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Classification and evaluation of myoclonus

Classification and evaluation of myoclonus
Author:
John N Caviness, MD
Section Editor:
Howard I Hurtig, MD
Deputy Editor:
April F Eichler, MD, MPH
Literature review current through: Dec 2022. | This topic last updated: Oct 10, 2022.

INTRODUCTION AND DEFINITION — Myoclonus is a clinical sign that is characterized by brief, shock-like, involuntary movements caused by muscular contractions or inhibitions [1]. Muscular contractions produce positive myoclonus, whereas muscular inhibitions produce negative myoclonus (ie, asterixis). Patients will usually describe myoclonus as consisting of "jerks," "shakes," or "spasms."

Myoclonic movements have many possible etiologies, anatomic sources, and pathophysiologic features [2]. Myoclonus may be classified by clinical presentation, examination findings, clinical neurophysiology testing, and etiology.

This topic will review the classification and evaluation of myoclonus. Treatment is discussed separately. (See "Treatment of myoclonus".)

ANATOMIC AND PHYSIOLOGIC CLASSIFICATION — In addition to the clinical and etiologic classification discussed below, myoclonus can be classified by the localization of the physiologic mechanism that generates it (table 1). The categories are cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral.

This classification paradigm can help with localization of the underlying lesion, aid in the diagnosis of certain disorders that have a characteristic myoclonus physiology, and guide treatment options that may be useful for some physiologic types of myoclonus but not others [3].

Cortical myoclonus originates with a focal discharge from the primary sensorimotor cortex, which causes a myoclonic jerk after a time interval required for corticospinal transmission. This type of myoclonus occurs because of insufficient inhibition within neuronal circuits of the primary motor cortex, primary sensory cortex, or both.

The detailed body mapping found in the sensorimotor cortex explains the common occurrence of multifocal myoclonus when there is bilateral diffuse dysfunction of the sensorimotor cortex. It likewise explains the occurrence of focal myoclonus when the lesion has a focal distribution. Bisynchronous, generalized myoclonus and generalized tonic-clonic seizures may occur when the focal discharge spreads through cortico-cortico and transcallosal pathways [4].

Cortical myoclonus may occur with reflex sensory stimulation (cortical reflex myoclonus), with muscle activation (cortical action myoclonus), with rest (eg, focal motor seizure), or with any combination of the above.

In cortical reflex myoclonus, an exaggerated cortical response to somatosensory stimuli produces the jerk, but subsequently the whole sensorimotor cortex generates giant somatosensory evoked cortical potentials (SEPs) and reflex myoclonus [5]. Rhythmic or semirhythmic discharges from the sensorimotor cortex can produce a repetitive movement that resembles tremor [6].

A unifying pathogenic mechanism for cortical myoclonus remains elusive, and there may be mechanism heterogeneity. The relative contribution of intracortical pathology versus abnormal activity projecting into the sensorimotor cortex is not known. Numerous abnormalities have been suspected to be important, including pathways involving GABAergic, serotoninergic, and other neurotransmitters, and cerebellar systems.

Cortical-subcortical myoclonus is the major mechanism for myoclonic seizures that occur in primary generalized epileptic syndromes (eg, juvenile myoclonic epilepsy [JME]) and in some other instances (eg, minipolymyoclonus).

With JME and absence epilepsy, thalamic networks are believed to abnormally couple with widespread cortical areas to produce excessive neuronal activity and myoclonic seizures [7,8]. The resulting myoclonic jerks are commonly generalized or bisynchronous.

The physiology of cortical-subcortical myoclonus involves abnormal, paroxysmal, and excessive oscillation in bidirectional connections between cortical and subcortical sites.

Subcortical-nonsegmental myoclonus is generated from a site that is subcortical, but the crucial feature is that the myoclonus manifests far beyond the segments that are near the originating site.

The best characterized types of subcortical-nonsegmental physiologies are reticular-reflex myoclonus and propriospinal myoclonus. In both of these examples, the abnormal activity begins in a focal area of the neuraxis and then spreads in both rostral and caudal directions, producing generalized myoclonus due to the bilateral pathways involved.

There is also evidence of a subcortical-nonsegmental physiology for the myoclonus-dystonia syndrome [9]. The exact subcortical generating site of myoclonus-dystonia is unknown, but the myoclonus distribution extends across the head, neck, upper torso, and bilateral arm segments.

Segmental myoclonus is generated at a particular segment or contiguous segments of the brainstem and/or spinal cord. The pathologic motor oscillations in this type of myoclonus occur at a lower frequency than what is usually seen in tremor.

Segmental myoclonus manifests at, or close to, that particular segment or contiguous segments of the body (eg, palatal myoclonus, spinal segmental myoclonus).

Peripheral myoclonus arises as a consequence of a peripheral nervous system lesion producing hyperactive motor discharges to its muscle (eg, hemifacial spasm). The possible role of central reorganization is not well defined.

EPIDEMIOLOGY — In Olmsted County, Minnesota, the average annual incidence rate for myoclonus was 1.3 cases per 100,000 person-years [10]. The lifetime prevalence of myoclonus in 1990 was 8.6 per 100,000 population. Secondary (symptomatic) myoclonus (72 percent) was the most common clinical category, followed by epileptic myoclonus (17 percent) and essential myoclonus (11 percent) [10].

Posthypoxic state (Lance-Adams syndrome), neurodegenerative disease, and epilepsy syndromes are the most common causes of myoclonus. Toxic-metabolic and drug-induced cases are particularly common in the hospital setting.

CAUSES — The classification scheme of Marsden and colleagues organizes the numerous etiologies of myoclonus into four major categories [1]:

Physiologic

Essential

Epileptic

Secondary (symptomatic)

Each clinical category contains myoclonus arising from various etiologies and pathophysiologic mechanisms. Thus, differentiation by clinical-etiologic category is not always pure. In addition, a single etiology can produce different types of myoclonus, and occasional patients may demonstrate more than one type of myoclonus.

The classification scheme shown in the table (table 2) has been modified from the original [1] to account for subsequent discoveries and etiologies.

Physiologic myoclonus — Physiologic myoclonus is a normal phenomenon that occurs in healthy people [1]. There is minimal or no associated disability and the physical examination is typically without abnormality.

The most familiar examples of physiologic myoclonus are jerks during sleep or sleep transitions (table 2). Others include anxiety-induced myoclonus, exercise-induced myoclonus, hiccups (singultus), and benign infantile myoclonus with feeding.

Jerks associated with sleep — Varieties of sudden movement that occur during sleep or sleep transitions are partial myoclonic jerks, massive myoclonic jerks (hypnic jerks), and periodic movements of sleep [11].

Partial myoclonic jerks are usually multifocal and occur in distal muscles.

Massive myoclonic jerks are generalized and affect trunk and proximal muscles.

Periodic limb movements of sleep (PLMS; nocturnal myoclonus) consist of stereotyped repetitive dorsiflexion of the toes and feet, sometimes with flexion of the knees and hips [12]. The same types of movements occur in the restless legs syndrome (RLS) and can disrupt sleep [13]. When PLMS cause sleep disturbance and/or excessive daytime sleepiness in the absence of another sleep disorder such as RLS, the condition is termed "periodic limb movement disorder" (PLMD). (See "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults", section on 'Periodic limb movements of sleep' and "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults", section on 'Periodic limb movement disorder'.)

Since these types of myoclonus occur around or during sleep, a bed partner is often more aware of the myoclonus than the affected individual.

Essential myoclonus — In essential myoclonus, the myoclonus is the most prominent or only clinical finding (ie, an "essential" phenomenon). The patient usually experiences some mild disability. Progression is slow or absent [1]. Cognition is normal.

Essential myoclonus is divided into sporadic and hereditary forms (table 2).

Sporadic (or idiopathic) essential myoclonus is a heterogeneous entity regarding distribution, exacerbating factors, and findings on neurologic examination [14]. Some cases probably have false-negative family histories and actually represent hereditary disease.

Palatal myoclonus — Palatal myoclonus is most often secondary to a brainstem and/or cerebellar lesion. (See "Symptomatic (secondary) myoclonus", section on 'Palatal myoclonus'.)

However, some patients have no apparent structural lesion and are considered to have essential palatal myoclonus. In such cases, the myoclonus is usually characterized by contractions of the tensor veli palatini. By contrast, secondary (symptomatic) palatal myoclonus is usually characterized by contractions of the levator veli palatini. Middle ear myoclonus can be either essential or secondary and is characterized by contractions of the tensor tympani and/or stapedius muscles [15-22]. These conditions may cause tinnitus or ear-clicking.

Hereditary essential myoclonus — Hereditary essential myoclonus has the following clinical characteristics [23]:

Onset typically before age 20 years

Autosomal-dominant inheritance with variable expressivity

A relatively benign course compatible with an active life and normal lifespan

Absence of cerebellar ataxia, spasticity, dementia, and seizures

The myoclonus usually occurs throughout the arms and axial muscles. It is exacerbated by muscle activation and is markedly diminished with alcohol ingestion. Hereditary essential myoclonus demonstrates a subcortical-nonsegmental physiology [9].

Myoclonus-dystonia — Dystonia is a common feature of hereditary essential myoclonus, and when present, the condition is termed "myoclonus-dystonia syndrome." In addition to myoclonus, this syndrome is characterized by dystonia of variable, but typically mild, severity that often presents as cervical and/or limb dystonia [24]. The mean age of symptom onset is six years [25], occurring earlier in girls than in boys (median five versus eight years) [26]. Although unusual after age 20, onset as late as 75 years has been reported [27].

In a prospective report of 41 patients with myoclonus-dystonia syndrome and mutations of the sarcoglycan epsilon (SGCE or DYT11) gene on chromosome 7q21, the myoclonus was predominantly localized to the neck and trunk or proximal upper limbs [25]. The myoclonic movements consisted of short jerks (mean duration 95 ms, range 25 to 256 ms) occurring at rest, during action, and during posture. Myoclonus was either isolated or associated with mild to moderate dystonia. Twenty-two percent of patients had spontaneous improvement in dystonia lasting 1 to 20 years.

In most cases, myoclonus-dystonia confers little or no functional disability and is compatible with a normal lifespan [24,28]. However, the course is unpredictable, and a minority of patients develops progressive symptoms that can lead to severe motor disability [24,28,29].

Myoclonus-dystonia is genetically heterogeneous. Mutations involving the SGCE gene are the most frequent identified cause but are found in less than one-half of cases [30-34]. Small studies have identified other putative genetic causes including mutations in the reelin (RELN) gene [35], the calcium voltage-gated channel subunit alpha1 B (CACNA1B) gene [36], the tyrosine hydroxylase (TH) gene [37], and the DYT15 locus on chromosome 18p11 [38]. Additional genes are likely to be associated with this syndrome.

Some SGCE mutation carriers have psychiatric disturbances, mainly obsessive-compulsive disorder and alcohol dependence [39-42].

In contrast to other types of sarcoglycan, which are expressed mainly in muscle and are associated with muscular dystrophy, epsilon-sarcoglycan is expressed in the brain and other non-muscle tissues, but its normal function is unknown [30]. Most SGCE mutations are "loss of function," and maternal imprinting has been associated with reduced penetrance [43]. Exactly how the loss of SGCE function results in myoclonus or dystonia is not known, but epsilon-sarcoglycan has been localized to areas important for movement, such as the cerebellum and monoamine brainstem nuclei, including dopaminergic neurons [44].

Epileptic myoclonus — Epileptic myoclonus refers to the presence of myoclonus in the setting of epilepsy (table 2). Seizures dominate the clinical picture in epileptic myoclonus. The etiology may be idiopathic, genetic, or a static encephalopathy.

Myoclonus can occur as either one of several components of a seizure, the only seizure manifestation (myoclonic seizure), or one of multiple seizure types within an epileptic syndrome. Different types of epileptic myoclonus may demonstrate a cortical or cortical-subcortical physiology.

Fragments of epilepsy — "Fragments of epilepsy" designates myoclonic jerks in patients with epilepsy where myoclonus is not the main seizure phenotype and includes the following examples (table 2):

Isolated epileptic myoclonic jerks

Epilepsia partialis continua (focal status epilepticus)

Idiopathic stimulus-sensitive myoclonus

Photosensitive myoclonus

Absences with a minor myoclonic component

Epilepsy with myoclonic absences

In epilepsia partialis continua, the myoclonus is spontaneous and focal; it occurs irregularly or regularly at intervals no longer than 10 seconds, is confined to one part of the body, and continues for a period of hours, days, or weeks [45].

Myoclonic epilepsy syndromes — Myoclonus is the main seizure phenotype associated with a number of epilepsy syndromes that mostly present in infancy or childhood (table 2):

Infantile spasms (West syndrome)

Severe myoclonic epilepsy of infancy (Dravet syndrome)

Benign myoclonic epilepsy of infancy

Lennox-Gastaut syndrome

Myoclonic astatic epilepsy (Doose syndrome)

Cryptogenic myoclonus epilepsy (Aicardi)

Juvenile myoclonic epilepsy (JME; Janz syndrome)

Familial cortical myoclonic tremor with epilepsy

In myoclonic seizures, the characteristic seizure movement manifestation is myoclonus. They may be confused with other seizures that result in jerks (eg, atonic and tonic seizures). In myoclonic epilepsy syndromes, myoclonic seizures are usually accompanied by other seizure types, such as generalized tonic-clonic and/or absence in patients with JME. Uncommonly, myoclonus is the only seizure type and abnormal electroencephalography (EEG) or family history of epilepsy points to the diagnosis. (See "Juvenile myoclonic epilepsy", section on 'Clinical features'.)

True myoclonic seizures result in brief positive myoclonus [7]. Patients may be thought to be "clumsy" before the pathological nature of their symptoms is appreciated. On EEG, the myoclonus is accompanied by a generalized (primary or secondary) ictal epileptiform discharge, but the myoclonus itself may be generalized, segmental, or focal.

Myoclonic seizures occurring in a primary generalized epileptic syndrome exhibit a cortical-subcortical physiology, while those occurring in a secondary generalized epileptic syndrome exhibit a cortical physiology with a tendency to spread.

The genetics of the myoclonic epilepsies is heterogeneous, but in many instances, mutations have been found in ion channels or neurotransmitter receptor genes [46,47].

Familial cortical myoclonic tremor with epilepsy — The term "familial cortical myoclonic tremor with epilepsy" encompasses a large number of syndrome labels (table 2) used to describe a genetically heterogeneous phenotype with the following core clinical features [48-51]:

Autosomal-dominant inheritance

Adult onset

Distal action tremor and myoclonus

Infrequent, secondarily generalized tonic-clonic seizures

Relatively benign course, typically with normal cognition

Responsiveness to anticonvulsants

Occasional patients with this syndrome may exhibit frequent seizures, other seizure types, larger arrhythmic myoclonic jerks, or abnormal cognition.

Clinical neurophysiology testing reveals distal rhythmic small-amplitude myoclonus (tremor) with action (voluntary movement) produced by electromyographic (EMG) discharges exhibiting a cortical physiology. Additional typical features are enlarged (giant) somatosensory evoked potentials (SEPs) and enhanced long-latency EMG reflexes at rest, consistent with cortical reflex myoclonus [52].

Most of the reported pedigrees are in Japanese and European populations. Causative mutations span several different genes and seemingly unrelated gene products [51]. A common molecular pathology may relate to noncoding intronic repeat expansions and RNA toxicity [51,53].

Primary myoclonus — Isolated myoclonus is seen in primary progressive myoclonus of aging and familial cortical myoclonus.

Primary progressive myoclonus of aging — Older individuals may develop a progressive isolated myoclonus without any cause or other syndrome being identified, a condition termed "primary progressive myoclonus of aging" [54]. There is a progressive development of focal/asymmetric predominantly action myoclonus. The progression of the myoclonus may plateau once it is severe. The physiology is uniformly cortical with variable reflex features. These cases do respond to a cortical physiology treatment approach. (See "Treatment of myoclonus", section on 'Cortical myoclonus'.)

The association with older individuals suggests that primary progressive myoclonus of aging is a neurodegenerative syndrome, but the etiology awaits clarification. The cause of this syndrome is probably heterogeneous, and no autopsies have been reported.

Familial cortical myoclonus — Familial cortical myoclonus, described in one large Mennonite family from Canada, is an autosomal-dominant condition with onset from the second to seventh decade of life, and has been tentatively linked to a mutation in the nucleolar protein 3 (NOL3) gene [55]. The phenotype is characterized by a slowly progressive, stimulus-evoked, multifocal cortical myoclonus involving the face and limbs that becomes disabling late in the course. Neither seizures nor dystonia have been observed.

Symptomatic myoclonus — Myoclonus that occurs as a secondary symptom of a neurologic or nonneurologic disorder has been traditionally termed "symptomatic."

Symptomatic myoclonus can occur in association with conditions that span the entire spectrum of neurologic disease (table 2). Major categories include the following:

Drug-induced and toxic syndromes

Encephalopathies, including hypoxia [56]

Neurodegenerative diseases

Focal nervous system damage

Progressive myoclonic epilepsy

Progressive myoclonus ataxia

Infectious and postinfectious disorders

Autoimmune inflammatory disorders, including opsoclonus-myoclonus syndrome

Metabolic disorders

Disorders that affect multiple organ systems, including mitochondrial disorders

Storage diseases

Exaggerated startle syndromes

Psychogenic jerks

Often there is clinical or pathologic evidence of diffuse nervous system involvement. This category is reviewed in detail elsewhere. (See "Symptomatic (secondary) myoclonus".)

EVALUATION — Guidelines for the evaluation of a patient with myoclonus may be conceptualized into four parts:

Syndrome identification based upon clinical features

Ancillary laboratory testing

Clinical neurophysiology

Testing for rare causes of myoclonus

Syndrome identification — The initial steps in the evaluation of a patient with myoclonus are the history and examination, as outlined in the table (table 3). The findings should identify which major clinical and etiologic classification (physiologic, essential, epileptic, or secondary myoclonus) best reflects the circumstances of the patient (table 2) [1].

Most myoclonic movements are easily diagnosed by clinical observation [57]. The examination of a patient with myoclonus should delineate the distribution, temporal profile, and activation characteristics of the myoclonic movement.

The distribution can be focal, multifocal, segmental, or generalized. A multifocal distribution may have bilaterally synchronous movements as well.

The temporal profile can be continuous or intermittent, as well as rhythmic or irregular. Intermittent myoclonus can occur as isolated or repetitive trains of jerks.

The activation of the myoclonus may be at rest (spontaneous), induced by various stimuli (reflex myoclonus), induced by voluntary movement (action myoclonus), or some combination of these. All the possible activation characteristics should be noted as absent or present.

Occasionally, it may be difficult to differentiate myoclonus from other involuntary movements (eg, chorea, dystonia, tremor, tics) by observation [57]. Myoclonus is most easily confused with tics, though tics are usually repetitive, stereotypic, and semi-voluntary. In this situation, clinical neurophysiology studies can be particularly helpful [57]. (See 'Clinical neurophysiology' below.)

Myoclonus induced by drugs or toxins is potentially treatable, since the myoclonus typically resolves upon withdrawal of the offending agent(s). It is important to scrutinize all drugs, either in isolation or combination, when evaluating for a potential causative role in myoclonus. Agents most often associated with myoclonus include (see "Symptomatic (secondary) myoclonus", section on 'Drug-induced and toxic syndromes'):

Levodopa

Psychiatric medications (eg, tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, lithium)

Antibiotics (eg, penicillins, cephalosporins, quinolones)

Narcotics

Anticonvulsants

Anesthetics

Contrast media

Cardiac medications (eg, calcium channel blockers, antiarrhythmic agents)

Drug withdrawal from certain agents (eg, sedatives)

Ancillary studies — Ancillary testing should be performed if the myoclonus etiology is unclear from the history and examination findings. Suggested studies are as follows [58-60]:

Electrolytes (including calcium and magnesium)

Bismuth

Glucose

Renal function tests

Liver function tests

Thyroid antibodies and thyroid function tests

Paraneoplastic antibodies (comprehensive panel)

Vitamin E level

Drug and toxin screen if clinical suspicion of undisclosed substance intake or use of illicit or prescribed psychoactive medications

Electroencephalography (EEG)

Brain imaging

Spine imaging if there is focal or segmental myoclonus

Infection workup (complete blood count, urinalysis, chest radiograph, blood cultures, lumbar puncture) if localizing signs of fever, leukocytosis, or encephalopathy

Cerebrospinal fluid analysis in cases with encephalopathy, signs of infection, suspicion for immune-mediated disorder, or suspicion for prion disease (eg, Creutzfeldt-Jakob disease)

Such testing covers the most common disturbances of electrolyte balance and acquired metabolic disorders that can cause myoclonus. Imaging of the brain and spinal cord may reveal lesions or atrophy supporting a specific myoclonus etiology. Cerebrospinal fluid analysis is useful to differentiate an infectious/inflammatory etiology from a toxic, drug-induced, or metabolic etiology.

EEG can identify both ictal and interictal patterns in the epileptic myoclonus category. As examples, generalized spikes and a 3 to 6 Hz spike-and-wave pattern are typical for primary generalized myoclonic epilepsy, whereas a 3 Hz spike-and-wave is seen in absence epilepsy syndromes.

Clinical neurophysiology — When the diagnosis and physiology of myoclonus remain unclear after the initial evaluation above, clinical neurophysiology testing (table 4) is useful to determine the physiologic classification of myoclonus and support or confirm the neuroanatomic localization and etiology (table 5). In addition, it is helpful when clinical observation alone is unable to distinguish myoclonus from other involuntary movements such as chorea, dystonia, and tremor [57].

When using multiple techniques for physiologic classification of myoclonus, the results from the EEG obtained in basic ancillary testing (discussed above) are combined with the following methods [3,57]:

Surface electromyography (EMG)

Simultaneous EEG-EMG polygraphy

Somatosensory evoked potentials (SEPs)

Jerk-locked back-averaging of EEG transients and/or SEPs to EMG discharges

Long-latency EMG responses to peripheral nerve stimulation (eg, C reflex)

Surface EMG recording can demonstrate the abrupt and brief muscle contraction that is characteristic of positive myoclonus [57]. In addition, EMG can reveal the silent period of negative myoclonus (asterixis).

EEG-EMG polygraphy (ie, the combined, simultaneous recording of EEG and surface EMG) is the most important clinical neurophysiology study, since it can show the approximate relationship of EEG activity with myoclonus, and determine which muscles are most frequently involved with the myoclonic jerks [57]. As an example, jerk-locked back-averaging of EEG waveforms to EMG discharges can detect small EEG potentials that are temporally related to myoclonus [57].

We suggest clinical neurophysiology testing if a diagnosis is not forthcoming after the history, examination, and ancillary testing are performed. The treatment implications of physiologic classification are discussed separately. (See "Treatment of myoclonus".)

Major categories of the physiologic classification used here primarily refer to the neuroanatomic source of the myoclonus. (See 'Anatomic and physiologic classification' above.)

Findings associated with major anatomic-physiologic categories — The basic clinical neurophysiology findings for each major anatomic-physiologic category of myoclonus are discussed here briefly and are summarized in the tables (table 5 and table 6) [3,57].

Cortical – Cortical myoclonus originates as a focal discharge from the primary sensorimotor cortex. The EMG discharge duration is typically <75 ms, and a focal back-averaged EEG transient is present. Enlarged (giant) SEPs and enhanced long-latency EMG responses (eg, the C reflex) are characteristic of cortical reflex myoclonus physiology.

Cortical-subcortical – The physiology of cortical-subcortical myoclonus involves abnormal, paroxysmal, and excessive oscillation in bidirectional connections between cortical and subcortical sites. On surface EMG, discharge duration is typically <100 ms, and the associated EEG transient (eg, spike-and-wave) is usually diffuse. With back-averaging, time-locked correlation of EEG transients to EMG discharges is typical. Giant SEPs and enhanced long-latency reflexes are sometimes seen.

Subcortical-nonsegmental – Subcortical-nonsegmental myoclonus is generated from subcortical but not segmental sources (eg, myoclonus-dystonia syndrome). Variable EMG discharge duration is characteristic. Jerk-locked back-averaging shows no correlation of EEG transients to EMG discharges. SEPs are normal. Some cases have an EMG reflex response to sound stimulation.

Segmental – Segmental myoclonus is generated at a particular segment or contiguous segments of the brainstem and/or spinal cord. EMG discharge duration is typically >100 ms. There are usually rhythmic EMG discharges. With EMG reflex testing, some types of segmental myoclonus may show a very short latency response that is incompatible with a supraspinal origin.

Peripheral – Peripheral myoclonus is driven from a peripheral site (ie, a peripheral nerve). Variable EMG discharge duration and irregularity is characteristic.

Testing for rare causes of myoclonus — Additional testing for conditions that rarely cause myoclonus may be needed when the standard evaluation, including clinical neurophysiology studies, fails to reveal a cause. Some examples include the following:

Body imaging for occult cancer, even in the absence of paraneoplastic antibodies (eg, suggested by older age, a rapid decline in general health, and/or weight loss) (see "Overview of paraneoplastic syndromes of the nervous system", section on 'Diagnostic evaluation')

Evaluation for malabsorption disorders such as celiac sprue and Whipple's disease (eg, suggested by diarrhea, gastric distress, and/or weight loss) (see "Diagnosis of celiac disease in adults" and "Whipple's disease", section on 'Differential diagnosis')

Enzyme assays for neuraminidase deficiency (sialidosis) and biotinidase deficiency (multiple carboxylase deficiency; eg, suggested by ataxia, cherry red spot in macula, hearing/vision loss, and/or skin rash) (see "Overview of the hereditary ataxias", section on 'Sialidosis' and "Overview of water-soluble vitamins", section on 'Multiple carboxylase deficiency')

Evaluation for Wilson disease (eg, suggested by the presence of liver disease, Kayser-Fleischer rings, or extrapyramidal movement disorders, and/or young age) (see "Wilson disease: Diagnostic tests")

Evaluation for ataxia-telangiectasia (eg, suggested by the presence of ataxia, telangiectasia, immunodeficiency, and/or a cancer predisposition) (see "Ataxia-telangiectasia", section on 'Diagnosis')

Genetic testing (and tissue biopsy if indicated) for inherited disorders, such as Unverricht-Lundborg disease (cystatin B [CSTB] gene), Lafora body disease (EPM2A and EPM2B genes), neuronal ceroid lipofuscinosis, and Huntington disease (eg, suggested by family history, seizures, young onset, and progression) (see "Huntington disease: Clinical features and diagnosis")

Evaluation for mitochondrial disorders, including serum lactate, muscle biopsy, and genetic testing (eg, suggested by family history, multiple organ system failure, hearing/vision problems, ataxia, muscle weakness, and/or lipomas) (see "Mitochondrial myopathies: Clinical features and diagnosis", section on 'Evaluation and diagnosis')

The choice and order of such testing is guided by the clinical circumstances and suspicion for a specific diagnosis or group of etiologies. Of note, a paraneoplastic antibody screen is a basic evaluation when the etiology of the myoclonus is unclear, since it is less expensive than an extensive imaging screen. Detection of a paraneoplastic antibody can direct the workup for particular underlying neoplasms. However, cases of paraneoplastic myoclonus can occur without the presence of a known antibody; the corollary is that failure to detect a paraneoplastic antibody does not exclude a paraneoplastic syndrome. Therefore, imaging for occult malignancy is necessary if no etiology for myoclonus has been identified. In children with typical opsoclonus-myoclonus syndrome, evaluation for neuroblastoma should proceed regardless of the antibody screen.

Inpatient evaluation of new-onset myoclonus — For hospitalized patients with new or recent onset of myoclonus, the most common causes are toxic-metabolic and drug-induced etiologies. The initial evaluation should focus on these potential causes and look for subacute or acute systemic and neurologic conditions that are associated with myoclonus (algorithm 1).

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Basics topics (see "Patient education: Myoclonus (The Basics)")

SUMMARY AND RECOMMENDATIONS

Definition – Myoclonus is characterized by brief, shock-like, involuntary movements caused by muscular contractions or inhibitions. Muscular contractions produce positive myoclonus, whereas muscular inhibitions produce negative myoclonus (asterixis). (See 'Introduction and definition' above.)

Clinical/etiologic classification – The clinical and etiologic classification scheme uses four major categories to organize myoclonus (table 2) (see 'Causes' above):

Physiologic myoclonus – Physiologic myoclonus is a normal phenomenon that can occur in healthy people. There is minimal or no associated disability and the physical examination is typically without abnormality. The most familiar examples of physiologic myoclonus are jerks during sleep or sleep transitions (table 2). (See 'Physiologic myoclonus' above.)

Essential myoclonus – In essential myoclonus, the myoclonus is the most prominent or only clinical finding. Hereditary and sporadic forms exist (table 2). (See 'Essential myoclonus' above.)

Epileptic myoclonus Epileptic myoclonus refers to the presence of myoclonus in the setting of epilepsy (table 2). Seizures dominate the clinical picture in epileptic myoclonus. The etiology may be idiopathic, genetic, or a static encephalopathy. Subcategories of epileptic myoclonus include the following (see 'Epileptic myoclonus' above):

-Fragments of epilepsy, in which myoclonus is not the main seizure phenotype

-Myoclonic epilepsy syndromes

-Familial cortical myoclonic tremor with epilepsy

Symptomatic myoclonus – Symptomatic myoclonus is the most common type of myoclonus. It occurs as a secondary symptom of a neurologic or nonneurologic disorder. Symptomatic myoclonus can occur in association with conditions that span the entire spectrum of neurologic disease (table 2). (See 'Symptomatic myoclonus' above.)

Symptomatic myoclonus is discussed in greater detail separately. (See "Symptomatic (secondary) myoclonus".)

Anatomic/physiologic classification – The anatomic and physiologic classification scheme categorizes myoclonus according to the localization of the mechanism that generates it (table 1). The categories are cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral. (See 'Anatomic and physiologic classification' above.)

Evaluation Guidelines for the evaluation of a patient with myoclonus may be conceptualized into four parts (table 3) (see 'Evaluation' above):

Syndrome identification – Most myoclonic movements are easily diagnosed by clinical observation. The examination of a patient with myoclonus should delineate the distribution, temporal profile, and activation characteristics of the myoclonus (table 6).

Ancillary laboratory testing – Ancillary testing should be performed if the etiology remains unclear. (See 'Syndrome identification' above and 'Ancillary studies' above.)

Clinical neurophysiology – Neurophysiology testing is useful when clinical observation alone is unable to distinguish myoclonus from other involuntary movements such as chorea, dystonia, and tremor (table 5). Simultaneous electroencephalography-electromyography (EEG-EMG) polygraphy is the most important clinical neurophysiology study, since it can show the approximate relationship of EEG activity with myoclonus, and determine which muscles are most frequently involved with the myoclonic jerks. (See 'Clinical neurophysiology' above.)

Testing for rare causes – Additional testing for conditions that rarely cause myoclonus may be needed when the standard evaluation, including clinical neurophysiology studies, fails to reveal a cause. (See 'Testing for rare causes of myoclonus' above.)

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