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Historical note and nomenclature

Myoclonus was first coined by Friedreich to describe a young adult with erratic jerks that predominated in the extremities (Friedreich 1881). Gastaut distinguished generalized, partial, and segmental myoclonus, according to whether the jerks affected respectively the whole body, one limb or half the body, or only part of one limb (Gastaut 1968). From the neurophysiologic point of view, he distinguished types A and B (Gastaut and Remond 1952). Type A was brief and combined with a generalized spike-wave, corresponding to what occurs in myoclonus of idiopathic generalized epilepsy (Janz 1989). Type B, on the other hand, was long and not associated with any spike but, rather, with a slow wave on the EEG, corresponding to spasms or “myoclonus” of subacute measles encephalitis. Using back averaging, Halliday then distinguished cortical from subcortical myoclonus, according to whether a cortical event could be identified before the occurrence of the jerk (Halliday 1967). In this summary, massive bilateral myoclonus will refer to jerks affecting the whole body (mainly the upper limbs) combined with a generalized spike wave or polyspike-wave.

Clinical manifestations

Jerks of massive bilateral myoclonus mainly involve the upper limbs, with elevation of the shoulders producing slight contraction of the trunk. This rarely causes the patient to fall. Massive bilateral myoclonus can be asymmetrical, and it is a challenge in clinical practice to distinguish within asymmetrical jerks those that correspond to focal jerk with secondary generalization from those that correspond to generalized although asymmetrical jerks. The pathophysiologic and etiologic significance and, therefore, the therapeutic decisions are different. Jerks are clearly increased by waking up and falling asleep; a child with massive bilateral myoclonus may have sleep difficulties caused by jerks that wake him up each time he starts to fall asleep. Jerks may also be precipitated by photic stimulation (Kasteleijn-Nolst Trenite 1998).

Polygraphy recording shows that during a jerk there is a spike or a polyspike of a spike wave complex. Video alone is not precise enough to show this evidence. This kind of jerk can occur in idiopathic myoclonic epilepsy of adolescence (Janz syndrome) and in benign myoclonic epilepsy in infancy (Dravet et al 1992).

Case 1: A 14-month-old infant had jerks of the upper limbs for a few weeks. The jerks never caused him to fall but were repeated several dozens of times each day, including when falling asleep. Polygraphy showed that the jerks were combined in all instances with spike-waves and that there was an increase of jerks and spike waves when falling asleep, to the extent that the infant often woke up, resulting in a sleep pattern of quite poor quality (Dravet et al 1992). Valproate rapidly controlled the jerks. This is a typical case of benign myoclonic epilepsy in infancy.

Case 2: A 13-year-old adolescent suffered from jerks. He could not recall precisely when the jerks started, but he estimated that they had started several months prior to presentation to the doctor’s office. When performing the first movements of the morning, he was upset by the jerks and sometimes dropped objects. Jerks were sometimes precipitated by photic stimulation. An EEG showed that each jerk was combined with the spike of a spike-wave complex, often occurring in brief and regular bursts. This is a typical case of juvenile myoclonic epilepsy that is part of idiopathic generalized epilepsy.

Localization

Jerks predominate in the extremities, often causing the patient to drop objects; this indicates that the motor strip is affected. However, the rhythmicity of the spike-wave complex suggests that the reticular structure of the thalamus is also involved and that there is, in fact, a loop between the motor strip and the thalamus. The jerks do not, therefore, constitute a generalized seizure because they predominate in one neurophysiological pathway. Rather, they are usually called “generalized myoclonus” because no site of onset can be identified, and the whole motor structure seems to be hyperexcitable.

Pathophysiology

Hyperexcitability in the motor pathways permits synchronization in the rolandic and thalamic structures, the discharge in one structure triggering the discharge in the other structure, and the cycle is closed. The discharge then goes along the pyramidal pathway. Polygraphy recording of several muscles, including the eyelid, neck, and upper and lower limbs, shows that the contraction reaches the eyelid before continuing to the upper limb and then the lower limb, demonstrating that the discharge is produced in the brain cortex.

Differential diagnosis

Other kinds of seizures that could resemble massive bilateral myoclonus are myoclonic-astatic seizures and spasms. Myoclonic-astatic seizures cause the patient to fall because of the atonic component of the seizure combined with the jerk. EEG for these seizures shows polyspike and waves similar to an EEG for massive bilateral myoclonus; only the polygraphic recording reveals the atonic component. Epileptic spasms last longer and are combined with either fast, low amplitude activity or a high amplitude slow wave. Progressive myoclonic epilepsy, mainly Unverricht-Lundborg disease and Lafora body disease, may generate massive myoclonus, usually triggered by photic stimulation (Rubboli et al 1999).

Massive jerks can also be produced by nonepileptic events, including hiccups and startle. In these cases, there is no concomitant cortical activity. In the newborn, hyperekplexia may produce massive jerks, and the diagnosis relies on triggering the jerks by tapping the nose.

Diagnostic workup

Following the clinical description, there is need for EEG recording combined with EMG recording, mainly of the deltoids, in order to determine the correlation between the EEG activity and the jerk. Awake and sleep recording are required. The basic activity is essential in order to exclude Lafora body disease, which slows down the basic activity quite early in the course of the disease (Tassinari et al 1978).

Syndromes and diseases in which the seizure type occurs

Massive myoclonus occurs in benign myoclonic epilepsy, Dravet syndrome, and myoclonic-astatic epilepsy.

Prognosis and complications

Prognosis depends of the type of epilepsy, which is determined by to the syndrome, thus, the combination of the seizure type, the interictal EEG, and the age of onset. In juvenile myoclonic epilepsy, the prognosis is favorable, particularly when there is no other type of seizure present; the prognosis is less favorable when there is a combination with generalized tonic-clonic seizures. In benign myoclonic epilepsy in infancy, the prognosis is good in cases with later onset (after the first birthday) than in cases with onset during the first year of life. If onset occurs during the first year of life, intractable epilepsy with the same phenotype at onset may occur.

Management

Valproate is the first-line treatment for both juvenile myoclonic epilepsy and benign myoclonic epilepsy in infancy. Cases resistant to valproate may benefit from ethosuximide. Lamotrigine gives conflicting results because some patients improve, whereas others experience worsening of myoclonic seizures (Guerrini et al 1999). Preliminary data suggest good effect of topiramate (Mikaeloff et al 2003) and levetiracetam (Genton and Gelisse 2000).

References cited

Dravet C, Bureau M, Genton P. Benign myoclonic epilepsy of infancy: electroclinical symptomatology and differential diagnosis from the other types of generalized epilepsy of infancy. Epilepsy Res Suppl 1992;6:131-5.

Friedreich N. Neuropathologische beobachtung beim paramyoclonus multiplex. Virch Arch Pathol Anat Physiol Klin Med 1881;86:421-34.

Gastaut H. Sémiologie des myoclonies et etude analytique des syndromes myocloniques. Rev Neurol (Paris) 1968;119:1-30.

Gastaut H, Remond A. Etude électroencéphalographique des myoclonies. Rev Neurol 1952;86:596-609.

Genton P, Gelisse P. Antimyoclonic effect of levetiracetam. Epileptic Disord 2000;2:209-12.

Guerrini R, Belmonte A, Parmeggiani L, Perucca E. Myoclonic status epilepticus following high-dosage lamotrigine therapy. Brain Dev 1999;21:420-4.

Halliday AM. The electrophysiological study of myoclonus in man. Brain 1967;90:241-84.

Janz D. Juvenile myoclonic epilepsy: epilepsy with impulsive petit mal. Cleve Clin J Med 1989;56 Suppl Pt 1:S23-33.

Kasteleijn-Nolst Trenite DG. Reflex seizures induced by intermittent light stimulation. Adv Neurol 1998;75:99-121.

Mikaeloff Y, Saint-Martin A, Mancini J, et al. Topiramate: efficacy and tolerability in children according to epilepsy syndromes. Epilepsy Res 2003;53:225-32.

Rubboli G, Meletti S, Gardella E, et al. Photic reflex myoclonus: a neurophysiological study in progressive myoclonus epilepsies. Epilepsia 1999;40 Suppl 4:50-8.

Tassinari CA, Bureau-Paillas M, Dalla BB, et al. [Lafora disease (author's transl)]. Rev Electroencephalogr Neurophysiol Clin 1978;8:107-22.

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Abbreviations

REM:rapid eye movement

MRI:magnetic resonance imaging

Major keyword descriptors

Dravet syndrome

idiopathic generalized epilepsy

Janz syndrome

jerks

upper limbs

myoclonic epilepsy

myoclonic-astatic epilepsy

myoclonus

Minor keyword descriptors

motor

photic stimulation

polyspike wave

spike wave

thalamus

Age of presentation

0-01 month

01-23 months

02-05 years

06-12 years

13-18 years

19-44 years

Permuted topic, synonyms, variants

Massive bilateral myoclonus

bilateral myoclonus, Massive

myoclonus, Massive bilateral

Related summaries

Dravet syndrome (severe myoclonic epilepsy in infancy)

Benign myoclonic epilepsy in infancy

Juvenile myoclonic epilepsy

Myoclonic-astatic epilepsy of childhood

Sleep starts

Differential diagnosis

myoclonic-astatic seizures

epileptic spasms

Unverricht-Lundborg disease

Lafora body disease

hiccups

startle

hyperekplexia