Treatment of typical absence seizures and related epileptic syndromes

Typical absences are brief (seconds) generalised seizures of sudden onset and termination. They have 2 essential components: clinically, the impairment of consciousness (absence) and, generalised 3 to 4Hz spike/polyspike and slow wave discharges on electroencephalogram (EEG). They differ fundamentally from other seizures and are pharmacologically unique. Their clinical and EEG manifestations are syndrome-related. Impairment of consciousness may be severe, moderate, mild or inconspicuous. This is often associated with motor manifestations, automatisms and autonomic disturbances. Clonic, tonic and atonic components alone or in combination are motor symptoms; myoclonia, mainly of facial muscles, is the most common. The ictal EEG discharge may be consistently brief (2 to 5 seconds) or long (15 to 30 seconds), continuous or fragmented, with single or multiple spikes associated with the slow wave. The intradischarge frequency may be constant or may vary (2.5 to 5Hz). Typical absences are easily precipitated by hyperventilation in about 90% of untreated patients. They are usually spontaneous, but can be triggered by photic, pattern, video games stimuli, and mental or emotional factors. Typical absences usually start in childhood or adolescence. They occur in around 10 to 15% of adults with epilepsies, often combined with other generalised seizures. They may remit with age or be lifelong. Syndromic diagnosis is important for treatment strategies and prognosis. Absences may be severe and the only seizure type, as in childhood absence epilepsy. They may predominate in other syndromes or be mild and nonpredominant in syndromes such as juvenile myoclonic epilepsy where myoclonic jerks and generalised tonic clonic seizures are the main concern. Typical absence status epilepticus occurs in about 30% of patients and is more common in certain syndromes, e.g. idiopathic generalised epilepsy with perioral myoclonia or phantom absences. Typical absence seizures are often easy to diagnose and treat. Valproic acid, ethosuximide and lamotrigine, alone or in combination, are first-line therapy. Valproic acid controls absences in 75% of patients and also GTCS (70%) and myoclonic jerks (75%); however, it may be undesirable for some women. Similarly, lamotrigine may control absences and GTCS in possibly 50 to 60% of patients, but may worsen myoclonic jerks; skin rashes are common. Ethosuximide controls 70% of absences, but it is unsuitable as monotherapy if other generalised seizures coexist. A combination of any of these 3 drugs may be needed for resistant cases. Low dosages of lamotrigine added to valproic acid may have a dramatic beneficial effect. Clonazepam, particularly in absences with myoclonic components, and acetazolamide may be useful adjunctive drugs. Typical absences (previously known as petit mal) are brief (3 to 30 seconds) generalised epileptic seizures of abrupt onset and termination. The main clinical manisfestations are impairment of consciousness and an electroencephalogram (EEG) with generalised 3 to 4Hz spike and slow wave discharges (table I).[1-4] Typical absences are fundamentally different from any other type of seizures, and therefore unique in terms of pharmacological treatment.[5-8] Despite requiring different treatment strategies, typical absences and related epileptic syndromes are often erroneously grouped with focal and other epilepsies, under the broad term 'epilepsy'.[9-11] Furthermore, new antiepileptic drugs are mainly tested and licensed for partial epilepsies and there may be inappropriate generalisations for their use in 'epilepsy'.[9-11] Even major journals and official national formularies do not specify the different therapeutic requirements for absences compared with other types of seizure. The result is avoiable morbidity. [10-11] This is exemplified by vigabatrin and tiagabine which induce absences (proabsence drugs); they are contraindicated in idiopathic generalised epilepsy (IGE) which constitutes more than one-third of epilepsy.[9-11] Children are even more vulnerable. Controlled studies of new antiepileptic drugs in paediatric populations are significantly behind those for adults, consequently, such agents are initially licensed for adults only. Paediatricians have to learn by success or failure in daily practice.