Treatment of myoclonus

INTRODUCTION — Myoclonus is a sudden, involuntary, shock-like movement caused by sudden muscular contraction (positive myoclonus) or inhibition (negative myoclonus). Among movement disorder phenotypes, myoclonus is the most transient: it is essentially the quickest abnormal movement with a given body part.

Myoclonic movements have many possible etiologies, and treatment is generally guided by the anatomic/physiologic type of myoclonus. Although there are some treatable underlying etiologies, myoclonus management is primarily symptomatic, and medications often have limited benefits.

This topic will review the treatment of myoclonus. The evaluation, classification, and etiologies of myoclonus are reviewed separately. (See "Classification and evaluation of myoclonus" and "Symptomatic (secondary) myoclonus".)

GENERAL PRINCIPLES — The clinical sign of myoclonus is uniform, but different distributions occur, and there are myriad etiologies (table 1) and multiple anatomic/physiologic types (table 2). Both elements of classification help to guide therapy.

Treat the underlying disorder — When the etiology of myoclonus is treatable or reversible, treatment of the underlying condition may partially or completely relieve the myoclonus. Examples include myoclonus caused by an acquired abnormal metabolic state (eg, hepatic failure), a removable medication or toxin (eg, selective serotonin reuptake inhibitors, opioids), an excisable lesion (eg, thoracic meningioma for spinal myoclonus), or functional myoclonus.

The myoclonus that occurs in certain noninfectious inflammatory syndromes may respond to immunomodulatory treatments such as high-dose glucocorticoids, intravenous immune globulin, monoclonal antibodies, and plasmapheresis. Such treatment is often attempted in inflammatory/autoimmune conditions, with or without an antibody identified. These disorders and their treatments, which are discussed separately, include the following:

●Autoimmune encephalitis of paraneoplastic and nonparaneoplastic origin, including progressive encephalomyelitis with rigidity and myoclonus (PERM) (see "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis", section on 'Anti-GlyR encephalopathy')

●Sydenham chorea (see "Sydenham chorea", section on 'Treatment')

●Opsoclonus-myoclonus syndrome (see "Opsoclonus-myoclonus-ataxia syndrome")

●Systemic lupus erythematosus (see "Neurologic and neuropsychiatric manifestations of systemic lupus erythematosus", section on 'Chorea')

●Primary antiphospholipid syndrome (see "Management of antiphospholipid syndrome")

●Celiac disease and gluten sensitivity (see "Management of celiac disease in children" and "Management of celiac disease in adults")

●Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS) (see "PANDAS: Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci")

Assess need for symptomatic therapy — With most types of myoclonus, treatment of the underlying disorder is impossible or ineffective. In these cases, symptomatic treatment is indicated for patients with significant disability related to the myoclonus, whether physical or social, or when myoclonus causes high levels of distress for family and caretakers. Physiologic myoclonus (myoclonus during sleep that worries the bed partner only) almost never needs to be treated.

There are no highly effective medications for myoclonus, and some therapies may worsen cognitive status or coordination of movements [1,2]. Therefore, decisions about symptomatic treatment always weigh the risks of medication side effects with the potential benefits in terms of symptom severity and quality of life.

It is important to review goals and expectations prior to starting symptomatic therapy. High expectations for a marked decrease or total elimination of myoclonus are usually unrealistic. In addition, multiple medication trials are sometimes necessary to find the best drug or drug combination to control myoclonus.

Choose therapy based on physiology — Symptomatic treatment of myoclonus is guided by the anatomic/physiologic type, of which there are five major groups: cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral (table 2). (See "Classification and evaluation of myoclonus", section on 'Anatomic and physiologic classification'.)

This strategy is based upon the premise that an agent or treatment that is effective for one type of myoclonus is likely to be effective for other causes of myoclonus that share the same underlying physiologic mechanism. Furthermore, an agent or treatment that is effective for one physiologic type of myoclonus may be less effective or ineffective for another physiologic type or may even cause worsening.

Some clinical phenotypes of myoclonus have more than one potential physiologic mechanism. In cases when the myoclonus physiologic classification cannot be determined, presuming the myoclonus physiology that usually occurs in that diagnosis is a reasonable way to proceed (table 3). This should be done with close monitoring, since the myoclonus physiology is not confirmed. As examples, a cortical myoclonus physiology may be presumed in a child with Unverricht-Lundborg disease confirmed by genetic testing (cystatin B [CSTB] mutation) and in an adult with Creutzfeldt-Jakob disease who cannot cooperate with electrophysiology testing.

When both the specific etiology and myoclonus physiology are uncertain, treatments that have evidence of effectiveness for cortical myoclonus can be tried first, since a cortical physiology is the most common mechanism for myoclonus. (See 'Cortical myoclonus' below.)

An approach to symptomatic treatment of each physiologic/anatomic type of myoclonus is presented in the sections that follow.

CORTICAL MYOCLONUS — Cortical myoclonus is probably the most commonly encountered type of myoclonus in hospital settings and in cases of new-onset myoclonus in adults. Most cases of symptomatic myoclonus represent cortical myoclonus, including those associated with posthypoxic injury, toxic/metabolic derangements, inflammatory/infectious processes, and neurodegeneration (table 2).

First-line therapies — Symptomatic treatment is primarily aimed at suppressing cortical hyperexcitability with antiseizure medications. Among antiseizure medications, levetiracetam (and piracetam outside the United States), clonazepam, valproate, and perampanel seem to be the most effective for cortical myoclonus. However, there is no singularly effective drug, and treatment often proceeds sequentially using a trial-and-error approach.

Levetiracetam — We suggest levetiracetam as initial therapy for most patients with cortical myoclonus. Although no trials have compared various drugs head to head, clinical experience suggests that levetiracetam may work the best, and it tends to be well tolerated and has fewer drug interactions relative to clonazepam and valproate.

Levetiracetam a broad-spectrum antiseizure medication that binds to the synaptic vesicle protein 2A (SV2A) receptor. Its antimyoclonus effect may be related to modulation of calcium ion channels [1].

●Dosing – Levetiracetam is initiated at 500 to 1000 mg daily given in two divided doses. It can be titrated up by 1000 mg every two weeks as needed, up to 3000 mg daily. If it is well tolerated and the response is suboptimal, a maximum daily dose of 4000 mg can be tried. Therapeutic levetiracetam doses for myoclonus usually range between 1000 to 3000 mg daily.

●Side effects – The most common adverse events associated with levetiracetam are fatigue, somnolence, and dizziness. Most adverse events are mild to moderate in intensity and typically occur during the initial titration phase (table 4A-B). Mood and behavioral disturbances may be the most common adverse effects leading to discontinuation of therapy, particularly in children. Abrupt withdrawal of levetiracetam may precipitate seizures or worsening of myoclonus.

●Efficacy – Limited evidence from small open-label studies [3-5], case series [6-9], and case reports [10-14] suggests that levetiracetam is effective or partially effective for various causes of cortical myoclonus. Patients treated in these studies included those with progressive myoclonic epilepsy and progressive myoclonic ataxia syndromes (due to Unverricht-Lundborg disease, Lafora disease, and myoclonus epilepsy with red ragged fibers), benign adult familial myoclonic epilepsy, asterixis (ie, negative myoclonus), posthypoxic myoclonus, Creutzfeldt-Jakob disease, and corticobasal degeneration.

The best-designed of these uncontrolled studies was an open-label evaluation of add-on levetiracetam (mean dose 3214 mg daily after titration phase) for the treatment of chronic refractory cortical myoclonus [5]. Compared with the pretreatment phase, all 14 patients who completed the study had significant improvement in myoclonus, as assessed by the Unified Myoclonus Rating Scale (UMRS). However, there was no significant change in the negative myoclonus (asterixis) scores of the UMRS.

Piracetam (outside the US) — Piracetam is an SV2A receptor antagonist that is structurally related to levetiracetam. It is available in Europe and elsewhere as an antimyoclonus agent and for treatment of cognitive impairment. Although it is marketed as a nutritional supplement in the United States, this formulation is not recommended for treatment of myoclonus due to gastrointestinal side effects and lack of evidence that it is superior to other antimyoclonus agents.

Where available as a prescription medication, piracetam is usually started at 2.4 g daily, given in three divided doses. Therapeutic doses of piracetam range between 2.4 to 24 g daily [15-18]. Abrupt discontinuation of piracetam should be avoided since it may precipitate myoclonus exacerbation and/or seizures.

A few small controlled studies have found that piracetam is beneficial for cortical myoclonus [15-18]. As an example, a six-week randomized double-blind crossover trial involving 20 adults with Unverricht-Lundborg disease, a cause of progressive myoclonic ataxia, reported that the highest dose of piracetam (total of 24 g daily given in two divided doses) was significantly more effective than placebo for improvement in the primary outcome measure (the mean sum score of six components of a myoclonus rating scale) [17]. The improvement was considered clinically relevant. Lower doses of piracetam (total daily doses of 16.8 and 9.6 g) were associated with a nonsignificant improvement in the primary outcome measure.

Alternatives and add-on therapies — Clonazepam, valproate, and perampanel are reasonable first-line alternatives to levetiracetam or can be used as add-on therapy. The choice among these medications depends largely on side effect profiles and patient comorbidities.

Many patients require more than one medication to gain adequate relief from myoclonus [19]. Any of the four first-line medications (levetiracetam, clonazepam, valproate, and perampanel) can be used together or combined with other second-line medications. (See 'Others' below.)

Clonazepam — Clonazepam has a longer duration of action compared with other benzodiazepines, which is its main advantage when treating myoclonus or seizures. For patients with acute hypoxic myoclonus who are intubated and sedated, intravenous benzodiazepines are more commonly used. (See "Intensive care unit management of the intubated post-cardiac arrest adult patient", section on 'Myoclonic jerks'.)

The possible mechanism of action of benzodiazepines for myoclonus is facilitation of gamma-aminobutyric acid (GABA) signaling and a decrease in 5-hydroxytryptophan utilization in the brain [1].

●Dosing – Clonazepam is typically started at 0.25 mg twice daily and gradually increased to a total daily dose of 1.5 to 3 mg given in two to three divided doses. Clonazepam doses ranging from 6 to as high as 12 mg daily are often necessary but should be introduced slowly [19,20].

●Side effects – The most common side effects of clonazepam are drowsiness, dizziness, fatigue, and sedation. These can sometimes be ameliorated by adjusting the dose. Abrupt reductions or withdrawals of clonazepam can cause both an exacerbation of myoclonus and withdrawal seizures. As with other benzodiazepines, clonazepam may produce physical and psychologic dependence. In addition, tolerance with loss of effectiveness may develop over a period of several months in some patients.

●Efficacy – The benefit of clonazepam for cortical myoclonus is supported by data from uncontrolled observational studies and clinical experience [19-21]. Response rates from controlled studies are not available; in the author's experience, clonazepam is helpful in suppressing myoclonus in 50 percent or more of patients.

Valproic acid — Valproic acid (valproate) likely acts to suppress myoclonus through multiple mechanisms, including increased GABA synthesis in nerve terminals and decreased GABA degradation in the synapse [1]. It may also reduce excitability by blocking sodium and potassium conductance.

●Dosing – Valproate is introduced slowly, starting at 15 mg/kg daily in three divided doses. It may be increased by 5 to 10 mg/kg per day every week as needed. Therapeutic doses are typically in the range of 1200 to 2000 mg daily. Monitoring and serum target levels are the same as when using valproate as an antiseizure medication. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Valproate'.)

●Side effects – During initial treatment with valproate, transient gastrointestinal upset may occur, sometimes with nausea and vomiting, and less often with abdominal pain and diarrhea. Other side effects of valproate include weight gain, obesity, hair loss, easy bruising, and tremor (table 4A-B). Rare side effects include agranulocytosis, Stevens-Johnson syndrome, aplastic anemia, hepatic failure, dermatitis/rash, serum sickness, and pancreatitis.

●Efficacy – Evidence from uncontrolled observational studies suggests that valproate is effective for cortical myoclonus due to various underlying causes [19-22], and randomized trials support its efficacy for generalized epilepsy syndromes, with or without cortical-subcortical myoclonus [23].

Perampanel — Perampanel is an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist used for treatment of both focal and generalized epilepsies. It may suppress myoclonus through reduction of cortical hyperexcitability and hypersynchronization [24].

Supporting evidence of clinical activity includes case reports and case series in up to 18 patients with seizures and cortical myoclonus of various etiologies [24-27]. In the largest case series, the mean dose was 3.2 mg per day. Dosing is the same as for seizure disorders, with a maximum daily dose of 12 mg. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Perampanel'.)

Others — Other antiseizure medications for which at least some evidence suggests a potential role in suppressing cortical myoclonus include brivaracetam, zonisamide, primidone, and lacosamide [1].

●Brivaracetam – Brivaracetam has a similar mechanism of action as levetiracetam and has shown the ability to suppress cortical myoclonus in animal models; however, clinical data are not as convincing. In two randomized trials in patients with Unverricht-Lundborg disease (cortical myoclonus), doses of 50 to 150 mg per day did not show statistically significant differences compared with placebo [28]. Dosing and adverse effects are reviewed separately. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects", section on 'Brivaracetam'.)

●Zonisamide – Zonisamide is a broad-spectrum antiseizure medication that blocks voltage-dependent sodium and T-type calcium channels. Limited data suggest zonisamide may be beneficial as adjunctive therapy for cortical myoclonus at doses ranging from 100 to 300 mg daily [29,30], as well as for other types of myoclonus. (See 'Zonisamide' below.)

●Primidone – Primidone is a phenobarbital precursor with GABAergic properties. Limited data suggest some efficacy in treating cortical myoclonus using relatively high doses (eg, 500 to 1500 mg per day) [1].

●Lacosamide – Lacosamide is a broad-spectrum antiseizure medication with multiple potential mechanisms of action, including effects on voltage-dependent sodium channels. At least one case report describes response to lacosamide in a patient with posthypoxic myoclonus [31].

Medications to avoid — Certain agents can worsen cortical or cortical-subcortical myoclonus, particularly in progressive myoclonic epilepsy syndromes. These agents include phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin [32].

Options for refractory symptoms — Treatment of cortical myoclonus is challenging, and polytherapy is often required for optimal symptom control. Gait disturbance tends to be the feature of myoclonus that is most resistant to treatment. A bouncy, unsteady gait with frequent falls may persist despite better control of action and reflex myoclonus in the upper limbs. In addition, there is no consistent evidence that any of the available agents are beneficial for negative myoclonus (asterixis). However, asterixis can have a potentially reversible etiology and will respond to such treatment (eg, correction of metabolic derangement, removal of offending medication).

Sodium oxybate, the sodium salt form of gamma hydroxybutyrate, has been used for refractory cortical myoclonus and myoclonus-dystonia [33]. However, sodium oxybate is a restricted drug in the United States that is approved only for the treatment of narcolepsy and idiopathic hypersomnia. (See "Treatment of narcolepsy in adults", section on 'Oxybates'.)

Intrathecal baclofen has been tried in a few cases of posthypoxic myoclonus that was refractory to other therapies [34,35]. At baclofen doses of 75 to 105 micrograms per hour, both the resting and action myoclonus were controlled. In another report, two cases of spinal myoclonus had marked response to this therapy [36]. Further examples are needed for verification.

Repetitive transcranial magnetic stimulation (rTMS) has been used rarely for cases of either cortical or subcortical myoclonus [37]. More studies are needed before this therapy can be applied regularly.

In refractory cases of posthypoxic myoclonus, deep brain stimulation (DBS) may offer some chance of benefit. Responses have been reported with a variety of stimulation targets, including bilateral globus pallidus interna (GPi), bilateral ventral intermediate (VIM) nucleus of the thalamus, and subthalamic nucleus/pars reticulata [38-40].

CORTICAL-SUBCORTICAL MYOCLONUS — The myoclonus in patients with primary generalized epilepsy syndromes falls under the cortical-subcortical physiologic classification (table 2) [41]. The treatment of these disorders is discussed separately. (See "Juvenile myoclonic epilepsy" and "Epilepsy syndromes in children".)

SUBCORTICAL-NONSEGMENTAL MYOCLONUS — Subcortical-nonsegmental myoclonus is a heterogeneous entity that includes rare entities such as essential myoclonus, myoclonus-dystonia syndrome, reflex myoclonus, hyperekplexia, and propriospinal myoclonus.

Standard antiseizure medications such as levetiracetam and valproate are usually not helpful in most types of subcortical-nonsegmental myoclonus (table 2). Clonazepam is a good first choice, based on clinical experience and largely anecdotal evidence.

Clonazepam — We suggest initial treatment with clonazepam for most patients with subcortical-nonsegmental myoclonus physiology. Dosing is the same as described for cortical myoclonus. (See 'Clonazepam' above.)

Supporting evidence includes case series in patients with essential myoclonus [42], myoclonus-dystonia, reticular reflex myoclonus [21], hyperekplexia [43], and propriospinal myoclonus [44].

Zonisamide — Zonisamide is an alternative for myoclonus-dystonia and should be tried if there is insufficient improvement with clonazepam.

A single-center, placebo-controlled, randomized crossover trial of 24 patients with myoclonus-dystonia found that zonisamide (starting at 50 mg daily and titrating up to a maximum dose of 300 mg daily) led to significant improvement in action myoclonus and functional disability [45]. Limited data also suggest zonisamide may be beneficial for propriospinal myoclonus [46].

Others — Benztropine or trihexyphenidyl are alternate choices for initial or add-on therapy for patients with essential myoclonus, including myoclonus-dystonia [47,48]. Responses to sodium oxybate, the sodium salt of gamma hydroxybutyrate, have been described in patients with essential myoclonus, and further studies seem warranted [33].

For propriospinal myoclonus, there are case reports of responses to levetiracetam, valproate, oxcarbazepine, carbamazepine, and baclofen [1,49].

Of note, essential myoclonus (including myoclonus-dystonia) tends to be responsive to alcohol, similar to the effect seen in essential tremor. Some patients self-medicate and should be monitored for unhealthy or excessive alcohol use.

Role of surgical therapy — Select patients with refractory myoclonus-dystonia syndrome may be candidates for deep brain stimulation (DBS) [50]. It should be considered only for refractory cases with significant disability.

A systematic review identified 40 unique patients with myoclonus-dystonia syndrome treated with DBS with a mean follow-up of 27 months and noted that all patients improved with treatment; the mean improvement in myoclonus scores was 73 percent, and the mean improvement in dystonia scores was 53 percent [51]. The degree of improvement in myoclonus was similar for stimulation of both the globus pallidus interna (GPi) and ventral intermediate nucleus of the thalamus (VIM; 76 and 70 percent, respectively). However, improvement in dystonia was greater with GPi stimulation compared with VIM stimulation (60 and 33 percent, respectively).

These findings suggest that GPi is the preferred DBS target for myoclonus-dystonia syndrome. However, the results should be interpreted with caution since the data come from retrospective and nonrandomized reports. Moreover, myoclonus-dystonia syndrome has different causes, and treatment response may vary depending on etiology; most of the studies suggesting the benefit of DBS have evaluated patients with myoclonus-dystonia syndrome (DYT11) caused by sarcoglycan epsilon (SGCE) gene mutations, which is the most commonly identified cause of myoclonus-dystonia [52]. DBS for dystonia is reviewed separately. (See "Treatment of dystonia in children and adults", section on 'Surgical therapy'.)

SEGMENTAL OR PERIPHERAL MYOCLONUS — The most common types of segmental myoclonus are palatal myoclonus and segmental spinal myoclonus. Hemifacial spasm is the main example of peripheral myoclonus. Based on their localized nature, botulinum toxin injections are an alternative option to oral medication trials in selected patients.

Palatal myoclonus — Palatal myoclonus is difficult to treat [53]. For most patients with debilitating symptoms, we suggest botulinum toxin injections as initial treatment. The injections should be performed by a practitioner (often an otolaryngologist) or center with sufficient expertise in the anatomic area.

The target muscles for injection of botulinum toxin are the levator veli palatini and/or tensor veli palatini muscles [54-56]. In the largest case series, botulinum toxin injections were associated with complete resolution of symptoms (objective, intrusive clicking tinnitus) in four of five treated patients [55]. One patient had transient side effects that included dysphagia and nasal speech.

Other pharmacologic interventions for palatal myoclonus generally provide only limited benefit, or more commonly no benefit. However, the list of possibly useful drugs for this condition includes clonazepam [57], piracetam, valproate, baclofen, carbamazepine, lamotrigine, phenytoin, sumatriptan [57,58], and tetrabenazine.

Because the ear clicking associated with palatal myoclonus is so disabling, surgical treatments including tensor veli palatini tenotomy and occlusion of the eustachian tube can be considered for patients refractory to pharmacologic therapy (including botulinum toxin injection) [59]. Surgical interventions for middle ear myoclonus include tensor tympani and/or stapedius tenotomy and placement of ventilation tubes [60-63].

Spinal segmental myoclonus — Like palatal myoclonus, spinal segmental myoclonus is often difficult to treat and not very responsive to oral medications. If the underlying cause is a structural abnormality such as a thoracic disc herniation, appropriate surgery can alleviate symptoms [64].

Among oral medications, clonazepam is most commonly used; doses of up to 6 mg daily may be needed [21,53,65]. However, benefit is often limited. Other medications with possible benefit include levetiracetam [66], carbamazepine [49], lamotrigine [67], topiramate [68], diazepam, and tetrabenazine [65].

There are a few reports of some success with botulinum toxin injections for the pain and movements of spinal segmental myoclonus [69,70].

Hemifacial spasm — We suggest botulinum toxin injections for patients with disabling hemifacial spasm and other types of peripheral myoclonus. The botulinum toxin usually treats the faster phasic (myoclonus) movements as well as more tonic movements (spasm). It should be administered by clinicians with expertise in treating these disorders [71-74].

In a randomized controlled trial, 11 patients with hemifacial spasm were randomly cycled through four treatment arms, which consisted of three different doses of botulinum toxin injection and one saline placebo injection [75]. There was objective improvement in symptoms after 84 percent of botulinum toxin injections versus 0 percent of placebo injections. Facial weakness was an expected side effect and was observed after 97 percent of botulinum toxin injections. Facial bruising, diplopia, and ptosis occurred after 20, 13, and 7 percent of injections, respectively. In another small trial, the mean duration of benefit after botulinum toxin injection for hemifacial spasm was 16.5 weeks [76].

Oral medications for peripheral myoclonus are usually ineffective, but carbamazepine may have some effect [49].

Microvascular decompression is an option for patients with severe hemifacial spasm. In a retrospective review of 5685 patients treated with microvascular decompression for hemifacial spasm, there was complete resolution of symptoms over a median three-year follow-up in 91 percent [77]. Complications included transient facial palsy in 10 percent, permanent facial palsy in 1 percent, permanent hearing loss in 2 percent, and stroke and death in <0.1 percent each.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

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

SUMMARY AND RECOMMENDATIONS

●General principles – There are myriad etiologies (table 1) and multiple anatomic/physiologic types of myoclonus (table 2). Both elements of classification help to guide therapy.

•Treat the underlying disorder – Certain types of myoclonus can be partially or totally reversed by treating the underlying condition. Examples include myoclonus due to an acquired metabolic abnormality, a medication or toxin, or an excisable lesion. (See 'Treat the underlying disorder' above.)

•Decide whether symptomatic therapy is indicated – There is no singularly effective therapy for myoclonus, and benefits and side effects may be closely matched. Symptomatic treatment is typically indicated for patients with significant disability related to the myoclonus, whether physical or social, or when myoclonus causes high levels of distress to family and caretakers. (See 'Assess need for symptomatic therapy' above.)

●Symptomatic therapy – Symptomatic treatment of myoclonus is guided by the anatomic/physiologic type, of which there are five major groups: cortical, cortical-subcortical, subcortical-nonsegmental, segmental, and peripheral (table 2). In cases when the etiology and myoclonus physiology are uncertain, it is reasonable to follow guidance for cortical myoclonus.

•Cortical myoclonus – For patients with debilitating cortical myoclonus, we suggest levetiracetam as initial therapy (Grade 2C). Piracetam (outside the United States), clonazepam, valproate, and perampanel are reasonable alternatives for initial or add-on therapy. (See 'Cortical myoclonus' above and 'Levetiracetam' above and 'Piracetam (outside the US)' above and 'Clonazepam' above and 'Valproic acid' above and 'Perampanel' above.)

Certain antiseizure medications can worsen cortical or cortical-subcortical myoclonus, particularly in progressive myoclonic epilepsy syndromes. These agents include phenytoin, carbamazepine, oxcarbazepine, lamotrigine, vigabatrin, tiagabine, gabapentin, and pregabalin. (See 'Medications to avoid' above.)

•Cortical-subcortical myoclonus – Cortical-subcortical myoclonus occurs primarily in association with generalized epilepsy syndromes (table 2). The treatment of these disorders is discussed separately. (See "Juvenile myoclonic epilepsy" and "Epilepsy syndromes in children".)

•Subcortical-nonsegmental myoclonus – For patients with subcortical-nonsegmental myoclonus (eg, essential myoclonus, myoclonus-dystonia syndrome, reticular reflex myoclonus, hyperekplexia, or propriospinal myoclonus), we suggest initial treatment with clonazepam (Grade 2C). Zonisamide is an alternative for myoclonus-dystonia and should be tried if there is insufficient improvement with clonazepam. Benztropine and trihexyphenidyl are additional options for essential myoclonus. (See 'Subcortical-nonsegmental myoclonus' above.)

•Palatal myoclonus – Palatal myoclonus is typically refractory to oral medications and can be debilitating, most commonly from the clicking noise that it creates. For debilitating palatal myoclonus, we suggest treatment with botulinum toxin injections (Grade 2C). Injections are typically administered by an otolaryngologist with experience in treating myoclonus. (See 'Palatal myoclonus' above.)

•Spinal segmental myoclonus – For spinal segmental myoclonus, we suggest clonazepam as initial treatment (Grade 2C). Botulinum toxin injections are sometimes helpful as an alternative. (See 'Spinal segmental myoclonus' above.)

•Hemifacial spasm – For most patients with disabling hemifacial spasm, we suggest treatment with botulinum toxin injections rather than oral medications (Grade 2C). Injections should be performed by a practitioner or center with the necessary anatomic and technical expertise. (See 'Hemifacial spasm' above.)