HISTORICAL NOTE AND NOMENCLATURE

Severe myoclonic epilepsy in infancy was described by Dravet in 1978 (Dravet 1978). In 1992, Dravet and colleagues found at least 172 published cases. Since then there has been at least 118 new cases.

The 1989 revised classification of the International League Against Epilepsy places this syndrome under "epilepsies and syndromes undetermined as to whether they are focal or generalized," since the syndrome shows both generalized and localized seizure types and EEG paroxysms (Commission on Classification and Terminology of the International League Against Epilepsy 1989).

Many children have been reported to have symptoms similar to Dravet's syndrome only without myoclonias (Sugama et al 1987; Ogino et al 1989; Kanazawa 1992; Yakoub et al 1992). This has also been mentioned by Dravet (Dravet et al 1992). These patients may have different EEG features but they share the same course and outcome as the patients with myoclonias. Thus, they can be included in Dravet's syndrome. This seems to be supported by the genetic studies performed by Doose and colleagues (Doose et al 1998). Thus it has been proposed to change its name, first to "epilepsy with polymorphic seizures" and then to "Dravet's syndrome".


CLINICAL MANIFESTATIONS

Severe myoclonic epilepsy begins during the first year of life. Development is normal prior to the onset of seizures. Affected infants develop either generalized or unilateral clonic seizures without prodromal signs. Myoclonic jerks and partial seizures usually appear later. Psychomotor retardation and other neurologic deficits occur in affected children.

The first seizure type that appears is a clonic seizure, either generalized or unilateral. These seizures may be brief or long in duration. In many cases, the first seizure appears in association with fever. The febrile seizures in these cases often recur in 6 to 8 weeks and may be prolonged, leading to status epilepticus. Later in the course, the seizures may recur without rise of body temperature (Dravet et al 1992). The seizures, which have been carefully analyzed with video-EEG recordings, have peculiar clinical and EEG features that do not permit classification under generalized clonic or tonic-clonic seizures. They are characterized by clonic and/or tonic components, initially predominating in the head and the face, evolving to variable, bilateral localization, and loss of consciousness. When they are short in duration there are no autonomic symptoms.

The second seizure type is myoclonic seizures. They sometimes begin focally and are limited to one limb or the head prior to becoming generalized seizures (Dravet et al 1992). The myoclonic jerks are usually frequent, occurring several times a day. Some children become continuous status epilepticus though consciousness is usually preserved.

The third seizure type is absence seizures, which are atypical and of rather short duration, though status episodes of spike-and-wave EEG abnormality and clinical accompaniment with erratic small myoclonic jerks might persist for several hours.

The fourth seizure type is complex partial seizures with atonic or adversive and autonomic phenomena as well as automatisms. Occasionally they secondarily generalize.

The occurrence of status epilepticus is frequent, either convulsive (often febrile), or as obtundation status with myoclonias (Dravet et al 1992).

Psychomotor retardation is observed usually during the second year after the onset of seizures. Progressive neurologic deficits such as ataxia and corticospinal tract signs subsequently develop.


ETIOLOGY

No association between obstetric complications or perinatal abnormality and severe myoclonic epilepsy in infancy has been reported. Only three cases with neonatal anoxia were included in Dravet's first collection of 42 cases (Dravet et al 1992). Brain imaging studies have occasionally shown diffuse atrophy, but no specific abnormalities have emerged and the majority of patients have shown no abnormalities on CT or MR scanning. Moreover, while the first neuropathologic description of severe myoclonic epilepsy of infancy revealed microdysgenesis of cerebral cortex and cerebellum and malformation of the spinal cord (Renier and Renkawek 1990), no other such abnormalities have subsequently been reported. The most probable etiological background is of genetic nature.


BIOLOGICAL BASIS

In 15% to 25% of cases there is a family history of either epilepsy or febrile convulsions, suggesting a genetic basis for this disorder (Dravet et al 1992). A case report of monozygotic twins with severe myoclonic epilepsy in infancy demonstrated that the clinical picture, EEG, and prognosis were virtually identical in each (Fujiwara et al 1990). The genetic factor and mode of inheritance, however, are unknown. They are extensively discussed by Doose and colleagues (Doose et al 1998). When performed muscular and skin biopsies were negative (Guerrini and Dravet 1998).


EPIDEMIOLOGY

Severe myoclonic epilepsy in infancy is a rare disease, with an incidence probably less than 1 per 40,000 (Hurst 1990). Almost the same figure (1 per 20,000 or 30,000) was later reported (Yakoub et al 1992). Males are more often affected than females in the ratio of 2 to 1. A large percentage of cases have a family history for epilepsy or convulsions, and Fujiwara and associates reported monozygotic twins who had a family history of febrile convulsions (Fujiwara et al 1990).


PREVENTION

No information is available.


DIFFERENTIAL DIAGNOSIS

Since the first clonic seizures in severe myoclonic epilepsy are often associated with fever, distinction from febrile convulsions is important. In severe myoclonic epilepsy, (1) the onset is earlier (before 1 year of age) than in febrile convulsions, where the age of onset is between 18 and 22 months; (2) the seizure type is clonic and often unilateral instead of generalized tonic-clonic; and (3) the seizure episodes are more prolonged and frequent. The diagnosis can be established if other seizure types, particularly myoclonic jerks, and photically induced spike-waves are observed (Dravet et al 1992). When no myoclonias occur, the diagnosis is also that of severe myoclonic epilepsy but in its variant without myoclonias.

Lennox-Gastaut syndrome is virtually excluded by a history of seizures in the first year of life and is characterized by drop attacks, atypical absences, axial tonic seizures, and specific electroencephalographic abnormalities.

Difficulties may arise in differentiating severe myoclonic epilepsy from myoclonic-astatic epilepsy. In some cases of the latter, there is an early onset with febrile convulsive seizures but during the course of the epilepsy there are neither partial seizures nor focalization on the EEGs, and the main seizure type is myoclonic-astatic (Doose et al 1998).

The progressive myoclonic epilepsies due to storage could be evoked, but at this age run a different course and can be eliminated by biological and neurophysiological investigations and by fundus.


DIAGNOSTIC WORKUP

In the initial stage of severe myoclonic epilepsy, the EEG may not show any abnormal patterns. As the syndrome evolves, generalized spike-waves and polyspike-waves become apparent. The paroxysmal discharges may occur either in single episodes or in clusters, and there is usually a predominance on one side of the hemispheres. Intermittent photic stimulation and drowsiness may facilitate the appearance of EEG paroxysms. In addition to the generalized discharges, localized paroxysms of spikes and spike-waves are also common and mostly multifocal (Dravet et al 1992). The interictal background activity is normal at onset and has a tendency to deteriorate afterwards. Paroxysmal activities tend to disappear on awake EEGs and be prominent on sleep EEGs.

Laboratory tests are usually within normal limits. CT and MRI are usually normal except for a few cases with dilatation of the cisterna magna or slight diffuse atrophy (Dravet et al 1992).


PROGNOSIS

The outcome of severe myoclonic epilepsy in infancy is unfavorable. The affected children will persistently be affected with seizures. Partial seizures disappear and myoclonic jerks disappear or attenuate. Convulsive seizures are mainly localized at the end of the night. Fever remains a triggering factor and can still provoke epileptic status. Neurologic abnormalities remain stable. All patients are cognitively impaired (severely in 50%) but without deterioration after the age of 4 years (Guerrini and Dravet 1998). Many also have behavioral disorders, including psychosis. Approximately 14% of children die during a seizure, because of infection, or suddenly due to uncertain causes (Dravet et al 1992).


MANAGEMENT

Treatment is disappointing. Valproate and benzodiazepines (clonazepam, lorazepam) are the most useful drugs. Phenobarbital (convulsive seizures) and ethosuximide (myoclonic seizures and absences) can help some children. The effect of vigabatrin is variable. Carbamazepine and lamotrigine often have an aggravating effect (Guerrini et al 1998; Wallace 1998). The helpfulness of ketogenic diet needs to be proven (Caraballo et al 1998). The most important thing is to avoid the long, generalized, unilateral seizures by preventing infectious diseases and hyperthermia which are their triggering factors.


PREGNANCY

Not applicable.


ANESTHESIA

Not applicable.


REFERENCES

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