Myoclonus …

Behzad Elahi MD PhD

Movement Disorders

Updated 11.27.2023
Released 04.07.1994
Expires For CME 11.27.2026

Myoclonus

Author: Behzad Elahi MD PhD

See Contributor Disclosures

Editor: Robert Fekete MD

Myoclonus

In This Article

Quick Link

Introduction

Overview

Myoclonus, characterized by involuntary, abrupt muscle contractions followed by relaxation, presents a complex clinical landscape. This article offers a comprehensive overview of myoclonus, focusing on differential diagnosis, etiology, and therapeutic strategies. Myoclonus manifests across a spectrum of diseases and conditions, necessitating a systematic diagnostic approach. Understanding the clinical context surrounding myoclonus is paramount. The initial step involves categorizing myoclonus based on its clinical features, followed by additional testing as needed. Physiological classification augments diagnostic insights. Once the diagnosis is established, interventions targeting the underlying cause or providing symptomatic relief become crucial. In this update, we organize the treatment of myoclonus according to its pathophysiology, incorporating recent advancements, including the potential use of deep brain stimulation or botulinum toxin injection for management.

Key points

	• Myoclonus can be a symptom or a sign, but it is not a diagnosis.
	• Myoclonus occurs in numerous diseases and conditions, necessitating an organized approach to diagnostic evaluation.
	• Classification based on examination findings, clinical circumstances, and pathophysiology offers complimentary, not redundant, information.
	• A symptomatic treatment approach is best strategized based on the physiology classification of the myoclonus.
	• There should be a thorough search for myoclonus etiology and consideration for etiology treatment before symptomatic treatment is considered.

Historical note and terminology

Myoclonus was initially described as "paramyoklonus multiplex" by Friedreich in 1881 when he observed it in a patient with myoclonus. The term "myo" was employed to differentiate these rapid movements from epileptic disorders, "para" indicated their symmetry, and "multiplex" underscored the multifocal nature of the condition. It was not until 1986 that Lowenfeld proposed a shortened version, simply "myoklonus" (70). In 1899, Rabot contributed to the field by delineating nonprogressive familial myoclonic epilepsy. Subsequently, in 1903, Lundborg classified myoclonus into three distinct groups: essential, symptomatic, and familial myoclonic epilepsy.

Etymologically, "myoclonus" itself signifies "a quick movement of muscle." Clinically, myoclonus encompasses sudden, brief, shock-like involuntary muscle movements, which can result from muscular contractions (positive myoclonus) or inhibitions (negative myoclonus). These manifestations usually originate within the central nervous system (31; 28).

The classification of myoclonus can be approached from various angles, including clinical presentation, etiology, examination findings, or physiological characteristics. When considering clinical presentation, four primary categories are employed: physiologic, essential, epileptic, or symptomatic myoclonus. Each of these categories encompasses a range of underlying causes and clinical scenarios.

On examination, myoclonus may exhibit rhythmic characteristics, which some movement disorder specialists may refer to as "tremor," or it may more commonly present as arrhythmic. Stimulus-sensitive myoclonus is denoted as "reflex myoclonus," whereas action-sensitive myoclonus is described as "action (or intention) myoclonus."

Myoclonus can also be classified based on its distribution within the body: focal or segmental (confined to a specific region), multifocal (involving various body parts, not necessarily simultaneously), or generalized (affecting an entire body part in a single jerk).

Furthermore, the physiological classification considers the type and location of electrical discharge, resulting in categories such as cortical, cortical-subcortical, subcortical-nonsegmental, segmental, or peripheral myoclonus.

Clinical manifestations

Presentation and course

• Myoclonus presentation varies with its underlying cause, including acute onset in hypoxia, vascular issues, or drug-related side effects, subacute presentation in infectious, inflammatory, and metabolic conditions, and chronic onset in cases of neurodegeneration, neoplasms, and genetic mutations.

Major clinical categories of myoclonus are distinguished by presentation and course:

	(1) Physiologic myoclonus represents a benign manifestation occurring in the absence of significant neurologic dysfunction. This category includes phenomena like jerking during sleep and other innocuous instances.
	(2) Essential myoclonus etiologies generally exhibit clinical stability, resulting in minimal disability and no extensive neurologic dysfunction. Patients in this category often experience myoclonic jerks without accompanying neurologic deficits.
	(3) Epileptic myoclonus emerges within the context of epileptic syndromes, particularly as a manifestation of seizures. Clinically, this category is characterized by the presence of epilepsy-related symptoms alongside myoclonic jerks.
	(4) Symptomatic myoclonus, conversely, arises as a secondary manifestation of an underlying medical or neurologic disorder. In such cases, myoclonus typically represents just one facet of a broader clinical picture, with multiple significant clinical problems affecting the patient.

Myoclonic jerks can exhibit a broad spectrum of characteristics, varying from mild muscular contractions with small amplitude movements to pronounced jerks that affect the entire body (26). These movements may manifest in diverse distributions, either symmetric or asymmetric. The consequential disability stems from the loss of muscle control during these sudden jerking episodes. In cases where myoclonus affects the lower extremities, patients may experience abnormal balance and gait disturbances, contributing to functional impairment.

Myoclonus is often stimulus- and activity-sensitive.

Myoclonus, ataxia, and hung-up knee-jerk reflexes in juvenile Huntington disease

This young woman has juvenile Huntington disease manifested by ataxia and generalized action myoclonus. She has jerky tremors (properly termed "myoclonic movements") mostly in her upper extremities, worse on intention, and hung-up...
Myoclonus, blepharospasm, ataxia, chorea, and other findings in juvenile Huntington disease

This young man has juvenile Huntington disease. Initially, he appears bright but displays blepharospasm, sometimes accompanied by facial grimacing, apraxia of eye opening, impersistence of tongue protrusion, generalized chorea, an...

Sudden and unexpected noise, bright lights, or muscle stretch can trigger a myoclonic jerk. The jerks may be present at rest or may be triggered or aggravated by attempts to perform fine movements. Myoclonus may be rhythmic, in which case, it is usually due to a focal lesion of the spinal cord or brainstem (segmental myoclonus). As a result of the rhythmicity, some refer to this as tremor instead of myoclonus.

Myoclonus-dystonia syndrome, alcohol responsive (1)

This man has a jerky tremor and dystonic posturing of both hands characteristically seen in alcohol-responsive, myoclonus-dystonia syndrome (DYT11) due to mutation in the epsilon-sarcoglycan (SGCE) gene on chromosome 7q. (Contribu...

Focal myoclonus. Focal myoclonus is characterized by the involvement of a specific group of muscles. This form of myoclonus can manifest differently depending on its origin and location within the nervous system.

Cortical myoclonus. One notable subtype of focal myoclonus is cortical myoclonus, which exhibits distinct features:

	• In cortical myoclonus, the jerks typically affect distal muscles more than proximal ones, often involving flexor muscles more than extensor muscles.
	• Cortical myoclonus tends to be stimulus-sensitive, meaning that external stimuli can trigger or exacerbate the myoclonic jerks. However, this sensitivity may not be as pronounced when the jerks are of small amplitude.
	• Common triggers for cortical myoclonus include sudden loud noises or visual stimuli, highlighting its stimulus sensitivity.
	• Epilepsia partialis continua refers to a specific manifestation of cortical myoclonus, characterized by repetitive focal cortical myoclonus with some rhythmicity.

It is important to note that cortical myoclonus often exhibits multifocality, affecting multiple brain areas rather than remaining strictly focal. Additionally, some forms of focal myoclonus, such as palatal myoclonus, are typically rhythmic in nature.

Palatal myoclonus. Palatal myoclonus represents a distinctive subtype of myoclonus characterized by continuous and rhythmic movements of the palate. These movements may resemble tremors in some patients, although a jerky component is typically present, justifying use of the term "myoclonus" (segmental myoclonus). Key features of palatal myoclonus include:

	• Continuous nature. Palatal myoclonus is usually continuous and persists regardless of rest, activity, sleep, or distractions, setting it apart from other movement disorders.
	• Unilateral or bilateral involvement. It can occur unilaterally (affecting one side) or bilaterally (affecting both sides).
	• Frequency. Palatal myoclonus typically exhibits movements at a frequency ranging from 1.5 to 3 Hz.
	• Involvement of other muscles. In addition to the palate, these rhythmic myoclonic movements may extend to affect other muscles, including those of the eye, tongue, neck, and diaphragm (112).
	• Clicking noise. In some cases, there may be an associated rhythmic clicking noise. This auditory phenomenon is more likely to occur in instances of essential palatal myoclonus than in symptomatic palatal myoclonus(53).

Palatal myoclonus

Rhythmic 2 to 3 Hz muscular contractions are evident in the midline of the neck and in the pharynx. (Contributed by Dr. Joseph Jankovic.)

Types of myoclonus

The physiological classification of myoclonus in clinical neurophysiology is based on identifying its neuroanatomic source. Physiological classification further categorizes myoclonus according to the clinical syndrome it presents and the specific disease causing it. This approach aids in diagnosis and treatment by providing insights about the origin and nature of myoclonus (Table 1).

Table 1. Physiological Classification of Myoclonus

Cortical
	• Cortical reflex myoclonus • Cortical origin myoclonus without reflex activation • Focal motor seizures • Alzheimer disease • Creutzfeldt-Jakob disease • Subacute sclerosing panencephalitis • Myoclonus of corticobasal degeneration • Asterixis
Cortical-subcortical
	• Absence seizures • Primary generalized myoclonic seizures • Primary generalized epileptic myoclonus
Subcortical
	• Essential myoclonus • Reticular reflex myoclonus • Opsoclonus-myoclonus syndrome • Propriospinal myoclonus • Focal subcortical reflex myoclonus
Segmental
	• Brainstem • Spinal cord • Combined brainstem and spinal cord
Peripheral
	• Hemifacial spasms • Others
(71)

Myoclonus can take on various forms, each exhibiting distinct characteristics and underlying mechanisms. It is crucial to understand these differences for accurate diagnosis and effective management. Here, we discuss different types of myoclonus.

Multifocal myoclonus. Multifocal myoclonus involves individual jerks affecting different parts of the body, often occurring unpredictably. Cortical myoclonus frequently exhibits multifocality as well (72).

Generalized myoclonus. In generalized myoclonus, each jerk simultaneously affects a large area or the entire body. This type of myoclonus can be sensitive to external stimuli and may worsen during voluntary actions. It can originate from cortical-subcortical pathways, as seen in juvenile myoclonic epilepsy, or from subcortical-nonsegmental sources, as observed in reticular reflex myoclonus (72).

Asterixis typically occurs alongside multifocal myoclonus in the context of metabolic encephalopathy and is generally generalized. However, focal asterixis may be observed in lesions affecting the thalamus, putamen, or parietal lobe.

Reticular reflex myoclonus. Reticular reflex myoclonus typically originates in the brainstem. It primarily affects proximal muscles, with a preference for flexor muscle involvement (72).

Minipolymyoclonus. Minipolymyoclonus is characterized by small jerks occurring in various locations. This term has also been used to describe small-amplitude jerks in patients with spinal muscular atrophy. Distinguishing the origin may require considering associated signs like denervation in spinal muscular atrophy (141).

Cortical tremor. Cortical tremor manifests as fine, shivering finger twitching, primarily provoked by action and posture. It may resemble essential tremor phenomenologically and can exhibit familial patterns (77; 56).

Orthostatic myoclonus. Orthostatic myoclonus presents as leg shaking when standing, similar to orthostatic tremor. Unlike orthostatic tremor, it impairs gait and is often associated with more significant neurologic problems (74). Electromyographically, orthostatic myoclonus shows greater variability in discharge duration, with many brief discharges (shorter than 100 ms) (74).

Accompanying clinical features of myoclonus depend on its etiology. Progressive myoclonic epilepsies are a heterogeneous group of disorders associated with multifocal or generalized myoclonus and epileptic seizures. Under this category, two major groups exist: (1) progressive myoclonic epilepsies and (2) progressive myoclonic ataxias (04). Progressive myoclonic epilepsies refer to a combination of severe myoclonus, generalized tonic-clonic or other seizures, and progressive neurologic decline, particularly dementia. Progressive myoclonic ataxia (also known as Ramsay Hunt syndrome) is distinguished from progressive myoclonic epilepsy as seizures are mild or absent, with ataxia as the major problem.

Startle syndromes and related disorders. Startle syndromes are characterized by an exaggerated startle response to a surprising stimulus. In a typical startle response, there is a blink and activation of craniocervical muscles, with an EMG activity latency of 30 to 40 milliseconds (142). This response habituates quickly in normal individuals.

One specific condition related to startle syndromes is hyperekplexia, which is a familial condition typically beginning in infancy. It is characterized by an enhanced startle response to various stimuli, often leading to generalized stiffening and falling to the ground. In hyperekplexia, the EMG latency is shorter than in the normal startle response, and the burst duration is brief (48). Some cases may exhibit EEG correlates, and enhanced somatosensory evoked potentials have been reported (91).

Certain startle disorders have been categorized as "culture-specific" startle syndromes, although the relationship between these conditions and myoclonus is poorly understood. For instance, "latah," primarily observed in Indonesia and Malaysia, is characterized by exaggerated startle responses accompanied by vocalizations, echolalia, and echopraxia. Latah displays two phases in the startle response: a short latency motor startle reflex initiated in the lower brainstem (less than 100/120 ms) and a later second phase influenced more by psychological factors (the "orienting reflex") occurring 100/120 to 1000 ms after the stimulus (13). It has been suggested that latah should be considered a "neuropsychiatric startle syndrome." Other culture-specific syndromes include the "jumping Frenchman of Maine" and "myriachit" in Siberia. These syndromes share common features of a nonfatigable startle response followed by bizarre and stereotyped behaviors, often linked to cultural factors. Besides echolalia and echopraxia in latah, reports include forced obedience, coprolalia, and strange motor actions (55). Reliable treatment options for these syndromes are largely unknown.

Prognosis and complications

The prognosis depends on the underlying disorder causing myoclonus. No complications are related to isolated myoclonic jerks, but accompanying seizures may lead to hypoxia, injuries, and aspiration.

Clinical vignette

The patient, a 21-year-old, right-handed female college student, presented with 16 years of involuntary movements. At 5 years of age, she began experiencing jerking of the head from right to left in the horizontal plane. By 10 years of age, the jerking involved her upper extremities and slowly spread to her lower extremities. The patient denied an urge to move and could not suppress the movements. Family history revealed jerky movements in her sister and brother, along with slight torticollis. Examination revealed mild rotational torticollis and myoclonic jerks, most prominent in the head and proximal upper extremities. The remainder of the neurologic examination, brain MRI, and EEG were normal.

Myoclonus-dystonia (DYT11)

This patient displays multifocal myoclonic jerks predominantly affecting the head, torso, and proximal upper extremities. While writing, she tightly grips the pen and flexes involuntary at the wrist (writer’s cramp). (Contributed ...

Biological basis

Etiology and pathogenesis

Causes of myoclonus can be categorized into clinical presentation categories, including physiological, essential, epileptic, and symptomatic causes. Notably, most myoclonus cases fall into the symptomatic category (30).

Clinical neurophysiological tests play a crucial role in pinpointing the anatomical origin of myoclonic jerks. Recognition of reversible forms of myoclonus is essential to initiate prompt treatment. Next-generation sequencing techniques allow for a rapid diagnosis, particularly in cases where myoclonus has a genetic basis.

An innovative eight-step algorithm has been proposed to guide clinicians in detecting myoclonus, assessing its anatomical subtype, and diagnosing its underlying cause. This algorithm is a valuable tool for clinical decision-making (147).

Several types of symptomatic myoclonus warrant discussion, including psychogenic jerks or spasms seen in patients with a conversion disorder or malingering. These psychogenic presentations exhibit distinctive features, such as inconsistency in character (amplitude, frequency, distribution), accompanying psychopathological symptoms, distractibility, suggestibility, acute onset, spontaneous remissions, and a tendency to show improvement with placebo interventions (101).

Each of these myoclonus categories is elaborated below, including insights into common etiologies within each category.

Physiological myoclonus

Physiological myoclonus refers to muscle jerks occurring in specific circumstances in normal individuals. Examples include hypnic jerks and hiccups (singultus). Research indicates that hypnic jerks originate from the brainstem (37). Some forms of myoclonus during sleep have been quantified (59). Fragmentary myoclonus during sleep is observed in all healthy individuals, with neck myoclonus occurring in 35%. Interestingly, some individuals exhibit movements that are considered "excessive" based on established criteria. It is crucial to emphasize that in all cases of myoclonus during sleep, the clinical implications of the movements, rather than just their amplitude or frequency, are of paramount importance.

Essential myoclonus

Essential myoclonus is characterized by myoclonus as the primary symptom, and it typically follows a nonprogressive course. Onset usually occurs at a young age, and the condition tends to have a chronic course. The term "essential" is used because of the condition's monosymptomatic focus on myoclonus and its chronic nature. The associated disability is generally minimal, and patients maintain functional abilities. Essential myoclonus can be further divided into hereditary and sporadic forms. Sporadic myoclonus cases are challenging to characterize because they appear clinically heterogeneous, possibly indicating undiscovered static lesions or genetic abnormalities. In contrast, hereditary forms of essential myoclonus exhibit greater uniformity, with most described as the myoclonus-dystonia syndrome, which has a genetic basis.

Myoclonus-dystonia

Familial myoclonus-dystonia is characterized by brief, "lightning-like" myoclonic jerks, primarily affecting the neck and upper limbs. Diagnostic criteria for myoclonus-dystonia (DYT 11) include (1) onset of myoclonus in the first or second decade of life with mild dystonic features, (2) equal prevalence in males and females, (3) a benign course compatible with a normal lifespan, (4) autosomal dominant mode of inheritance with incomplete penetrance, (5) absence of other neurologic deficits, and (6) normal EEG and neuroimaging (62). Mild dystonia often presents as cervical dystonia or task-specific focal dystonia (42). The myoclonus can exhibit rhythmic or arrhythmic patterns, be provoked by actions, or respond to alcohol.

Myoclonus-dystonia syndrome, alcohol responsive (1)

Various combinations of myoclonus and dystonia in members of the same family have been seen.

Myoclonus-dystonia syndrome, alcohol responsive (2)

Three members of a family with alcohol-responsive, myoclonus-dystonia (DYT11) with a mutation in the epsilon-sarcoglycan (SGCE) gene on chromosome 7q (Cazurro-Gutiérrez A, Marcé-Grau A, Correa-Vela M, et al. ε-Sarcogly...

Several investigators have reported an association with intellectual disability and psychiatric disturbances: obsessive-compulsive disorder, panic attacks, and alcoholism (42; 115).

Epileptic myoclonus

Epileptic myoclonus is a category of myoclonus that occurs in the context of a seizure disorder and is frequently accompanied by EEG abnormalities, such as generalized spike and wave discharges (26). In children, myoclonus is commonly associated with epilepsy, and major syndromes within this category include infantile spasms and Lennox-Gastaut syndrome (18; 60). It is crucial to differentiate between infantile spasms and benign myoclonus of infancy, where EEG findings are normal, and the condition follows a nonprogressive course (54). Juvenile myoclonic epilepsy represents a classic idiopathic epileptic disorder in which myoclonus can manifest alongside various seizure types, including myoclonic, absence, and generalized seizures. For the diagnosis of juvenile myoclonic epilepsy, obtaining a comprehensive medical history that includes inquiring about early morning jerks is critical because most juvenile myoclonic epilepsy cases initially present with generalized tonic-clonic seizures (61).

Symptomatic myoclonus

Progressive myoclonus epilepsy-ataxia (including genetic metabolic disorders). Progressive myoclonic epilepsy is characterized by cortical myoclonus, myoclonic seizures, tonic-clonic seizures, and neurologic deterioration, which often includes dementia. Myoclonus in this context is typically multifocal, action-induced, and triggered by external stimuli like touch, sound, or light (15).

Several conditions fall under the category of progressive myoclonic epilepsy:

	• Lafora disease. Lafora disease is an autosomal recessive disorder characterized by pathognomonic periodic acid-Schiff-positive intracellular polyglucosan inclusions, known as Lafora bodies. These inclusions are found in various tissues, including the heart, skeletal muscles, liver, sweat glands, and neurons. Diagnosis can be established by examining sweat gland eccrine ducts in a skin biopsy. Unlike the relatively benign course of Unverricht-Lundborg disease, Lafora disease has a uniformly fatal outcome within 10 years of onset. Classically, patients present in adolescence with stimulus-sensitive absence, grand mal, and myoclonic seizures, along with rapidly progressive dementia, ataxia, muscle wasting, bulbar symptoms, and eventual respiratory failure. Unfortunately, no preventive or curative treatment exists (100).
	• Ceroid lipofuscinoses. Five types of neuronal ceroid lipofuscinoses may lead to progressive myoclonic epilepsy (120). These include classic late infantile (Jansky-Bielschowsky disease or epilepsy progressive myoclonus type 2), juvenile (Batten disease, Spielmeyer-Vogt-Sjögren disease, or epilepsy progressive myoclonus type 3), adult (Kuf disease, Parry disease, or epilepsy progressive myoclonus type 4), late infantile Finnish variant (epilepsy progressive myoclonus type 5), and late infantile variant (epilepsy progressive myoclonus type 6). All these conditions share a common feature: the accumulation of abnormal lipopigments in lysosomes. Clinical features vary among the five categories but typically encompass various seizure types, ataxia, neurologic decline, and a shortened lifespan.
	• Unverricht-Lundborg disease. Unverricht-Lundborg disease or epilepsy with progressive myoclonus type 1 is an autosomal recessive disorder characterized by stimulus-sensitive myoclonus, tonic-clonic seizures, dysarthria, ataxia, and mild dementia. Onset occurs between 6 and 15 years of age, making it the most common form of progressive myoclonic epilepsy. Multifocal action myoclonus with a cortical origin is a characteristic clinical and neurophysiological signature (69).
	• Myoclonic epilepsy with ragged red fibers. This condition is a common cause of progressive myoclonic epilepsy and can be sporadic or maternally inherited. Patients typically present with myoclonus, generalized seizures, and ataxia. Other clinical manifestations may include myopathy, neuropathy, hearing loss, optic atrophy, and dementia. Muscle biopsy often reveals ragged red fibers in over 90% of patients.
	• Sialidoses. Rarely, sialidoses of two types can lead to progressive myoclonic epilepsy. Sialidoses type I (cherry-spot myoclonus syndrome) results in juvenile or adult-onset action myoclonus related to the deficiency of alpha-neuraminidase. Patients also exhibit visual failure, grand mal seizures, ataxia, and a characteristic cherry-red spot on funduscopy. Type II sialidosis is caused by a deficiency of N-acetyl neuraminidase and beta-galactosidase; it presents with learning disability, hepatomegaly, corneal clouding, skeletal dysplasia, and myoclonus, typically occurring between the neonatal period and the second decade of life.
	• Adult dentatorubral-pallidoluysian atrophy. In adults, dentatorubral-pallidoluysian atrophy should be considered in the differential diagnosis of patients presenting with familial myoclonus and epilepsy, although chorea is also a common feature (103).

Progressive myoclonic ataxia (Ramsay Hunt syndrome). Known causes of progressive myoclonic ataxia include mitochondrial encephalomyopathy (14), celiac disease, late-onset neuronal ceroid lipofuscinosis, biotin-responsive encephalopathy (19), adult Gaucher disease (104), action myoclonus renal failure syndrome, May-White syndrome, and Ekbom syndrome (93). Neurodegenerative diseases, such as spinocerebellar degeneration (110) or dentatorubral-pallidoluysian atrophy (95), may also manifest as progressive myoclonic ataxia. Some disorders may present with both progressive myoclonic epilepsy and ataxia, and in such cases, the syndromic classification may not be straightforward. Various genetic mutations, including MRE11, GOSR2, and SCARB2, have been described in progressive myoclonic ataxia syndromes (99; 109; 136).

Neurodegenerative and other dementia syndromes. Dementia and myoclonus frequently coexist in neurodegenerative syndromes such as Creutzfeldt-Jakob disease, Alzheimer disease, and Lewy body disease (29; 75). In some cases of Creutzfeldt-Jakob disease, patients present with myoclonus and dementia that progress rapidly (117). In a series of 150 patients with variant Creutzfeldt-Jakob disease, myoclonus and chorea were the most common movement disorders (75). Among the elderly, myoclonus associated with clinical parkinsonism, originating from a cortical source due to various disorders, is prevalent (82). On rare occasions, myoclonus can occur in older individuals without other symptoms of neurodegenerative disease (03).

Myoclonus has also been described in patients with Parkinson disease, with or without dementia. It usually occurs distally and bilaterally, affecting the patient’s wrist and fingers. It is characteristically provoked during action, irregular, small amplitude, and multidirectional, with an average frequency of one jerk every 1 to 5 seconds. The myoclonus is smaller than that seen in dementia with Lewy bodies but still of cortical origin. No relation to levodopa or motor severity of parkinsonism exists (26).

Infectious syndromes. Infectious syndromes, including viral and postviral conditions, can lead to the development of myoclonus. One notable example is Whipple disease, a rare yet treatable bacterial infection affecting multiple body systems. Systemic symptoms like gastrointestinal issues, fever, weight loss, joint problems, and CNS involvement characterize this condition. The presence of dementia, ophthalmoplegia (especially supranuclear gaze palsy), characteristic oculomasticatory myorhythmia, and myoclonus strongly suggests Whipple disease. Diagnosis relies on PCR-based detection of Tropheryma whipplei in cerebrospinal fluid or duodenal biopsy samples.

Acquired metabolic syndromes. Multifocal myoclonus is frequently due to metabolic causes, including hepatic failure, uremia, hyponatremia, hypoglycemia, and nonketotic hyperglycemia. Asterixis results in lapses of maintained postures and is considered a form of negative myoclonus (145). It usually occurs in conjunction with metabolic derangements, such as hepatic encephalopathy. Myoclonus can also be associated with malabsorption syndromes. Multiple malabsorption disorders have been identified as potential causes of myoclonus (26).

Drug-induced and toxic syndromes. Drug-induced myoclonus typically manifests suddenly on starting a medication or, in some cases, after prolonged use, especially when concurrent illnesses are present. Importantly, discontinuing the causative drug often leads to a rapid resolution of drug-induced myoclonus. Some medications and substances known to induce myoclonus include serotonin reuptake inhibitors, antiepileptic drugs, narcotics, levodopa, lithium, selegiline, amantadine, and others (58; 90; 25; 78; 02; 43; 138; 52).

Toxic encephalopathies causing myoclonus can occur after exposure to substances like bismuth, methyl bromide, and toxic cooking oil (105).

Clinicians must understand the potential for drug-induced and toxic myoclonus when evaluating patients presenting with myoclonic symptoms. Discontinuing the causative medication or addressing the underlying toxic exposure can often lead to symptom improvement or resolution.

Static encephalopathies secondary to diffuse brain injuries. Static encephalopathies secondary to diffuse brain injuries can result in myoclonus-related syndromes. Lance-Adams syndrome, described by Lance and Adams in 1963, is characterized by action myoclonus following hypoxic brain injury, often accompanied by asterixis, seizures, and gait problems (87).

Recent studies have emphasized the distinction between acute post-hypoxic myoclonus and chronic post-hypoxic myoclonus (68). Acute post-hypoxic myoclonus typically emerges immediately or within a day after hypoxic insult, often within 24 to 48 hours. It is generalized, occurs in the context of coma, and may manifest at rest or in response to stimuli. In contrast, chronic post-hypoxic myoclonus, commonly referred to as Lance-Adams syndrome, appears after some neurologic recovery, tends to be multifocal, and is predominantly triggered by muscle activation (action myoclonus).

Acute post-hypoxic myoclonus is associated with a less favorable prognosis, irrespective of whether hypothermia treatment is administered (131). Recent evidence suggests that acute post-hypoxic myoclonus originates in the brainstem as reticular reflex myoclonus (106). This distinction is crucial for guiding treatment decisions between acute and chronic post-hypoxic myoclonus.

Paraneoplastic, other autoimmune, and idiopathic inflammatory syndromes.

(A) Opsoclonus-myoclonus syndrome is characterized by involuntary, arrhythmic, chaotic, multidirectional, fast eye movements in combination with brainstem myoclonus involving the axial muscles and limbs (33). Opsoclonus-myoclonus syndrome is usually a manifestation of a paraneoplastic syndrome and is associated with breast cancer or small-cell lung carcinoma in adults (80) and neuroblastoma in children (06). Other causes of opsoclonus-myoclonus include viral infections such as West Nile virus (01), drugs, toxins, nonketotic hyperglycemia, and celiac disease (143; 50). Notably, the antibodies associated with opsoclonus-myoclonus syndrome have been found to attack dendritic neuronal surface antigens, with significant pathophysiological implications (108). Idiopathic opsoclonus-myoclonus occurs in younger patients, and its clinical course is generally more benign (07).

(B) A growing number of paraneoplastic and autoimmune disorders are associated with myoclonus and various antibodies (11; 10). One such disorder is anti-N-methyl-D-aspartate receptor encephalitis, which can affect both children and adults and is linked to a range of psychiatric symptoms as well as movement disorders, including chorea, stereotypies, dystonia, myoclonus, and myorhythmia (12). Both GABA-A and glycine receptor antibodies can produce myoclonus or stiff-person syndrome in patients (51; 144). Patients with antibodies to voltage-gated potassium channels have also been identified in myoclonus cases (127). Although this syndrome may resemble Creutzfeld-Jakob disease, its diagnosis is crucial because a positive response to therapy may be observed. The immunology of this antibody has become more complex as it has been suggested that other antigens may be causing the clinical syndromes associated with voltage-gated potassium channels (11). Other rare antibody-associated myoclonus syndromes have been linked to thyroid-stimulating hormone antibodies (24) and Ophelia syndrome (86). A comprehensive search for possible antibodies and cancer presence is warranted in such disorders.

Regarding anti-NMDAR encephalitis, this condition is characterized by a combination of psychiatric symptoms, seizures, movement disorders, and encephalopathy (11). EEG typically reveals abnormal activity or a distinctive extreme delta-brush pattern. In cerebrospinal fluid, elevated cell counts with CSF-specific oligoclonal bands and the presence of NMDAR antibodies are indicative. Notably, individuals with anti-NMDAR encephalitis should be meticulously screened for solid tumors, particularly ovarian teratoma, which is identified in more than half of adult female patients with this condition (11). The likelihood of underlying tumors is lower in younger patients (under 18 years) (45).

Pathophysiology

Electrophysiology. Myoclonus arises due to excessive neuronal discharge, which can originate in various locations within the nervous system. This electrical discharge can spread rapidly through pathways, as observed in cortical myoclonus (73), or through slower pathways, as seen in propriospinal myoclonus (20). The pattern and timing of muscle activation resulting from this discharge can offer insights into the source of the abnormal activity, which has diagnostic and treatment implications. However, the rapidity of discharge propagation often necessitates neurophysiological studies for a detailed assessment.

Neurophysiological studies for myoclonus typically include methods such as multichannel surface EMG recording, testing for long latency EMG responses to mixed nerve stimulation, EEG, EEG-EMG polygraphy with back averaging, and evoked potentials (eg, median nerve stimulation somatosensory evoked potential). Positive and negative findings from these methods contribute to determining the physiological type of myoclonus (25). For instance, the presence of a back-averaged focal cortical EEG transient, enlarged cortical somatosensory evoked potential, and enhanced long EMG responses suggests cortical origin myoclonus (122). Myoclonus is categorized into various physiological types, including cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral.

Cortical myoclonus, originating from the cerebral cortex, is the most common form and can be associated with various neurodegenerative diseases, toxic-metabolic conditions, and other disorders. Typically, it manifests as brief, stimulus-sensitive muscle jerks, often involving antagonist muscle pairs. Cortical myoclonus can result from a range of conditions, including tumors, angiomas, and encephalitis (132; 34). It may also present as epilepsia partialis continua, occurring in focal encephalitis, stroke, tumors, and, infrequently, multiple sclerosis (76). Other conditions like Rett syndrome and Angelman syndrome have also been associated with cortical myoclonus (67; 66).

Cortical-subcortical myoclonus corresponds to myoclonus observed in myoclonic and absence seizures, often involving interactions between cortical and subcortical centers, such as the thalamus (26). These jerks are typically bilaterally synchronous or generalized.

Subcortical-nonsegmental myoclonus, seen in conditions like essential myoclonus and reticular reflex myoclonus, originates below the cortical level and can spread beyond the source to multiple segmental levels. Reticular reflex myoclonus, for instance, is characterized by generalized jerks, sometimes stimulus-sensitive (72). It is thought to originate in the caudal brainstem and spreads both rostrally and caudally. Essential myoclonus, characterized by an EMG burst length of 50 to 150 msec, may also have a subcortical origin (89; 113).

Two major forms of spinal myoclonus are recognized: segmental myoclonus, originating from segmental brainstem or spinal generators, and propriospinal myoclonus, causing generalized axial movements (39). Propriospinal myoclonus is considered subcortical-nonsegmental myoclonus as it can spread both rostrally and caudally within the spinal cord (114).

Segmental myoclonus arises from segmental brainstem (palatal) or spinal generators (27). Symptomatic palatal myoclonus, for example, arises from lesions within the Guillain-Mollaret triangle, a neural pathway connecting various brainstem nuclei. On the other hand, spinal segmental myoclonus typically affects muscles innervated by adjacent spinal segments and may persist during sleep (27).

Peripheral myoclonus, except for hemifacial spasm, is relatively rare and may occur in conditions affecting peripheral nerves, plexuses, or roots or through a proposed mechanism called "ephaptic" transmission of peripheral ectopically generated potentials (94).

Biochemistry. The biochemical basis of myoclonus appears to be heterogeneous and may involve various mechanisms. In some forms of myoclonus, such as posthypoxic myoclonus, there is a characteristic reduction in 5-hydroxyindoleacetic acid levels in the cerebrospinal fluid (137). This specific biochemical profile may respond to treatment with 5-hydroxytryptophan and carbidopa.

Animal studies have shown that myoclonus can be induced by pp-dichlorodiphenyltrichloroethane (a chemical compound) and improved by agonists of 5-hydroxytryptophan while worsening with antagonists of 5-hydroxytryptophan (137). However, it's worth noting that L-5-hydroxytryptophan can also produce myoclonus that is not stimulus-sensitive.

In the context of Parkinson disease, myoclonus induced by L-dopa treatment may potentially improve with the use of 5-hydroxytryptophan receptor blockers (83).

Furthermore, experiments involving the injection of GABA antagonists into the putamen have demonstrated the ability to produce myoclonus (44).

Genetics. Myoclonus is associated with various genetic conditions, shedding light on the underlying causes and mechanisms of this phenomenon.

The International Parkinson and Movement Disorder Society Task Force has proposed a new nomenclature for genetically determined myoclonus syndromes, aiming to provide clarity for clinicians in their daily practice. This classification categorizes these genetic disorders into three main groups based on their clinical presentation:

(1) Prominent myoclonus syndromes. Genetic disorders in this group primarily manifest with prominent myoclonus in the majority of cases.

(2) Combined myoclonus syndromes. Genetic disorders falling into this category present with prominent myoclonus as well as another prominent movement disorder, such as dystonia or ataxia, in most cases.

(3) Disorders that can manifest as prominent myoclonus syndromes. In this group, genetic disorders typically present with other clinical phenotypes but can occasionally exhibit prominent myoclonus as part of the disorder's phenotypic spectrum, although this occurs in a minority of cases (135).

This new classification system provides a more precise framework for understanding and diagnosing genetically determined myoclonus syndromes, enabling clinicians to better identify and manage these conditions in clinical practice.

Autosomal recessive disorders. Progressive myoclonic epilepsy, Lafora disease, neuronal ceroid lipofuscinosis, Unverricht-Lundborg disease, and sialidosis are all autosomal recessive conditions.

Maternally inherited disorder. Myoclonic epilepsy with ragged red fibers is inherited through maternal lineage. Myoclonic epilepsy with ragged red fibers may result from an adenosine-to-guanine substitution in the tRNA gene, MTTK, in mitochondrial DNA (120).

Genetic abnormalities in specific disorders.

	• Unverricht-Lundborg disease is associated with chromosome 21q 22.3 and involves mutations in the cystatin B gene (79). The major mutation worldwide is an unstable expansion of a dodecamer repeat (CCCCGCCCCGCG) in the promoter region of the Cystatin B gene
	• Lafora disease is linked to genes EPM2A and NHLRC1, with EPM2A encoding laforin and NHLRC1 encoding malin (100). Up to 80% of patients with Lafora disease harbor EPM2A mutations and tend to have a more severe clinical course with shorter life expectancy compared to those with NHLRC1 mutations.
	• Neuronal ceroid lipofuscinosis has distinct genetic mutations for each type, with the late infantile form potentially resulting from mutations in the tripeptidyl peptidase 1 gene (120).
	• Progressive myoclonus epilepsy may involve mutations in KCNC1 and LMNB2 genes (46; 102).
	• Angelman syndrome is associated with various genetic mechanisms, including deletions, uniparental disomy, imprinting defects, and mutations within the ubiquitin protein ligase E3A gene (63).
	• Spinocerebellar ataxias, such as SCA3, may be associated with myoclonus (41).
	• Dentatorubral-pallidoluysian atrophy is caused by unstable CAG repeat expansion in the atrophin 1 gene (81).
	• Ataxia with oculoapraxia type 2 may involve mutations in SETX and AFG3L2 (88).
	• Familial myoclonus-dystonia (DYT 11) is linked to mutations in the epsilon-sarcoglycan gene and calcium channel CACNA1B gene (64). Loss-of-function mutations in the epsilon-sarcoglycan gene are causative in most familial myoclonus-dystonia (DYT 11) cases. However, investigators report 30% cases with the typical phenotype lack the epsilon-sarcoglycan mutation (130). Myoclonus-dystonia is inherited as an autosomal dominant trait with incomplete penetrance. The mutant allele undergoes genomic imprinting during maternal inheritance, leading to reduced expression of clinical features when compared to paternal transmission (115). Patients with the epsilon-sarcoglycan mutation demonstrate a particular pattern of truncal myoclonus and axial dystonia compared to familial myoclonus-dystonia without the epsilon-sarcoglycan mutation.
	• DYT26, another genetic form of myoclonus-dystonia, is associated with mutations in the KCTD17 gene (96).
	• Other genetic forms of myoclonus include DYT-SGCE, HSP-KIF1C, SCA-PRKCG, SCA-ATXN2, SCA-ATN1, CHOR/DYT-ADCY5, and C9orf72 (92).

Hereditary hyperekplexia. Hereditary hyperekplexia, transmitted as an autosomal dominant trait, is linked to chromosome 5q33-q35 and involves a point mutation in the alpha-1 subunit of the glycine receptor.

Familial adult myoclonic epilepsy. Familial adult myoclonic epilepsy, characterized by "cortical tremor" and myoclonus, has been linked to chromosome 8q24 (111). It can also show genetic heterogeneity and linkage to chromosome 2p11.1-q12.2 (49).

22q11.2 deletion syndrome (DiGeorge syndrome). Myoclonus has been reported in association with the 22q11.2 deletion syndrome, which may present with neuropsychiatric disorders, seizures, parkinsonism, and tremor (17).

Differential diagnosis

To distinguish an isolated myoclonic jerk from other movement disorders (myoclonus mimics), such as chorea, tic, dystonia, and tremor, it is important to consider the following characteristics.

Chorea. Chorea movements are dance-like and lack a rhythmic quality. They integrate with normal movements and appear as a continuous flow of irregular motions. There is variability in burst duration and muscle recruitment order. In advanced chorea, motor impersistence can occur, leading to difficulty maintaining specific postures or movements, such as keeping the tongue protruded or grip strength fluctuations (milkmaid's grip).

Motor tics. Tics are stereotypic or repetitive movements typically seen in childhood. They may coexist with other tics and are often characterized by premonitory sensations preceding the movements. Tics can be voluntarily suppressed, and relief is experienced after performing the movement. Burst duration in tics typically exceeds 100 ms, and pre-movement potentials on back-averaging may be present. Conditions like Tourette syndrome may involve multiple motor and vocal tics, along with coprolalia (involuntary swearing) and obsessive-compulsive symptoms.

Dystonic jerks. Dystonic jerks occur alongside dystonia, which involves sustained muscle contractions. Sensory tricks (geste antagoniste) can temporarily alleviate dystonic symptoms. Dystonia entails the co-contraction of agonist and antagonist muscles. Burst duration in dystonic jerks usually exceeds 100 ms, and overflow (unintentional muscle contractions accompanying primary dystonic movements) may occur.

Tremor. Tremor is characterized by sinusoidal and rhythmic movements involving alternating contractions of antagonistic muscles. Tremor maintains a steady frequency, measurable with accelerometry. Myoclonus and ataxia can occasionally coexist, as seen in progressive myoclonic ataxia. In such cases, it may be necessary to treat the myoclonus first to accurately assess the underlying ataxia's severity.

Functional (psychogenic) jerks. Functional jerks may exhibit inconsistent movements that lack a specific pattern. They are often reduced or altered by distraction or entrainment. Variability is observed in muscle involvement, recruitment order, burst duration, and amplitude. Pre-movement potentials on back-averaging may be present, indicating a psychogenic origin.

Diagnostic workup

It is imperative to systematically investigate the underlying causes of myoclonus (31; 28). The initial approach should be guided by the clinical context, treating myoclonus as a symptom rather than the primary condition. This approach is essential because most instances of myoclonus are secondary and arise from various underlying diseases and conditions. For example, if there are indications of an infectious or inflammatory syndrome, conducting a cerebrospinal fluid examination is crucial. Furthermore, recent advancements in next-generation sequencing techniques have introduced an innovative eight-step diagnostic framework for patients with myoclonus.

Confirming myoclonus. The first step involves confirming that the observed movements indeed represent myoclonus. This distinction is critical in ruling out other hyperkinetic movement disorders, such as tremor, motor tics, chorea, dystonic jerks, and functional (psychogenic) jerks. The differentiation relies on a combination of clinical assessment and electrophysiological features.

Defining the anatomical bases of myoclonus. Myoclonus can manifest in various anatomical regions of the nervous system, including the peripheral, spinal (segmental and propriospinal), subcortical, and cortical areas. Different types of myoclonus have distinct etiologies, necessitating tailored clinical approaches. Cortical and subcortical myoclonus can either be acquired or result from genetic disorders, necessitating genetic testing in addition to MRI and laboratory investigations. Conversely, spinal and peripheral myoclonus are typically acquired.

Identifying the underlying cause. In cases of spinal or peripheral myoclonus, precisely determining the source is paramount. This necessitates a comprehensive assessment for signs of muscle denervation and the presence of structural lesions, using suitable electrophysiological and imaging examinations. Potential origins encompass conditions such as brachial plexus or spinal root lesions, which can be elucidated through EMG and MRI. It is worth noting that peripheral myoclonus can also emerge following limb amputation.

Spinal myoclonus, although rare, is typically associated with lesions affecting the spinal cord. The presence of acute or subacute onset, rapid disease progression, symptoms like radiculopathy or polyradiculopathy, and systemic manifestations, such as fever, skin rashes, or joint issues, may suggest an infectious or autoimmune etiology. Confirmatory laboratory tests should be conducted in such cases.

It is important to acknowledge that most instances of propriospinal myoclonus are categorized as functional movement disorders. However, in exceptional circumstances, medication or infections can trigger spinal myoclonus. Therefore, a thorough evaluation remains essential for these cases.

Cortical and subcortical myoclonus encompass a broad spectrum of potential causative factors. An acute or subacute onset with rapid disease progression may indicate an acquired origin, whereas early-onset disease with a more gradual progression often suggests a genetic disorder. Additional clinical features frequently yield valuable insights for accurately diagnosing the underlying condition.

Evaluation for toxic or medication-induced causes. Numerous drugs are recognized for their potential to induce or exacerbate myoclonus, including medications like lithium, antidepressants, anti-infectious agents, and narcotics, among others. When there is suspicion that a medication is responsible for a patient's myoclonus, careful consideration should be given to the gradual reduction or discontinuation of the drug. This change in medication not only serves therapeutic purposes but also contributes to the diagnostic process.

Laboratory testing. Cortical or subcortical myoclonus can often be linked to disturbances in homeostasis, organ failure, or infections. Examples of common underlying conditions include acute or chronic renal failure, acute or chronic hepatic failure, chronic respiratory failure leading to hypercapnia, disruptions in glucose regulation, hyperthyroidism, and metabolic imbalances, such as alkalosis or acidosis.

A meticulous assessment for potential infectious or immune-mediated causes of myoclonus is imperative. This evaluation may involve the following:

	• Measurement of electrolytes and glucose levels
	• Comprehensive drug and toxin screening, including substances like bismuth, calcium, and magnesium
	• EEG to identify abnormal brain activity
	• Assessment of renal function through relevant tests
	• Evaluation of hepatic function using appropriate assessments
	• Paraneoplastic testing to investigate possible cancer-related factors

These tests primarily focus on assessing metabolic, toxic, and structural brain abnormalities, as well as identifying seizure disorders and potential cancer-related triggers of myoclonus. Although routine surface EEG may reveal epileptiform discharges or other diagnostic indicators, it may not always detect spikes in cases of cortical reflex myoclonus and can sometimes be normal in epilepsia partialis continua. Notably, the presence of antibodies to voltage-gated potassium channels has been observed in patients with myoclonus, and this often responds positively to treatment (127).

If the results of these initial tests fail to provide a definitive diagnosis, the next step involves considering more advanced diagnostic procedures. The clinical information accumulated thus far plays a crucial role in guiding this comprehensive evaluation, which may encompass cerebrospinal fluid examination, enzyme activity assessments, imaging studies to investigate the possibility of cancer, tissue biopsy procedures, and other specialized tests.

Cerebrospinal fluid analysis is especially warranted when infection is suspected (119). In cases of generalized and multifocal myoclonus, the metabolic workup should involve tests related to liver and kidney functions, blood gases, and blood sugar levels. For patients with progressive myoclonic epilepsy and progressive myoclonic ataxia, the diagnostic workup should encompass visual evoked responses and electroretinography to identify potential neuronal ceroid lipofuscinosis. Elevated plasma and cerebrospinal fluid lactate levels can point to a mitochondrial encephalopathy. It is also essential to perform white cell or fibroblast lysosomal enzyme estimations and screen for urinary oligosaccharides and organic acids. Additional diagnostic tools should be considered, such as skin and conjunctival biopsy with electromicroscopy to detect inclusions in nerves (especially in eccrine sweat glands), muscle biopsy to identify ragged-red fibers and study mitochondrial metabolism, and jejunal biopsy to explore conditions like celiac disease and Whipple disease. Furthermore, the presence of anti-Ri antibodies may yield positive results in cases of opsoclonus-myoclonus syndrome.

Brain imaging. An imperative component of the diagnostic process involves brain imaging, with MRI being the preferred modality. This imaging study aims to identify focal lesions or other indicators of specific conditions, including neurodegeneration with brain iron accumulation disorders, leukodystrophy, or mitochondrial disorders.

In the context of cortical myoclonus, a SPECT activation study can be employed. This specialized study helps pinpoint hyperexcitable regions within the cortex (128).

For cases of palatal myoclonus, it is essential to conduct an MRI scan to explore potential lesions in the Guillain-Mollaret triangle. MRI findings may reveal signs of olivary hypertrophy and hyperintensity on T2 sequences. The type and location of the lesion, such as distinguishing between a stroke and multiple plaques, will guide the subsequent diagnostic workup.

In situations involving spinal myoclonus, appropriate imaging studies are of paramount importance. Depending on the clinical presentation, an examination of cerebrospinal fluid may also be indicated to rule out potential underlying causes.

Additionally, despite negative results from paraneoplastic testing, considering body imaging for cancer remains crucial.

It is noteworthy that late-onset neurodegenerative disorders often coincide with myoclonus. These disorders may encompass Alzheimer disease, Parkinson disease, multiple system atrophy, and, less frequently, dementia with Lewy bodies, Huntington disease, and corticobasal degeneration. In cases of myoclonus associated with Parkinson disease and multiple system atrophy, manifestations typically include irregular, small-amplitude myoclonic jerks in the fingers, often characterized by their sensitivity to external stimuli. This phenomenon is referred to as cortical polyminimyoclonus (29).

Genetic testing considerations. In select cases, the option of genetic testing should be contemplated as part of the diagnostic process. However, patients must be fully informed about the potential implications of both positive and negative test results. When appropriate, genetic counseling is highly recommended to provide patients with a comprehensive understanding of their genetic testing journey.

Incorporating genetic testing into the diagnostic framework is essential not only for nuclear gene mutations but also for mitochondrial disorders stemming from mutations in mitochondrial DNA. These mitochondrial disorders can manifest with myoclonus, among a range of other clinical features.

The implementation of next-generation sequencing techniques offers distinct advantages. Next-generation sequencing can detect mutations associated with atypical clinical presentations, recognizing that patients with myoclonus-related disorders may exhibit a spectrum of symptoms that deviate from classic phenotypes.

It is important to acknowledge that several limitations exist with current next-generation sequencing methodologies. These techniques may overlook certain genetic anomalies, including repeat expansions, extensive structural rearrangements, and mutations located in noncoding regions, such as deep intronic mutations and promoter regions. Additionally, mutations in mtDNA may elude detection.

Therefore, in cases where the diagnostic puzzle remains unsolved after exhaustive genetic evaluation, it becomes prudent to consider targeted mtDNA analysis as a potential avenue for uncovering the underlying genetic basis of myoclonus-related disorders. This comprehensive approach ensures that even elusive genetic factors are thoroughly explored in the pursuit of an accurate diagnosis.

Management

Treatment of myoclonus. The initial step in addressing myoclonus involves classifying its type and identifying the underlying disease process, which should be treated or reversed whenever possible. In cases where the etiology remains elusive or is irreversible, treatment strategies are best guided by neurophysiological classification, which categorizes myoclonus into various types based on the location of its origin (cortical, cortical-subcortical, subcortical-nonsegmental, segmental, or peripheral) (28).

It is important to note that the evidence for myoclonus treatments is limited, and multiple trials of different treatments may be necessary to achieve optimal symptom suppression. Often, a combination of medications is required for the best response, although this approach may pose challenges due to potential side effects. Consequently, close monitoring of both treatment response and side effects is strongly advised.

Treatment for cortical myoclonus. For cortical myoclonus, several medications have been explored for symptomatic relief. Levetiracetam has shown promise in alleviating cortical myoclonus, although other similar drugs like brivaracetam have not demonstrated confirmed efficacy. Clonazepam, sodium valproate, and piracetam have also been found to be effective for cortical myoclonus. Anesthetic agents may suppress generalized myoclonus immediately post-hypoxia, although the overall prognosis for such patients often remains poor. Some less effective drugs for cortical myoclonus include lisuride, acetazolamide, and carbamazepine. Combining several of these drugs may be necessary to achieve a response, but side effects can be a limiting factor, and the evaluation of polytherapy can be complex.

It is worth noting that phenytoin may exacerbate cortical myoclonus in progressive myoclonic epilepsy and other cortical myoclonus cases. Acetazolamide can be beneficial for myoclonus in Ramsay Hunt syndrome. Negative myoclonus often resolves when the underlying metabolic derangement is corrected, with ethosuximide being particularly useful for symptomatic treatment in some cases. Sodium oxybate has shown promise in improving post-hypoxic myoclonus of cortical origin, and intrathecal baclofen has been reported to be beneficial in selected cases of post-hypoxic myoclonus. Although deep brain stimulation is not a primary choice for cortical myoclonus therapy, there have been isolated case reports of success, such as with bilateral globus pallidus stimulation in Lance-Adams syndrome (08).

Treatment of cortical-subcortical myoclonus. Cortical-subcortical myoclonus, as seen in conditions like juvenile myoclonic epilepsy, often responds well to specific medications. Valproic acid is a commonly used drug and is considered a major treatment choice, supported by controlled evidence (140). Although the evidence is not definitive, valproic acid is also used for other myoclonic seizure disorders (22). Lamotrigine can be employed either alone or as an adjunct to valproic acid (21). Levetiracetam is another option, particularly as a second-line drug for cortical-subcortical myoclonus in primary generalized epilepsy. Brivaracetam, a medication similar in nature to levetiracetam but with potentially fewer side effects, has shown promise in this type of myoclonus physiology (126). However, caution should be exercised when treating with certain antiseizure medications, as some agents can worsen myoclonus or seizures in these disorders (98). Treating less common myoclonic epilepsy syndromes can be particularly challenging (118).

Treatment of subcortical-nonsegmental myoclonus. Essential myoclonus, a form of subcortical-nonsegmental myoclonus, may be effectively managed with medications such as clonazepam or anticholinergics (40). In cases where essential myoclonus is part of the myoclonus-dystonia syndrome, there is increasing evidence that deep brain stimulation surgery can provide significant therapeutic benefits. Although earlier attempts focused on the ventral intermediate thalamic nucleus, more recent reports have targeted the globus pallidus (84). Multiple studies on globus pallidus stimulation have shown greater than 50% improvement in myoclonus and dystonia in patients with myoclonus-dystonia syndrome (85). Some reports even include cases of myoclonus-dystonia without the epsilon-sarcoglycan gene mutation (65; 107). Although a few studies have compared globus pallidus stimulation to ventral intermediate thalamic nucleus stimulation, there appears to be a slight advantage for globus pallidus stimulation, including a more favorable side effect profile (65). Because myoclonus can have various etiologies and locations, the response to deep brain stimulation may vary. Some studies suggest that patients with the epsilon-sarcoglycan gene mutation tend to respond better to deep brain stimulation, although some gene-negative patients also show improvement (139; 123). There is evidence of long-term benefits from globus pallidus stimulation or ventral intermediate thalamic nucleus stimulation (116; 146).

Paraneoplastic opsoclonus-myoclonus syndrome treatment. Paraneoplastic causes of opsoclonus-myoclonus syndrome may exhibit a response to cancer treatment. Additionally, on a symptomatic basis, myoclonus may improve with clonazepam use, regardless of its underlying cause (33). In cases with paraneoplastic or idiopathic inflammatory origins, immunomodulation therapies can be beneficial and may lead to the amelioration of opsoclonus-myoclonus. Conventional management typically involves the use of ACTH or corticosteroids. However, some experts recommend concomitant treatment with plasmapheresis (121) or intravenous immunoglobulin (09). Rituximab, a monoclonal antibody that targets mature B cells for apoptosis, has also shown promise in improving opsoclonus-myoclonus, including in pediatric patients with neuroblastoma (125). It is important to note that there are variations in treatment strategies for children compared to adults (129).

Propriospinal myoclonus treatment. Propriospinal myoclonus is a rare disorder characterized by repetitive, typically flexor, arrhythmic brief jerks affecting the trunk, hips, and knees in a fixed pattern. It is believed to originate in the spinal cord, and its diagnosis relies on specific features observed during polymyography. However, there has been a recent shift in the understanding of propriospinal myoclonus, with reports suggesting that it is, in most cases, a functional (or psychogenic) movement disorder (134).

For symptomatic relief in propriospinal myoclonus, clonazepam is the most commonly prescribed treatment (31). Other medications, including zonisamide, lioresal, valproic acid, and carbamazepine, have also demonstrated effectiveness in some cases (114).

Segmental myoclonus treatment. Segmental myoclonus presents unique challenges in terms of treatment options, and the effectiveness of therapies can vary depending on the specific type and location of the myoclonus.

Palatal segmental myoclonus. Palatal segmental myoclonus, particularly when associated with ear clicking, has proven resistant to therapy. Various agents have been attempted, including clonazepam, anticholinergics, 5-hydroxytryptophan, and carbamazepine (28). In cases where ear clicking significantly impairs the patient's quality of life, surgical interventions such as tensor veli palatini tenotomy and eustachian tube occlusion have been performed with varying success rates (57). Botulinum toxin injections have shown promise in managing palatal myoclonus, with studies indicating their usefulness (124). The choice between injections into the tensor-veli-palatini or medial uvula (levator-veli-palatini) may depend on the specific symptoms, such as clicking tinnitus or perceived palatal movements.

Middle ear myoclonus. Treatment for middle ear myoclonus, which can cause troublesome tinnitus, has not been extensively studied. Therapeutic approaches have included both medical and surgical methods (16). Given the limited data available, treatment decisions should be made on a case-by-case basis, considering the severity of symptoms and the patient's response to different interventions.

Spinal myoclonus. The management of spinal myoclonus can be challenging, and treatment options depend on the underlying cause. Surgical removal may be attempted to alleviate symptoms in cases where a compressing lesion is identified (47). Complete spine imaging is crucial for identifying such lesions. If the lesion cannot be treated surgically, medications such as clonazepam, carbamazepine, lioresal, or tetrabenazine may be considered. Some cases of spinal segmental myoclonus have responded positively to botulinum toxin injections, particularly when used to manage associated pain (133). Intrathecal baclofen has also been reported as beneficial in certain instances of spinal myoclonus (38).

Peripheral myoclonus. Hemifacial spasm is a common form of peripheral myoclonus and is effectively treated with botulinum toxin injections to reduce quick movements and spasms. Botulinum toxin has also shown promise in managing other forms of peripheral myoclonus, potentially alleviating associated discomfort (23). Carbamazepine may be considered as a drug therapy option for peripheral myoclonus, although achieving a satisfactory response with this medication is uncommon.

Uncertain pathophysiology. If the pathophysiology of the myoclonus cannot be determined, medications for the most common source (cortical) are often employed. If the diagnosis is known, the common pathophysiology of the myoclonus for that condition may be known in the literature (25). Gabapentin was effective in myoclonus induced by chronic opiate medication in cancer patients with pain (97). Immunotherapy may help patients with myoclonus associated with voltage-gated potassium channel antibodies (05).

Media

References

01: Afzal A, Ashraf S, Shamim S. Opsoclonus myoclonus syndrome: an unusual presentation for West Nile virus encephalitis. Proc (Bayl Univ Med Cent) 2014;27(2):108-10. PMID 24688189
02: Algahtani HA, Aldarmahi AA, Al-Rabia MW, Almalki WH, Bryan Young G. Myoclonus and spasticity induced by lamotrigine toxicity: a case report and literature review. Clin Neuropharmacol 2014;37(2):52-4. PMID 24614666
03: Alvarez M, Caviness JN. Primary progressive myoclonus of aging. Mov Disord 2008;23(12):1658-64. PMID 18709679
04: Anonymous. Classification of progressive myoclonus epilepsies and related disorders. Marseille Consensus Group. Ann Neurol 1990;28:113-6. PMID 2115761
05: Antozzi C, Binelli S, Frassoni C, et al. Immunotherpay responsive startle with antibodies to voltage gated potassium channels. J Neurol Neurosurg Psychiatry 2007;78:1281-90. PMID 17940176
06: Arino H, Hofberger R, Gresa-Arribas N, et al. Paraneoplastic neurological syndromes and glutamic acid decarboxylase antibodies. JAMA Neurol 2015;72(8):874-81. PMID 26099072
07: Armangue T, Sabater L, Torres-Vegas E, et al. Clinical and immunological features of opsoclonus-myoclonus syndrome in the era of neuronal cell surface antibodies. JAMA Neurol 2016;73(4):417-24. PMID 26856612
08: Asahi T, Kashiwazaki D, Dougu N, et al. Alleviation of myoclonus after bilateral pallidal deep brain stimulation for Lance-Adams syndrome. J Neurol 2015;262(6):1581-3. PMID 25929661
09: Aysun U, Sumer M, Atasoy T, Nuray A. Treatment of idiopathic opsoclonus-myoclonus with intravenous immunoglobulin. Neurol India 2004;52(4)520-1.
10: Baizabal-Carvallo JF, Bonnet C, Jankovic J. Movement disorders in systemic lupus erythematosus and the antiphospholipid syndrome. J Neurol Transm 2013a;120(11):1579-89. PMID 23580159
11: Baizabal-Carvallo JF, Jankovic J. Movement disorders in autoimmune diseases. Mov Disord 2012;27(8):935-46. PMID 22555904
12: Baizabal-Carvallo JF, Stocco A, Muscal E, Jankovic J. The spectrum of movement disorders in children with anti-NMDA receptor encephalitis. Mov Disord 2013b;28(4):543-7. PMID 23400857
13: Bakker MJ, van Dijk JG, Pramono A, Sutarni S, Tijssen MA. Latah: an Indonesian startle syndrome. Mov Disord 2013;28(3):370-9. PMID 23283702
14: Berkovic SF, Andermann F, Karpati G, et al. Mitochondrial encephalomyopathies: a solution to the enigma of the Ramsay Hunt syndrome. Neurology 1987;37(Suppl 1):127.
15: Bhat S, Ganesh S. New discoveries in progressive myoclonus epilepsies: a clinical outlook. Expert Rev Neurother 2018;18(8):649-67. PMID 30032677
16: Bhimrao SK, Masterson L, Baguley D. Systematic review of mangement strategies for middle ear myoclonus. Otolaryngol Head Neck Surg 2012;146:698-706. PMID 22261497
17: Boot E, Butcher NJ, van Amelsvoort T, et al. Movement disorders and other motor abnormalities in adults with 22q11.2 deletion syndrome. Am J Med Genet A 2015;167A(3):639-45. PMID 25684639
18: Bourgeois BF, Douglass LM, Sankar R. Lennox-Gastaut syndrome: a consensus approach to differential diagnosis. Epilepsia 2014;55 Suppl 4:4-9. PMID 25284032
19: Bressman S, Fahn S, Eisenberg M, Maltese W. Adult onset encephalopathy with myoclonus, ataxia, deafness, hemianopsia, and hemiparesis responsive to biotin. Ann Neurol 1983;14:109-10.
20: Brown P, Thompson PD, Rothwell JC, Day BL, Marsden CD. Axial myoclonus of propriospinal origin. Brain 1991;114(Pt 1A):197-214. PMID 1998882
21: Buchanan N. The use of lamotrigine in juvenile myoclonic epilepsy. Seizure 1996;5:149-51. PMID 8795132
22: Calleja S, Salas-Puig J, Ribacoba R, et al. Evolution of juvenile myoclonic epilepsy treated from the outset with sodium valproate. Seizure 2001;10:424-7. PMID 11700996
23: Carnero-Pardo C, Sanchez-Alvarez JC, Gomez-Camello A, Minguez-Castellanos A, Hernandez-Ramos FJ, Garcia-Gomez T. Myoclonus associated with thoracodorsal neuropathy. Mov Disord 1998;13(6):971-2. PMID 9827626
24: Castillo P, Woodruff B, Caselli R, et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 2006;63(2):197-202. PMID 16476807
25: Caviness JN. Clinical neurophysiology of myoclonus. In: Hallett M, editor. Movement Disorders. Handbook of Clinical Neurophysiology. Vol 1. Amsterdam: Elsevier, 2003:521-48.**
26: Caviness JN. Epileptic myoclonus. In: Sirven JI; Stern JM, editors. Atlas of video-EEG monitoring. New York: McGraw-Hill Medical, 2011:309-28.
27: Caviness JN. Segmental Myoclonus. In: Hyperkinetic Movement Disorders. Albanese A, Jankovic J, editors. West Sussex, UK: Wiley-Blackwell, 2012:221-36.
28: Caviness JN. Treatment of Myoclonus. Neurotherapeutics 2014;11(1):188-200.** PMID 24037428
29: Caviness JN, Adler CH, Beach TG, Wetjen KL, Caselli RJ. Small-amplitude cortical myoclonus in Parkinson's disease: physiology and clinical observations. Mov Disord 2002;17(4):657-62. PMID 12210853
30: Caviness JN, Alving L, Maraganore D, Black RA, McDonnell SK, Rocca WA. The incidence and prevalence of myoclonus in Olmsted County, Minnesota. Mayo Clin Proc 1999;74(6):565-9. PMID 10377930
31: Caviness JN, Brown P. Myoclonus: current concepts and recent advances. Lancet Neurol 2004;3:598-607. PMID 15380156
32: Caviness JN, Evidente VG. Cortical myoclonus during lithium exposure. Arch Neurol 2003;60(3):401-4. PMID 12633152
33: Caviness JN, Forsyth PA, Layton DD, McPhee TJ. The movement disorder of adult opsoclonus. Mov Disord 1995;10(1):22-7. PMID 7885352
34: Caviness JN, Kurth M. Cortical myoclonus in Huntington's disease associated with an enlarged somatosensory evoked potential. Mov Disord 1997;12(6):1046-51. PMID 9399235
35: Caviness JN, Lue LF, Beach TG, et al. Parkinson’s disease, cortical dysfunction, and alpha-synuclein. Movement Disorders 2011;26(8):1436-1442. PMID 21542019
36: Caviness JN, Truong DD. Myoclonus. Handbook of Clinical Neurology 2011;100:399-420. PMID 21496598
37: Chiaro G, Calandra-Buonaura G, Sambati L, et al. Hypnic jerks are an underestimated sleep motor phenomenon in patients with parkinsonism. A video-polysomnographic and ndurophysiological study. Sleep Med 2016;26:37-44. PMID 28007358
38: Chiodo AE, Saval A. Intrathecal baclofen for the treatment of spinal myoclonus: a case series. J Spinal Cord Med 2012;35(1):64-7. PMID 22330193
39: Chokroverty S. Propriospinal myoclonus. Clin Neurosci 1995-96;3(4):219-22. PMID 8891395
40: Chokroverty S, Manocha MK, Duvoisin RC. A physiologic and pharmacologic study in anticholinergic-responsive essential myoclonus. Neurology 1987;37:608-15. PMID 3561772
41: Choubtum L, Witoonpanich P, Hanchaiphiboolkul S, et al. Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 in patients with unknown spinocerebellar ataxia: a Thai multicenter study. BMC Neurology 2015;15:166. PMID 26374734
42: Coughlin DG, Bardakjian TM, Spindler M, Deik A. Hereditory myoclonus dystonia: a novel SGCE variant and penotype including intellectual disability. Tremor Other Hyperkinet Mov (N Y) 2018;8:547. PMID 29607243
43: Courtois F, Borrey D, Haufroid V, Hantson P. Pregabalin-associated myoclonic encephalopathy without evidence of drug accumulation in a patient with acute renal failure. Indian J Nephrol 2014;24(1):48-50. PMID 24574633
44: Crossman AR, Sambrook MA, Jackson A. Experimental hemichorea/hemiballismus in the monkey. Studies on the intracerebral site of action in a drug-induced dyskinesia. Brain 1984;107:579-96. PMID 6722517
45: Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10(1):63-74. PMID 21163445
46: Damiano JA, Afawi Z, Bahlo M, et al. Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia. Human Mol Genet 2015;24(16):4483-90. PMID 25954030
47: Daniel DG, Webster DL. Spinal segmental myoclonus. Successful treatment with cervical spinal decompression. Arch Neurol 1984;41:898-9. PMID 6466169
48: Day BL, Marsden CD. The hyperexplexias and their relationship to the normal startle reflex. Brain 1991;114:1903-28. PMID 1884185
49: De Falco FA, Striano P, De Falco A, et al. Benign adult familial myoclonic epilepsy: Genetic heterogeneity and allelism with ADCME. Neurology 2003;60(8):1381-5. PMID 12707452
50: Deconinck N, Scaillon M, Segers V, et al. Opsoclonus-myoclonus associated with celiac disease. Pediatr Neurol 2006;34(4):312-4. PMID 16638509
51: DeFelipe-Mimbrera A, Masjuan J, Corral I, Villar L, Graus F, Garcia-Barragan N. Opsoclonus-myoclonus syndrome and limbic encephalitis associated with GABAB receptor antibodies in CSF. J Neuroimmunol 2014;272(1-2):91-3. PMID 24814391
52: Desai A, Kherallah Y, Szabo C, Marawar R. Gabapentin or pregabalin induced myoclonus: A case series and literature review. J Clin Neurosci 2019;61:225-34. PMID 30381161
53: Deuschl G, Mischke G, Schenck E, Schulte-Monting I, Lucking CH. Symptomatic and essential rhythmic palatal myoclonus. Brain 1990;113:1645-72. PMID 2276039
54: Dravet C, Bureau M. Benign myoclonic epilepsy in infancy. Adv Neurol 2005;95:127-37. PMID 15508918
55: Dreissen YE, Tijssen MA. The startle syndromes: physiology and treatment. Epilepsia 2012;53(Suppl 7):3-11. PMID 23153204
56: Elia M, Musumeci S, Ferri R, et al. Familial cortical tremor, epilepsy, and mental retardation: a distinct clinical entity. Arch Neurol 1998;55(12):1569-73. PMID 9865802
57: Ensink RJH, Vingerhoets HM, Schmidt CW, Cremers CW. Treatment for severe palatoclonus by occlusion of the eustachian tube. Otol Neurotol 2003;24:714-6. PMID 14501444
58: Fernandez HH, Friedman JH. Carvedilol-induced myoclonus. Mov Disord 1999;14:703. PMID 10435516
59: Frauscher B, Gabella D, Mitterling T, et al. Motor events during healthy sleep: a quantitative polysomnographic study. Sleep 2014;37(4):763-73. PMID 24744455
60: Galanopoulou AS, Moshe SL. Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: a view from preclinical studies. Neurobiology of Disease 2015;79:135-149. PMID 25968935
61: Genton P, Thomas P, Kasteleijn-Noist Trenite DGA, Medina MT, Salas-Puig J. Clinical aspects of juvenile myoclonic epilepsy. Epilepsy Behav 2013;28 Suppl 1:S8-14. PMID 23756488
62: Gerrits MC, Foncke EM, de Haan R, et al. Phenotype-genotype correlation in Dutch patients with myoclonus-dystonia. Neurology 2006;66(5):759-61. PMID 16534121
63: Goto M, Saito Y, Honda R, et al. Episodic tremors representing cortical myoclonus are characteristic in Angelman syndrome due to UBE3A mutations. Brain Dev 2015;37(2):216-22. PMID 24796722
64: Groen JL, Andrade A, Ritz K, et al. CACNA1B mutation is linked to unique myoclonus-dystonia syndrome. Human Mol Genet 2015;24(4):987-93. PMID 25296916
65: Gruber D, Kuhn A, Schoenecker T, et al. Pallidal and thalamic deep brain stimulation in myoclonus-dystonia. Mov Disord 2010;25(11):1733-43. PMID 20623686
66: Guerrini R, Bonanni P, Parmeggiani L, Santucci M, Parmeggiani A, Sartucci F. Cortical reflex myoclonus in Rett syndrome. Ann Neurol 1998;43(4):472-9. PMID 9546328
67: Guerrini R, De Lorey TM, Bonanni P, et al. Cortical myoclonus in Angelman syndrome. Ann Neurol 1996;40(1):39-48. PMID 8687190
68: Gupta HV, Caviness JN. Post-hypoxic myoclonus: current concepts, neurophysiology, and treatment. Tremor Other Hyperkinet Mov (N Y) 2016;6:409-16. PMID 27708982
69: Hainque E, Blancher A, Mesnage V, et al. A clinical and neurophysiological motor signature of Unverricht-Lundborg disease. Revue Neurol (Paris) 2018;174(1-2):56-65. PMID 28688606
70: Hallett M. Early history of myoclonus. In: Fahn S, Marsden CD, Van Woert MH, editors. Advances in neurology: myoclonus. New York: Raven, 1986;43:7-10.
71: Hallett M. In: Hallett M, editor. Movement Disorders: Handbook of Clinical Neurophysiology. Vol 1. Elsevier, 2003.
72: Hallett M, Chadwick D, Adam J, Marsden CD. Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus. J Neurol Neurosurg Psychiatry 1977;40:253-64. PMID 301926
73: Hallett M, Chadwick D, Marsden CD. Cortical reflex myoclonus. Neurology 1979;29:1107-25. PMID 572498
74: Hassan A, van Gerpen JA. Orthostatic tremor and orthostatic myoclonus: weight-bearing hyperkinetic disorders: a systematic review, new insights, and unresolved questions. Tremor Other Hyperkinet Mov (N Y) 2016;6:417. PMID 28105385
75: Heath CA, Cooper SA, Murray K, et al. Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK. J Neurol Neurosurg Psychiatry 2011;82(6):646-51. PMID 21172857
76: Hess DC, Sethi KD. Epilepsia partialis continua in multiple sclerosis. Int J Neurosci 1990;50:109-11. PMID 2176651
77: Ikeda A, Kakigi R, Funai N, Neshige R, Kuroda Y, Shibasaki H. Cortical tremor: a variant of cortical reflex myoclonus. Neurology 1990;40(10):1561-5. PMID 2215948
78: Jimenez-Jimenez FJ, Puertas I, de Toledo-Heras M. Drug-induced myoclonus: frequency, mechanisms and management. CNS Drugs 2004;18(2):93-104. PMID 14728056
79: Joensuu T, Lehesjok AE, Kopra O. Molecular background of EPM1-Unverricht-Lundborg disease. Epilepsia 2008;49(4):557-63. PMID 18028412
80: Jung KY, Youn J, Chung CS. Opsoclonus-myoclonus syndrome in an adult with malignant melanoma. J Neurol 2006;253(7):942-3. PMID 16715202
81: Kanazawa I. Molecular pathology of dentatorubral-pallidoluysian atrophy. Philos Trans R Soc Lond B Biol Sci 1999;354(1386):1069-74. PMID 10434307
82: Kiziltan ME, Gunduz A, Tutuncu M, Ertan S, Apaydin H, Kiziltan G. Myoclonus in the elderly: A retrospective analysis of clinical and electrophysiological characteristics of patients referred to an electrophysiology laboratory. Parkinsonism Relat Disord 2018;49:22-7. PMID 29326035
83: Klawans HL, Carvey PM, Tanner CM, Goetz CG. Drug induced myoclonus. In: Fahn S, Mardsen CD, Van Woert MH, editors. Advances in neurology: myoclonus. New York: Raven, 1986;43:251-64.
84: Kuncel AM, Turner DA, Ozelius LJ, Greene PE, Grill WM, Stacy MA. Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonus-dystonia syndrome. Clin Neurol Neurosurg 2009;111:303-6. PMID 19081669
85: Kurtis MM, San Luciano M, Yu Q, et al. Clinical and neurophysiological improvement of SGCE myoclonus-dystonia with GPi deep brain stimulation. Clin Neurol Neurosurg 2010;112(2):149-52. PMID 19896264
86: Lancaster E, Martinez-Hernandez E, Titulaer MJ, et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 2011;77:1698-1701. PMID 22013185
87: Lance JW, Adams RD. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. Brain 1963;86:111-36. PMID 13928398
88: Mancini C, Orsi L, Guo Y, et al. An atypical form of AOA2 with myoclonus associated with mutations in SETX and AFG3L2. BMC Med Genet 2015;16:16. PMID 25927548
89: Marelli C, Canafoglia L, Zibordi F, et al. A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome. Mov Disord 2008;23:2041-8. PMID 18759336
90: Marinella MA. Myoclonus and generalized seizures associated with gatifloxacin treatment. Arch Intern Med 2001;161(18):2261-2. PMID 11575986
91: Markand ON, Garg BP, Weaver DD. Familial startle disease (hyperexplexia). Arch Neurol 1984;41:71-4. PMID 6689893
92: Marras C, Lang A, van de Warrenburg BP, et al. Nomenclature of genetic movement disorders: recommendations of the international Parkinson and movement disorder society task force. Mov Disord 2016;31(4):436-57. PMID 27079681
93: Marsden CD, Obeso JA. The Ramsay-Hunt syndrome is a useful clinical entity. Mov Disord 1989;4:6-12. PMID 2494439
94: Martinez MS, Fontoira M, Celester G, Castro del Rio M, Permuy J, Iglesias A. Myoclonus of peripheral origin: case secondary to a digital nerve lesion. Mov Disord 2001;16(5):970-4. PMID 11746636
95: Martins S, Matama T, Guimaraes L, et al. Portuguese families with dentatorubropallidoluysian atrophy (DRPLA) share a common haplotype of Asian origin. Eur J Hum Genet 2003;11(10):808-11. PMID 14512972
96: Mencacci NE, Rubio-Agusti I, Zdebik A, et al. A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia. Am J Hum Genet 2015;96(6):938-47. PMID 25983243
97: Mercadante S, Villari P, Fulfaro F. Gabapentin for opioid-related myoclonus in cancer patients. Support Care Cancer 2001;9:205-6. PMID 11401105
98: Michelucci R, Pasini E, Riguzzi P, Andermann E, Kälviäinen R, Genton P. Myoclonus and seizures in progressive myoclonus epilepsies: pharmacology and therapeutic trials. Epileptic Disord 2016;18(S2):145-53. PMID 27629998
99: Miyamoto R, Morino H, Yoshizawa A, et al. Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia. J Neurol Sci 2014;337(1-2):219-23. PMID 24332946
100: Monaghan TS, Delanty N. Lafora disease: epidemiology, pathophysiology and management. CNS Drugs 2010;24(7):549-61. PMID 20527995
101: Monday K, Jankovic J. Psychogenic myoclonus. Neurology 1993;43(2):349-52. PMID 8437701
102: Muona M, Berkovic SF, Dibbens LM, et al. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet 2015;47(1):39-46. PMID 25401298
103: Naito H, Oyanagi S. Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral-pallidoluysian atrophy. Neurology 1982;32:798-807. PMID 6808417
104: Nishimura RN, Barranger JA. Neurologic complications of Gaucher's disease, type 3. Arch Neurol 1980;37:92-3. PMID 6766716
105: Obeso JA, Artieda J, Marsden CD. Different clinical presentations of myoclonus. In: Jankovic J, Tolosa E, editors. Parkinson's disease and movement disorders. 2nd ed. Baltimore: Williams and Wilkins Co, 1993:315-28.
106: Ong MT, Sarrigiannis PG, Baxter PS. Post-anoxic reticular reflex myoclonus in a child and proposed classification of post-anoxic myoclonus. Pediatr Neurol 2017;68:68-72. PMID 28233665
107: Oropilla JQ, Diesta CC, Itthimathin P, Suchowersky O, Kiss ZH. Both thalamic and pallidal deep brain stimulation for myoclonic dystonia. J Neurosurg 2010;112(6):1267-70. PMID 19929196
108: Panzer J, Anand R, Dalmau J, Lynch D. Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia syndrome. J Neuroimmunol 2015;286:86-92. PMID 26298330
109: Perandones C, Pellene LA, Micheli F. A new SCARB2 mutation in a patient with progressive myoclonus ataxia without renal failure. Mov Disord 2014;29(1):158-9. PMID 24339182
110: Perlman SL. Spinocerebellar degenerations. Handb Clin Neurol 2011;100:113-40. PMID 21496573
111: Plaster NM, Uyama E, Uchino M, et al. Genetic localization of the familial adult-myoclonic epilepsy (FAME) gene to chromosome 8q24. Neurology 1999;53(6):1180-3. PMID 10522869
112: Ross S, Jankovic J. Palatal Myoclonus: an unusual presentation. Mov Disord 2005;20(9)1200-3. PMID 15929094
113: Roze E, Apartis E, Clot F, et al. Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations. Neurology 2008;70:1010-6. PMID 18362280
114: Roze E, Bounolleau P, Ducreux D, et al. Propriospinal myoclonus revisited: clinical, neurophysiologic, and neuroradiologic findings. Neurology 2009;72:1301-9. PMID 19365051
115: Roze E, Lang AE, Vidailhet M. Myoclonus-dystonia: classification, phenomenology, pathogenesis, and treatment. Curr Opin Neurol 2018;31(4):484-90. PMID 29952836
116: Roze E, Vidailhet, Hubsch C, Navarro S, Grabli D. Pallidal stimulation for myoclonus-dystonia: ten years’ outcome in two patients. Mov Disord 2015;30(6):871-2. PMID 25787304
117: Saifudheen K, Jose J, Anoop TM. Rapidly progressive dementia and myoclonus. QJM 2010;103(6):427-8. PMID 20410016
118: 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
119: Shah BB, Lang AE. A case of neurosyphilis presenting with myoclonus, cerebellar ataxia, and speech disturbance. Mov Disord 2012;27:794. PMID 22407549
120: Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol 2005;4(4):239-48. PMID 15778103
121: Sheela SR, Mani PJ. Opsoclonus myoclonus syndrome: response to plasmapheresis. Indian Pediatrics 2003;41(5):499-502.
122: Shibasaki H. Electrophysiological studies of myoclonus. AAEM Minimonograph #30. Muscle Nerve 2000;23:321-35. PMID 10679708
123: Sidiropoulos C, Mestre T, Hutchison W, et al. Bilateral pallidal stimulation for sargoglycan epsilon negative myoclonus. Parkinsonism Relat Disord 2014;20(8):915-8. PMID 24812007
124: Sinclair CF, Gurey LE, Blitzer A. Palatal myoclonus: algorithm for management with boutlinum toxin based on clinical disease characteristics. Laryngoscope 2014;124(5):1164-9. PMID 24668771
125: Sinha S, Sarin YK. Rituximab for opsoclonus myoclonus ataxia syndrome associated with neuroblastoma. Indian J Pediatr 2014;81(2):218-9. PMID 23625470
126: Steinig I, von Podesils F, Moddel G, et al. Postmarketing experience with brivaracetam in the treatment of epilepsies: a multicenter cohort study from Germany. Epilepsia 2017;58(7):1208-16. PMID 28480518
127: Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2008;70:1883-90. PMID 18474843
128: Tanaka K, Suga R, Yamada T, et al. Idiopathic cortical myoclonus restricted to the lower limbs: correlation between MEPs and 99mTc-ECD single photon emission computed tomography activation study. J Neurol Sci 1999;163(1):58-60. PMID 10223412
129: Tate ED, Pranzatelli MR, Verhuist SJ, et al. Active comparator-controlled, rater-blinded study of corticotropin-based immunotherapies for opsoclonus-myoclonus syndrome. J Child Neurol 2012;27:875-84. PMID 22378659
130: Tezenas du Montcel S, Clot F, Vidailhet M, et al. Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes. J Med Genet 2006;43(5):394-400. PMID 16227522
131: Thomke F. Assessing prognosis following cardiopulmonary resuscitation and therapeutic hyothermia-a critical discussion of recent studies. Dtsch Arztebl Int 2013;110(9):137-43. PMID 23533554
132: Thompson PD, Bhatia KP, Brown P, et al. Cortical myoclonus in Huntington’s disease. Mov Disord 1994a;9(6):633-41. PMID 7845404
133: Tyvaert L, Krystkowiak P, Cassim F, et al. Myoclonus of peripheral origin: two case reports. Mov Disord 2009;24:274-300. PMID 19086086
134: van der Salm SM, Erro R, Cordivari C, et al. Propriospinal myoclonus: clinical reappraisal and review of literature. Neurology 2014;83(20):1862-70. PMID 25305154
135: van der Veen S, Zutt R, Klein C, et al. Nomenclature of genetically determined myoclonus syndromes: recommendations of the International Parkinson and Movement Disorder Society Task Force. Mov Disord 2019;34(11):1602-13. PMID 31584223
136: Van Egmond ME, Verschuuren-Bernelmans CC, Nibbeling EA, et al. Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation. Mov Disord 2014;29(1):139-43. PMID 24458321
137: Van Woert MH, Rosenbaum D, Chung E. Biochemistry and therapeutics of posthypoxic myoclonus. In: Fahn S, Marsden CD, Van Woert M, editors. Advances in neurology: myoclonus. New York: Raven, 1986;43:171-82.
138: Velasco SL, Sierra-Hidalgo F, Rodriguez RM, Guerreo AJ, Morales JR. Flecainide-induced myoclonus. Clin Neuropharmacol 2014;37(2):65-6. PMID 24614665
139: Vidailhet M, Jutras MF, Grabli D, Roze E. Deep brain stimulation for dystonia. J Neurol Neurosurg Pyschiatry 2013;84(9):1029-42. PMID 23154125
140: Wallace SJ. Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res 1998;29:147-54. PMID 9477147
141: Wilkins DE, Hallett M, Erba G. Primary generalized epileptic myoclonus: a frequent manifestation of minipolymyoclonus of central origin. J Neurol Neurosurg Psychiatry 1985;48:506-16. PMID 3925089
142: Wilkins DE, Hallett M, Wess MM. The audiogenic startle reflex of man and its relationship to startle syndromes. Brain 1986;109:561-73. PMID 3719291
143: Wolpow ER, Richardson EP. A 57-year old woman with dizziness, nausea, and visual abnormalities. N Engl J Med 1988;31:563-70.
144: Wuerfel E, Bien C, Vincent A, Woodhall M, Brockmann K. Glycine receptor antibodies in a boy with focal epilepsy and episodic behavioral disorder. J Neurol Sci 2014;343(1-2):180-2. PMID 24880541
145: Young RR, Shahani BT. Asterixis: one type of negative myoclonus. In: Fahn S, Marsden CD, Van Woert M, editors. Advances in neurology: myoclonus. New York: Raven, 1986;43:137-56.
146: Zhang YQ, Wang JW, Wang YP, Zhang XH, Li JP. Thalamus stimulation for myoclonus dystonia syndrome: five cases and long-term follow-up. World Neurosurg 2019;122:e933-9. PMID 30419400
147: 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

Behzad Elahi MD PhD

Dr. Elahi of Loyola Medical Center has no relevant financial relationships to disclose.
See Profile

Editor

Robert Fekete MD

Dr. Fekete of New York Medical College received consultation fees from Acadia Pharmaceutical, Acorda, Adamas/Supernus Pharmaceuticals, Amneal/Impax, Kyowa Kirin, Lundbeck Inc., Neurocrine Inc., and Teva Pharmaceutical, Inc.
See Profile

Former Authors

John N Caviness MD
Joseph Jankovic MD
Kapil Sethi MD (original author), Hubert H Fernandez MD, Mauricio Rueda-Acevedo MD, and Christopher Kenney MD

Patient Profile

Age range of presentation: 1 month to 65+ years
Sex preponderance: male=female
Heredity: heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Myoclonus: 333.2
ICD-10: Myoclonus: G25.3
OMIM: Myoclonus and ataxia: 159700

Myoclonus epilepsy, progressive: 310370

Myoclonus, hereditary essential: #159900

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

Myoclonus

Associated Disorders

Acquired metabolic syndromes
Action myoclonus renal failure syndrome
Adult Gaucher disease
Alcohol-sensitive myoclonus with dystonia
Alzheimer disease
- Angelman syndrome
- Antibody-associated myoclonus syndromes
- Anti-N-methyl-D-aspartate receptor encephalitis
- Autoimmune myoclonus syndromes
- Benign adult familial myoclonic epilepsy
- Benign myoclonic epilepsy in infancy
- Benign sleep myoclonus of infancy
- Biotin responsive encephalopathy,
- Bismuth encephalopathy
- Celiac disease
- Ceroid lipofuscinosis
- Cherry-red spot myoclonus syndrome
- Corticobasal degeneration
- Creutzfeldt-Jakob disease
- Dentatorubral-pallidoluysian atrophy
- Dentatorubropallidoluysian atrophy
- Dravet syndrome
- Drug-induced myoclonus
- Early myoclonic encephalopathy
- Ekbom syndrome
- Epilepsia partialis continua
- Epilepsy progressive myoclonus type 1
- Epilepsy with myoclonic absences
- Epilepsy with myoclonic-atonic seizures
- Familial adult myoclonic epilepsy
- FAME
- Familial myoclonic epilepsy
- GM2 gangliosidoses
- Hemifacial spasm
- Hepatic encephalopathy
- Hypoxic-ischemic encephalopathy
- Idiopathic inflammatory syndromes
- Infectious syndromes
- Juvenile myoclonic epilepsy
- Juvenile Huntington disease
- Juvenile myoclonic epilepsy
- Lafora body disease
- Lance-Adams syndrome
- Late onset neuronal ceroid lipofuscinosis
- Lewy body disease
- Malabsorption syndromes
- May-White syndrome
- MERRF
- Mitochondrial encephalomyopathy
- Mitochondrial encephalopathy
- Multiple system atrophy
- Myoclonic absences
- Myoclonic-astatic epilepsy of childhood
- Myoclonic-atonic seizures
- Myoclonic epilepsy in infancy
- Myoclonic epilepsy with ragged red fibers
- Myoclonic seizures
- Myoclonic status epilepticus
- Myoclonic status in nonprogressive encephalopathies
- Neurodegenerative and other dementia syndromes
- Olivopontocerebellar degeneration
- Opsoclonus-myoclonus
- Paraneoplastic syndromes
- Parkinson disease
- Paramyoclonus multiplex of Friedreich
- Progressive myoclonic ataxia
- Postencephalitic myoclonus
- Postanoxic action myoclonus
- Progressive encephalomyelitis with rigidity and myoclonus and glycine receptor antibodies
- Progressive myoclonus epilepsies
- Progressive myoclonic ataxia
- Ramsay Hunt syndrome
- Renal failure myoclonus syndrome
- Reticular reflex myoclonus
- SCA
- Severe myoclonic epilepsy in infancy
- Sialidosis
- Sleep starts
- Spinal muscular atrophy
- Spinocerebellar ataxias
- Spinocerebellar degeneration
- Static encephalopathies secondary to diffuse brain injuries
- Toxin-induced myoclonus
- Unverricht-Lundborg disease
- Uremic encephalopathy

Differential Diagnosis

Chorea
Tremor
Tic
Dystonia
Ataxia

Also Relevant

Epidemiology of movement disorders
Movement disorders in childhood
Posttraumatic movement disorders
Rating scales of movement disorders
Sleep-related movement disorders

Myoclonus

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Types of myoclonus

Table 1. Physiological Classification of Myoclonus

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Physiological myoclonus

Essential myoclonus

Myoclonus-dystonia

Epileptic myoclonus

Symptomatic myoclonus

Paraneoplastic, other autoimmune, and idiopathic inflammatory syndromes.

Pathophysiology

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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

Questions or Comment?

Also in This Category

Hemifacial spasm

Wilson disease

Neuroacanthocytosis

Restless legs syndrome

Dementia in Parkinson disease

ALS-like disorders of the Western Pacific

Sleep-related leg cramps

Sleep and cerebral degenerative disorders

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