Idiopathic Epilepsy Syndromes
by Michael Wong, MD, PhD
Dr. Wong is an Assistant Professor of Neurology at Washington University School of Medicine and an epileptologist in the Pediatric Epilepsy Center at St. Louis Children’s Hospital.
This article will discuss idiopathic epilepsy syndromes. Before proceeding, some basic definitions are warranted. A syndrome is a collection of abnormal signs and symptoms that commonly occur together. An epilepsy syndrome is a syndrome that has seizures as the central symptom but also includes other characteristic features, such as specific EEG findings and age dependence. Idiopathic is usually defined as “of unknown cause”. More precisely, an idiopathic disease is a “primary” or “intrinsic” disorder that cannot be attributed to any other underlying condition. For example, while other types of epilepsy may be caused by a brain tumor, stroke, or other neurological disorder, idiopathic epilepsy syndromes are primary brain disorders that have no other identifiable causes. In fact, most idiopathic epilepsy syndromes are presumed to be due to a genetic cause, but in most cases the specific genetic defect is not known and a family history of epilepsy may not be present.
There are a number of different types of idiopathic epilepsy syndromes. Each individual syndrome generally has its own characteristic seizure type(s), typical age of onset, and specific EEG patterns. Idiopathic epilepsy syndromes usually start in childhood, and compared to many other forms of epilepsy, often have a good prognosis. The seizures in idiopathic epilepsy syndromes usually, but not always, respond well to medication, and several of the idiopathic epilepsy syndromes typically remit spontaneously by teenage years. People with pure idiopathic epilepsy syndromes usually have normal or near-normal development and intelligence. Several of the more common idiopathic epilepsy syndromes are discussed below.
Childhood Absence Epilepsy
As the name suggests, childhood absence epilepsy (CAE) generally presents in early childhood, around age 4-8, and involves primarily absence seizures. Absence seizures are characterized by brief staring spells or lapses of consciousness, usually lasting only a few seconds each but often occurring dozens or even hundreds of times a day. There may be some subtle movements of the face or hands (automatisms), such as eyelid blinking, but overall the patient remains very still. The patient has no memory of the staring spell and after it is over, continues his prior activity as if nothing happened. Although absence seizures are usually not dangerous (unless they occur at an inopportune time, such as driving a car), the frequent lapses of consciousness may make it difficult for the child to focus on tasks, such as school work. Occasionally, patients with childhood absence epilepsy will also have other seizure types, most commonly generalized tonic-clonic seizures.
CAE is considered a type of generalized epilepsy, implying that the seizures appear to start simultaneously over the entire cortex, not from any one location. The classic EEG pattern is 3 Hertz generalized spike-and-wave, which is time-locked to the absence seizures, but may also occur in shorter bursts with no evident seizure. In rare families, a genetic defect involving GABAa receptors has been recently discovered. Treatment of absence epilepsy traditionally involves the medications valproate or ethosuximide, although ethosuximide is not effective against coexisting generalized tonic-clonic seizures. The prognosis of CAE is usually very good. Most patients become seizure-free on medication, “outgrow” their seizures by adolescence, and then can be taken off medication successfully. However, a significant minority of patients with CAE do not respond well to medication or may continue to have absence seizures or develop other seizure types that continue into adulthood (See Juvenile Myoclonic Epilepsy below). Similarly, while most patients with CAE have normal intellectual development, some patients experience significant learning disabilities.
Juvenile Myoclonic Epilepsy
Juvenile myoclonic epilepsy (JME) is related to childhood absence epilepsy in that it is also a generalized epilepsy and some patients with childhood absence epilepsy may subsequently evolve into JME. JME usually presents in adolescence and persists into adulthood. It is one of the only idiopathic epilepsy syndromes commonly seen in adults. Although generalized tonic-clonic seizures are usually what brings the patient to medical attention, the cardinal feature of JME are myoclonic seizures. Myoclonic seizures are very brief, uncontrollable, shock-like movements, typically involving the arms, legs or trunk. In JME, the myoclonic seizures tend to occur most frequently in the morning upon awakening. The classic history is of a person who keeps dropping, or more accurately throwing, his toothbrush in the morning. Most people understandably don’t recognize these movements as seizures and attribute them to clumsiness. It is only when the patient presents with generalized tonic-clonic seizures that an astute physician may elicit the history of early morning myoclonic seizures. In addition to myoclonic and generalized tonic-clonic seizures, patients with JME often have absence seizures.
The typical EEG findings of JME share some similarity to childhood absence epilepsy in having generalized spike-and-wave discharges, although in JME the spike discharges are usually at a higher frequency of 4-6 Hertz and may have a “polyspike” morphology. Although familial cases of JME are well-described, a precise genetic defect has not been identified. The drug of first choice is usually valproate, but lamotrigine, topirimate, and perhaps zonisamide are reasonable alternatives. Patients with JME, CAE, or other types of generalized epilepsy frequently do not respond to or actually worsen on drugs traditionally used to treat partial seizures (e.g. carbamazepine, phenytoin). Overall, the prognosis of JME is good in that the seizures in most patients are controlled on medication and intellectual outcome is usually normal. However, seizures almost always recur upon discontinuing medication and therefore JME generally represents a life-long condition requiring chronic treatment.
Benign Rolandic Epilepsy
Benign Rolandic Epilepsy (BRE) or benign childhood epilepsy with central-temporal spikes (BECTS) is one of the few recognized idiopathic epilepsy syndromes that consists of a partial epilepsy, in which partial seizures originate from a localized region of the brain. BRE usually presents in mid-childhood. The classic story involves the patient awakening shortly after going to sleep with a focal motor seizure that often just involves one side of the face and perhaps the arm or leg on the same side. Because of the facial movements, the patient may have difficulty speaking, but remains completely alert and aware during the focal seizure. Sometimes, the seizure may spread into a generalized tonic-clonic seizure or the patient will be noted to have a generalized-tonic clonic seizure during sleep. Although the seizures in BRE tend to occur out of sleep, less frequently they may also occur during waking hours.
The signature EEG findings of BRE are bilateral, independent central-temporal spikes, which are greatly activated during sleep. Although the specific genetic defect is unknown, familial cases are common and interestingly the EEG abnormalities may be inherited as a genetic trait, even in the absence of the seizures. Because many patients with BRE only have focal seizures at nighttime, which causes minimal functional or practical problems for the patients, BRE is often not treated with medication. For patients with generalized tonic-clonic seizures or any seizures in the daytime, carbamazepine and gabapentin represent good options. The majority of patients with BRE enter permanent remission in adolescence and do not need long-term treatment. However, some patients do not have a completely “benign” outcome, having severe seizures that do not respond well to medication and persist into adulthood.
Childhood epilepsy with occipital paroxysms
Previously felt to be rare, childhood epilepsy with occipital paroxysms (CEOP) or benign occipital epilepsy has recently received increasingly recognition and in fact probably represents more than one syndrome. Like BRE, CEOP is also a partial epilepsy that occurs primarily in childhood and adolescence. Classically, seizures start with visual symptoms ranging from flashing lights to well-formed hallucinations, which are a result of the region of the brain, the occipital lobe, where the seizures originate. The seizures then may spread to produce altered consciousness or motor manifestations, such as hemiclonic convulsions. In a more recently described form (Panayiotopoulos-type), ictal vomiting and deviation of the eyes are the primary manifestations, often followed by impairment of consciousness or progression to convulsions.
The EEG in CEOP shows characteristic, high amplitude repetitive spike discharges over the occipital regions. While it can also be a familial condition, some authorities postulate a close relationship of CEOP to migraine. Seizures are usually treated with medications targeted at partial seizures, such as carbamazepine. Patients with CEOP usually have a good outcome with respect to response to medication and chance of complete remission by adolescence, but some subtypes or variants of this syndrome may have intractable seizures.
A number of other less common or less distinctive idiopathic epilepsy syndromes have been described, mostly consisting of other generalized epilepsies. Basically all the idiopathic epilepsy syndromes typically share the common properties of a relatively good prognosis, normal or near-normal developmental outcome, and absence of another underlying neurological disorder. Future advances in the field of neurology, especially with regard to genetics, should continue to define the features of these various syndromes and help guide appropriate treatments.
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