factors that may contribute to these seizures include screen brightness, sleep deprivation, fatigue, fever and short distance from the screen. Video game playing does not precipitate seizures in most people with epilepsy even if a photoconvulsive effect is seen on EEG.10
Value of EEG
The diagnosis of a seizure is based on the clinical history and not necessarily on the EEG. This neurologic tenet is based on the fact that many children with seizures have normal interictal EEGs. In addition, the sensitivity of an interictal EEG for different seizure types is highly variable. Only epilepsy syndromes such as absence epilepsy and infantile spasms are invariably associated with an abnormal EEG. The abnormal EEG findings that are most likely to correlate with clinical seizures include spikes or sharp waves, with or without concomitant slow waves, that are generalized, multifocal or localized to the temporal and frontal regions. Spikes in the occipital or central regions may not necessarily relate to clinical seizures in children.11
Although interictal EEGs are often normal in many types of childhood seizures, any child suspected of having a seizure (except febrile seizures) should have an EEG. Early EEG testing (within 24 to 48 hours of a seizure) may demonstrate more abnormalities.12 Serial EEGs (especially if performed after sleep deprivation and including one obtained during sleep) will increase the yield of abnormalities when the diagnosis cannot be established on a clinical basis. The severity of the EEG abnormality does not necessarily correlate with the clinical severity of the seizures. Routine follow-up EEGs generally do not serve any useful purpose in management, unless discontinuing anticonvulsant therapy is being considered. A normal or mildly abnormal EEG may indicate a good chance of remaining seizure free after anticonvulsant therapy is withdrawn.13
Up to 3 percent of children who have never had a seizure demonstrate abnormalities on their EEG, especially if there is evidence of neurologic injuries on neuroimaging, abnormal neurologic examination or neurodevelopmental evaluation, or a genetic predisposition to epilepsy.14 Several neurologic conditions, such as autism, pervasive developmental disorder and fragile X syndrome, are associated with severe EEG abnormalities in the absence of clinical seizures. The EEG can be helpful in ascertaining specific epileptic syndromes (e.g., benign focal epilepsy of childhood and juvenile myoclonic epilepsy) when the presenting seizure is nonspecific, as in tonicclonic seizures.
Value of Neuroimaging
Studies of children with seizures have demonstrated varying rates of abnormality on computed tomography (CT), especially abnormalities of therapeutic importance that may require additional neuroimaging studies or surgical intervention (Table 2).15–19 Certain epileptic syndromes such as febrile seizures, absence epilepsy, benign focal epilepsy of childhood and juvenile myoclonic epilepsy are typically associated with normal results on neuroimaging.
| Study | Number of children | Seizure type | Abnormal findings (%) | Therapeutic significance (%) |
|---|---|---|---|---|
| Gilanz,15 1979 | 169 | Idiopathic epilepsy | 3.6 | 2.4 |
| McAbee,16 1989 | 101 | New-onset seizures/neurologically “normal” child | 7 | 4 |
| Warden,17 1997 | 203 | New onset and recurrent presenting for emergency care | 12 | NR |
| Garvey,18 1998 | 99 | New onset seizures/neurologically “normal” child presenting for emergency care | 19 | 7 |
| Stroink,19 1998 | 112 | New onset unprovoked seizures | 11 | NR |
The ability of MRI to support diagnosis of specific seizure types is not yet known. However, MRI is considered to be more sensitive than CT in children because of its ability to detect developmental abnormalities in the brain. Limitations of MRI include an inability to detect calcification, which is important when a diagnosis of congenital infection, certain neurocutaneous disorders or certain tumors is being considered. In one study of children with new-onset complex partial epilepsy, nearly 40 percent had abnormalities on MRI.8 The most common finding was mesial temporal sclerosis, which is typically not detected on CT. MRI should be considered in children with refractory seizures, in those with temporal lobe epilepsy (even if CT findings are normal), in infants and young children (to detect developmental abnormalities not evident on CT) and when equivocal lesions are present on CT.
Anticonvulsant Drugs
Most children's seizures will be controlled by the anticonvulsant drug that is initially selected. Side effects and compliance can be improved by starting the drug at a low dosage and increasing it slowly. If satisfactory control is not established within the first three to six months, another anticonvulsant drug should be added, with the eventual goal of eliminating the first agent and achieving monotherapy.20
Six new anticonvulsants have been introduced since 1993, some of which may become drugs of choice for some seizures in children21 (Table 3). Several are labeled by the U.S. Food and Drug Administration for the treatment of certain childhood seizures, although all are currently used in children.22 Other promising anticonvulsant drugs are expected to be released in the next several years.
| Drug, date FDA-labeled | FDA-labeled for children | Usual maintenance dosage | Advantages | Disadvantages | Possible clinical uses |
|---|---|---|---|---|---|
| Felbamate (Felbatol), 1993 | Lennox-Gastaut syndrome | 15 to 45 mg per kg per day | Good efficacy Nonsedating | Relatively frequent aplastic anemia and liver failure | Highly refractory seizures |
| Gabapentin (Neurontin), 1994 | Not labeled | 30 to 90 mg per kg per day | Virtually no drug interactions Serum monitoring not needed | Low efficacy | Benign partial seizures |
| Lamotrigine (Lamictal), 1996 | Lennox-Gastaut syndrome | 1 to 15 mg per kg per day | Good efficacy Low incidence of dose-related side effects | Frequent rash, sometimes serious, may be more frequent with concomitant valproic acid therapy | Intractable seizures or replacement for drug with unacceptable side effects |
| Topiramate (Topamax), 1997 | Partial seizures in children over 2 years of age | 3 to 9 mg per kg per day | Good efficacy Low incidence of dose-related side effects | Possible cognitive-behavior side effects, weight loss, renal calculi (rare) | Monotherapy or add to ACD for partial seizures |
| Tiagabine (Gabitril), 1997 | Not labeled | 16 to 32 mg per day | Novel GABA-related mode of action | Efficacy not fully established | Same as lamotrigine |
| Zonisamide (Zonegran), 2000 | Not labeled | 100 to 400 mg per day | Once or twice daily dosing | — | — |
A few of the older anticonvulsant agents are now available in newer preparations. Rectal diazepam (Diastat), a gel in a single-dose syringe, is FDA-labeled for reducing the number of seizures in patients whose seizures occur in clusters.6 Because of its extremely low rate of respiratory compromise, this agent holds promise for other uses in the acute treatment of seizures. Carbamazepine, a drug of choice for many seizure types in children, is now available in two sustained-release preparations that permit twice-daily dosing. Carbatrol capsules can be opened and mixed with food or liquid. Tegretol XR tablets must be swallowed whole, can be given twice daily and are available in dosages of 100, 200 and 400 mg. Trileptal has fewer side effects and does not require monitoring of hepatic or hematologic parameters. Serum carbamazepine levels should be obtained when switching a patient to a sustained-release form because identical doses do not always produce equivalent serum levels.
‘Therapeutic’ Drug Levels
Changing the dosage of an anticonvulsant drug solely on the basis of a serum drug level is “like driving a car looking at the speedometer and not out the window. Wrecks are going to be frequent and inevitable.”23
The concept of the “therapeutic” drug level is frequently misunderstood. These levels are established by animal and human studies, the latter involving patients with refractory seizures who are generally taking multiple anticonvulsants. Thus, the serum drug concentration that is effective in a typical child with infrequent seizures has not yet been established and may be lower than the usual reported therapeutic level. For example, patients taking phenytoin have had seizures controlled with levels ranging from 5 to 25 mg per dL; the usual “therapeutic” range is 10 to 20 mg per dL.23
In general, starting dosages of anticonvulsants should be based on weight, age and intake of other medication, and should be individualized for each patient. Routinely increasing a dosage to reach a “magic” level might not be necessary to prevent recurrent seizures and might result in increased side effects.23 It should also be remembered that toxicity can occur at therapeutic levels, especially when more than one drug is used. Serum drug levels are primarily helpful in determining compliance, documenting a level at which a therapeutic failure (i.e., seizure) has occurred, analyzing drug-drug interactions and assessing side effects. For most anticonvulsants, serum levels need not be obtained on a routine or arbitrary basis, particularly if a child is seizure free and without side effects.24
It is important to tell parents that anticonvulsant therapy lowers the risk of recurrences (in some patients, to zero) but does not guarantee that a child will not have a seizure while taking the anticonvulsant, even if the serum level is in the therapeutic range. In addition, parents should also be aware that these drugs may prevent recurrences but do not alter the long-term prognosis for attaining seizure remission.