Myoclonic Status
by Olivier Dulac
Date of submission: August 8, 1999

Date of update: August 23, 2003
Medline SEARCH DATE: August 22, 2003

 

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Historical note and nomenclature

The term myoclonic status designates a prolonged condition in which a patient is affected by nearly continuous myoclonic jerks. It is often considered to be one of the various types of status epilepticus, not a specific condition (Treiman 1995). Status epilepticus is a condition in which epileptic seizures are prolonged or repeated at a high frequency to produce a lasting epileptic condition with disorders of consciousness as a nearly constant component. There are many types of status epilepticus.

Myoclonic status was recognized in acute conditions such as postanoxic coma (Jumao-as and Brenner 1990). In progressive myoclonus due to inborn error of metabolism, particularly Jansky-Bielschowsky disease and Unverricht-Lundborg disease, this condition is usual in the late stages of the disorder. These conditions are viewed as symptomatic myoclonic status.

In epilepsy, myoclonic status was initially reported as minor epileptic status (Brett 1966), thus recalling the classical triad of minor motor seizures. Following his usual pathophysiological classification, Gastaut introduced the distinction between primary and secondary myoclonic status (Gastaut 1983), a distinction relating to the concept of primary versus secondary generalized epilepsy (Merlis 1970). However, in so-called primary cases due to idiopathic generalized epilepsy, in which jerks are symmetrical and synchronous, the consciousness is not affected; therefore, the term "status" is questionable. In so-called secondary myoclonic status due to symptomatic generalized epilepsy in which jerks are predominantly asymmetrical and asynchronous, the consciousness is severely affected; this condition may last for weeks, months, or even years with persistent deterioration of mental functions, making this a variant of “epileptogenic encephalopathy.” This is the condition we will focus on here.

A distinct condition with negative myoclonic status has been reported, in which a sudden drop is due to loss of tone, but there is no jerk (Gambardella et al 1997); this condition may also persist for days or months.

Clinical manifestations

In so-called secondary myoclonic status, nearly continuous myoclonic jerks are mainly asymmetrical and asynchronous, but they are occasionally symmetrical and synchronous. The EEG shows continuous spike and slow wave activity and an absence of physiologic activities that last for several days or months. Usually, the condition begins insidiously in the course of generalized epilepsy with myoclonic and absence components. Parents notice progressive deterioration of consciousness; the child drools and becomes more and more ataxic. EEG shows continuous generalized asynchronous slow wave activity intermingled with multifocal spikes, occasionally resulting in spike-wave complexes. The course may be fluctuating, particularly in cases complicating epilepsy and as a consequence of medication.

Children affected by myoclonic status usually have myoclonic-astatic epilepsy (Doose et al 1970). Myoclonic status occurs 1 month to 60 months after the first epileptic seizure (Kaminska et al 1999). It may last for a few weeks, be controlled, and then recur a few months later, with 1 episode to 20 such episodes for a given patient. In unfavorable cases, the full duration of myoclonic status, which ranges from 1 month to 90 months, contributes to the poor outcome. In contrast, shorter episodes may affect patients who later recover completely (Dulac et al 1990). In Dravet syndrome, myoclonic status used to be a frequent complication (Dravet et al 1992). It began between 4 years and 6 years of age and could last several days or weeks before the patient returned to the previous condition.

Myoclonic status may also be observed in infants. Its recognition is then even more difficult because it develops insidiously in previously hypotonic patients who become more and more hypotonic and often dystonic (Dalla Bernardina et al 1992). Thus, the overall picture is that of a progressive disease and suggests an inborn error of metabolism; only close observation combined with prolonged EEG-recording reveals the deterioration that results from myoclonic status. Angelman syndrome and 4p-chromosomal aberration (Sgro et al 1995) are the most frequently encountered causes of infantile myoclonic status (Matsumoto et al 1992).

A previously normal five-year-old child developed nonfebrile generalized tonic-clonic seizures that occurred repeatedly for a few weeks before massive jerks, drop attacks, and brief episodes of atonic absences began. Six months after the first drop attacks, the child’s parents noticed progressive drooling, slowness, and unsteadiness, and the child became drowsy. Fine observation disclosed erratic jerks affecting the mouth, tongue, fingers, and feet. The high amplitude EEG was diffusely slow with frequent multifocal spikes. Night recording disclosed a series of tonic seizures at the end of the night, between 5 o’clock and 7 o'clock, with a vibratory component. This lasted for several months. Language expression became slow and poor. At the end of myoclonic status, the child was left, at the end of the night, with intractable tonic seizures as the only seizure type. This is the usual presentation of a patient with myoclonic-astatic epilepsy experiencing unfavorable outcome.

A four-year-old child who started clonic (affecting both sides alternatively) polymorphic febrile and nonfebrile seizures at the age of 5 months and exhibited myoclonus from the age of 3 years became drowsy with asynchronous jerks of the extremities and had drooling and drowsiness. An EEG showed asynchronous generalized slow wave activity with rare spikes. The status lasted for 5 days and improved progressively, but the patient was left with worsened motor and cognitive condition. This is a historical case of severe myoclonic epilepsy in infancy (Dravet syndrome).

A three-year-old child who had delayed motor milestones, excellent eye contact with a round face, and ataxia, who never acquired the ability to walk, and who exhibited major hypotonia became drowsy, drooled, and had fine jerks of the extremities. This condition lasted a few weeks before recovery and is characteristic of Angelman syndrome, a cause of myoclonic epilepsy in nonprogressive encephalopathy.

Localization

Although myoclonic status clearly affects most of the brain cortex, myoclonus indicates major involvement of pathways. The predominance of jerks in the extremities and facial muscles indicates that the pyramidal tract is mostly affected. This location could be clearly demonstrated for Angelman syndrome by means of back-averaging (Guerrini et al 1996). Although the same investigation failed for severe myoclonic epilepsy in infancy, similar clinical expression suggests a similar location but a distinct mechanism.

Pathophysiology

The pathophysiology of myoclonic status remains unknown, and it may differ in various conditions. Although Angelman syndrome has been shown to produce cortical myoclonus (Guerrini et al 1996), this was not the case with other conditions such as severe myoclonic epilepsy in infancy.

Differential diagnosis

Several conditions, both epileptic and nonepileptic, must be distinguished. Frequent myoclonus may occur transiently in idiopathic generalized epilepsy, the type of juvenile myoclonic epilepsy in which there is no deterioration of consciousness and the EEG background remains normal.

Subcontinuous negative myoclonus may produce frequent jerks due to the ineffective attempt to oppose gravity between the repeat episodes of loss of tone. However, when the patient lies down, there is no jerk, and the motor phenomenon is purely negative. The EEG shows continuous spike waves in slow sleep.

Frequent asymmetric and asynchronous jerks with ataxia, with or without major mental deterioration, are usual in the late course of the various types of progressive myoclonic epilepsy (eg, Lafora body disease, ceroid-lipofuscinosis, Unverrich-Lundborg disease, and mitochondrial encephalopathy).

Acute encephalopathy following ischemia is an occasional condition in which nearly continuous myoclonus appears several hours after cardiac arrest and lasts several days (Young et al 1990).

Erratic myoclonus is combined with ataxia and opsoclonus in infants with the opsoclonus-myoclonus syndrome that is due to nephroblastoma in half of the cases and whose cause remains unknown in the other half. Although this is a nonepileptic condition, the distinction may be difficult when patients have received steroid therapy or when the EEG exhibits rhythmic slow wave activity because of drowsiness.

Diagnostic workup

The diagnosis is based on the clinical story and EEG. There is no specific biochemical, radiological, or neurophysiological investigation to support the diagnosis. The differential diagnosis depends on specific biochemical, neurophysiological, and histological investigations.

Syndromes and diseases in which the seizure type occurs

Myoclonic status occurs in Dravet syndrome, myoclonic-astatic epilepsy, and myoclonic epilepsy of nonprogressive encephalopathy.

Prognosis and complications

The outcome depends on the etiology and the ability to control myoclonic status since its duration is a major component of prognosis. Therapeutic strategies also seem to play a role that could be of major importance (Perucca et al 1998). Drugs such as carbamazepine and vigabatrin may precipitate myoclonic status due to myoclonic-astatic epilepsy (Dulac et al 1991; Kaminska et al 1999), and lamotrigine may precipitate myoclonic status due to Dravet syndrome (Guerrini et al 1998).

Management

There is still no specific treatment for myoclonic status. Benzodiazepines and steroids are only transiently effective. Only prevention based on appropriate early diagnosis and management of these patients is useful. Valproate and lamotrigine may prevent or improve myoclonic status due to myoclonic-astatic epilepsy (Dulac and Kaminska 1997), and the combination of stiripentol (a nonapproved drug) with clobazam (also nonapproved in the United States) and valproate may prevent myoclonic status in severe myoclonic epilepsy in infancy (Chiron et al 2000). For Angelman syndrome, piracetam is often useful (Guerrini et al 1996).

References cited

Brett EM. Minor epileptic status. J Neurol Sci 1966;3:52-75.

Chiron C, Marchand MC, Tran A, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group. Lancet 2000;356(9242):1638-42.

Dalla Bernardina B, Fontana E, Sgro V, Colamaria V, Elia M. Myoclonic epilepsy (‘myoclonic status’) in non-progressive encephalopathies. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P. Epileptic syndromes in infancy, childhood and adolescence. 2nd edition. London: John Libbey & Company Ltd 1992, 89-96.

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

Dravet Cbureau M, Guerrini R, Giraud N, Roger J. Severe myoclonic epilepsy in infants. In: Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P. Epileptic syndromes in infancy, childhood and adolescence. 2nd edition. London: John Libbey & Company Ltd 1992, 75-88.

Dulac O, Chiron C, Luna D, et al. Vigabatrin in childhood epilepsy. J Child Neurol 1991;Suppl 2:S30-7.

Dulac O, Kaminska A. Use of lamotrigine in Lennox-Gastaut and related epilepsy syndromes. J Child Neurol1997;12 Suppl 1:S23-8.

Dulac O, Plouin P, Chiron C. Forme "benigne" d'epilepsie myoclonique de l'enfant. Neurophysiol Clin 1990;20:115-29.

Gambardella A, Aguglia U, Oliveri RL, Russo C, Zappia M, Quattrone A. Negative myoclonic status due to antiepileptic drug tapering: report of three cases. Epilepsia 1997;38:819-23.

Gastaut H. Classification of status epilepticus. Adv Neurol 1983;34:15-35.

Guerrini R, De Lorey TM, Bonanni P, et al. Cortical myoclonus in Angelman syndrome. Ann Neurol 1996;40(1):39-48.

Guerrini R, Dravet C, Genton P, Belmonte A, Kaminska A, Dulac O. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epliepsia 1998;39:508-12.

Jumao-as A, Brenner RP. Myoclonic status epilepticus: a clinical and electroencephalographic study. Neurology 1990;40:1199-202.

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

Matsumoto A, Kumagai T, Miura K, Miyazaki S, Hayakawa C, Yamanaka T. Epilepsy in Angelman syndrome associated with chromosome 15q deletion. Epilepsia 1992;33:1083-90.

Merlis JK. Proposal for an international classification of the epilepsies. Epilepsia 1970;11:114-9.

Perucca E, Gram L, Avanzini G, Dulac O. Antiepileptic drugs as a cause of worsening seizures. Epilepsia 1998;39:5-17.

Sgro V, Riva E, Canevini MP, et al. 4p(-) syndrome: a chromosomal disorder associated with a particular EEG pattern. Epilepsia 1995;36(12):1206-14.

Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol 1995;12:343-62.

Young GB, Gilbert JJ, Zochodne DW. The significance of myoclonic status epilepticus in postanoxic coma. Neurology 1990;40:1843-8.

ILAE
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Major keyword descriptors

4p-syndrome

Angelman syndrome

epileptogenic encephalopathy

myoclonic astatic epilepsy

myoclonic epilepsy

Minor keyword descriptors

benzodiazepines

carbamazepine

idiopathic generalized epilepsy

ischemic-anoxic encephalopathy

lamotrigine

myoclonus

opsoclonus

valproate

vigabatrin

Age of presentation

01-23 months

02-05 years

Age of typical presentation

01-23 months

02-05 years

Permuted topics

Myoclonic status

status, Myoclonic

Related topics

Myoclonic status in nonprogressive encephalopathies

Progressive-myoclonic ataxias

Differential diagnosis

idiopathic generalized epilepsy

subcontinuous negative myoclonus

progressive myoclonic epilepsy

Lafora body disease

ceroid-lipofuscinosis

Unverrich-Lundborg disease

mitochondrial encephalopathy

acute encephalopathy following ischemia

opsoclonus-myoclonus syndrome

 

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