Here you will find general information about Dravet's Syndrome (or: Severe Myoclonic Epilepsy in Infancy).
From: PubMed: HISTORICAL NOTE AND NOMENCLATURE
Unfortunately, there is not so much information available, but sometimes you can find some on the internet. It is listed below in random order.
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Where does the name "Dravet's Syndrome" come from?
From the person who "discovered" this unique form of epilepsy: Charlotte Dravet, French psychiatrist and epileptologist, born July 14, 1936. From 1965 to 2000 Charlotte Dravet worked in the Centre St. Paul at the University of Marseille, where Henri Jean Pascal Gastaut (1915-1995) and J. Roger were her ‘masters’.
Charlotte graduated from Marseilles University as a psychiatrist specialising in infantile neuropsychiatry. In her medical doctoral thesis, under Henri Gastaut’s direction, in 1965, she studied the epilepsy which would be later named the Lennox-Gastaut syndrome. Charlotte has always worked in the Centre Saint-Paul, in Marseilles, with Joseph Roger, Michelle Bureau and Pierre Genton.
Her interests were focused towards the delineation of epileptic syndromes in childhood epilepsy, the psychological consequences of epilepsy, the progressive myoclonus epilepsies and their genetics, the congenital malformations of the offspring of epileptic women and related studies. Her main contribution was in myoclonia epilepsy with emphasis on benign and severe myoclonic epilepsies in infancy. The later, Dravet syndrome, is now recognised as one of the most malignant syndromes at this age and is widely studied by other authors and clinicians as well as geneticists.
Charlotte Dravet has been President of the French League Against Epilepsy and a member of the Commission on Classification of Epilepsies of the ILAE. She is also an Ambassador for epilepsy. She has participated in numerous congresses, lectures and is the author of a number of published works. Now retired, she continues to work in France and Italy to improve the care of people with epilepsy.
Epilepsy with polymorphic seizures, polymorphic epilepsy of early infancy, severe myoclonic epilepsy of/in infancy.
Associated persons: Charlotte Dravet
Severe myoclonic epilepsy of infancy. This very rare syndrome is delimitated from benign myoclonic epilepsy by its severity and must be differentiated from the Lennox-Gastaut syndrome and Doose’s myoclonic-astatic epilepsy. Onset in first year of life. Symptoms peak at about 5 months of age with febrile hemiclonic or generalized status epilepticus. Boys twice as often affected as girls. Prognosis is poor. In 2005, there were at least around 450 cases reported in the worldwide literature but, now, it is impossible to count the known cases because many probably have been published twice because of the genetic reserach. Most cases are sporadic. Family history of epilepsy and febrile convulsions is present in around 25 percent of the cases, but familial cases are exceptionnal.
C. Dravet: Les epilepsies graves de l’enfant. Vie Médicale 1978, 8: 543–548.
Severe myoclonic epilepsy in infancy (Dravet's syndrome). Its nosological characteristics and therapeutic aspects
By Nieto Barrera M, Candau Fernandez Mensaque R, Nieto Jimenez M. Unidad de Neurologia Pediatrica, Hospital Universitario Virgen del Rocio, Sevilla, Espana. July 2003
AIMS: Severe myoclonic epilepsy in infancy (SMEI) is an epileptic syndrome recognised by the ICE of 1985 and 1989 and in the proposal put forward by the ILAE Task Force on Classification and Terminology in 2001. In this paper, its historical development, nosological characteristics and treatment are described.
DEVELOPMENT: Although identified by Dravet in 1978, it has been called severe myoclonic epilepsy in infancy since 1981. As an alternative the name polymorphic epilepsy has also been put forward and in 2001 the ILAE recognised the eponym Dravet's syndrome. We describe how it may be mistaken for febrile convulsions in the early stages and later for Lennox Gastaut syndrome, Doose's myoclonic astatic epilepsy and certain progressive myoclonic epilepsies. We outline the risk factors, recognised in 1992, that facilitate an early diagnosis and the defining clinical criteria established in 1984. We point out the existence of atypical forms due to the absence of some of the defining criteria, which will never be above one, to formulate a diagnosis of SMEI. The frequency with which a family background of febrile convulsions and epilepsy appears seems to point to a genetic origin. Recently, de novo mutations have been found in the alpha subunit of the voltage dependent sodium channel as well as mutations in the gamma subunit of the GABAA receptor. Nosologically, it is located in group 3 of the 1989 ICE, which corresponds to epileptic syndromes without a focal determination, or which are generalised, and on the list of epilepsy/syndromes that was presented in 2001. SMEI is an epilepsy syndrome which is, in most cases, resistant to classical and new AED, and other more unusual treatment. The drugs that have proved to be more effective, although only relatively so, are topiramate, valproate and the benzodiazepines. At present another alternative that has appeared is stiripentol. Intravenous use of immunoglobulins can be useful.
CONCLUSIONS: Dravet's syndrome, admitted as such by the ILAE in 2001 and probably caused by de novo mutations in the sodium channels or in the GABAA receptors, is one of the severest forms of epilepsy in infancy with very little or no response to current antiepileptic drugs. Those that have been seen to be most effective are topiramate, the benzodiazepines, valproate and, more recently, stiripentol.
(severe myoclonic epilepsy in infancy)
By Charlotte Dravet
Date of submission: August 16, 1993
Date of update: August, 1999
Medline SEARCH DATE: August, 1999
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".
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.
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.
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).
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).
No information is available.
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.
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).
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).
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.
Caraballo R, Tripoli J, Escobal L, Cersosimo R, et al. Ketogenic diet: efficacy and tolerability in childhood intractable epilepsy. Rev Neurol 1998;26:61-4.
Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:289-99.
Doose H, Lunau H, Castiglione E, Waltz S. Severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 1998;2:229-38.**
Dravet C. Les epilepsies graves de l'enfant. Vie Med 1978;8:543-8.
Dravet C, Bureau M, Guerrini R, Giraud N, Roger J. Severe myoclonic epilepsy in infants. In: Roger J, Dravet C, Bureau M, Dreifuss FE, Perret A, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. London: John Libbey, 1992:75-88.**
Fujiwara T, Nakamura H, Watanabe M, Yagi K, Seino M, Nakamura H. Clinicoelectrographic concordance between monozygotic twins with severe myoclonic epilepsy in infancy. Epilepsia 1990;31:281-6.
Guerrini R, Dravet C. Severe epileptic encephalopathies of infancy, other than West syndrome. In: Engel J and Pedley TA, editors. Epilepsy. A comprehensive textbook. Vol. 3, Philadelphia-New-York: Lippincott-Raven, 1998:2285-302.
Guerrini R, Dravet C, Genton P, Belmonte A, Kaminska A, Dulac O. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia 1998;39:508-12.**
Hurst DL. Epidemiology of severe myoclonic epilepsy of infancy. Epilepsia 1990;31;397-400.
Kanazawa O. Medically intractable generalized tonic-clonic or clonic seizures in infancy. J Epilepsy 1992;5:143-8.**
Ogino T, Ohtsuka Y, Yamatogi Y, Oka E, Ohtahara S. The epileptic syndrome sharing common characteristics during early childhood with severe myoclonic epilepsy of infancy. Jpn J Psychiatry Neurol 1989;43:479-81.
Renier WO, Renkawek K. Clinical and neuropathologic findings in a case of severe myoclonic epilepsy of infancy. Epilepsia 1990;31:287-91.
Sugama M, Oguni H, Fukuyama Y. Clinical and electroencephalographic study of severe myoclonic epilepsy in infancy (Dravet). Jpn J Psychiatry Neurol 1987;41:463-5.
Wallace SJ. Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res 1998;29:147-54.
Yakoub M, Dulac O, Jambaque I, Plouin P. Early diagnosis of severe myoclonic epilepsy in infancy. Brain Dev 1992;14;299-303.**
Here you will find general information about Dravet's Syndrome (or: Severe Myoclonic Epilepsy in Infancy).
HISTORICAL NOTE AND NOMENCLATURE