Epilepsy with grand mal seizures on awaking

Epilepsy with grand mal seizures on awakening
by Peter Wolf
Date of submission: March 10, 1999
Medline SEARCH DATE: March 1993

HISTORICAL NOTE

Grand mal seizures (comprising, in present terminology, generalized tonic-clonic and some variants of generalized tonic and generalized clonic seizures) were among the first epileptic seizures clearly described. In 1881, Gowers first reported a group of patients in whom grand mal seizures occurred exclusively in the morning. For a historic review, please refer to Janz and Wolf's review (Janz and Wolf 1997). The revised classification of epilepsies and epileptic syndromes includes the syndrome under "generalized idiopathic epilepsies with age-related onset" (Commission 1989).

CLINICAL MANIFESTATIONS

The age of onset varies relatively widely for epilepsy with grand mal seizures on awaking. In the majority of patients, the first seizures begin in the second decade, around puberty (Commission 1989; Janz and Wolf 1997). There is a slight male preponderance (Janz and Wolf 1997). Generalized tonic-clonic seizures are the predominant seizure type in this syndrome. The seizures may be associated with absences or generalized myoclonic seizures. There is no focal onset. All three seizure types may occur in succession or as isolated events. It is not uncommon for myoclonic jerks or absences to occur immediately prior to a generalized tonic-clonic seizure. The occurrence of seizures is related not to the time of the day but to the sleep-wake interface (Janz 1962). The seizures typically occur shortly after awaking from night or nap sleep but may also occur in the evening period of relaxation or drowsiness. The seizures are characteristically precipitated by factors such as sleep deprivation and excessive alcohol ingestion. Although gross physical or neurologic abnormalities are absent in the affected cases, unstable, unreliable, and neglectful traits in personality have been reported (Janz and Wolf 1997).

ETIOLOGY

Epilepsy with grand mal seizures on awaking is an idiopathic disorder. Approximately 12.5% of cases have a family history of seizure disorder (Janz and Wolf 1997). The mode of inheritance is not known (Natale et al 1988). There is a genetic relationship between this disorder and other idiopathic generalized epilepsies such as juvenile myoclonic epilepsy or childhood or juvenile absence epilepsy, since more than one phenotype may occur in the same family (Delgado-Escueta et al 1990). In a study of 10 patients where the diagnosis of the affected relatives could be ascertained, the diagnosis was epilepsy with grand mal seizures on awaking in 1, and absence or juvenile myoclonic epilepsy in 4, whereas 4 had only isolated seizures (ie, a mild manifestation of risk, possibly idiopathic generalized). Only 1 diagnosis of neonatal seizures did not belong to the idiopathic generalized epilepsies (Janz and Wolf 1997).

BIOLOGICAL BASIS

In eight cases of epilepsy with grand mal seizures on awaking that came to autopsy, microdysgenesias such as increased nerve cell density in the stratum moleculare, indistinct boundary between lamina 2 and stratum moleculare, protrusion of nerve cells into the pia mater, increased number of nerve cells in white matter, disorganized columnar cortical neuronal architecture, and Purkinje cell dystopia were observed (Meencke and Janz 1984). Since migration of nerve cells and layer organization occur between the seventh embryonic month and the neonatal period, disturbance in that period may be implicated in the pathogenesis. Microdysgenesias of this type are also seen in other forms of epilepsy and may be a nonspecific marker for epileptogenic predisposition (Meencke and Veith 1992). Research into mechanisms of generalized epilepsies is receiving increasing attention from basic scientists (Avoli et al 1990).

EPIDEMIOLOGY

The incidence and the prevalence of epilepsy with grand mal seizures on awaking in the general population are unknown. In a large survey of 8570 patients of 14 epilepsy centers in Lombardy (Osservatore Regionale per l'Epilessia Lombard 1996), 1494 (17.4%) had an unequivocal diagnosis of idiopathic generalized epilepsy, and in 176 of these (11.8%, or 2.1% of all patients) the diagnosis was epilepsy with grand mal seizures on awaking.

PREVENTION

Epilepsy with grand mal seizures on awaking is a syndrome characterized by the most severe, potentially dangerous type of epileptic seizures, ie, generalized tonic-clonic seizures. These are accessible to secondary prevention both following an isolated seizure with typical precipitation, eg, by irregular sleep habits, excess alcohol intake, or intermittent lights if photosensitivity is present (Wolf 1997) or when the onset is with a minor seizure type such as absence or generalized myoclonic, and these are correctly diagnosed and treated before a first convulsive seizure.

DIFFERENTIAL DIAGNOSIS

Generalized tonic-clonic seizures are a common feature of many idiopathic and symptomatic, generalized and localization-related epilepsies. The concomitant nonconvulsive seizures may indicate the correct classification more clearly than the generalized tonic-clonic seizures. These, in epilepsy with grand mal seizures on awaking, are primarily generalized, ie, they have no aura or other focal onset. They may, however, develop out of a series of absences or myoclonic jerks that must not be mistaken as focal signs (Janz and Wolf 1997). The focal onset of secondarily generalized tonic-clonic seizures is not always easily recognized. If such seizures occur during sleep, or when they start in a so-called "silent area" of cortex, they can appear to be generalized from the start. The EEG is helpful when typical generalized spikes and waves are found; if it shows no epileptiform activity, a focal is more likely than a generalized epilepsy. There is overlap between epilepsy with grand mal seizures on awaking, childhood and juvenile absence epilepsy, and juvenile myoclonic epilepsy, and the assignation of a patient to one or the other of these diagnoses may be to some extent arbitrary. In epilepsy with grand mal on awaking the generalized convulsions are the presenting feature of the disorder, whereas in juvenile myoclonic epilepsy, the bilateral myoclonic seizures are the most prominent symptom. After the first few seizures, epilepsy with grand mal seizures on awaking may be difficult to diagnose because it takes some more seizures to ascertain the relation to the sleep-wake cycle. However, when the first seizure(s) occur(s) in typical situation of sleep withdrawal and shortly after waking up (at whatever time of day), and the EEG shows generalized spike wave activity, at least a tentative diagnosis of epilepsy with grand mal seizures on awaking can be made, whereas focal epileptiform discharges in the untreated patient almost exclude the diagnosis.

DIAGNOSTIC WORKUP

A detailed history is pivotal for the correct diagnosis. The relation of the seizures to the sleep-waking cycle is missed when patients are asked about the preferred "hour" of seizure occurrence because seizures on awaking may occur after an afternoon nap or at a nightly awaking, and they occur often when the patient has slept over time, and thus at a relatively late hour. There is also a possible second seizure peak in the evening leisure. The general physical and neurologic examinations and neuroimaging studies are normal. The EEG shows one of the typical patterns of idiopathic generalized epilepsies (Janz and Wolf 1997). Photosensitivity may be found in about 13 % of cases (Wolf and Goosses 1986).

PROGNOSIS

With correct treatment, the long-term prognosis is good. However, the risk of relapse after reduction or withdrawal of drugs is relatively high (about 83% if drugs are r educed or withdrawn after a minimum of 2 years without seizures) (Janz and Wolf 1997).

MANAGEMENT

Since disorganized sleep is one of the precipitating factors for epilepsy with grand mal seizures on awaking, the patients need to adopt a regular sleep-wake cycle, and avoidance of jobs that require night-shift work is advised. Avoidance of other precipitating factors, such as excessive alcohol intake, is also recommended. Valproate is the drug of first choice in this syndrome, with phenobarbital or primidone as a possible alternative (Bourgeois et al 1987; Wolf 1996). The general tonic-clonic seizures may respond to carbamazepine and phenytoin, but these drugs carry a risk to increase concomitant absences and myoclonic seizures. The possible role of the new antiepileptic drugs for this syndrome is not yet established.

PREGNANCY

Although no information is available that is specific to this syndrome and pregnancy, information is available on epilepsy and pregnancy in general.

ANESTHESIA

No specific information is available. The continuity of antiepileptic drug treatment must not be interrupted by anesthesia. Parenteral administration is possible with the drugs of first choice.

REFERENCES CITED

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Delgado-Escueta AV, Greenberg D, et al. Gene mapping in the idiopathic generalized epilepsies: juvenile myoclonic epilepsy, childhood absence epilepsy, epilepsy with grand mal seizures, and early childhood myoclonic epilepsy. Epilepsia 1990;31(Suppl 3):S19-29.

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