Myoclonic seizures …

Aristea S Galanopoulou MD PhD

Epilepsy & Seizures

Updated 04.03.2023
Released 09.09.2003
Expires For CME 04.03.2026

Myoclonic seizures

Author: Aristea S Galanopoulou MD PhD

See Contributor Disclosures

Editor: Solomon L Moshé MD

Myoclonic seizures

In This Article

Quick Link

Introduction

Overview

Myoclonic seizures are sudden, brief, involuntary, single or multiple jerks that are isolated or rapidly repetitive and of variable topography and pathophysiology. They are positive or negative, spontaneous or evoked, generalized or focal, and cortical or thalamocortical. They are clinical manifestations of numerous epileptic syndromes of different etiology, prognosis, and management. Juvenile myoclonic epilepsy is an archetype of thalamocortical seizures, and Lafora disease is an archetype of cortical epileptic myoclonus. The differential diagnosis of myoclonic seizures includes a long list of physiological phenomena, nonepileptic myoclonus, other types of seizure, and the various forms of epileptic myoclonus. The main antiepileptic drugs include clonazepam, valproate, and levetiracetam. A significant number of other antiepileptic drugs such as carbamazepine, gabapentin, and pregabalin are contraindicated. In this article, the author details the historical aspects, nomenclature, classification, clinical manifestations, pathophysiology, diagnostic workup, differential diagnosis, and management of the various types of myoclonic seizure, paying particular attention to recent advances.

Key points

	• Myoclonic seizures are transient (< 100 ms), involuntary, single, or multiple muscle jerks due to abnormal excessive or synchronous neuronal activity in the brain.
	• They are of variable amplitude, force, location, duration, and circadian distribution and have a number of precipitating factors.
	• They are associated with a significant number of heterogeneous syndromes such as myoclonic epilepsy in infancy and juvenile myoclonic epilepsy of the idiopathic generalized epilepsies, Unverricht-Lundborg and Lafora disease of the progressive myoclonic epilepsies, or Dravet syndrome and epilepsia partialis continua of the epileptic encephalopathies.
	• Differential diagnosis is demanding because of many physiological, nonepileptic, and epileptic imitators. Cortical myoclonic seizures have different neurophysiological properties from thalamocortical seizures.
	• Prognosis depends on etiology and varies significantly from very benign (myoclonic epilepsy in infancy) to very severe (Lafora disease).
	• The main antiseizure medications are clonazepam, valproate, and levetiracetam. Carbamazepine, oxcarbazepine, pregabalin, and many others are contraindicated.

Historical note and terminology

Nikolaus Friedreich is often cited as the first to describe myoclonus as "paramyoklonus multiplex" in a young adult patient who had brief, rapid contractions at short intervals in a number of muscles mainly in the extremities (31). This was a case of what would be diagnosed today as a form of essential (nonepileptic) myoclonus (41). However, the first description of epileptic myoclonic seizures in a 14-year-old boy with probable juvenile myoclonic epilepsy should be attributed to Herpin (Herpin 1867). There are many other publications of epileptic and nonepileptic myoclonus preceding this description by Friedreich, such as those by Dubini, Delasiauve, and Reynolds, as detailed by Inoue and colleagues, Hallett, and Fahn (41; 25; 46). Subsequently, certain diseases with epileptic myoclonus as a predominant symptom were described, such as familial myoclonic epilepsy, epilepsia partialis continua, nonprogressive myoclonic epilepsy, and juvenile myoclonic epilepsy (79; 51; 69; 47).

In 1903, Lundborg classified myoclonus into 3 etiologic categories: (i) symptomatic myoclonus, (ii) essential myoclonus, and (iii) familial myoclonic epilepsy (subdivided into nonprogressive and progressive forms) (55). In 1928, Louis Muskens highlighted a close nosologic link between myoclonus and epilepsy and coined the term “fragments of epilepsy” to designate the myoclonic jerks of patients with epilepsy (60).

Significant progress on the understanding and classification of myoclonus has been made by Gastaut as well as Marsden and associates (33; 42; 56; 07; 74). Using jerk-locked back averaging, Halliday distinguished cortical from subcortical myoclonus according to whether a cortical event could be identified before the occurrence of the jerk (43).

See also authoritative publications on the history and classification of myoclonic epilepsies and myoclonus (41; 25; 34).

Definition of myoclonus. There is no generally accepted, precise definition of myoclonus, and there is a longstanding source of confusion and debate about the term and the concept of epileptic and nonepileptic myoclonus (33; 01; 26; 13).

“Myoclonus” is a descriptive term for heterogeneous phenomena such as “sudden brief jerk caused by involuntary muscle activity,” “quick muscle regular or irregular jerks,” “a sudden brief, shock-like muscle contraction arising from the central nervous system,” and “abrupt, jerky, involuntary movements unassociated with loss of consciousness.” Myoclonus is probably best defined as sudden jerks typically lasting 10 to 50 ms and rarely longer than 100 ms (74). Most myoclonic jerks are caused by abrupt muscle contractions (positive myoclonus), but similar jerks are sometimes caused by a sudden cessation of muscle contraction associated with a silent period in the ongoing EMG activity (negative myoclonus) (74).

In the International League against Epilepsy’s (ILAE) glossary of descriptive terminology, the following definition is provided (05):

Myoclonic (adj.); myoclonus (noun): sudden, brief (< 100 ms) involuntary, single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal)

Negative myoclonus is an interruption of tonic muscular activity for less than 500 ms without evidence of preceding myoclonia.

The ILAE Task Force on Classification clarified the following (22):

The distinction between myoclonic seizures and clonic seizures is not clear. Classically, clonic seizures are rapid rhythmically-recurrent events, whereas myoclonic seizures are single, or irregularly recurrent events. The prototype of generalized myoclonic seizures are those occurring with juvenile myoclonic epilepsy. These are typically bilateral and symmetrical, but localized reflex myoclonus can also occur. The slowly rhythmic events of subacute sclerosing panencephalitis used to be considered epileptic myoclonus but are more accurately epileptic spasms, those with biPDs (bilaterally synchronous lateralizing periodic discharges) in comatose patients also are not necessarily epileptic, and their cause is usually not clearly defined. Differential diagnosis between myoclonic and clonic seizures can be difficult because a single jerk can be a fragment of a clonic seizure. Working groups will be convened to specifically evaluate myoclonic epileptic phenomena, including negative myoclonus and atonic seizures, compare them with non-epileptic myoclonic phenomena, and develop uniform criteria and terminology for these diagnoses.

Classification of myoclonus. Myoclonus may be:

	• a normal (physiological) phenomenon, such as hiccups (singultus) or hypnagogic jerks (sleep starts); or • an abnormal (epileptic or nonepileptic) symptom of a wide range of different disorders with regard to etiology, semiology, nosology, pathophysiology, and prognosis.
The 2 main classification systems of myoclonus are based on etiology and physiology. The etiologic classification is widely used to include the multiple and heterogeneous causes of myoclonus (56; 13):
	• Physiological myoclonus (normal myoclonus) • Essential myoclonus (idiopathic and often of autosomal dominant inheritance) • Epileptic myoclonus • Symptomatic myoclonus
The physiological classification is based on the presumed locations in which the myoclonus is generated (74):
	• Cortical • Subcortical (some authorities also include thalamocortical and reticular reflex myoclonus in this group) • Spinal • Peripheral

Definition of epileptic myoclonus. There are various definitions of epileptic myoclonus. “Myoclonus is termed epileptic when it occurs in combination with cortical epileptiform discharges. In some cases, the latter may be demonstrated only by the technique of back-averaging” (16). Others prefer indirect definitions: “epileptic myoclonus is the presence of myoclonus in the setting of epilepsy” or “myoclonic seizures are epileptic seizures in which the motor as well as the main manifestation is myoclonus” (13). Guerrini and Takahashi give a detailed description (39):

Epileptic myoclonus can be defined as an elementary electroclinical manifestation of an epileptic seizure or epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity and can be classified as cortical (positive and negative), secondarily generalized, thalamocortical, and reticular. Cortical epileptic myoclonus represents a fragment of partial or symptomatic generalized epilepsy; thalamocortical epileptic myoclonus is a fragment of idiopathic generalized epilepsy. Reflex reticular myoclonus represents the clinical counterpart of fragments of hypersynchronous epileptic activity of neurons in the brainstem reticular formation. Epileptic myoclonus, in the setting of an epilepsy syndrome, can be only one component of a seizure, the only seizure manifestations, one of the multiple seizure types or a more stable condition that is manifested in a nonparoxysmal fashion and mimics a movement disorder. This complex correlation is more obvious in patients with epilepsia partialis continua in which cortical myoclonus and overt focal motor seizures usually start in the same somatic (and cortical) region. In patients with cortical tremor this correlation is less obvious and requires neurophysiological studies to be demonstrated.

Panayiotopoulos proposed that “epileptic myoclonus is a transient (less than 100 ms), involuntary, single or multiple muscle jerk/s due to abnormal excessive or synchronous neuronal activity in the brain” (65). This is in compliance with the current ILAE definition of an epileptic seizure: “An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain” (29; 28; 27).

According to the 1981 ILAE classification of epileptic seizures (15),

Myoclonic jerks (single or multiple) are sudden, brief, shock-like contractions which may be generalized or confined to the face and trunk or to one or more extremities or even to individual muscles or groups of muscles. Myoclonic jerks may be rapidly repetitive or relatively isolated. They may occur predominantly around the hours of going to sleep or awakening from sleep. They may be exacerbated by volitional movement (action myoclonus). At times they may be regularly repetitive. Many instances of myoclonic jerks and action myoclonus are not classified as epileptic seizures. The myoclonic jerks of myoclonus due to spinal cord disease, dyssynergia cerebellaris myoclonica, subcortical segmental myoclonus, paramyoclonus multiplex, and opsoclonus-myoclonus syndrome must be distinguished from epileptic seizures.

Furthermore, the 1981 ILAE report classifies myoclonic seizures among generalized epileptic seizures (that simultaneously affect both cerebral hemispheres) (15):

Myoclonic seizures include massive bilateral myoclonus, eyelid myoclonia, myoclonic atonic seizures, myoclonic absence seizures, negative myoclonus.

Also, in tonic-clonic seizures, the ILAE include “variations beginning with a clonic or myoclonic phase.” However, it is also recognized that other types of myoclonus are focal, eg, epilepsia partialis continua or reading epilepsy (23).

Epileptic myoclonus may present as

	• the only manifestation of an epileptic seizure; or
	• one component of an epileptic attack occurring in continuity with another type of seizure, such as myoclonic-atonic seizures, myoclonic-absence seizures, or myoclonic tonic-clonic seizures.

Often, patients may have a combination of all of the above types of myoclonus. For example, massive epileptic myoclonus in nonprogressive generalized epilepsies could arise from either cortical epileptogenic foci or thalamocortical loops. Erratic myoclonus could be produced by either deafferentated cortical neurons in progressive diseases or as a combination of a corticothalamic loop and cortical hyperexcitability occurring as myoclonic status in the course of generalized (symptomatic or idiopathic) epilepsy (16).

Classification of epileptic myoclonus. The ILAE Commission on Pediatric Epilepsy categorized epileptic myoclonus as follows (16):

• Cortical myoclonus
• Thalamocortical myoclonus
• Reticular reflex myoclonus
• Negative myoclonus

Epileptic cortical myoclonus. This is the most common type of myoclonus and is due to hyperexcitability of the sensorimotor cortex. Each jerk results from a neuronal discharge in the sensorimotor cortex and manifests with brief (20 to 75 ms) contractions of both agonist and antagonist muscles.

"In cortical or thalamocortical myoclonus, the conduction velocity from cortex to muscles is fast at approximately 60 m/s. The timing of muscle innervation after a cortical discharge shows a rostrocaudal lag, with muscles innervated by the first cranial nerves contracting initially and those innervated by the last cranial nerves contracting later" (16). In reticular reflex myoclonus, “electromyographic events show a caudorostral sequence with muscles innervated by the last cranial nerves contracting initially and those innervated by the first cranial nerves contracting later.” Often, patients may have a combination of all of the above types of myoclonus. For example, massive epileptic myoclonus in nonprogressive generalized epilepsies could arise from either cortical epileptogenic foci or thalamocortical loops. Erratic myoclonus could be produced by either deafferentated cortical neurons in progressive diseases, or as a combination of a corticothalamic loop and cortical hyperexcitability occurring as myoclonic status in the course of generalized (symptomatic or idiopathic) epilepsy.

Epileptic cortical myoclonus is further subdivided into spontaneous cortical myoclonus, reflex cortical myoclonus, and epilepsia partialis continua. Cortical myoclonus may be focal or multifocal. Patients with cortical myoclonus commonly have both positive and negative myoclonus, together or independently. Cortical myoclonus is usually more severe than other categories of myoclonus, and patients often develop generalized convulsive seizures. In progressive encephalopathies, myoclonus is of the cortical type. Epilepsia partialis continua is a distinct form of cortical myoclonus caused by various heterogeneous conditions in children and adults. It is defined as “spontaneous, regular or irregular, clonic muscle twitching of cerebral cortical origin, sometimes aggravated by action or sensory stimuli, confined to 1 part of the body, and continuing for a period of hours, days or weeks.” The twitching is limited to a muscle or a small group of contiguous or unrelated muscles on 1 side of the body. Agonist and antagonist muscles are simultaneously contracted. Facial and hand muscles are preferentially affected. Activation of myoclonus by reflex action, movement, or other means is characteristic in some patients.

Action myoclonus in Unverricht-Lundborg disease)

(a) On execution of a requested movement (“raise your right hand toward the head”) intense repeated myoclonias maximal in the agonist arm muscles are followed by atonias of long (more than 500 ms) duration, with or without multipl...
Epilepsia partialis continua of unknown cause

(Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP. The epilepsies: seizures, syndromes and management. Oxford: Bladon Medical Publishing, 2005.)
Unverricht-Lundborg disease clinical manifestations

This 18-year-old girl has Unverricht-Lundborg disease that began at 12 years of age with action myoclonus and generalized tonic-clonic seizures. Despite major antimyoclonic therapy, including valproate, phenobarbital, benzodiazepi...
Focal clonic seizure of epilepsia partialis continua progressing to hemiconvulsions

Video-EEG of a 12-year-old girl with epilepsia partialis continua of unknown etiology. Note fast (3 to 10 Hz) twitching of the left eyelid also spreading to the right side. The seizure progressed to left-sided tonic and then cloni...

Epileptic negative myoclonus. Focal or generalized, epileptic negative myoclonus is a motor symptom characterized by abrupt and brief (< 500 ms) interruption of tonic muscle activity, not preceded by any enhancement of EMG activity (74; 71; 46). Negative myoclonus of cortical origin may be associated with an EEG spike or spike-wave complex, but it is often difficult to establish exactly the temporal and spatial relationship between the EMG silent period and the associated EEG spike on conventional EEG/EMG recordings. Patients may manifest with positive and negative myoclonus in various proportions, either independently or in combination. When both forms of myoclonus occur in combination, the abrupt increase in muscle discharge (positive myoclonus) often precedes the onset of the silent period (negative myoclonus), but occasionally follows its offset. In these cases, it is often difficult to determine precisely whether the EEG spike is directly related to the activated or inhibited EMG phase.

Negative myoclonus in Lafora disease

EEG and EMG details. Negative myoclonic drops of the fingers and hands are documented with suppression of the EMG activity (arrows). This shows some inconsistent correlation with fast diffuse bursts of polyspikes and polyspike-wav...
Negative myoclonus in Lafora disease (video-EEG)

This 17-year-old boy had at age 14 years generalized convulsive seizures and simple focal occipital seizures with elementary visual hallucinations. Progressive and severe cognitive deterioration started soon after onset of the epi...

In recent proposals of the ILAE Commission myoclonic seizures are grouped as:

• Myoclonic seizures
• Negative myoclonus
• Myoclonic tonic seizures, and
• Myoclonic atonic seizures

Myoclonic absences and eyelid myoclonia are considered as absence seizures with special features (04; 14). Focal myoclonic seizures are classified amongst motor focal seizures.

A complete description of myoclonic seizures, negative myoclonus, and myoclonic-atonic seizures is provided in the ILAE diagnostic manual as follows (14):

A myoclonic seizure is a single or series of jerks (brief muscle contractions). Each jerk is typically milliseconds in duration. Myoclonic status epilepticus is characterized by ongoing (> 30 minutes) irregular jerking, often with partially retained awareness.

NOTE: Myoclonic seizures are one type of seizure that can result in a "drop attack" (also known as astatic seizure), other causes of drop attacks include tonic, atonic, and myoclonic-atonic seizures.

Ictal EEG: The myoclonic jerk correlates with a generalized spike-and-wave or polyspike-and-wave.

A negative myoclonic seizure is a seizure with brief cessation of background muscle tone, lasting less than 500 milliseconds. The resulting movement produced can have two components, an initial loss of posture caused by the negative myoclonus, and a subsequent voluntary, compensatory movement to restore posture. Negative myoclonic seizures may occur in isolation or in a series.

Ictal EEG: Negative myoclonus is seen in association with the spike of a spike or spike-and-wave discharge on EEG.

A myoclonic-atonic seizure is a myoclonic seizure followed by an atonic seizure. Sometimes a series of myoclonic jerks occurs prior to the atonia. The head and limbs are affected, typically resulting in rapid fall. The myoclonic jerk may be subtle.

NOTE: Myoclonic-atonic seizures are one type of seizure that can result in a "drop attack" (also known as astatic seizure), other causes of drop attacks include myoclonic (especially in younger children), tonic and atonic seizures.

Ictal EEG: The myoclonic component is associated with a generalized spike or polyspike. The atonic component is associated with the aftergoing high voltage slow wave.

CAUTION Focal discharges are not seen; consider structural brain abnormality.

Finally, according to the newest ILAE position papers on seizures (28; 27):

	Myoclonic seizures can be of either focal or generalized onset.
	New generalized seizure types are myoclonic-atonic seizures, common in epilepsy with myoclonic-atonic seizures (Doose syndrome), myoclonic-tonic-clonic seizures common in juvenile myoclonic epilepsy, myoclonic absence and absence seizures with eyelid myoclonia seen in the syndrome described by Jeavons and elsewhere.

However, in this paper, absences are classified as "generalized nonmotor (absence) seizures," though this (nonmotor) does not convey the complex semiology of absence seizures, which often manifest with significant motor manifestations such as myoclonic jerks and as analyzed in a narrative review (78).

Clinical manifestations

Presentation and course

The clinical manifestations of epileptic myoclonus vary significantly between syndromes and diseases manifesting with this type of seizure, and it is often associated with other seizures and neurologic and cognitive symptoms (see, for example, MedLink clinical summaries Juvenile myoclonic epilepsy, Dravet syndrome, Unverricht-Lundborg disease, and Lafora disease).

Myoclonic jerks are shock-like, irregular, and often arrhythmic, unidirectional clonic-twitching movements that are singular or repetitive. They are of variable amplitude, force, location, duration, and circadian distribution, and have a number of precipitating factors.

Typical EEG manifestations of polyspikes during generalized myoclonic seizures

(Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994;35(2):285-96.)
Myoclonic jerks in myoclonic epilepsy in infancy (video EEG)

Clinically, the first symptom was a sudden jerk of the head and shoulders backwards. This coincided with a giant (approximately 1 mV) spike or multispike-slow-wave followed by rhythmic slow activity at around 3 to 5 Hz, together w...
Marked myoclonic jerks in juvenile myoclonic epilepsy (video EEG)

Note the asymmetrical onset of the discharges and that the myoclonic jerks occur during the polyspike phase of the EEG discharge. (Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP. A Clinical Guide to Epileptic Syndromes ...
Juvenile myoclonic epilepsy (1)

Marked myoclonic jerks in juvenile myoclonic epilepsy. Note the asymmetrical onset of the discharges and that the myoclonic jerks occur during the polyspike phase of the EEG discharge. (Used with permission from: Panayiotopoulos C...
Juvenile myoclonic epilepsy (2)

Marked myoclonic jerks on awakening in a boy with juvenile myoclonic epilepsy. Consciousness is intact. (Courtesy of Professor Pierre Thomas from: The Educational Kit on Epilepsies. Volume 2: Idiopathic Generalised Epilepsies With...
Myoclonic epilepsy in infancy

This 3-year-old boy with normal development had brief bilateral myoclonic jerks of the upper limbs. Benign myoclonic epilepsy in infancy was diagnosed, and valproate monotherapy led to a good outcome. (Courtesy of Professor Edouar...
Myoclonic status epilepticus progressing to generalized clonic-tonic-clonic seizure in juvenile myoclonic epilepsy

This 17-year-old untreated girl was admitted with early morning myoclonic jerks that started 3 months earlier. During a full-night video-EEG recording, she showed repetitive bilateral myoclonic jerks of the upper limbs that progre...
Spontaneous and photically induced myoclonic jerks in a girl with Jeavons syndrome

A girl aged 15 years with Jeavons syndrome (eyelid myoclonia with absences) had epileptic seizures that were spontaneous or reflex-elicited by eye closure and photic stimulation. Ictal clinical manifestations consisted of jerks of...

Epileptic myoclonus is commonly accompanied by generalized EEG discharges of mainly polyspikes, as in generalized epilepsies (15). However, the ictal EEG may show focal abnormalities only (idiopathic reading epilepsy), be entirely normal, or require processing using jerk-locked back-averaging techniques.

The myoclonic jerks may be:

• generalized, such as myoclonic jerks in juvenile myoclonic epilepsy;
• segmental, such as eyelid myoclonia in Jeavons syndrome;
• focal, such as epilepsia partialis continua of Kozhevnikov or jaw myoclonus of reading epilepsy;
• mild, causing minor and inconspicuous flickering, or massive with traumatic falls;
• arrhythmic or oscillatory (often resembling a very fast tremor);
• spontaneous or reflex (photic, acoustic, somatosensory, reading), or action-induced (movement or intention to move);
• positive or negative;
• related to sleep, awakening, or alert stages; or
• brief bursts or repetitive and continuous for hours and sometimes for days.

The clinical manifestations of myoclonic seizures show significant differences between idiopathic generalized epilepsy, such as juvenile myoclonic epilepsy, and progressive myoclonic epilepsies, such Lafora disease.

Juvenile myoclonic epilepsy. In juvenile myoclonic epilepsy, the myoclonic jerks are shock-like, irregular, and arrhythmic clonic movements of proximal and distal muscles, mainly of the upper extremities. They are of variable amplitude and force. They are often mild, restricted in the fingers or hands, making the patient prone to drop things unexpectedly or look clumsy. They are sufficiently violent to cause falls in more than half of the patients. The same patient usually experiences mild and violent jerks. One-fifth of the patients describe their jerks as unilateral, probably because jerks of the dominant hand become more apparent. Video-EEG studies on these patients show that the jerks affect both sides.

Marked myoclonic jerks in juvenile myoclonic epilepsy (video EEG)

Note the asymmetrical onset of the discharges and that the myoclonic jerks occur during the polyspike phase of the EEG discharge. (Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP. A Clinical Guide to Epileptic Syndromes ...

Consciousness is not impaired during the jerks. However, patients with pronounced myoclonic jerks and myoclonic status epilepticus may complain of lack of awareness. This may be due either to the distress caused by the continuous jerks or, most likely, to mild absences interspersed with jerks.

The myoclonic jerks of juvenile myoclonic epilepsy generally appear when the patient reaches their mid-teens, usually preceding the appearance of generalized tonic-clonic seizures by a few months. Some patients (less than 10%) with mild forms of juvenile myoclonic epilepsy never develop generalized tonic-clonic seizures, probably as the result of early diagnosis and treatment. Myoclonic jerks characteristically occur after awakening, particularly after sleep deprivation and excessive alcohol consumption. Patients who do not demonstrate this circadian pattern probably do not belong to juvenile myoclonic epilepsy but to other syndromes such as juvenile absence epilepsy. Myoclonic jerks are independent of typical absences and do not occur during the absence ictus. A series of myoclonic jerks often heralds generalized tonic-clonic seizures (clonic-tonic-clonic generalized convulsions).

Lafora disease. In Lafora disease, the jerks are massive and synchronous bilateral myoclonic jerks of brief duration, usually limited to 1 or more muscle groups. The myoclonic jerks are not associated with loss of consciousness and are usually triggered by visual stimulation or proprioceptive impulses. Epileptic visual seizures with elementary visual hallucinations may be an early sign of the disease. With progression, myoclonus increases in intensity and becomes severe and multifocal, precipitated by posture or action. At this point, intellectual deterioration occurs rapidly. A terminal stage of severe dementia, spastic quadriparesis, and almost constant myoclonic seizures is reached within 2 to 10 years after the onset of symptoms.

Negative myoclonus in Lafora disease (video-EEG)

This 17-year-old boy had at age 14 years generalized convulsive seizures and simple focal occipital seizures with elementary visual hallucinations. Progressive and severe cognitive deterioration started soon after onset of the epi...

Jerks of massive bilateral myoclonus mainly involve the upper limbs, with elevation of the shoulders producing slight contraction of the trunk. 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 and 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 the child up each time he or she starts to fall asleep. Jerks may also be precipitated by photic stimulation.

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 juvenile myoclonic epilepsy and in myoclonic epilepsy in infancy (19).

Myoclonic status epilepticus. Generalized myoclonic status epilepticus usually results from lack of avoidance of precipitating factors and/or inappropriate use of antiepileptic drugs (35). In idiopathic generalized epilepsy, it is more common in juvenile myoclonic epilepsy (mainly limb jerks), and consciousness may be unaffected. Myoclonic status epilepticus of perioral, eyelid, myoclonic absence epilepsy, and Doose syndrome usually manifests with myoclonus intermixed with or superimposed on absence seizures. Myoclonic status epilepticus often terminates with generalized tonic-clonic seizures.

Myoclonic status epilepticus progressing to generalized clonic-tonic-clonic seizure in juvenile myoclonic epilepsy

This 17-year-old untreated girl was admitted with early morning myoclonic jerks that started 3 months earlier. During a full-night video-EEG recording, she showed repetitive bilateral myoclonic jerks of the upper limbs that progre...

Myoclonic status epilepticus is commonly encountered in progressive myoclonic epilepsies, Dravet syndrome, and myoclonic encephalopathy in nonprogressive disorders of mainly chromosomal disorders such as Angelman syndrome, prenatal brain anoxia-ischemia, and congenital abnormalities. In the latter syndrome, myoclonic jerks are predominantly asymmetrical and asynchronous, consciousness is often severely affected, and the condition lasts for weeks, months, or even years, with persistent deterioration of mental function. This type of myoclonic status epilepticus usually starts insidiously with progressive deterioration of consciousness and drooling, and the patient becomes more and more ataxic (08; 21). The EEG shows continuous generalized asynchronous slow-wave activity intermingled with multifocal spikes, occasionally resulting in spike-wave complexes.

Acute symptomatic myoclonic status epilepticus after prolonged anoxia or other severe metabolic insults consists of very brief, sudden movements of restricted parts of the body that may be triggered by external stimuli, such as mechanical ventilation. Myoclonic status epilepticus of nearly continuous myoclonus may appear several hours after cardiac arrest and lasts for many days (45).

Negative myoclonic status epilepticus has been reported with subcontinuous negative myoclonus manifesting with segmental or axial loss of muscle tone. This condition may persist for days or months. Failing attempts to oppose gravity during the episodes of loss of tone produces jerk-like negative motor effects, which do not occur when the patient lies down. There is no positive myoclonus. The EEG shows continuous spike-waves during slow-wave sleep.

Prognosis and complications

Prognosis varies significantly depending on etiology and the type of epilepsy. It is relatively good in juvenile myoclonic epilepsy, poor in Dravet syndrome, and desperate in Lafora disease.

Clinical vignette

Case 1. Juvenile myoclonic epilepsy. A 38-year-old woman with juvenile myoclonic epilepsy experienced the onset of myoclonic jerks and generalized tonic-clonic seizures beginning in her mid-teens. She also had minor absences of which she was not aware, although these were documented with video EEG. She had frequent violent myoclonic jerks in the morning, which often ended with generalized tonic-clonic seizures. She had been treated with the inappropriate medications phenytoin and carbamazepine up to the age of 33 years, when she was referred for an EEG. EEG documented myoclonic status epilepticus with repetitive myoclonic jerks interspersed with mild absences. Subsequently, she remained free of generalized tonic-clonic seizures for 5 years of follow-up on valproate monotherapy. Myoclonic jerks occurred only occasionally on awakening after sleep deprivation.

Marked myoclonic jerks in juvenile myoclonic epilepsy (video EEG)

Note the asymmetrical onset of the discharges and that the myoclonic jerks occur during the polyspike phase of the EEG discharge. (Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP. A Clinical Guide to Epileptic Syndromes ...
Juvenile myoclonic epilepsy (1)

Marked myoclonic jerks in juvenile myoclonic epilepsy. Note the asymmetrical onset of the discharges and that the myoclonic jerks occur during the polyspike phase of the EEG discharge. (Used with permission from: Panayiotopoulos C...

Case 2. Myoclonic epilepsy in infancy. At 3 years of age, an otherwise normal girl developed frequent and violent myoclonic jerks, mainly in the head and shoulders, with grunting noises but no impairment of consciousness. These were spontaneous and occurred day and night. Routine EEG 6 weeks from the onset of the jerks documented forceful jerks. The seizures stopped only when clonazepam was added to valproate (valproate was probably not needed). At 6 years of age, she was no longer on medication, had developed well, was free of seizures, and had a normal EEG.

Myoclonic jerks in myoclonic epilepsy in infancy (video EEG)

Clinically, the first symptom was a sudden jerk of the head and shoulders backwards. This coincided with a giant (approximately 1 mV) spike or multispike-slow-wave followed by rhythmic slow activity at around 3 to 5 Hz, together w...

Case 3. Epilepsia partialis continua of unknown cause. An intelligent 12-year-old girl had epilepsia partialis continua, which started at 4 years of age and continued to the present with increasing frequency and duration. Fast (3 to 10 Hz) twitching of the left eyelid occurred simultaneously with the left rectus abdominis (she pointed close to the midline by the umbilicus) and a muscle in the armpit (probably the latissimus dorsi). This lasted from hours to 2 to 3 days and was continuous day and night. It was interspersed with ipsilateral left-sided, focal tonic-clonic motor seizures mainly affecting the face and upper limb. Additionally, there was postictal, and probably ictal, left hemiparesis, mainly of the upper limb. She did not lose consciousness during these attacks and communicated well. She was also able to understand, but could not speak, during the focal motor seizures. She had never had a full-blown generalized tonic-clonic seizure.

Epilepsia partialis continua of unknown cause

(Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP. The epilepsies: seizures, syndromes and management. Oxford: Bladon Medical Publishing, 2005.)
Focal clonic seizure of epilepsia partialis continua progressing to hemiconvulsions

Video-EEG of a 12-year-old girl with epilepsia partialis continua of unknown etiology. Note fast (3 to 10 Hz) twitching of the left eyelid also spreading to the right side. The seizure progressed to left-sided tonic and then cloni...

Initially, the seizures occurred once or twice per year but presently occurred every 2 weeks. Neurologic and mental status was normal. High-resolution brain MRI was normal. All appropriate tests for metabolic or other diseases associated with epilepsia partialis continua were normal. Drug treatments have failed; only rectal diazepam has provided temporary relief during the attacks.

Biological basis

Localization

Myoclonic seizures can arise from either neocortical or subcortical structures and may often be the result of abnormal interactions and connectivity of cortical-subcortical circuits (56; 38; 06; 82; 11; 77; 49). 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 1 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.

Hyperexcitability in the motor pathways permits synchronization in the rolandic and thalamic structures, the discharge in 1 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.

Pathophysiological hypotheses on the origin of negative myoclonus involve subcortical as well as cortical mechanisms. Neuroimaging and neurophysiologic investigations, including intracerebral recordings and electrical stimulation procedures in epilepsy, suggest the participation of premotor, primary motor, primary sensory, and supplementary motor areas in the genesis of negative myoclonus (70; 71).

Pathophysiology

The pathophysiology of myoclonus is complex. There are several genetic, chemical, and electrical stimulation models in animals that have provided significant insights on the basic circuitry and neurochemistry of myoclonus, though much additional work is needed.

The pathophysiology of myoclonic seizures depends on whether these are cortical or thalamocortical (cortical-subcortical) (56; 38; 06; 11; 77).

Cortical epileptic myoclonus is generated by a focal cortical discharge as demonstrated by a focal EEG transient back-averaged before the myoclonus EMG burst.

Epilepsia partialis continua of unknown cause

(Courtesy of C P Panayiotopoulos. From: Panayiotopoulos CP. The epilepsies: seizures, syndromes and management. Oxford: Bladon Medical Publishing, 2005.)

The myoclonus is focal or multifocal with frequent spreading. Examples include cortical reflex posthypoxic myoclonus, many instances of progressive myoclonic epilepsy, and epilepsia partialis continua.

Cortical myoclonus is precipitated by a cortical transient that represents an abnormal sudden and synchronous discharge of pyramidal neurons in the context of diffuse brain pathology. At this point, it is difficult to have confidence in a more specific mechanistic explanation. As far as the intrinsic cortical mechanism is concerned, the end result may be a “lack of inhibition of cortical neurons.” However, it is not known whether this constitutes a lack of inhibitory inputs, rebound excitation from excessive inhibition, alteration of intrinsic pyramidal neuron firing properties, or some combination of these mechanisms to cause sensorimotor pyramidal neurons to discharge too synchronously. It is critical to decipher which of these possibilities is important and how its basic mechanism may be treated (11).

Cortical-subcortical myoclonus of generalized epilepsies arises from paroxysmal, abnormal, and excessive oscillation in bidirectional connections between cortical and subcortical sites. This is associated with generalized polyspike EEG discharge (4 to 6 Hz for juvenile myoclonic epilepsy, slow spike-wave for epileptic encephalopathies).

Myoclonic seizures can be induced by photic stimulation in baboons, such as Papio papio, and are associated with dysfunction of GABAergic and monoaminergic neurotransmission (58). Seizures in this model appear to originate in the cerebral cortex.

In the tottering mouse, myoclonic seizures are also associated with abnormal monoaminergic circuits. The Otx1-/- mouse and flathead mutant rat both exhibit myoclonic seizures, which may be related mainly to loss of GABAergic interneurons. Myoclonic seizures can be induced in rats by a number of chemoconvulsant agents, including pentylenetetrazol, bicuculline, picrotoxin, flurothyl, and other compounds; all of these reduce neurotransmission at GABAA receptors, among other actions. In these models, isolated myoclonic seizures typically lead to and precede full-blown tonic-clonic seizures and, in this respect, may differ from human-isolated myoclonus (06).

The putative involvement of the cerebellum in the pathogenesis of cortical myoclonic syndromes has been long hypothesized, as neuropathological changes in patients with cortical myoclonus have most commonly been found in the cerebellum rather than in the suspected culprit, the primary somatosensory cortex. A model of increased cortical excitability due to loss of cerebellar inhibitory control via cerebello-thalamo-cortical connections has been proposed, though evidence remains equivocal (32). An important factor that may play a role in the expression of myoclonic/clonic seizures is the maturation of the endogenous brain mechanisms involved in seizure control (82). One of the structures involved in the regulation of the myoclonic seizures is the substantia nigra pars reticulata. The seizure-modulating effects are mediated chiefly via GABA A receptors. The substantia nigra pars reticulata has a strategic position in the brain influencing the output of the basal ganglia network--the thalamus, superior colliculus, and reticular formation, and back to the striatum. Disturbances in this network give rise to abnormal movements, including myoclonic seizures. There is evidence that substantia nigra pars reticulata-based seizure modulation has age-, sex-, and region-specific features that must be taken into account when novel treatments are contemplated (82; 37).

Several genes or loci have been associated with conditions manifesting myoclonic seizures, including GABA receptor, chloride or calcium channels, EF-hand domain containing protein 1 (EFHC1) for juvenile myoclonic epilepsy, cystitis B for Unverricht-Lundborg disease, EPM2A or EPM2B for Lafora disease, potassium channels (KCNC1 for myoclonus epilepsy and ataxia due to potassium channel mutation), battening and other genes linked to neuronal ceroid lipofuscinosis, sodium channels for Dravet syndrome, GABA transporter 1 (GAT1) for myoclonic-atonic epilepsy, kinesis family member 5A (KIF5A) for neonatal intractable myoclonus, and many others. Mitochondrial diseases can also manifest with myoclonus, such as myoclonus epilepsy with ragged-red fibers. Familial adult myoclonic epilepsy has been linked to chromosomal or genetic abnormalities, such as contactin-2 (CNTN2). Creutzfeldt-Jakob disease is a prion disease. For a more exhaustive list, please see (20). Autoimmune etiologies have also been reported.

Differential diagnosis

Confusing conditions

There is a long list of epileptic and nonepileptic paroxysmal events that should be differentiated from myoclonic seizures (65; 14). This first requires skillful assessment of the clinical and family history of the patient, such as distribution, temporal profile, and activation characteristics of the myoclonic movement; age at onset and progression; other types of seizure; neurologic and cognitive state; and other family members with similar events. Neurophysiologic tests and, particularly, polygraphic recordings are often mandatory for the proper diagnosis.

Broadly, the differential diagnosis is to exclude nonepileptic myoclonus such as hyperekplexia and associated diseases, as well as normal events such as hypnagogic myoclonus, hiccups, benign myoclonus of sleep, and tics.

Once the epileptic nature of the symptoms has been established, the distinction should be made between myoclonic and other types of epileptic seizure. Myoclonic seizures are briefer than tonic seizures and epileptic spasms. Myoclonic seizures are single or irregularly recurrent events, as opposed to clonic seizures, which are rapid rhythmically recurrent myoclonic-like events. Clonic seizures are rhythmical, regular repetitive myoclonic jerks at 2 to 3 Hz (range 1 to 5 Hz). Tonic seizures comprising a sustained increase in muscle contraction usually last a few seconds (> 2 to 10 seconds), but occasionally last minutes. They may be segmental or axial, and of variable severity, from inconspicuous to violent. They are associated with EEG flattening or low-amplitude fast activity. Epileptic spasms are sudden and brief bilateral tonic contractions of the axial and proximal limb muscles with abrupt onset and termination. They usually last for 0.4 to 0.8 seconds (range 0.2 to 2 seconds).

The specific etiology and epileptic syndrome should then be established, with particular emphasis between nonprogressive syndromes (eg, juvenile myoclonic epilepsy and myoclonic epilepsy in infancy), epileptic encephalopathies (eg, Dravet syndrome), progressive myoclonic epilepsies (eg, Unverricht-Lundborg and Lafora disease), and glucose transporter 1 deficiency syndrome (03).

Iatrogenic and drug-induced myoclonus may also need to be differentiated from other forms of nonepileptic or epileptic myoclonus. Serotonin syndrome, for example, may present with myoclonic jerks. Myoclonus can also be seen in older populations with neurodegenerative disorders, including Alzheimer disease, certain forms of Parkinson disease, Huntington disease, and, more classically, Creutzfeldt-Jakob disease. In Creutzfeldt-Jakob disease, myoclonus can be associated with the characteristic periodic discharges that can be detected by EEG studies; however, myoclonus can be seen in the absence of these discharges, suggesting subcortical generators.

Myoclonus can also be seen in certain forms of autoimmune disorders, including Isaac syndrome (neuromyotonia), although stiffness (neuromyotonia) and fasciculations or cramps are more characteristic. EMG is characteristic with neuromyotonic discharges and fibrillation potentials and fasciculations. Autoimmune workup may reveal autoantibodies, such as anti-GAD, anti-Caspr2, and others.

Post-hypoxic myoclonus can also be in the differential in the right setting (40). It manifests within hours from severe hypoxia, can be stimulus-induced, and may sometimes last even after mental status is improved, as described in 1963 for Lance-Adams syndrome. It can be multifocal.

Associated and underlying disorders

Myoclonus and epilepsy syndromes. Epileptic myoclonus is a common symptom in epileptic syndromes.

Idiopathic generalized epilepsies (63; 64; 65). The main and pure forms of myoclonic idiopathic generalized epilepsy in which all patients have myoclonic jerks include the following:

	• Juvenile myoclonic epilepsy. All patients have myoclonic jerks; 90% also have generalized tonic-clonic seizures, and 30% have mild absences.
	• Myoclonic epilepsy in infancy. All patients have myoclonic jerks as the only type of seizure; 20% may develop generalized tonic-clonic seizures in their early teens.
	• Familial adult myoclonic epilepsy is a high-penetrant autosomal dominant condition featuring cortical hand tremors, myoclonic jerks, and occasional/rare convulsive seizures (52). See MedLink Neurology article Benign adult familial myoclonic epilepsy.

Myoclonic seizures occur in a significant number of patients with juvenile absence epilepsy (severe absences are the main type of seizure, but 30% may also have random myoclonic jerks) and idiopathic generalized epilepsy with photosensitivity. In all these syndromes, myoclonic jerks are generalized and manifest in the EEG with generalized spike-waves or polyspike-waves. Myoclonic jerks occur independently and often precede other types of seizure, such as generalized tonic-clonic seizures and absences.

In a number of other generalized epilepsies of unknown etiology, myoclonic jerks are a component of complex seizures combined with absences or other types of seizure. In epilepsy with myoclonic absences, a combination of positive and negative myoclonus often exists. The positive muscle jerk is associated with the positive component of a spike that precedes its negative transient. The negative myoclonus follows the spike by 100 msec, and its onset occurs before that of the slow-wave. In epilepsy with myoclonic-atonic seizures (Doose syndrome), loss of muscle tone (postmyoclonic atonia) immediately follows the myoclonic jerks. Eyelid myoclonia with absences (Jeavons syndrome) is a reflex syndrome of idiopathic generalized epilepsy with predominant eyelid myoclonia alone or followed by a brief and mild absence. Myoclonic absences, myoclonic-atonic seizures, and eyelid myoclonia may often occur in structural etiology generalized epilepsies. In all types of generalized epilepsy of unknown etiology, the myoclonic jerks are probably of cortical-subcortical origin.

Idiopathic focal epilepsies. Idiopathic reading epilepsy is a characteristic syndrome with focal jaw myoclonus. In idiopathic focal epilepsies, such as Rolandic epilepsy and Panayiotopoulos syndrome, positive and negative myoclonus may occur in atypical evolutions or they may be induced by carbamazepine. EEG shows continuous spike-waves during slow-wave sleep. In these situations, atypical myoclonic status epilepticus may occur. This manifests with continuous unilateral or bilateral contractions of the mouth, tongue, or eyelids; positive or negative subtle perioral or other myoclonia; dysarthria, anarthria, or speech arrest; difficulties in swallowing; buccofacial apraxia; and hypersalivation.

Epileptic encephalopathies and congenital nonprogressive encephalopathies. Examples of epileptic encephalopathies with myoclonus include the following:

	• Dravet syndrome (severe myoclonic epilepsy of infancy) with massive, forceful, and continuous myoclonus in the vast majority of patients
	• Epilepsia partialis continua
	• Lennox-Gastaut syndrome with myoclonic jerks in 11% to 28% of patients
	• Myoclonic encephalopathy in nonprogressive disorders of mainly chromosomal disorders, such as Angelman syndrome, prenatal brain anoxia-ischemia, and congenital abnormalities
	• Epileptic encephalopathy with continuous spike-and-waves during sleep (mainly negative myoclonus)
	• Neonatal myoclonic encephalopathy with bursts of massive myoclonus and EEG suppression-burst pattern

Progressive myoclonic epilepsies. Progressive myoclonic epilepsies comprise a group of rare heterogeneous genetic (mainly autosomal recessive) disorders (30; 48). They are characterized by myoclonus, other types of epileptic seizures and progressive neurocognitive impairment. The most common and classical forms include the following:

	• Unverricht-Lundborg disease • Lafora disease • Neuronal ceroid lipofuscinoses • Sialidosis cherry-red spot myoclonus syndrome • Mitochondrial encephalopathy with ragged-red fibers • Dentatorubral-pallidoluysian atrophy
Less common forms include the following:
	• Alpers syndrome • Familial encephalopathy with neuroserpin inclusion bodies • Gaucher disease (type 3a) • Huntington disease (juvenile form) • The action-myoclonus renal-failure syndrome
Some authorities also include the following in progressive myoclonic epilepsies:
	• Angelman syndrome • Autosomal dominant cortical tremor, myoclonus, and epilepsy (benign adult familial myoclonic epilepsy, familial cortical tremor with epilepsy)

However, these are not progressive disorders, though epileptic cortical myoclonus may be a prominent and severe symptom.

Other syndromes or diseases included by some authors in progressive myoclonic epilepsies are Krabbe leukodystrophy, myoclonic encephalopathy and macular degeneration, atypical inclusion body disease, pantothenate-kinase-associated neurodegeneration (formerly Hallervorden-Spatz disease), infantile neuroaxonal dystrophy (Seitelberger disease), coeliac disease, GM2 gangliosidosis (Tay-Sachs disease), and early-onset Alzheimer disease (30 to 40 years of age). However, either these disorders are extremely rare, or epileptic myoclonus, when it occurs, is an occasional and exceptional clinical feature.

Myoclonic occipital photosensitive epilepsy with dystonia. This is a newly described epilepsy syndrome of autosomal dominant inheritance that involves a spectrum of phenotypes from juvenile myoclonic epilepsy, sometimes with an idiopathic occipital photosensitive epilepsy overlap, to progressive myoclonus epilepsy with paroxysmal dystonia (72).

Diagnostic workup

A comprehensive history of the illness, personal history, and family history, and a thorough clinical examination, are imperative and often sufficient to make a correct diagnosis of myoclonus. Important diagnostic clues for myoclonus include the following:

• Characteristic history of myoclonic jerks
• The site, distribution, and clinical manifestations of myoclonus
• Precipitating factors and stimuli that provoke myoclonus
• Effect of voluntary activity
• Circadian distribution
• Associated residual or progressive neurologic and cognitive impairment
• The presence of other types of epileptic seizures
• Age at onset and progression
• Family history of myoclonus
• Drugs or toxins that may induce myoclonus

Following the clinical assessment, there may be a need for certain diagnostic procedures, which are determined by the type, duration of, and possible etiology of myoclonus, as well as the age and neurologic and general physical status of the patient (13; 74; 54). They may include the following:

• Clinical neurophysiological testing
• Full blood and urine tests, including screening for metabolic disorders, toxic substances, and drugs
• Full biochemical and autoantibody screen
• Brain imaging (preferably magnetic resonance imaging)
• Examination of cerebrospinal fluid for acute-onset myoclonus
• Enzyme assays of urine and blood
• Molecular genetic testing
• Appropriate tissue biopsy
• Brain biopsy

Electrophysiological studies provide useful information for the diagnosis and classification of myoclonus (74; 10; 84). Routine and follow-up EEG is useful in determining the following:

	• Whether the myoclonus is epileptic or nonepileptic (not always easy because epileptic myoclonus can occur without EEG changes)
	• Whether there is an underlying progressive disorder (deterioration of background in serial EEGs)
	• Whether there is reflex precipitation of myoclonus (photic, somatosensory, reading, or other stimuli)

For the pathophysiologic categorization of myoclonus (cortical, thalamocortical), the following neurophysiological techniques are used:

• EEG with simultaneous surface EMG
• Jerk-locked back-averaging
• Measurement of evoked potentials
• Paired stimulation evoked potentials and long-loop reflex
• Corticomuscular coherence and frequency analysis

Epilepsia partialis continua in a 26-year-old man

Neurophysiological investigations in a 26-year-old man with onset of epilepsia partialis continua at the age of 25. (A,C) Dermatomal and somatosensory potentials are gigantic on the right side (from stimulation of the left). Note ...

Polygraphic monitoring is essential for the diagnosis of negative epileptic myoclonus, allowing the demonstration of brief interruptions of a tonic EMG activity, not preceded by a positive myoclonus in the agonist and antagonist muscles of the affected limb. Simultaneous EEG-EMG monitoring demonstrating the association of negative myoclonus with an epileptic potential is consistent with the diagnosis of epileptic negative myoclonus (71).

Action myoclonus in Unverricht-Lundborg disease)

(a) On execution of a requested movement (“raise your right hand toward the head”) intense repeated myoclonias maximal in the agonist arm muscles are followed by atonias of long (more than 500 ms) duration, with or without multipl...
Negative myoclonus in Lafora disease

EEG and EMG details. Negative myoclonic drops of the fingers and hands are documented with suppression of the EMG activity (arrows). This shows some inconsistent correlation with fast diffuse bursts of polyspikes and polyspike-wav...

Transcranial magnetic stimulation may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of myoclonus (61). According to 1 review, transcranial magnetic stimulation studies have detected abnormalities in motor cortex excitability and sensorimotor plasticity. Well-defined motor cortical excitability patterns can be identified in the different disorders characterized by myoclonus. The most consistent finding is a decrease in intracortical inhibition. Short-interval intracortical inhibition is reduced in myoclonic epilepsies. Unlike the juvenile and the benign myoclonus epilepsy, long-interval intracortical inhibition, interhemispheric inhibition, and sensorimotor integration were altered in patients with progressive myoclonic epilepsies. Furthermore, repetitive transcranial magnetic stimulation might have therapeutic potential at least in some patients with myoclonus (61).

A novel diagnostic approach to patients with myoclonus has been described (85). The initial step is to confirm whether the movement disorder phenotype is consistent with myoclonus and to define its anatomical subtype. The next steps are aimed at identification of both treatable acquired causes and those genetic causes of myoclonus that require a diagnostic approach other than next-generation sequencing. Finally, other genetic diseases that could cause myoclonus can be investigated simultaneously by next-generation sequencing techniques. To facilitate next-generation sequencing diagnostics, the authors provide a comprehensive list of genes associated with myoclonus (85).

Management

Good management of myoclonic seizures demands a thorough clinical and investigative approach in order to identify their cause and the needs of the patient (53; 76). Myoclonic seizures will usually resolve if the offending agent is withdrawn (drug- or toxin-induced myoclonus), if the metabolic disturbance is corrected (eg, hyponatremia or nonketotic hyperglycemia), or the treatment of the underlying disease is effective. Management also depends on whether the myoclonic seizures are severe or mild, static or progressive, and occur alone or in combination with other types of seizure (focal or generalized, convulsive or nonconvulsive). It should also be emphasized that current management is not limited to seizure control but includes measures to achieve optimal health-related quality of life with regard to the physical, mental, and psychological functioning of the patient within his/her family, and educational and social environment (80; 81).

Antiseizure medications are the basis of the symptomatic treatment of epileptic myoclonus (83; 67; 57; 73; 50; 12; 76). However, the selection of an antiseizure medication and its dosage is demanding. The antiseizure medication chosen should possess true antimyoclonic efficacy and should also be beneficial for any other types of coexisting seizure. The antiseizure medication safety profile is of paramount importance and may vary significantly depending on the patient's neurocognitive stage, age, and sex. Monotherapy is preferred, but polytherapy is often unavoidable, particularly in patients with progressive myoclonic epilepsy, either because of worsening myoclonus with the progression of the disease or the presence of multiple types of seizure. More than half of the current antiseizure medications make myoclonus worse or do not treat it effectively.

Currently, there is no preventive or curative treatment for most progressive myoclonic epilepsy. Despite significant advances in the management of some aspects of progressive myoclonic epilepsy, the neurologic manifestations are resistant to any treatment. For example, bone marrow transplantation may be curative for Gaucher disease type 1 and enzyme replacement therapy may be successful in reversing systemic manifestations, but neither of these has proven beneficial in the neurodevelopment of Gaucher disease type 3 or myoclonus. Management of progressive myoclonic epilepsy is, therefore, often only supportive and palliative (62). It includes the following:

	• Symptomatic treatment of myoclonus and other epileptic seizures with appropriate antiseizure medications
	• Appropriate management of psychiatric problems, including treatment with psychotropic medications (which sometimes exacerbate or induce myoclonus and other epileptic seizures)
	• Adaptation of educational programs and physical therapy to the patient’s physical and cognitive abilities
	• Supporting the family
	• Genetic counseling

Patients and their families have immense needs from the time that progressive myoclonic epilepsy (even 1 of the mildest forms) is first diagnosed. Medical therapeutic support is important but alone is not sufficient to achieve an acceptable quality of life. This requires a coordinated approach involving a wide range of healthcare professionals, including physicians, specialist nurses, psychologists, psychotherapists, and pharmacists (81).

Symptomatic treatment of myoclonus usually starts with a single appropriate antimyoclonic antiseizure medication, but this is often effective only in the initial stages of the disease and only for a few months. As the disease progresses, the myoclonus becomes relentlessly worse and requires multiple combinations and high doses of antiseizure medications. This may, in turn, increase the number of adverse effects and worsen the already disturbed neurologic and mental state of the patient.

Clonazepam, valproate, levetiracetam, topiramate, and zonisamide are antiseizure medications with antimyoclonic efficacy (65; 24; 12; 76). Piracetam is specifically effective against cortical myoclonus of progressive myoclonic epilepsy and myoclonus of hypoxic encephalopathy. Ethosuximide is mainly effective in negative myoclonus. Clobazam and phenobarbitone are secondary options. Lamotrigine is often a promyoclonic drug (65; 02). Lamotrigine monotherapy often worsens myoclonus but may be used in combination with another antimyoclonic antiseizure medication for the control of other types of coexisting seizure.

Fast-acting benzodiazepines are used by some patients to overcome temporarily disabling myoclonus during social events and the treatment of myoclonic status epilepticus. Chloral hydrate can be used to control daytime myoclonic exacerbations (68). A ketogenic diet should be considered for patients with severe myoclonic epilepsies such as Dravet syndrome (09). Carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, tiagabine, and vigabatrin may worsen myoclonus and should be avoided.

Clonazepam is probably the most effective antimyoclonic drug for any type of epileptic myoclonus of any cause (65). However, it has a narrow spectrum and, for this reason, is usually prescribed in polytherapy. Clonazepam monotherapy may be the first choice in myoclonic epilepsies in which other types of seizure do not occur or emerge from clusters of myoclonic jerks, such as reading epilepsy, benign myoclonic epilepsy in infancy, and mild forms of juvenile myoclonic epilepsy. Clonazepam alone may not suppress and may even precipitate generalized tonic-clonic seizures. Furthermore, clonazepam may deprive patients of the warning of impending generalized tonic-clonic seizures provided by the myoclonic jerks.

Small doses of clonazepam (0.5 to 2 mg at night) are usually sufficient in most patients with myoclonic jerks due to idiopathic generalized epilepsy. However, in progressive myoclonic epilepsy, doses of 20 to 30 mg/day are often required with the worsening of the disease or the development of tolerance to the drug.

Valproate has been recognized as the most effective drug to treat generalized epileptic seizures of all types and of all causes (65). In juvenile myoclonic epilepsy, for example, valproate monotherapy controls absence seizures in around 75%, generalized tonic-clonic seizures in 70%, and myoclonic jerks in 75% of patients. Its efficacy in focal epilepsies is less impressive and is inferior to carbamazepine. The broad-spectrum efficacy of valproate is ideal for patients with multiple types of seizure.

The major concern with valproate is that it is undesirable in women because of its teratogenic effects and its tendency to cause weight gain and polycystic ovary syndrome. The risk of major congenital malformations with valproate monotherapy is 5% to 8% compared with a background risk of 1.6% to 2.5%. This is higher with increasing doses of valproate and is double or more when given in combination with other antiseizure medications, particularly lamotrigine.

Hepatic failure resulting in fatalities occurs mainly in children receiving polypharmacy and with organic brain disease; the risk is 1/600 before the age of 3 years. Acute hemorrhagic pancreatitis is another rare, but serious, adverse effect of valproate in children and is seen particularly with polytherapy (see package insert for valproate).

Levetiracetam is probably the preferred newer antiseizure medication for the treatment of myoclonus (24; 12). It is the likely alternative to replace valproate in the treatment of epileptic myoclonic disorders and, particularly, juvenile myoclonic epilepsy (65).

Despite the lack of randomized trials, it is suggested that levetiracetam appears most effective in patients with cortical myoclonus, whereas clonazepam remains the only first-line therapeutic option in subcortical and spinal myoclonus (24; 12). However, this view may be challenged by the results of numerous studies showing that both of these drugs are effective in all types of epileptic myoclonus (65). For example, clonazepam has been suggested as the preferred antimyoclonic drug for juvenile myoclonic epilepsy and reading epilepsy with jaw myoclonus.

Ethosuximide is as effective as valproate in the treatment of absence seizures. It is also a useful adjunct for the treatment of negative myoclonus, certain types of myoclonic epilepsy, and drop attacks. It does not control generalized tonic-clonic seizures that, from anecdotal reports, may become worse.

Phenobarbital has moderate efficacy in controlling generalized tonic-clonic seizures and myoclonic jerks but may exacerbate absences.

Piracetam has an antimyoclonic efficacy in cortical myoclonus and progressive myoclonic epilepsy.

Perampanel may be effective as an add-on medication in drug-resistant epilepsies with myoclonic seizures (36).

In a case report lacosamide produced a progressive antiseizure effect on Jacksonian motor seizures and subsequently on positive myoclonus, which developed into negative myoclonus before complete resolution (75).

Ketogenic diet is the main treatment of patients with glucose transporter 1 deficiency syndrome (03).

There is a growing interest in the use of cannabidiol for the treatment of severe epilepsies in children, such as Dravet syndrome (17). In June 2018, Epidiolex^® (cannabidiol oral formulation) from GW Pharmaceuticals obtained marketing authorization by the U.S. Food and Drug Administration, becoming the ﬁrst drug to be approved for the treatment of Dravet syndrome in the United States market.

New therapies for refractory myoclonus, including sodium oxybate and even deep brain stimulation, are also being explored with increasing enthusiasm (59; 18).

Media

References

01: Agarwal P, Frucht SJ. Myoclonus. Curr Opin Neurol 2003;16(4):515-21. PMID 12869812
02: Algahtani HA, Aldarmahi AA, Al-Rabia MW, Almalki WH, Bryan Young G. Generalized myoclonus and spasticity induced by lamotrigine toxicity: a case report and literature review. Clin Neuropharmacol 2014;37(2):52-4. PMID 24614666
03: Appavu B, Mangum T, Obeid M. Glucose transporter 1 deficiency: a treatable cause of opsoclonus and epileptic myoclonus. Pediatr Neurol 2015;53(4):364-6. PMID 26385057
04: Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010;51(4):676-85. PMID 20196795
05: Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J Jr. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia 2001;42(9):1212-8. PMID 11580774
06: Blumenfeld H, Novotny EJ. Pathophysiology of myoclonus. In: Panayiotopoulos CP, editor. Volume 2: Idiopathic generalised epilepsies with myoclonic jerks. Oxford: Medicinae, 2007:30-6.
07: Brown P, Farmer SF, Halliday DM, Marsden J, Rosenberg JR. Coherent cortical and muscle discharge in cortical myoclonus. Brain 1999;122 (Pt 3):461-72. PMID 10094255
08: Caraballo RH, Cersosimo RO, Espeche A, Arroyo HA, Fejerman N. Myoclonic status in nonprogressive encephalopathies: study of 29 cases. Epilepsia 2007;48(1):107-13. PMID 17241216
09: Caraballo RH, Cersosimo RO, Sakr D, Cresta A, Escobal N, Fejerman N. Ketogenic diet in patients with Dravet syndrome. Epilepsia 2005;46(9):1539-44. PMID 16146451
10: Cassim F, Houdayer E. Neurophysiology of myoclonus. Neurophysiol Clin 2006;36(5-6):281-91. PMID 17336772
11: Caviness JN. Pathophysiology and treatment of myoclonus. Neurol Clin 2009;27(3):757-77. PMID 19555830
12: Caviness JN. Treatment of myoclonus. Neurotherapeutics 2014;11(1):188-200. PMID 24037428
13: Caviness JN, Brown P. Myoclonus: current concepts and recent advances. Lancet Neurol 2004;3(10):598-607. PMID 15380156
14: Commission on Classification and Terminology of the International League Against Epilepsy 2014. Epilepsy diagnosis 2014. Accessed July 2017. Available at: EpilepsyDiagnosis.org, 2014.
15: Commission of Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981;22(4):489-501. PMID 6790275
16: Commission on Pediatric Epilepsy of the International League Against Epilepsy. Myoclonus and epilepsy in childhood. Epilepsia 1997;38(11):1251-4. PMID 9579929
17: Devinsky O, Nabbout R, Miller I, et al. Long-term cannabidiol treatment in patients with Dravet syndrome: an open-label extension trial. Epilepsia 2019;60(2):294-302. PMID 30582156
18: di Giacopo A, Baumann CR, Kurthen M, Capecchi F, Surucu O, Imbach LL. Selective deep brain stimulation in the substantia nigra reduces myoclonus in progressive myoclonic epilepsy: a novel observation and short review of the literature. Epileptic Disord 2019;21(3):283-8. PMID 31225807
19: 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. PMID 1418473
20: Eberhardt O, Topka H. Myoclonic disorders. Brain Sci 2017;7(8):103. PMID 28805718
21: Elia M. Myoclonic status in nonprogressive encephalopathies: an update. Epilepsia 2009; 50 Suppl 5:41-4. PMID 19469845
22: Engel J Jr. Report of the ILAE classification core group. Epilepsia 2006;47(9):1558-68. PMID 16981873
23: Engel J Jr; International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42(6):796-803. PMID 11422340
24: Espay AJ, Chen R. Myoclonus. Continuum (Minneap Minn) 2013;19(5 Movement Disorders):1264-86. PMID 24092290
25: Fahn S. Overview, history, and classification of myoclonus. Adv Neurol 2002;89:13-17. PMID 11968437
26: Faught E. Clinical presentations and phenomenology of myoclonus. Epilepsia 2003;44 Suppl 11:7-12. PMID 14641566
27: Fisher RS, Cross JH, D'Souza C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 2017b;58(4):531-42. PMID 28276064
28: Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017a;58(4):522-30. PMID 28276060
29: Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46(4):470-2. PMID 15816939
30: Franceschetti S, Michelucci R, Canafoglia L, et al. Progressive myoclonic epilepsies: definitive and still undetermined causes. Neurology 2014;82(5):405-11. PMID 24384641
31: Friedreich N. Paramyoclonus multiplex. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin 1881;86:421-30.
32: Ganos C, Kassavetis P, Erro R, Edwards MJ, Rothwell J, Bhatia KP. The role of the cerebellum in the pathogenesis of cortical myoclonus. Mov Disord 2014;29(4):437-43. PMID 24634361
33: Gastaut H, Broughton R. Epileptic seizures. Clinical and electrographic features, diagnosis and treatment. Springfield, Illinois: Charles C Thomas, 1972.
34: Genton P, Roger J, Guerrini R, et al. History and classification of "myoclonic" epilepsies: from seizures to syndromes to diseases. Adv Neurol 2005;95:1-14. PMID 15508910
35: Gerard EE, Hirsch LJ. Generalized myoclonic status epilepticus. In: Panayiotopoulos CP, editor. Atlas of epilepsies. London: Springer, 2010:523-32.
36: Gil-Lopez FJ, Montoya J, Falip M, et al. Retrospective study of perampanel efficacy and tolerability in myoclonic seizures. Acta Neurol Scand 2018;138(2):122-9. PMID 29573400
37: Giorgi FS, Galanopoulou AS, Moshe SL. Sex dimorphism in seizure-controlling networks. Neurobiol Dis 2014;72 Pt B:144-52. PMID 24851800
38: Guerrini R, Bonanni P, Parmeggiani L, Hallett M, Oguni H. Pathophysiology of myoclonic epilepsies. Adv Neurol 2005;95:23-46. PMID 15508912
39: Guerrini R, Takahashi T. Myoclonus and epilepsy. Handb Clin Neurol 2013;111: 667-79. PMID 23622214
40: Gupta HV, Caviness JN. Post-hypoxic myoclonus: current concepts, neurophysiology, and treatment. Tremor Other Hyperkinet Mov (NY) 2016;6:409. PMID 27708982
41: Hallett M. Early history of myoclonus. Adv Neurol 1986;43:7-10. PMID 3511633
42: Hallett M, Chadwick D, Adam J, Marsden CD. Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus. J Neurol Neurosurg Psychiatry 1977;40(3):253-64. PMID 301926
43: Halliday AM. The clinical incidence of myoclonus. Mod Trends Neurol 1967;4(0):69-105. PMID 4277685
44: Herpin TH. Des access Incomplets d' Epilepsie. JB Ballierre et fils,1867.
45: Hui AC, Cheng C, Lam A, Mok V, Joynt GM. Prognosis following postanoxic myoclonus status epilepticus. Eur Neurol 2005;54(1):10-3. PMID 16015015
46: Inoue Y, Terada K, Dulac O, Rubboli G, Tassinari CA. Generalized myoclonic seizures and negative myoclonus. In: Engel J Jr, Pedley TA, editors. Epilepsy: a Comprehensive Textbook. Second edition. Philadelphia: Lippincott William & Wilkins, 2008:585-99.
47: Janz D, Christian W. Impulsiv-Petit mal. Zeitschrift f Nervenheilkunde 1957;176:346-86.
48: Kalviainen R. Progressive myoclonus epilepsies. Semin Neurol 2015;35(3):293-9. PMID 26060909
49: Kobayashi K, Ohuchi Y, Shibata T, et al. Detection of fast (40-150Hz) oscillations from the ictal scalp EEG data of myoclonic seizures in pediatric patients. Brain Dev 2018;40(5):397-405. PMID 29395662
50: Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord 2011;4:47-62. PMID 21339907
51: Kozhevnikov AYa. A peculiar kind of cortical epilepsy. [Article in Russian] Medicinskoe Obozrenie 1894;v XLII, 14:97-118.
52: Lagorio I, Zara F, Striano S, Striano P. Familial adult myoclonic epilepsy: a new expansion repeats disorder. Seizure 2019;67:73-7. PMID 30928698
53: Levy A, Chen R. Myoclonus: pathophysiology and treatment options. Curr Treat Options Neurol 2016;18(5):21. PMID 27039330
54: Livingston JH. Investigative procedures in IGE with myoclonic jerks: Blood screening and other investigations. In: Panayiotopoulos CP, editor. Volume 2: Idiopathic generalised epilepsies with myoclonic jerks. Oxford: Medicinae, 2007:155-61.
55: Lundborg H. Die progressive Myoklonus-Epilepsie (Unverricht's Myoklonie). Uppsala: Almqvist und Wiksell's Buchdruckerei-A-G, 1903:1-207.
56: Marsden CD, Hallett M, Fahn S. The nosology and pathophysiology of myoclonus. In: Marsden CD, Fahn S, editors. Movement disorders. London: Butterworths, 1982:196-248.
57: Medina MT, Martinez-Juarez IE, Duron RM, et al. Treatment of myoclonic epilepsies of childhood, adolescence, and adulthood. Adv Neurol 2005;95:307-23. PMID 15508934
58: Menini C, Brailowsky S, Silva-Barrat C, Riche D, Naquet R. Cortical GABAergic control of epilepsy in photosensitive baboons. Adv Neurol 1992;57:571-8. PMID 1311897
59: Mills K, Mari Z. An update and review of the treatment of myoclonus. Curr Neurol Neurosci Rep 2015;15(1):512. PMID 25398378
60: Muskens LJJ. Epilepsy: Comparative pathogenesis, symptoms, treatment. London: W. Wood and Co., 1928.
61: Nardone R, Versace V, Holler Y, et al. Transcranial magnetic stimulation in myoclonus of different aetiologies. Brain Res Bull 2018;140:258-69. PMID 29803873
62: Orsini A, Valetto A, Bertini V, et al. The best evidence for progressive myoclonic epilepsy: a pathway to precision therapy. Seizure 2019;71:247-57. PMID 31476531
63: Panayiotopoulos CP. The epilepsies: seizures, syndromes and management. Oxford: Bladon Medical Publishing, 2005a.
64: Panayiotopoulos CP. Idiopathic generalized epilepsies: a review and modern approach. Epilepsia 2005b;46 Suppl 9:1-6. PMID 16302869
65: Panayiotopoulos CP. A clinical guide to epileptic syndromes and their treatment. Revised 2nd edition. London: Springer, 2010.
66: Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994;35(2):285-96. PMID 8156946
67: Pellock JM. Myoclonic epilepsies: syndromes and their treatment. Suppl Clin Neurophysiol 2004;57:425-32. PMID 16106642
68: Pranzatelli MR, Tate ED. Chloral hydrate for progressive myoclonus epilepsy: a new look at an old drug. Pediatr Neurol 2001;25(5):385-89. PMID 11744313
69: Rabot L. De la myoclonie epileptique. Thesis. Paris, 1899.
70: Rubboli G, Mai R, Meletti S, et al. Negative myoclonus induced by cortical electrical stimulation in epileptic patients. Brain 2006;129(Pt 1):65-81. PMID 16272166
71: Rubboli G, Tassinari CA. Negative myoclonus. An overview of its clinical features, pathophysiological mechanisms, and management. Neurophysiol Clin 2006;36(5-6):337-43. PMID 17336779
72: Sadleir LG, Paterson S, Smith KR, et al. Myoclonic occipital photosensitive epilepsy with dystonia (MOPED): a familial epilepsy syndrome. Epilepsy Res 2015;114:98-105. PMID 26088892
73: Sankar R, Wheless JW, Dravet C, et al. Treatment of myoclonic epilepsies in infancy and early childhood. Adv Neurol 2005;95:289-98. PMID 15508932
74: Shibasaki H, Hallett M. Electrophysiological studies of myoclonus. Muscle Nerve 2005;31(2):157-74. PMID 15547927
75: Spalletti M, Comanducci A, Vagaggini A, Bucciardini L, Grippo A, Amantini A. Efficacy of lacosamide on seizures and myoclonus in a patient with epilepsia partialis continua. Epileptic Disord 2013;15(2):193-6. PMID 23761109
76: Striano P, Belcastro V. Update on pharmacotherapy of myoclonic seizures. Expert Opin Pharmacother 2017;18(2):187-93. PMID 28067060
77: Striano P, Zara F. Pathophysiology of myoclonic seizures. In: Panayiotopoulos CP, editor. Atlas of epilepsies. London: Spriengel, 2010:235-42.
78: Unterberger I, Trinka E, Kaplan PW, Walser G, Luef G, Bauer G. Generalized nonmotor (absence) seizures-what do absence, generalized, and nonmotor mean? Epilepsia 2018;59(3):523-9. PMID 29327337
79: Unverricht H. Die myoclonie. Leipzig: Franz Deuticke, 1891:1-128.
80: Valeta T. Impact of epilepsies: overview. In: Panayiotopoulos CP, editor. Atlas of epilepsies. London: Springer, 2010:1361-2.
81: Valeta T. The epilepsy book: a companion for patients. Optimizing diagnosis and treatment. London: Springer, 2017.
82: Veliskova J, Velisek L, Moshe SL. Are children more susceptible to epileptic myoclonic jerks than adults. In: Panayiotopoulos CP, editor. Volume 2: Idiopathic generalised epilepsies with myoclonic jerks. Oxford: Medicinae, 2007:37-50.
83: Wheless JW, Sankar R. Treatment strategies for myoclonic seizures and epilepsy syndromes with myoclonic seizures. Epilepsia 2003;44 Suppl 11:27-37. PMID 14641568
84: Zutt R, Elting JW, van Zijl JC, et al. Electrophysiologic testing aids diagnosis and subtyping of myoclonus. Neurology 2018;90(8):e647-57. PMID 29352095
85: Zutt R, van Egmond ME, Elting JW, et al. A novel diagnostic approach to patients with myoclonus. Nat Rev Neurol 2015;11(12):687-97. PMID 26553594

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Aristea S Galanopoulou MD PhD

Dr. Galanopoulou of Albert Einstein College of Medicine has no relevant financial relationships to disclose.
See Profile

Editor

Solomon L Moshé MD

Dr. Moshé of Albert Einstein College of Medicine has no relevant financial relationships to disclose.
See Profile

Former Authors

C P Panayiotopoulos MD PhD
Jerome Engel Jr MD PhD
Rima Nabbout MD PhD and Olivier Dulac MD (original authors)

Patient Profile

Age range of presentation: 0 month to 44 years
Heredity: Heredity may be a factor. See specific hereditary epileptic syndromes with epileptic myoclonus.

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Myoclonic seizures

Differential Diagnosis

nonepileptic seizure
myoclonic-atonic seizure
atonic seizure
negative myoclonic seizure: often compensatory movement to correct posture follows the negative myoclonic seizure
typical absence (with myoclonic components)
- myoclonic absence seizure
- nonepileptic myoclonus, eg, spinal myoclonus
- tremor
- fasciculation
- hyperekplexia
- hypnagogic myoclonus
- hiccups
- benign myoclonus of sleep
- tics
- clonic seizures
- tonic seizures
- epileptic spasms
- juvenile myoclonic epilepsy
- myoclonic epilepsy in infancy
- Dravet syndrome
- Unverricht-Lundborg disease
- Lafora body disease
- drug-induced myoclonus
- serotonin syndrome
- neurodegenerative disorders
- Alzheimer disease
- certain forms of Parkinson disease
- Huntington disease
- Creutzfeldt-Jakob disease
- autoimmune disorders
- Isaac syndrome
- post-hypoxic myoclonus

Also Relevant

Benign adult familial myoclonic epilepsy
Dravet syndrome
Epilepsy with myoclonic-atonic seizures
Eyelid myoclonia with and without absences
Generalized onset clonic seizures
- Juvenile myoclonic epilepsy
- Lafora disease
- Myoclonic absences
- Myoclonic-atonic seizures
- Myoclonic epilepsy in infancy
- Myoclonus
- Progressive myoclonus epilepsies

Myoclonic seizures …

Myoclonic seizures

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Localization

Pathophysiology

Epidemiology

Differential diagnosis

Confusing conditions

Associated and underlying disorders

Diagnostic workup

Management

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Alcohol withdrawal seizures

Epileptic lesions due to malformation of cortical development

Epileptic spasms

Sleep and epilepsy

Neocortical temporal lobe seizures

Jacksonian seizures

Myoclonic seizures

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Localization

Pathophysiology

Epidemiology

Differential diagnosis

Confusing conditions

Associated and underlying disorders

Diagnostic workup

Management

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Alcohol withdrawal seizures

Epileptic lesions due to malformation of cortical development

Epileptic spasms

Sleep and epilepsy

Neocortical temporal lobe seizures

Jacksonian seizures

This is an article preview.
Start a Free Account
to access the full version.