Involuntary movements

Involuntary movements are unwanted, purposeless movements that the patient cannot suppress at will, other than briefly. Most arise from basal ganglia, cerebellar or brainstem circuit dysfunction.

Clinical relevance. A drug is the commonest identifiable cause. Acute dystonia can compromise the airway within minutes, and abrupt onset movements point to a vascular, metabolic, toxic or autoimmune cause.

Phenomenology.

• Chorea: brief, irregular, flowing movements that move from one body part to another.
• Ballism: large amplitude, flinging proximal limb movements, usually one side (hemiballismus).
• Athetosis: slow, writhing distal movements.
• Dystonia: sustained or intermittent muscle contraction causing twisting movements or abnormal postures, often with a geste antagoniste (a sensory trick that relieves it).
• Myoclonus: sudden, brief, shock like jerks, positive (muscle contraction) or negative (asterixis, a lapse of tone).
• Tics: brief, stereotyped movements or sounds preceded by an urge and temporarily suppressible.
• Akathisia: inner restlessness with an urge to move.
• Tardive syndromes: orofacial dyskinesia and other movements appearing after 3 months or more of dopamine receptor blocker exposure.
• Stereotypies, hemifacial spasm and paroxysmal dyskinesias.

Tremor is assessed as its own presentation and is not described here.

Mechanisms. Chorea and ballism follow reduced inhibitory output from the indirect basal ganglia circuit (caudate, putamen, subthalamic nucleus). Dystonia reflects abnormal sensorimotor integration and loss of surround inhibition. Myoclonus arises from cortex, subcortex, brainstem, spinal cord or peripheral generators.

Temporal patterns. Acute (hours to days: drugs, stroke, metabolic, infective, autoimmune), subacute (weeks: autoimmune, Sydenham, paraneoplastic), chronic progressive (months to years: neurodegenerative), paroxysmal (minutes: paroxysmal dyskinesias, seizures).

History. Describe the movement in the patient's and an observer's words; ask for a video recording. Establish age and speed of onset, body distribution, variation with posture, action, stress, sleep and sensory tricks, ability to suppress, and associated urge. Ask about psychiatric symptoms, cognitive decline, falls, weight loss, fever, recent sore throat, seizures, pregnancy, and family history across generations including psychiatric illness, suicide and early dementia.

Drug and toxin history. Dopamine receptor blockers (haloperidol, risperidone, olanzapine, metoclopramide, prochlorperazine, domperidone), levodopa and dopamine agonists, phenytoin, carbamazepine, valproate, lithium, selective serotonin reuptake inhibitors, tricyclic antidepressants, stimulants, oestrogen containing contraceptives, anticholinergics, and cocaine. Record the time from drug start or dose change to onset.

Examination.

• Observe at rest, during distraction, on action, while walking and while talking.
• Tongue protrusion (inability to keep it out, darting), sustained hand grip (milkmaid grip), motor impersistence, saccade initiation, gait (dancing gait in chorea).
• Tone and rigidity, bradykinesia, reflexes (pendular reflexes in chorea), cerebellar signs, power, sensation and cognition.
• General: Kayser Fleischer rings, jaundice, hepatosplenomegaly, goitre and tachycardia, cardiac murmur, livedo reticularis, rash (lupus), spur cells or acanthocytes on blood film, pregnancy.

Red flags

• Abrupt onset, or onset within hours to days of a new drug
• Oculogyric crisis, trismus, tongue protrusion, stridor or dysphagia (laryngeal dystonia)
• Fever with rigidity, clonus, hyperreflexia or autonomic instability
• Unilateral ballism of sudden onset (stroke)
• Rapid cognitive decline with myoclonus
• Psychiatric symptoms with seizures, orofacial dyskinesia or reduced consciousness (autoimmune encephalitis)
• Onset under age 40 with liver disease or psychiatric symptoms
• Pregnancy or oestrogen exposure with new chorea
• Recent streptococcal infection, carditis or arthritis

Special groups. Children: Sydenham chorea, tics, paroxysmal dyskinesias, Wilson disease. Pregnancy: chorea gravidarum, antiphospholipid syndrome and lupus. Older adults: tardive syndromes and hyperglycaemic hemichorea. Region specific: rheumatic fever is more frequent in settings with limited access to primary care.

Chorea and ballism

• Huntington disease and Huntington disease like syndromes, neuroacanthocytosis, dentatorubral pallidoluysian atrophy, benign hereditary chorea
• Sydenham chorea (rheumatic fever)
• Drug induced: levodopa, dopamine agonists, antipsychotics (tardive), phenytoin, carbamazepine, oral contraceptives, stimulants, lithium
• Hyperglycaemic hemichorea hemiballismus
• Vascular: subthalamic or basal ganglia infarct or haemorrhage, moyamoya disease
• Chorea gravidarum, systemic lupus erythematosus and antiphospholipid syndrome, polycythaemia vera
• Thyrotoxicosis, hypo and hypernatraemia, hypocalcaemia, hypoparathyroidism, hepatic encephalopathy
• Infective and inflammatory: HIV related CNS disease, toxoplasmosis, post-infectious, autoimmune encephalitis, paraneoplastic chorea
• Wilson disease

Dystonia

• Acute dystonic reaction (dopamine blockers, metoclopramide, antiemetics)
• Tardive dystonia
• Primary dystonia: genetic, adult onset focal (cervical dystonia, blepharospasm, writer's cramp, spasmodic dysphonia)
• Dopa responsive dystonia, Wilson disease, neurodegeneration with brain iron accumulation, Parkinson disease (foot dystonia)
• Secondary: stroke, perinatal injury, tumour, trauma, demyelination, kernicterus
• Functional dystonia
• Mimics: tetany (hypocalcaemia), tetanus, strychnine toxicity, Sandifer syndrome, torticollis from ocular or cervical disease

Myoclonus

• Physiological (hypnic jerks, hiccups)
• Metabolic and toxic: uraemia, hepatic encephalopathy, hypoxia, hyponatraemia, hypoglycaemia, drug toxicity (opioids, gabapentinoids in renal failure, tricyclic antidepressants, lithium, penicillins and carbapenems at high dose, serotonin syndrome), bismuth
• Post-hypoxic (Lance Adams syndrome) and post-hypoxic coma myoclonus
• Epileptic: juvenile myoclonic epilepsy, progressive myoclonic epilepsies
• Neurodegenerative and infective: Creutzfeldt Jakob disease, Alzheimer disease, Lewy body disease, subacute sclerosing panencephalitis
• Autoimmune and paraneoplastic: opsoclonus myoclonus, Hashimoto encephalopathy
• Spinal and peripheral generators: spinal cord lesion, plexus or root injury
• Negative myoclonus: asterixis in hepatic, renal and respiratory failure

Tics and other

• Tourette syndrome and chronic tic disorders, secondary tics (infection, stroke, drugs, neuroacanthocytosis)
• Tardive dyskinesia, akathisia, restless legs syndrome
• Hemifacial spasm (vascular compression, Bell palsy sequel), blepharospasm
• Paroxysmal kinesigenic and non-kinesigenic dyskinesia
• Stereotypies in autism, intellectual disability and psychosis
• Functional movement disorder, seizures (focal motor, frontal lobe), periodic limb movements of sleep, REM sleep behaviour disorder

Reasoning. Name the movement, decide on acute or chronic course, review drugs, then test for reversible causes before genetic or imaging tests.

First line. Capillary glucose, urea, electrolytes, creatinine, calcium, magnesium, phosphate, liver function, full blood count with film, thyroid function, HbA1c, creatine kinase, pregnancy test, ECG.

Targeted tests

• Hyperglycaemic hemichorea: glucose often over 11 mmol/L with HbA1c raised; MRI shows T1 hyperintensity in the contralateral putamen.
• Wilson disease (any unexplained movement disorder under age 50): caeruloplasmin (low), serum copper, 24 hour urinary copper (over 100 micrograms in 24 hours supports the diagnosis), slit lamp examination for Kayser Fleischer rings, and genetic testing if equivocal. A low caeruloplasmin is not sufficient alone.
• Sydenham chorea: throat swab, antistreptolysin O titre and anti-DNase B (may be normal when chorea appears many months after infection), ECG and echocardiogram for carditis. Rheumatic fever is confirmed by major and minor manifestations; chorea alone can establish it.
• Autoimmune: antinuclear antibody, antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta 2 glycoprotein I), serum and CSF NMDA receptor antibodies and wider autoimmune and paraneoplastic panels.
• Infective: HIV and syphilis serology, CSF analysis.
• Polycythaemia vera: haemoglobin, JAK2 testing.
• Huntington disease: CAG repeat length in the HTT gene (40 or more repeats fully penetrant; 36 to 39 reduced penetrance; 27 to 35 intermediate and may expand on transmission), only after genetic counselling and with consent.
• Myoclonus: ammonia, urea and creatinine, EEG with back averaging, MRI, CSF including real time quaking induced conversion testing when prion disease is suspected, and somatosensory evoked potentials.
• Imaging: MRI brain (with susceptibility sequences for iron and calcification) for focal, acute, young onset or unexplained movements; CT head in emergencies.
• Blood film for acanthocytes (multiple fresh films) and creatine kinase in suspected neuroacanthocytosis.

Limitations. Normal MRI does not exclude Huntington disease, Wilson disease or functional disorders. Antibodies may be negative in autoimmune disease. Tardive dyskinesia and drug induced parkinsonism are clinical diagnoses.

Airway and life threats. Laryngeal dystonia with stridor needs airway support and immediate anticholinergic treatment. Suspected neuroleptic malignant syndrome or serotonin syndrome: stop the offending drug, give IV fluids and external cooling, and admit for monitoring. Give diazepam 5 to 10 mg IV repeated as needed for agitation and rigidity. Refer to intensive care for temperature over 38.5 degrees Celsius, severe rigidity or autonomic instability.

Acute dystonic reaction

• Procyclidine 5 to 10 mg IV or IM, repeated after 20 minutes if needed; maximum 20 mg in 24 hours. Alternative: benzatropine (benztropine) 1 to 2 mg IV or IM; maximum 6 mg daily. Effect is expected within 5 to 20 minutes.
• Continue an oral anticholinergic for 2 to 3 days (procyclidine 5 mg three times daily, or benzatropine 1 to 2 mg twice daily) because the causative drug may outlast the antidote. Review and change the causative drug.
• Avoid anticholinergics in angle closure glaucoma, urinary retention, gastrointestinal obstruction and tachyarrhythmia; use lower doses in older adults and dementia.

Tardive dyskinesia

• Reduce or stop the dopamine blocker when the psychiatric condition allows, or switch to clozapine or quetiapine; do not give anticholinergics (they can worsen tardive dyskinesia).
• Valbenazine 40 mg orally once daily for 1 week, then 80 mg once daily; reduce to 40 mg daily in moderate to severe hepatic impairment or with strong CYP3A4 inhibitors.
• Deutetrabenazine 6 mg orally twice daily with food, increased by 6 mg each day weekly to a tolerated effective dose; maximum 48 mg daily, and 36 mg daily with strong CYP2D6 inhibitors.
• Both can cause somnolence, parkinsonism, QT prolongation and depression; screen for mood disorder before and during treatment. Avoid deutetrabenazine in hepatic impairment and within 20 days of reserpine, and with monoamine oxidase inhibitors.

Akathisia. Reduce the dopamine blocker dose or change the drug. Propranolol 10 mg orally two or three times daily, increased to a usual 20 to 80 mg daily (avoid in asthma, heart block and bradycardia), or mirtazapine 15 mg orally at night. A short course of lorazepam 0.5 to 1 mg orally two or three times daily can be used for severe distress.

Huntington disease chorea. Treat only when chorea affects function or safety. Tetrabenazine 12.5 mg orally daily for 1 week, then 12.5 mg twice daily, increased by 12.5 mg each week to the lowest effective dose. Doses up to 50 mg daily can be given without genotyping. Higher doses (maximum 100 mg daily, single dose maximum 37.5 mg) need CYP2D6 genotyping, with a maximum of 50 mg daily in poor metabolisers.

Contraindicated in untreated depression, suicidal thoughts and hepatic impairment, and with monoamine oxidase inhibitors. Alternatives: olanzapine 2.5 to 5 mg at night (monitor weight and glucose). Screen for depression and suicidality at every visit. Genetic counselling for the family. Specialist care.

Sydenham chorea

• Eradicate streptococci: benzathine benzylpenicillin 1.2 million units IM as a single dose (600,000 units for weight under 27 kg), or phenoxymethylpenicillin 250 mg orally twice daily for 10 days (500 mg twice daily for adults).
• Penicillin allergy: azithromycin 500 mg orally on day 1, then 250 mg daily for 4 days, with an alternative of erythromycin 250 mg twice daily for 10 days.
• Secondary prophylaxis: benzathine benzylpenicillin 1.2 million units IM every 3 to 4 weeks, or phenoxymethylpenicillin 250 mg orally twice daily. Continue until age 21 or 5 years after the last attack (whichever is longer), and for 10 years or until age 40 with carditis (lifelong if severe valve disease).
• Symptomatic: valproate 15 to 20 mg/kg daily in 2 or 3 divided doses, or carbamazepine 7 to 20 mg/kg daily in 2 divided doses, for severe chorea (valproate is avoided in women who could become pregnant).
• Haloperidol is avoided because of the risk of severe extrapyramidal reactions in this condition. Chorea usually settles over 2 to 6 months.
• Evidence for corticosteroids is limited; they are reserved for refractory severe cases under specialist care.
• Echocardiography at baseline and annually for carditis.

Hyperglycaemic hemichorea hemiballismus. Correct hyperglycaemia with insulin and fluids; the movements usually resolve over days to weeks. Tetrabenazine 12.5 mg twice daily or low dose haloperidol 0.5 mg twice daily while waiting.

Vascular hemiballismus. Manage the stroke. Symptomatic: tetrabenazine 12.5 mg orally twice daily, increased by 12.5 mg each week (maximum 50 mg daily without genotyping), or haloperidol 0.5 mg orally twice daily in short courses, increased to a usual maximum of 5 mg daily, with ECG monitoring.

Myoclonus. Treat the cause first: dialysis or dose reduction in uraemia and drug accumulation, lactulose and precipitant control in hepatic encephalopathy, drug withdrawal or substitution (opioids, gabapentinoids, antibiotics).

Symptomatic therapy:

• levetiracetam 500 mg orally twice daily, increased by 500 mg twice daily each week to a usual 1.5 g twice daily, maximum 3 g daily (halve or reduce in renal impairment: 250 to 500 mg every 12 hours when creatinine clearance is under 30 mL/min)
• clonazepam 0.25 to 0.5 mg orally at night, increased every 3 to 7 days to a usual 2 to 6 mg daily in divided doses (sedation, falls, dependence)
• sodium valproate 600 mg orally daily in 2 doses increased by 200 mg every 3 days to 1 to 2 g daily (avoid in women who could become pregnant; monitor liver function, platelets)

Valproate and levetiracetam are first choices for epileptic and cortical myoclonus. Specialist care.

Tics. Explanation and behavioural therapy (full behavioural intervention for tics, habit reversal) first. Use pharmacological treatment when tics cause pain, injury or social impairment. Clonidine 0.05 mg orally at night, increased weekly by 0.05 mg to a usual 0.1 to 0.3 mg daily in 2 or 3 doses (maximum 0.4 mg daily; monitor blood pressure and pulse; avoid abrupt withdrawal). Or aripiprazole 2 mg orally daily, increased by 2 mg every 1 to 2 weeks to a usual 5 to 15 mg daily (monitor weight, glucose, lipids, akathisia). Specialist care.

Dystonia and other focal movements. Botulinum toxin injections by a specialist for cervical dystonia, blepharospasm, hand dystonia and hemifacial spasm. Young onset dystonia: levodopa with carbidopa 25 mg/100 mg, 1 tablet three times daily for 4 to 6 weeks as a diagnostic test for dopa responsive dystonia (dramatic response supports the diagnosis). Wilson disease: same day hepatology and neurology referral for chelation or zinc.

Autoimmune encephalitis. Methylprednisolone 1 g IV daily for 3 to 5 days, with IV immunoglobulin 0.4 g/kg daily for 5 days or plasma exchange; tumour search (ovarian teratoma in NMDA receptor encephalitis). Specialist care.

Functional movement disorder. Positive diagnosis with explanation, physiotherapy, occupational therapy and psychological therapy through a specialist service.

Monitoring. Video and validated movement rating scores at each visit, mood and suicidality on VMAT2 inhibitors, weight, glucose and lipids on antipsychotics, ECG with QT prolonging drugs, sodium and liver function on anticonvulsants, echocardiography in rheumatic fever.

Referral and escalation. Neurology for any new movement disorder not explained by a drug. Same day for abrupt onset, laryngeal dystonia, suspected encephalitis, or rapid cognitive decline. Psychiatry for drug choice in tardive syndromes. Genetic counselling for Huntington disease and other hereditary disorders. Cardiology for rheumatic carditis.

Admission criteria. Airway compromise, neuroleptic malignant syndrome or serotonin syndrome, suspected encephalitis, severe ballism or chorea with exhaustion, rhabdomyolysis, rapidly progressive myoclonus, or hyperglycaemic emergency.

Discharge and safety netting. Return urgently for stridor, difficulty swallowing, fever with rigidity, confusion, new weakness, seizure, or worsening mood with suicidal thoughts on a VMAT2 inhibitor. Follow up in 2 to 4 weeks.