Generalized tonic–clonic seizures (GTCS) or “grand-mal seizures” are easily recognizable and their selective occurrence during early morning in some patients has been identified for many years (Gowers, 1885). Epilepsy with GTCS on awakening (EGTCSA) was identified early as part of idiopathic generalized epilepsy (Janz, 1953),¹ and abundant literature is available for review (Wolf, 2002). In contrast, little attention has been dedicated to the epilepsies with GTCS occurring during sleep or at random.

Clinical and electroencephalographic (EEG) characteristics of the EGTCSA were defined in the 1989 ILAE classification of seizures and epilepsy as a “Syndrome with onset mostly on the second decade of life. The generalized tonic–clonic seizures occur exclusively or predominantly (>90 per cent of the time) shortly after awakening or around a second peak in the evening period of relaxation. Absence or myoclonic seizures may occur. Seizures may be precipitated by sleep deprivation. The EEG shows one of the patterns of idiopathic generalized epilepsy. The patient may be photosensitive.”

EGTCSA is no longer an isolated syndrome in the new proposed diagnostic scheme from the ILAE² but is part of “Epilepsy With Generalized Tonic–Clonic Seizures Only.” It is unclear if the patients with associated absences and/or myoclonic seizures are included. “Epilepsy With Generalized Tonic–Clonic Seizures Only” implies inclusion of only those patients with GTC alone as recommended by some authors.³ Others consider the epilepsies with GTCS only as a broader category rather than a syndrome and include also patients with mild absences, myoclonic jerks, or both.⁴

EGTCSA is a diagnosis currently used by many groups that emphasize specific management issues including the importance of precipitating factors and the difficulties of pharmacological control in some cases.⁵ In most of the literature available for review, the presence or the absence of minor seizures is not established.

EGTCSA is part of the idiopathic generalized epilepsies (IGEs); well-defined partial epilepsies that closely mimic the EEG and clinical features of EGTCSA⁶ are excluded. EGTCSA is genetically determined.⁷ Between 3.3% and 26% of patients with EGTCSA have a positive family history^5,7 and good concordance is noted within the syndrome.⁵

EGTCSA has a complex mode of inheritance and, like other IGE syndromes, probably results from the interaction of multiple genes and environmental factors.^8,9

Multiple susceptibility factors for IGE have been identified. Interestingly, some are common to Juvenile myoclonic epilepsy (JME) and EGTCSA suggesting a closely shared genetic background. EJM1, for example, is a locus of susceptibility for JME on chromosome 6 that is also noted in patients with EGTCSA but not in patients with sporadic GTCS.⁸ Another group using genome-wide linkage scans has determined recently that susceptibility loci on 5q34, 6p12, and 19q13 confer susceptibility to both myoclonic and GTCSA as predominant seizure types.¹⁰ Rare channelopathies with Mendelian transmission have been identified in generalized epilepsies. Among them, mutations in voltage-gated channel CLCN2 are described in patients with idiopathic generalized epilepsy with and without GTCSA.¹¹

PREVALENCE

Janz reported EGTCSA in 10% of patients having GTCS without and 17% with additional minor seizures.¹² The percentage of epilepsy with pure GTCS is low if seizures are studied with prolonged video-EEG.¹³

All syndromes of IGE characterized by minor seizures starting during childhood and adolescence may be associated with GTCS usually of the awakening type.⁷ When GTCS occur, they are of the GTCSA type in 96% of cases of childhood absence epilepsy and 90% of cases in JME.⁷

SEX DISTRIBUTION

EGTCSA shows a male preponderance that is more pronounced in pure EGTCSA than in GTCA associated with minor seizures.⁷ Differences between sexes regarding alcohol exposure and sleep habits are proposed to explain these differences.⁴

AGE AT ONSET

Age at onset varies from 6 to 47 years with a peak in the second decade of life.⁷ More than two-third of the patients experience their first attack before the age of 19 years. The onset of seizures coincided with menarche in one-third of female patients.

SEIZURES

All patients have GTCS, which occur within 1–2 hours after awakening either from nocturnal or diurnal sleep. A second peak is noted during the period of rest in the evening. Minor seizures when present are also activated upon awakening and patients may report prolonged confusional episodes during this period.