HISTORICAL NOTE

Benign myoclonic epilepsy in infancy was not clearly identified before the first description by Dravet and Bureau in 1981 (Dravet and Bureau 1981). Many other cases have since been published. Some authors have described cases with reflex myoclonias triggered by noise or contact and have proposed to distinguish 2 separate entities, the second one being named “reflex myoclonic epilepsy in infancy” (Vigevano et al 1997). We do not think this distinction is necessary, and we describe all the cases as benign myoclonic epilepsy.

To our knowledge, there are presently 67 cases published in the literature, of which 10 reported as “reflex” (Dravet and Bureau 2002). Also of mention is that in the first description the onset age was before 3 years, whereas in the following reports some authors have described a later onset age, up to 4 years 8 months of age (Giovanardi Rossi et al 1997). That means the same type of epilepsy can appear at different ages, but with a trend to be more frequent in some periods (Guerrini et al 1994).


CLINICAL MANIFESTATIONS

Benign myoclonic epilepsy is characterized by brief myoclonic attacks in normal infants between the ages of 6 months and 3 years. An earlier onset is uncommon. A family history of epilepsy or febrile convulsions is present in 30% of cases. As a rule, patients do not have any pathological history prior to the onset of the myoclonic fits. However, the occurrence of febrile convulsion has been reported in 20% of patients. They were always rare, simple febrile convulsions, usually preceding the onset of myoclonias. Two patients had an associated disease, one had Down syndrome (Dravet and Bureau 2002) and the other diabetes (Colamaria et al 1987).

The myoclonic attacks involve the upper limbs and the head, though rarely the lower limbs. Their intensity is variable, rarely inducing a fall. In babies they are not easy to describe; parents report a head nod. They occur several times a day at irregular and unpredictable times. They are not favored by awakening, but they can be triggered by a sudden noise or sudden contact. The state of consciousness is difficult to assess, but the isolated seizures do not interrupt activity. Only when they are grouped in clusters of 2 or 3 pseudorhythmically repeated elements, lasting up to 5 to 10 seconds, is there a slight impairment of consciousness. They are more or less massive, involving the axis of the body and the limbs, provoking a head drop and an upwards-outwards movement of the upper limbs, with flexion of the lower limbs, and sometimes a rolling of the eyeballs.

Initially, the development continues normally, and parents and pediatricians tend not to consider these movements as pathological events.

When an EEG is performed, it can be normal if no myoclonic fit is recorded. But myoclonias are always associated with fast generalized spike waves and polyspike waves at more than 3 Hz, that are more or less regular, lasting 1 to 3 seconds.|{diagram:bmei1.bmp}{caption:Polysomnogram of myoclonic jerks in the head and arms}{label:Several myoclonic jerks are polygraphically recorded when awake, when persisting during drowsiness, and, attenuated, during sleep stage II in a 2-year-old girl before any treatment. The jerks are accompanied by generalized spike wave, sometimes preceded by spike wave localized in the anterior regions. The same type of generalized discharge appears during REM sleep without concomitant clinical event. R. DELT = right deltoid muscle, L. DELT = left deltoid muscle}| During drowsiness, there is an enhancement of the myoclonias that usually, but not always, disappear during sleep. Intermittent photic stimulation can also provoke myoclonic fits.

Polygraphic recordings demonstrate the association of myoclonias and spike wave or polyspike wave discharges. Myoclonias are brief (1 to 3 seconds)|{diagram:bmei1.bmp}{caption:Polysomnogram of myoclonic jerks in the head and arms}{label:Several myoclonic jerks are polygraphically recorded when awake, when persisting during drowsiness, and, attenuated, during sleep stage II in a 2-year-old girl before any treatment. The jerks are accompanied by generalized spike wave, sometimes preceded by spike wave localized in the anterior regions. The same type of generalized discharge appears during REM sleep without concomitant clinical event. R. DELT = right deltoid muscle, L. DELT = left deltoid muscle}| and usually isolated. Myoclonias may be followed by a brief atonia. Sometimes, after the attack, there is a voluntary movement that is visible as a normal muscular contraction.

The interictal EEG is normal for the child’s age. Spontaneous spike wave discharges are rare; some slow wave may be found over the central areas. Intermittent photic stimulation does not provoke spike wave without concomitant myoclonia. Nap sleep recordings have shown a normal organization of the sleep; generalized spike wave discharges may occur during REM sleep.

No other type of seizure is observed in children with benign myoclonic epilepsy, even if they are left untreated (for up to 8.5 years in one of our patients), particularly, no absence or tonic seizures. Clinical examination is normal. Interictal myoclonus is described only by Giovanardi Rossi and colleagues in 6 patients (Giovanardi Rossi et al 1997). Many patients were not investigated, but when CT and MRI were performed, they were normal.

The outcome seems to depend on an early diagnosis and treatment. If left untreated, the patient continues to experience myoclonic attacks, and this may lead to impaired psychomotor development and behavioral disturbances. Myoclonias are easily controlled by valproate alone and the child may then develop regularly, according to normal milestones.


CLINICAL VIGNETTE

The patient was the second of 2 brothers. The oldest brother was in good health. There were childhood febrile convulsions in one of the father’s cousins and a hormonal deficit in the first months of pregnancy. The birth delivery was normal and there was normal psychomotor development. The first myoclonic attacks were between 8 and 9 months of age, with a slight forward movement of the head, upward movement of the upper limbs, and rolling balls of the eyes several times a day. At 14 months the first EEG showed generalized spike wave and polyspike wave. Low doses of valproate and clonazepam did not completely control seizures that were sometimes provoked by sudden contacts or noises. First referred to our center at 16 months, several spontaneous or reflex myoclonic jerks associated with brief generalized spike wave in polygraphic video EEG were recorded. There was no photosensitivity. Clinical examination was normal. No neuroimaging was performed. The development quotient measured by the Brunet-Lézine scale was 96, and the child attended normal kindergarten. Plasma level of valproate was low (62 mg/mL). Clonazepam was not well-tolerated. Valproate monotherapy with 30 mg/k per day was established, and seizures disappeared totally.

In following years, the patient was regularly seen in our center. He continued to be seizure-free and to develop normally.
At 5 years 6 months, valproate was stopped. The last EEG control showed a normal awake trace and the persistence of rare generalized spike wave during drowsiness and slow sleep. PSI and videotape watching did not provoke discharges. At 6 years 3 months, he attended his first elementary class without difficulties.


ETIOLOGY

Benign myoclonic epilepsy belongs to the group of idiopathic generalized epilepsies (Commission 1989). It seems to be the equivalent of juvenile myoclonic epilepsy, but the 2 syndromes have never been observed successively in the same patient. We only know of one unpublished case in our population who probably started at 3 years what has been considered as juvenile myoclonic epilepsy later on. But we have few data concerning the onset.


BIOLOGICAL BASIS

There is no constant biological background; diabetes and Down syndrome are probably fortuitous associations.

Genetics is unknown. Cases are rare and no family cases have been described. Genetic relationships with other types of idiopathic generalized epilepsies are not established. Delgado-Escueta and colleagues did not find cases of juvenile myoclonic epilepsy in their study of 24 affected family members of early childhood myoclonic epilepsy (Delgado-Escueta et al 1990). The case described by Arzimanoglou and colleagues is the second child of 2 brothers the oldest of whom was affected by a typical epilepsy with myoclonic-astatic seizures, Doose syndrome. This association raises the question of the relationships between these 2 epilepsies in the large frame of generalized idiopathic epilepsies in early childhood. In the family of the patient described by Biondi and colleagues, other members had dubious epilepsy (Biondi et al 1991). Sleep EEGs were obtained for the father and his 2 sisters and demonstrated brief bursts of generalized spike waves.


EPIDEMIOLOGY

According to the few epidemiological data available, benign myoclonic epilepsy seems to represent less than 1% of all the epilepsies (Loiseau et al 1991; Centre Saint-Paul 1997, unpublished data), but around 2% of those epilepsies that begin in the first 3 years of life (Dalla Bernardina et al 1983) and 2% of all the idiopathic generalized epilepsies (Centre Saint-Paul 1997, unpublished data).



PREVENTION

Not applicable.


DIFFERENTIAL DIAGNOSIS

When myoclonias start in the first year of life, the other diagnosis that comes to mind is that of cryptogenic infantile spasms. Spasms are clinically different from benign myoclonias. They are more intense and involve a strong flexion of the whole body, which is never observed in benign myoclonic epilepsy. Isolated, sporadic spasms are always associated with serial spasms in the same infant. Polygraphic recordings of infantile spasms show a typical pattern of a brief tonic contraction, well-described by Fusco and Vigevano, rarely a prolonged myoclonia (Fusco and Vigevano 1993). The ictal EEG is not a fast, generalized polyspike wave. It is variable: sudden interruption of hypsarrhythmia by a flattening with or without superimposed fast rhythms, large slow wave followed by a flattening, or even no visible change. The occurrence of infantile spasms is associated with behavioral changes, poor quality of contact, and a slowing down of psychomotor acquisitions leading to arrest and regression. The interictal EEGs are always abnormal, demonstrating either a true hypsarrhythmia or a modified hypsarrhythmia or focal abnormalities; they never show the isolated or brief bursts of bilateral synchronous spike wave as in benign myoclonic epilepsy.

When both the psychomotor development and the EEG remain normal after several examinations performed awake and asleep, seizures resembling infantile spasms must suggest the diagnosis of benign nonepileptic myoclonus described by Lombroso and Fejerman (Lombroso and Fejerman 1977). In these patients, even the ictal EEG is normal (Dravet et al 1986; Pachatz et al 1999).

In the first year of life, severe myoclonic epilepsy of infancy could be evoked but it always starts with long and repeated febrile seizures and not by isolated myoclonic attacks, and the psychomotor development is retarded (Dravet and Bureau 2002).

When myoclonias begin after the end of the first year of life, the diagnosis of a cryptogenic Lennox-Gastaut syndrome may come to mind. In the Lennox-Gastaut syndrome (Beaumanoir and Blume 2002) seizures are not mainly myoclonic but myoclonic-atonic, or purely atonic, or more often tonic, leading to sudden falls and injuries. Their polygraphic expression is heterogeneous and the ictal EEG is either a recruiting rhythm or a flattening, or a high slow wave followed by runs of low voltage rapid rhythms. Interictal EEGs can be normal at the onset and the typical diffuse slow spike wave discharges may appear progressively. The typical electroclinical features during sleep can be delayed in time. But the diagnosis is based on the rapid association of different types of seizures such as atypical absences and axial tonic seizures, the constant impairment of behavior and learning, and the lack of efficacy of antiepileptic drugs.

If myoclonic seizures remain isolated or are associated with generalized tonic-clonic seizures, the diagnosis of myoclonic astatic epilepsy of early childhood must be entertained, although the onset of myoclonic astatic seizures in this syndrome is rare before the age of 3 years (Doose 1992). There are 2 essential differences: (1) the clinical aspect of the seizures, which always consist of falls in epilepsy with myoclonic astatic seizures, whereas falls are rare in benign myoclonic seizures, and are combined with other types of seizures, particularly status of minor seizures with stupor, which are never observed in benign myoclonic epilepsy (Guerrini et al 1994); (2) the EEG features are also different. Spike waves and polyspike waves are more numerous and grouped in long bursts, associated with a typical theta rhythm over the centroparietal areas. But some cases included by Doose should probably be classified as benign myoclonic epilepsy. In the same way, the group studied by Delgado-Escueta (Delgado-Escueta et al 1990), under the name of early childhood myoclonic epilepsy, seems to include cases of both epilepsy with myoclonic astatic seizures and benign myoclonic epilepsy in infancy.

Finally, one should consider other epilepsies beginning in the first 3 years of life in which myoclonias are the main type of seizure and which have variable prognosis. They are heterogeneous combinations of other types of seizures, presence of EEG focal abnormalities, previous delayed psychomotor development, poor response to drugs, and uncertain prognosis (Dravet 1990).


DIAGNOSTIC WORKUP

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The diagnostic workup is simple. It needs a good clinical description and repeated polygraphic video-EEG recordings in order to demonstrate the presence of myoclonic attacks with generalized spike wave discharges, either spontaneous or facilitated by drowsiness, noise, contact, or intermittent photic stimulation. A sleep recording is able to show the slight activation of discharges without change in morphology and the appearance of rapid rhythms and focal abnormalities. Neuroimaging is useful to affirm the absence of brain lesions but is not mandatory. Neuropsychological assessment is also useful in order to check good psychomotor development. Biological investigation can be necessary if there is another symptomatology evoking another disease.
|{RelList:AthenaDiagnostic}{Icon:mAthenaSponsored.bmp}|


PROGNOSIS

By definition, prognosis is good, and myoclonic attacks disappear with an appropriate treatment consisting of valproate monotherapy. Only in 5 patients was bitherapy necessary to control seizures (Giovanardi Rossi et al 1997). The length of follow-up is variable according to the series (9 months to 27 years). In 10 patients rare generalized tonic-clonic seizures occurred without associated myoclonias; in 3 they occurred during the drug withdrawal, and in others they occurred at adolescence (Dravet and Bureau 2002). The attacks provoked by noise or contact were more easily controlled than the spontaneous ones. Conversely, the photosensitivity was more difficult to control and persisted several years after the arrest of seizures.

The psychological outcome is more variable. On the whole it is rather good. The isolated cases published continue to have normal psychomotor development. However, in the series with a long-term follow-up, there are 12 patients who present moderate mental retardation, personality disturbances, or slight behavioral impairment (Colamaria et al 1987; Todt and Muller 1992; Giovanardi Rossi et al 1997; Dravet and Bureau 2002). No patient has been institutionalized. This psychological outcome partly depends on an early diagnostic, allowing appropriate treatment and family reassurance. But, there are also other factors related to an abnormal family structure and a disturbed mother-infant relationship.



MANAGEMENT

The first intention treatment is valproate monotherapy, which must be applied as soon as possible. The use of solution is preferable to that of syrup to avoid a rejection by the infant. Plasma levels must be monitored carefully because an irregular intake can lead to a relapse and falsely mimic a drug-resistant epilepsy. A daily dose of 30 mg/kg is usually sufficient, but higher doses can be necessary (Lin et al 1998). Valproate is also effective against the possible febrile convulsions. If myoclonias are not completely controlled by valproate, the addition of either one benzodiazepine (clobazam or nitrazepam) or ethosuximide can be proposed and the diagnostic revised. The treatment should be maintained for 3 or 4 years after the onset if it is well-tolerated, a longer time in cases with photosensitivity. In the cases of purely reflex seizures it may be avoided. When applied, it can be stopped earlier. The occurrence of one generalized tonic-clonic seizure in adolescence can require a new, brief period of treatment.


PREGNANCY

Not applicable.


ANESTHESIA

Not applicable.


REFERENCES CITED

Arzimanoglou A, Prudent M, Salefranque F. Epilepsie myoclono-astatique et épilepsie myoclonique bénigne du nourrisson dans une même famille: quelques réflexions sur la classification des épilepsies. Epilepsies 1996;8:307-15.**

Beaumanoir A, Blume W. The Lennox-Gastaut syndrome. In: Roger J, Bureau M, Dravet Ch, Genton P, Tassinari CA, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 3rd ed. London: John Libbey Ltd, 2002:113-35.

Biondi R, Sofia V, Tarascone M, Leocata R. Epilessia mioclonica benigna dell’infanzia: contibuto clinico. Boll Lega Ut Epil 1991;74:93-4.

Colamaria V, Andrighetto G, Pinelli L, Olivieri A, Alfieri P, Dalla Bernardina B. Iperinsulinismo, ipoglicemia ed epilessia mioclonica benigna del lattante. Boll Lega It Epi 1987;58/59:231-3.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989;30:389-99.

Dalla Bernardina B, Colamaria V, Capovilla G, Bondavalli S. Nosological classification of epilepsies in the first three years of life. In: Nistico G, Di Perri R, Meinardi H, editors. Epilepsy: an update on research and therapy. New-York: Alan Liss, 1983:165-83.

Delgado-Escueta AV, Greenberg D, Weissbecker K, 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.

Doose H. Myoclonic astatic epilepsy of early childhood. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence, 2nd ed. London: John Libbey Eurotext Ltd., 1992:103-14.

Dravet C. Les épilepsies myocloniques bénignes du nourrisson. Epilepsies 1990;2:95-101.

Dravet C, Bureau M. L’épilepsie myoclonique bénigne du nourrisson. Rev Electroenceph Neurophysiol Clin 1981;11:438-44.

Dravet C, Bureau M, Giraud N, Roger J, Gobbi G, Dalla Bernardina B. Benign myoclonus of early infancy or benign non-epileptic spasms. Neuropediatrics 1986;17:33-8.

Dravet C, Bureau M. Benign myoclonic epilepsy in infancy. In: Roger J, Bureau M, Dravet Ch, Genton P, CA Tassinari, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 3rd ed. London: John Libbey Ltd., 2002:69-79.**

Fusco L, Vigevano F. Ictal clinical and electroencephalographic findings of spasms in West syndrome. Epilepsia 1993;34:671-8.

Giovanardi Rossi P, Parmeggiani A, Posar A, Santi A, Santucci M. Benign myoclonic epilepsy: long-term follow-up of 11 new cases. Brain Dev 1997;19:473-9 **

Guerrini R, Dravet CH, Gobbi G, Ricci S, Dulac O. Idiopathic generalized epilepsies with myoclonus in infancy and childhood. In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalized epilepsies: clinical, experimental, and genetic aspects. London: John Libbey Eurotext Ltd., 1994:267-80. **

Lin YP, Itomi K, Takada H, et al. Benign myoclonic epilepsy in infants: video-EEG features and long-term follow-up. Neuropediatrics 1998;29:268-71.

Loiseau P, Duche B, Loiseau J. Classification of epilepsies and epileptic syndromes in two different samples of patients. Epilepsia 1991;32:303-9.

Lombroso CT, Fejerman N. Benign myoclonus of early infancy. Ann Neurol 1977;1:138-43.

Pachatz C, Fusco L, Vigevano F. Benign myoclonus of early infancy. Epil Disord 1999;1:57-61.

Ricci S, Cusmai R, Fusco L, Cilio R, Vigevano F. Reflex myoclonic epilepsy of the first year of life. Epilepsia 1995;35:47.**

Todt H, Muller D. The therapy of benign myoclonic epilepsy in infants. In: Degen R, Dreifuss FE, editors. Epilepsy research. Suppl 6. The benign localized and generalized epilepsies in early childhood. Amsterdam: Elsevier, 1992:137-9.

Vigevano F, Cusmai R, Ricci S, Watanabe K. Benign epilepsies of infancy. In: Engel Jr J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia: Lippincott-Raven Publishers, 1997:2267-76.

ILAE

ILAE Copyright Notice

ICD-9 Code

333.2

ASSOCIATED DISORDERS

Simple febrile convulsions
Benign reflex myoclonic epilepsy in infants

MAJOR KEYWORD DESCRIPTORS

benign epilepsy
convulsions
generalized epilepsy
idiopathic epilepsy
infancy epilepsy
myoclonic seizures
photic stimulation

MINOR KEYWORD DESCRIPTORS

genetic epilepsy
head nod
reflex epilepsy

AGE OF PRESENTATION

01-23 months
02-05 years

AGE OF TYPICAL PRESENTATION

01-23 months

POPULATION GROUP(S) PREFERENTIALLY AFFECTED

none selectively affected

OCCUPATION GROUP(S) PREFERENTIALLY AFFECTED

none selectively affected

SEX

male>female, >2:1
male>female, >1:1

FAMILY HISTORY

none

HEREDITY

heredity may be a factor

GLOSSARY

term1:definition idiopathic generalized epilepsy in infancy term2:definition reflex idiopathic generalized epilepsy in infancy

ILLUSTRATION CAPTIONS

Title : figure 1
Legend : in a 2- year- old girl, before any treatment, several myoclonic jerks are polygraphically recorded when awake, persisting during drowsiness and, attenuated, during sleep stage II. They are accompanied by generalized SW, sometimes preceded by SW localized in the anterior regions. The same type of generalized discharge appears during REM without concomitant clinical event. R. DELT: right deltoid muscle; L. DELT: left deltoid muscle.

PERMUTED TOPIC, SYNONYMS, VARIANTS

Benign myoclonic epilepsy in infancy
myoclonic epilepsy in infancy, Benign
epilepsy in infancy, Benign myoclonic

RELATED TOPICS

Benign epilepsy of infancy with partial seizures
Epilepsy

DIFFERENTIAL DIAGNOSIS

cryptogenic infantile spasms
severe myoclonic epilepsy
benign nonepileptic myoclonus
cryptogenic Lennox-Gastaut syndrome
myoclonic astatic epilepsy of early childhood
minor seizures with stupor
other epilepsies beginning in the first 3 years of life with myoclonias as the main seizure type

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