HISTORICAL NOTE AND NOMENCLATURE

A disorder in which sleep induced an EEG pattern characterized by "subclinical" spikes and waves occurring almost continuously during slow sleep and appearing every night for a variable length of time in children was reported in 1971 by Patry and coworkers under the title of "subclinical electrical status epilepticus induced by sleep in children" (Patry et al 1971). The disorder was later termed "electrical status epilepticus during sleep" (Tassinari et al 1985).

The 1989 revised classification of epilepsies and epileptic syndromes of the International League Against Epilepsy refers to this syndrome as electrical status epilepticus during slow sleep and places the disorder under "epilepsies and syndromes undetermined as to whether they are focal or generalized"(Commission 1989).


CLINICAL MANIFESTATIONS

The clinical manifestations of this syndrome include:

• A heterogeneous epileptic disorder
• A deterioration of neuropsychological functions associated with or independent from the epileptic disorder
• A deterioration of motor functions

The typical EEG pattern of continuous spikes and waves during slow sleep is also an essential and absolute feature for the recognition of the syndrome.

The epilepsy. The age at which the first seizure occurs ranges between 2 months (Dalla Bernardina et al 1989) and 12 years (Bureau 1995), with a peak around 4 and 5 years (Tassinari et al 1985). This event can be preceded by either normal psychomotor development or abnormal signs indicating pre-existing encephalopathy, such as hemiparesis, hemiplegia, spastic quadriplegia, diffuse hypotonia, and ataxia.

The seizure types occurring in the disorder can be both partial and generalized. They include unilateral or bilateral clonic seizures, generalized tonic-clonic seizures, absences, partial motor seizures, complex partial seizures or epileptic falls. They may occur during wakefulness or sleep. Tonic seizures, however, never occur.

The first seizure is reported to be nocturnal and of unilateral type in almost one half of the cases reported. At onset, the frequency of seizure attacks is low. At the time of discovery of the typical nocturnal EEG pattern, however, the epileptic seizures frequently change in severity and frequency. Absences and epileptic falls herald the appearance of continuous spikes and waves during slow sleep and seizure frequency increases, both during wakefulness and sleep. About 60% of patients also exhibit several types of seizures (Tassinari et al 1985; 1992).

Neuropsychological deterioration. There is a constant and severe deterioration in neuropsychological functions associated with the disorder, and language capacity can be particularly affected. Patients also may show a profound decrease in intellectual level, poor memory, impaired temporospatial orientation, reduced attention span, hyperkinesis, aggressive behavior, and even psychosis (Jayakar and Seshia 1991; Tassinari et al 1992).

Motor impairment. Motor impairment, in the form of dyspraxia, dystonia, ataxia, or unilateral deficit, has been emphasized as one of the outstanding disturbances occurring in this syndrome (Dalla Bernardina et al 1989; Neville et al 1998).

The characteristic feature of this disorder is the appearance of continuous spike-wave discharges on the EEG during slow sleep.|{diagram:ecst1.bmp}{caption:Typical case of electrical status epilepticus during slow wave sleep}{label:Continuous and "generalized" spike waves during slow wave sleep in a 7-year-old child.}||{video:ecst2.avi}{Caption:Electrical status epilepticus during slow wave sleep; transition from wakefulness to sleep}{label:Left: The patient is in the dark of the recording room. Right: The EEG is normal during wakefulness but as soon as the patient falls asleep, continuous and generalized spike waves appear.}| Most researchers assert that more than 85% of NREM sleep is occupied by spike-wave discharges; however, quantitative studies of different sleep stages and of temporal evolution of this EEG disturbance have not been carried out (Jayakar and Seshia 1991). The typical EEG changes appear 1 year to 2 years after the first seizure and are associated with behavioral deterioration. Focal and generalized interictal spikes occur before this time and persist during wakefulness and REM sleep after the appearance of continuous spike waves during slow wave sleep.


ETIOLOGY

The cause of electrical status epilepticus during slow sleep is unknown. The affected children may have either normal psychomotor development (cryptogenic cases) or abnormal signs indicating pre-existing encephalopathy such as congenital hemiparesis, hemiplegia, spastic quadriplegia, diffuse hypotonia, and ataxia (symptomatic cases) before onset of the disorder. There is no increased incidence of seizure disorders in the relatives of affected children (Jayakar and Seshia 1991; Tassinari et al 1992).


BIOLOGICAL BASIS

The mechanism of neuropsychological impairment. Long-lasting persistence of continuous spike waves during sleep is postulated to be responsible for the neuropsychiatric abnormalities in electrical status epilepticus during slow sleep. Three main arguments are in favour of this hypothesis:

• There is a close temporal association between electrical status epilepticus during slow sleep and neurologic regression (the latter beginning at the time electrical status epilepticus during slow sleep is discovered and improving after electrical status epilepticus during slow sleep disappearance) (Tassinari et al 1985).

• The duration of electrical status epilepticus during slow sleep is correlated with the final neuropsychological outcome (Rousselle and Revol 1995).

• There is a strict association between the pattern of neuropsychological derangement and the location of the interictal focus (Rousselle and Revol 1995). A deterioration of language is observed in cases showing the predominance of paroxysmal abnormalities over one or both temporal regions (Billard et al 1982), whereas a mental deterioration and an autistic behaviour evoking a frontal lobe syndrome has been described in children exhibiting interictal frontal foci or clear cut anterior predominance of the discharges (Roulet Perez et al 1995). On the other hand, causative factors for motor impairment in the form of dyspraxia, dystonia, ataxia, or unilateral deficit observed in some children during the period of continuous spikes and waves during slow sleep would be a predominant involvement of motor areas by continuous spike-wave activity and the appearance of negative myoclonus during wakefulness (Dalla Bernardina et al 1989; Neville et al 1998).

The above observations suggest that electrical status epilepticus during slow sleep is a model for prolonged cognitive impairment induced by so called "interictal paroxysmal activity"(Tassinari 1995). "Interictal paroxysmal activity" may interfere with different cognitive processes, as demonstrated by neurophysiological, neuropsychological, and biochemical studies (Binnie 1993; Wasterlain et al 1993; Seri 1998). There is now increasing evidence that many autistic children with a history of language regression have epileptiform abnormalities, suggesting a role of subclinical epileptic discharges in relatively common developmental syndromes of infancy (Ballaban-Gil et al 1998; Goldberg et al 1998; Sotero De Menezes et al 1998).

The mechanism generating electrical status epilepticus during slow sleep. Secondary bilateral synchrony is the mechanism underlying continuous spikes and waves during slow sleep. In this respect the apparently generalized seizures (absences, tonic-clonic attacks) occurring in this condition have, in fact, a focal onset (Tassinari 1995), as demonstrated by interhemispheric peak latencies of their EEG correlates (Morikawa et al 1989; Morrell 1995), phase reversal of spikes on unilateral frontal regions (Morikawa et al 1985), and studies of coherence and phase analyses (Kobayashi et al 1990; 1994). A localized metabolic abnormality has been also revealed by means of PET studies (Maquet et al 1990). Therefore, although electrical status epilepticus during slow sleep is currently classified among the epilepsies undetermined whether focal or generalized, consistent data support the view that this syndrome is to be included in the domain of localization-related epilepsies, of cryptogenic or symptomatic nature.


EPIDEMIOLOGY

Electrical status epilepticus during slow sleep is a rare disorder. One study revealed an incidence of 0.5% among 12,854 children evaluated during a 10-year period (Morikawa et al 1989). There is no obvious gender preponderance (Tassinari et al 1985).


PREVENTION

No information is available.


DIFFERENTIAL DIAGNOSIS

Lennox Gastaut syndrome. In the presence of atypical absence seizures, deterioration of intellectual levels, and behavioral and language disturbances, electrical status epilepticus during slow sleep can be confused with the Lennox-Gastaut syndrome. The distinguishing features include the characteristic EEG pattern, as well as the following: (1) partial motor seizures often occur in electrical status epilepticus during slow sleep but are rare in Lennox-Gastaut syndrome; (2) tonic seizures occur commonly in Lennox-Gastaut syndrome but are essentially absent in electrical status epilepticus during slow sleep; and (3) in electrical status epilepticus during slow sleep, seizure frequency declines over the course of the illness, whereas seizures usually remain frequent throughout the evolution of the Lennox -Gastaut syndrome.

Acquired epileptic aphasia. The distinction between electrical status epilepticus during slow sleep and the Landau-Kleffner syndrome or acquired epileptic aphasia is disputed. All-night EEGs reveal that many children diagnosed with the Landau-Kleffner disorder actually have the electrical status epilepticus during slow sleep. In Landau-Kleffner syndrome, however, acquired aphasia is the most predominant neuropsychological symptom; bilateral temporal EEG spikes are present but epileptic seizures do not always occur. In our opinion, electrical status epilepticus during slow sleep and Landau Kleffner syndrome are two facets of a same entity, in which the type of neuropsychological dysfunction depends on the location (frontal in continuous spike and waves during slow wave sleep and temporal in Landau Kleffner syndrome) of interictal foci (Tassinari 1995; De Negri 1997).

Benign epilepsy with rolandic spikes. Both benign childhood epilepsy with centrotemporal spikes and epilepsy with continuous spikes and waves discharges during slow wave sleep commonly present with nocturnal seizures, interictal focal spikes on the EEG, and a marked activation of the discharges during sleep. The diagnosis of benign childhood epilepsy is usually made apparent by the characteristic interictal EEG spike morphology and the absence of severe behavioral deterioration. However, when neuropsychological impairment or motor impairment or both occurs in patients with a diagnosis of benign epilepsy with rolandic spikes, the electrical status epilepticus during slow sleep pattern should be looked for and is usually present (Dalla Bernardina et al 1989; Colamaria et al 1991).


DIAGNOSTIC WORKUP

After the seizures appear, but before the continuous spike waves during slow wave sleep develop, the EEG during wakefulness may show both diffuse spike waves, sometimes in bursts, and focal abnormalities such as spikes and slow spikes, with or without associated slow waves, which usually involve the frontotemporal or the centrotemporal region. Sleep EEG performed at an early stage shows an increase of the aforementioned abnormalities without the features of the continuous spike waves during slow wave sleep (Tassinari et al 1985).

After "electrical status" develops, the wakeful EEG patterns do not differ much from the previous ones, except that both the diffuse and focal abnormalities tend to increase in frequency. Tassinari and coworkers emphasized the occurrence of diffuse spike waves at 2- to 3-Hz, organized in bursts, with or without clinical manifestations (Tassinari et al 1985; 1992). When the affected child falls asleep, however, the characteristic continuous bilateral and diffuse slow spike waves (electrical status) appear abruptly, lasting throughout almost the entirety of slow wave sleep. The spike-wave index ranges from 85% to 100%. Cases with relatively focal albeit continuous discharges mainly involving the temporal or frontal regions or markedly asymmetrical spike-wave activity over the two hemispheres have been also described (Billard et al 1982; Morikawa et al 1985).

During REM sleep, electrical status disappears suddenly and paroxysms become either bursts of diffuse spike waves or focal, predominantly frontal, discharges. The cyclic organization of sleep, however, in which NREM sleep occupies 80% and REM 20% of the sleeping period, remains grossly unchanged.

Diagnosis of electrical status epilepticus during slow sleep can be suspected with brief sleep recordings but all-night sleep recordings are highly recommended. Computed tomography may be unremarkable or show unilateral or bilateral atrophic features (Morikawa et al 1985).


PROGNOSIS AND COMPLICATIONS

The seizures in electrical status epilepticus during slow sleep are self-limited and disappear in the mid-teens. The good seizure outcome is independent of the etiology and is observed also in cases with cortical malformations such as multilobar polymicrogyria (Guerrini et al 1998). The characteristic EEG patterns during slow wave sleep also disappear at approximately the same time, but focal interictal spikes may persist (Morikawa et al 1989; Bureau 1995). Improvement in language dysfunction, mental retardation, and psychiatric disturbances generally occurs but is variable and individualized. The majority of affected children never return to normal levels, particularly in the verbal area and attention (Roulet Perez et al 1993; Morikawa et al 1985).


MANAGEMENT

Epileptic seizures may or may not respond to a variety of drugs including benzodiazepines, valproate, ethosuximide, carbamazepine, and phenytoin. Despite the fact that the seizures may be refractory to therapy for months to years, the long-term prognosis of epilepsy is favorable with disappearance of seizures in all cases. Only benzodiazepines and adrenocorticotrophic hormone have been reported to suppress the electrical status and perhaps to improve language function. However, the positive effects are often transient (Tassinari et al 1985). In individual cases, chronic oral treatment with clobazam, lorazepam, and clonazepam, associated with other antiepileptic drugs, usually valproate, seemed to have a long-lasting effect (Yasuhara et al 1991). Short cycles (3 to 4 weeks) of relatively high daily doses of diazepam (0.5 mg/kg) following a rectal diazepam bolus of 1 mg/kg have also been reported to be effective (De Negri 1997).

At the present time, the combined use of benzodiazepines and valproate is considered the treatment of choice in this condition. On the other hand, polytherapy should be avoided. A detailed evaluation of antiepileptic regimens in 88 patients demonstrated that the reduction in polytherapy coincided with an improvement of the syndrome (Van Lierde 1995). It was also suggested that the drug overload and some medications (such as carbamazepine) could play a role in the maintenance of continuous spikes and waves during slow sleep (Van Lierde 1995).

In cases of electrical status epilepticus during sleep with severe language impairment, a progressive and long-lasting improvement of the language function has been obtained applying the surgical procedure of multiple subpial transections in the region of focal epileptic discharges (Morrell 1995).


PREGNANCY

No information is available.


ANESTHESIA

No information is available.


REFERENCES CITED

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