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Current thumbnail: Atypical absence (AA) is distinct from typical absence by the presence of modifications of tone – hypotonia more frequently than hypertonia – without precise beginning and end. The ictal EEG shows spike-waves that are slower than the typical absence, usually between 1.5 and 2.5 HZ. Eyelid clonia and automatisms may occur. Although AA is a hallmark of the Lennox-Gastaut syndrome, it may also occur in epileptic encephalopathy with continuous spike waves in slow sleep and in myoclonic-astatic epilepsy.

Historical note and nomenclature
The first description of absence seizure was probably given by Poupart in 1705; this was soon followed by Tissot who distinguished the “petits acces” from the “grands acces.” The features of good prognosis in children with absence seizures were recognized in 1921 (Adie 1924), before the EEG identified the generalized spike-wave pattern (Gibbs and Gibbs 1935). However, the distinction and clinical correlates of fast and slow spike waves was identified in 1950 (Lennox and Davis 1950). This gave the first description of atypical absences combined with slow spike waves. The clinical correlates of the major condition in which atypical absences are combined with slow spike waves were further determined by the Marseilles group (Gastaut et al 1966), thus delineating what is presently named the Lennox-Gastaut syndrome. Epileptic encephalopathy with continuous spike waves in slow sleep (Patry et al 1971) and myoclonic-astatic epilepsy (Doose et al 1970), 2 other conditions that produce atypical absences, were distinguished from Lennox-Gastaut syndrome soon thereafter. Therefore, the combination of slow spike-waves, atypical absences, and drop attacks is by no means specific of the Lennox-Gastaut syndrome, which has and impact on inclusion criteria for drug trials.

Clinical manifestations
Atypical absences are associated with a high incidence of changes in postural tone. The beginning and end are usually difficult to identify because they are more progressive and because this type of seizure affects children whose mental function is altered. It is, therefore, difficult to determine the duration that ranges from 5 seconds to 20 seconds. The axial tone is affected, and this may cause the patient to fall. Eyelid clonus, mild tonic or autonomic features, or automatisms may also be observed. There is, therefore, a whole spectrum of clinical manifestations, varying from typical absence to mild manifestations. Because the clinical features may be mild in an intellectually impaired child, it is often difficult to count such seizures, even with video EEG monitoring. Attention may decrease seizure frequency, whereas drowsiness may increase it. The frequency of atypical absences varies from a few a day to nearly continuous.

The frequency of generalized spike-and-waves discharge on EEG is less than 3Hz. Only an EEG can identify this type of seizure. Many patients have, in addition to clinical seizures, subclinical discharges. Counting the seizures is, therefore, an unresolved challenge since isolated clinical observation omits subclinical discharges that can affect cognition. Counting EEG discharges would ignore differences in the impact of clinical versus subclinical discharges, and video EEG is reliable only if permanent clinical observation is also used to determine whether the discharge is clinical or subclinical. Such observation would alter the frequency of seizures, though, since it would raise the vigilance of the child and, therefore, prevent the occurrence of absences and discharges. However, the practical implications of this difficulty are moderate because the aim of treatment, including those used in clinical trials, should be the disappearance of seizures and of spikes on EEG.

Atypical absences may be combined with tonic seizures and slow spike waves, and this combination defines the Lennox-Gastaut syndrome, which is usually symptomatic and may follow West syndrome in 40% of the cases. Atypical absences may be atonic or tonic. They may occur as the only type of seizure in a patient who exhibits continuous spike waves in slow sleep. In such patients, the absences are mainly atonic. Atypical absences may be combined with generalized tonic-clonic and myoclonic seizures in myoclonic-astatic epilepsy. In this condition, the absences are also mainly atonic.

A seven-year-old child without any history of brain damage but who had mild speech delay and hyperkinesia started having brief episodes of fixed gaze and falls. In sleep, the parents observed tonic fits. The awake EEG showed slow spike waves, and the sleep recording showed generalized bursts of polyspikes and tonic seizures. This is a frequent mode of onset of Lennox-Gastuat syndrome in patient without previous evidence of brain damage. The diagnosis may be more difficult at the beginning when there is no tonic seizure.

A three-year-old boy suffered a few nonfebrile generalized tonic-clonic seizures for 2 months, and he began to fall. In the morning, his parents noticed generalized jerks, and there were brief episodes of staring during which the child’s head suffered from mild atonia. An EEG showed irregular slow spike-and-waves, and the basic activity was slow with a high amplitude and brief bursts of polyspikes in sleep. The diagnosis of myclonic astatic epilepsy was likely. The presence of rare tonic seizures did not exclude the diagnosis or indicate poor prognosis (Kaminska et al 1999).
A five-year-old child suffered from major hyperkinesia and progressive deterioration of cognitive functions, mainly consisting of repetitive activity with loss of the ability to anticipate. Episodes of atonia with loss of contact were observed. An EEG showed generalized bursts of slow spike waves and a frontal spike wave focus when awake and continuous slow spike waves in sleep.

A four-year-old child with congenital hemiplegia suffered several focal motor seizures from the age of 3 years. EEG showed slow basic activity on the contralateral side with bursts of spike waves on the same area and diffusion to the contralateral side. The first automated external defibrillator failed to control the fits, and 2 months after switching to a second drug, the child started to fall; however, the first type of seizures had not recurred. The EEG showed a considerable increase of “interictal” spike wave activity that became nearly continuous in slow sleep. This is a typical case of symptomatic epilepsy switching to continuous slow spike waves in sleep, possibly with iatrogenic contribution due to an inappropriate choice of medication.

Localization
The understanding of the basic mechanism of atypical absences is much less advanced than that of typical absences. The respective contributions of the thalamus, cortex, and other structures is unknown. However, one remarkable feature is the lack of rhythmicity that is so characteristic of typical absences and seems to involve the reticular substance of the thalamus. Dipole studies suggest that, depending on the syndrome, 1 or both frontal lobes are involved via the corpus callosum and that the thalamic contribution is moderate or lacking (Blume 2001).

Pathophysiology
Pathophysiology remains mysterious. However, it is remarkable that the 3 major syndromes in which atypical absences occur all begin in school age. This is not explained by etiology, which is prenatal in most instances, whether genetic (in myoclonic-astatic epilepsy), due to brain lesions (in Lennox-Gastaut syndrome), or even both (cryptogenic and symptomatic cases of continuous spike waves in slow sleep). Therefore, a common etiologic factor is likely to contribute; this would be related to maturation. One possibility would be that maturation of the brain comprises excess of both excitability and inhibition, explaining the alternation of spikes and slow waves. This excess is well established in all studied species and could account for the excess of epilepsy in this age range. The brain would also exhibit an excess of inhibition as an attempt to compensate the effects of hyperexcitability. Brains in which this physiologic phenomenon would be more prominent than usual would be at risk of developing epileptogenic encephalopathies such as Lennox-Gastaut syndrome, myoclonic-astatic epilepsy, or continuous spike waves in slow sleep.

Differential diagnosis
There is no major differential diagnosis. The primary problem in diagnosis is the possibility of omitting atypical absence because the onset is so insidious. Often, atypical absences need to be recorded with video-EEG in order to identify them and to approach the diagnosis. When there is deterioration (for instance, in an inborn error of metabolism or in subacute encephalitis), the patient may have poor attention; this is suggestive of atypical absences.

Diagnostic workup
Apart from the cases with progressive metabolic or infectious diseases that require specific etiologic investigations, the diagnosis relies on clinical and EEG observations.

Syndromes and diseases in which the seizure type occurs
Atypical absences are observed in Lennox-Gastaut syndrome, continuous spike waves in slow sleep, and myoclonic-astatic epilepsy. The most difficult diagnostic issue concerns the patients for whom atypical absences appear as the main or only type of seizure. This has not been identified as a specific condition, however, and it could later turn to Lennox-Gastaut syndrome.

Prognosis and complications
The consequences of atypical absences are those of the underlying disorder. Thus, the seizures by themselves are not the cause of injury unless the patient experiences a fall without proper support.

Management
Proper management requires precise syndromic diagnosis. Indeed, Lennox-Gastaut syndrome, myoclonic-astatic epilepsy, and continuous spike waves in slow sleep do not require the same treatment. One major issue with new compounds is that this distinction is not made. Indeed, there are controlled trials for so-called Lennox-Gastaut syndrome, with inclusion criteria that do not make this distinction.

For Lennox-Gastaut syndrome, the combination of valproate with lamotrigine and phenytoin (Dulac and Kaminska 1997) and, more rarely, with felbamate (Siegel et al 1999) have greatly modified the outcome of cases that are not preceded by West syndrome. The latter are most resistant to drug treatment. Steroid treatment and ketogenic diet may be useful, provided they are administered early enough. Callosotomy has been performed with clinically relevant, but usually incomplete, success. In cases beginning after the age of 3, callosotomy is usually sufficient, but for cases following West syndrome, callosotomy must be complete in order to be effective. However, this requires that the operation be performed before the age of 10 years in order to avoid deterioration of speech (Pinard et al 1999). In any case, carbamazepine, vigabatrin, phenobarbital, and tiagabin may worsen the condition.

For myoclonic-astatic epilepsy, the combination of valproate with lamotrigine and either ethosuximide or a benzodiazepine has considerably modified the course of the disorder (Dulac and Kaminska 1997).

Levetriacetam may be effective. Carbamazepine, vigabatrin, tiagabin, oxcarbazepine, phenobarbital, and phenytoin may worsen the condition.
For continuous spike waves in slow sleep, benzodiazepine, ethosuximide, or sultiam rarely suffice, and combining them with steroids is most useful, provided that the steroids are given for more than 1 year in decreasing doses to prevent major side effects (Marescaux et al 1990).

Carbamazepine, phenobarbital, phenytoin, oxcarbazepine, lamotrigine, vigabatrin (Cerminara et al 2004), tiagabin may worsen the condition.

References cited

Adie WJ. Pyknolepsy: a form of epilepsy occurring in children with good prognosis. Brain 1924;47:96-102.

Blume WT. Pathogenesis of Lennox-Gastaut syndrome: considerations and hypotheses. Epileptic Disord. 2001;3:183-96.

Cerminara C, Montanaro ML, Curatolo P, Seri S. Lamotrigine-induced seizure aggravation and negative myoclonus in idiopathic rolandic epilepsy. Neurology 2004;64:373-5.

Doose H, Gerken H, Leonhardt R, Volzke E, Volz C. Centrencephalic myoclonic-astatic petit mal. Clinical and genetic investigation. Neuropadiatrie 1970;2:59-78.

Dulac O, Kaminska A. Use of lamotrigine in Lennox-Gastaut and related epilepsy syndromes. J Child Neurol 1997;12 Suppl 1:S23-8

Gastaut H, Roger J, Soulayrol R, Tassinari CA, Regis H, Dravet C. Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia 1966;7:139-79.

Gibbs FA, Gibbs EL. Atlas of electroencephalography, II. Cambridg, MA: Addison-Wesley, 1935:9-10.

Kaminska A, Ickowicz A, Plouin P, Bru MF, Dellatolas G, Dulac O. Delineation of cryptogenic Lennox-Gastaut syndrome and myoclonic astatic epilepsy using multiple correspondence analysis. Epilepsy Res 1999;36:15-29.

Lennox WG, Davis JP. Clinical correlates of the fast and slow spike wave elecctroencephalogram. Pediatrics 1950;5:626-44.

Marescaux C, Hirsch E, Finck S, et al. Landau-Kleffner syndrome: a pharmacologic study of five cases. Epilepsia 1990;31(6):768-77

Patry G, Lyagoubi S, Tassinari CA. Subclinical "electrical status epilepticus" induced by sleep in children. A clinical and electroencephalographic study of six cases. Arch Neurol 1971;24:242-52.

Pinard JM, Delalande O, Chiron C, et al. Callosotomy for epilepsy after West syndrome. Epilepsia 1999;40(12):1727-34.

Siegel H, Kelley K, Stertz B, et al. The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome. Epilepsy Res 1999;34(2-3):91-7

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Major keyword descriptors
absences
epilepsy
myoclonic-astatic epilepsy
spike-wave pattern
spike waves

Minor keyword descriptors
seizures

Age of presentation
01-23 months
02-05 years

Age of typical presentation
01-23 months
02-05 years

Permuted topics, synonyms, variants
Atypical absences

Related topics
Absence status epilepticus
Epilepsy
Lennox-Gastaut syndrome
Myoclonic-astatic epilepsy of childhood

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