Chorea

Chorea 

Chorea is the term used to describe brief movements that involve contiguous muscle groups. The term comes from the Greek word meaning dance.

Synonyms

• Sydenham chorea
• Saint Vitus dance

Epidemiology & Demographics

Incidence

No published data exist on the incidence of chorea in the U.S.

Can affect any age and sex depending on the cause

What increases the Risk of Chorea?

The most important risk factors are a family history of Huntington disease, exposure to rheumatic fever as a child, or being pregnant with a history of rheumatic fever.

Physical Findings & Clinical Presentation

• •Presentation depends on the underlying cause. Huntington disease (HD) typically presents with neuropsychiatric symptoms predating choreiform movements. In the case of Sydenham chorea, drug-induced chorea, or chorea gravidarum, hyperkinetic movements involving the hands and face may be noticed first. Nonrhythmic, random, brief, contiguous movement and facial grimacing can be clues to the presence of chorea. Writhing movement of the hands or feet is known as athetosis. An enlarged tongue and self-mutilation may accompany chorea in patients with neuroacanthocytosis. Choreiform movements tend to be suppressed during physical examination; look for suppressive techniques such as holding of the face or crossing of the legs.

• Chorea involving specific body parts can be a clue to the proper differential diagnosis. For example, chorea involving the forehead muscles is seen in HD. These muscles typically are spared in tardive dyskinesia. Orobuccolingual chorea is seen in tardive dyskinesia, acquired hepatocerebral degeneration, and neuroacanthocytosis. Hemichorea/hemibalism can be seen arising in nonketotic hyperglycemia, polycythemia vera, Sydenham chorea, antiphospholid antibody syndrome, and structural lesions (such as ischemic strokes) affecting the contralateral thalamus or subthalamic nucleus, basal ganglia, or even corona radiata.

What causes Chorea?

• •The most common genetic causes of chorea include benign hereditary chorea, Huntington disease, C9orf72 hexanucleotide repeat expansion (first described in families with frontotemporal dementia and ALS but then discovered to have an expanded phenotype include an HD phenocopy in those of European origin), and spinocerebellar ataxia type 17. Other genetic causes are neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), neurodegeneration with brain iron accumulation, and Wilson disease.
• •Infectious causes include rheumatic fever causing Sydenham chorea (most common cause of chorea in children), toxoplasmosis of the basal ganglia, and prion disease.
• •Drug-induced causes include cocaine, amphetamine, oral contraceptives, tricyclic antidepressants, cimetidine, digoxin, verapamil, baclofen, steroids, antiepileptics, and neuroleptics. Tardive dyskinesia, most typically from dopamine-blocking agents such as neuroleptics or some antiemetics, can result in choreiform movements.
• •Hemichorea may be due to antiphospholipid antibody syndrome, systemic lupus erythematosus, or hemichorea-hemiballismus syndrome due to severe nonketotic hyperglycemia, polycythemia vera, or contralateral structural lesion, such as ischemic stroke of the basal ganglia, thalamus, or subthalamic nucleus.
• •Acquired causes of chorea are summarized in the below table.

Inherited Causes of Childhood-Onset Chorea

From Kliegman RM: Nelson textbook of pediatrics, ed 21, Philadelphia, 2020, Elsevier.

Disease Name	Inheritance	Associated Gene	Age Of Onset	Neurologic Or Psychiatric Manifestations	Systemic Symptoms
Chorea Prominent Feature
Ataxia- telangiectasia	AR	ATM	18 mo-3 yr	Chorea often initial symptom; also have oculomotor apraxia, ataxia, and dystonia	Telangiectasias, increased sinopulmonary infections, increased incidence of cancer
Ataxia with oculomotor apraxia 1 and 2 (especially type 1)	AR	APTX	Onset later than ataxia-telangiectasia	Chorea, dystonia, oculomotor apraxia, ataxia, distal sensory axonal neuropathy
Friedreich ataxia	AR	GAAn in FRDA	Over 2 yr, usually teenagers	Gait ataxia, axonal neuropathy, areflexia, extensor plantar response. Can have various movements (tremor, dystonia, chorea, myoclonus). Cases of chorea without cerebellar signs described	Cardiomyopathy, diabetes
GNAO1- related dyskinesias	AR	GNAO1	Infancy	Ballismus, chorea, orofacial dyskinesias; can alternatively cause Ohtahara syndrome
Benign hereditary chorea	AD	NKX2-1	Prior to age 5 yr	Chorea; can have myoclonus, learning disability	Thyroid disease, lung disease
Benign hereditary chorea with or without facial “myokymia”	AD	ADCY5	Infancy to late adolescence	Chorea, choreic facial twitches (previously called myokymia); can have myoclonus or dystonia	Some reports of congestive heart failure
PDE10A- associated chorea	AD or AR	PDE10A	AD: Childhood AR: Infancy	Chorea, MRI striatal changes in AD form
Paroxysmal nonkinesigenic dyskinesias	AD	MR1	Infancy to 10 yr	Dystonia, chorea, or a combination
3-methylglutaconic aciduria type III (Costeff syndrome)	AR	OPA3	Infancy	Bilateral optic atrophy and chorea early; spasticity, ataxia, and dementia later
Congenital cataracts, facial dysmorphism, and neuropathy	AR	CTDP1	Infancy or childhood	Progressive neuropathy, delayed psychomotor development, mild chorea, hypomyelination, hearing loss	Skeletal abnormalities, dysmorphic face, congenital cataracts, microcornea, hypogonadism
Dentatorubral-pallidoluysian atrophy	AD	CAGn in atrophin-1	Mostly adults but seen in a few children	Neurodegeneration, chorea, tics, dementia, seizures, ataxia, psychiatric symptoms
Huntington chorea/disease	AD	CAGn in HTT	Adolescence to 40s	Younger onset without chorea and with parkinsonism, but later, teenagers can manifest chorea, emotional disturbances similar to adult form
Huntington disease-like-3 (HDL3)	AR	Linked to chromosome 4p15.3	Childhood	Neurodegeneration, chorea, dystonia, ataxia, dementia, seizures
Idiopathic basal ganglia calcification (IBGC), childhood onset (bilateral striopallidodentate calcinosis)	AR or AD	SLC20A2 or PDGFRB	Infancy to second decade of life	Tetraplegia, chorea, severe cognitive impairment, microcephaly, basal ganglia calcifications	Early death
Choreoacanthocytosis	AR	VPS13A	Mean age 20 yr but described in childhood	Psychiatric symptoms (e.g., obsessive-compulsive disorder) can precede neurologic symptoms Neurodegeneration, progressive hyperkinetic movements (limb chorea, orofacial dyskinesias, tics, dystonia), dementia, seizures, cognitive decline, sensorimotor polyneuropathy	Acanthocytosis, increased CK and/or liver transaminases
Spinocerebellar ataxia 1	AD	CAGn in ATXN1	Childhood	Neurodegeneration, progressive ataxia, mild cognitive impairment, dysarthria, ophthalmoplegia, optic atrophy, spasticity, dystonia or chorea
Spinocerebellar ataxia 17	AD	CAGn or CAAn in TBP	Mostly early adulthood but some teenagers reported	Neurodegeneration, psychiatric symptoms (depression, hallucinations), frontal release signs, chorea, dystonia, and parkinsonism; may have ocular movement abnormalities
Leigh syndrome	X-linked	PDHA1	Infancy or childhood	Neurodegeneration, psychomotor delay, hypotonia and chorea and other hyperkinetic movements can be prominent, progresses to feeding and swallowing defects, nystagmus, ophthalmoplegia, optic atrophy, seizures Lesions in basal ganglia, cerebrum, cerebellum, spinal cord	Lactic acidemia, respiratory failure
Nonketotic hyperglycemia (glycine encephalopathy)	AR	GLDC, GCST, or GCSH	Neonates/infancy	Hypotonia, severe myoclonic epilepsy, profound cognitive impairment, restlessness	Hyperglycemia
Infantile bilateral striatal necrosis	AR	NUP62	Infancy	Developmental regression, intellectual disability, pendular nystagmus, optic atrophy, dysphagia, dystonia, choreoathetosis, spasticity, and severe bilateral striatal atrophy
Chorea Sometimes Present
Spinocerebellar ataxia 7	AD	CAGn in ATXN7	Childhood	Neurodegenerative mitochondrial disorder, progressive ataxia, dysarthria, dysphagia, optic atrophy, ophthalmoplegia, spasticity, dystonia or chorea may occur	Retinal degeneration
Wilson disease	AR	ATP7B	12 yr to early 20s	Dysarthria, drooling, pharyngeal dysmotility, clumsiness, tremor (“wing-beating”), psychiatric symptoms (decline in school, anxiety, depression, psychosis); chorea and dystonia variable	Hepatic dysfunction (asymmetric hepatomegaly, acute transient or fulminant hepatitis), Kayser-Fleischer rings of cornea
Lesch-Nyhan disease	X-linked	HPRT	Early childhood	Self-injurious behaviors, intellectual disability, motor disability, pyramidal signs, dystonia superimposed on hypotonia, may have chorea or ballismus, abnormal ocular motility	Hyperuricemia, nephrolithiasis, gout
Pantothenate kinase–associated neurodegeneration (PKAN), classic form	AR	PANK2	Prior to 6 yr old (in classic onset)	Progressive motor difficulties, personality changes, cognitive decline, dysarthria, spasticity; later onset of movements (dystonia most common, chorea or tremor may also be present); “eye of the tiger” sign on MRI of brain	Pigmentary retinal degeneration, acanthocytosis
Paroxysmal kinesigenic dyskinesia (PKD)	AD	PRRT2	1-20 yr	Short episodes triggered by sudden movement; dystonia is most common movement but can have chorea
Biopterin-dependent hyperphenylalaninemia (group of disorders)	Usually AR	Multiple genetic causes	Neonate	Initially hypotonic with poor suck, decreased movements, and microcephaly; months later, oculogyric crises, swallowing difficulties, variable hypo- and hyperkinetic movements, seizures, cognitive impairment	Elevated phenylalanine level at birth; autonomic symptoms start several months later
Glutaric aciduria	AR	GCDH	First 6 mo	Hypotonia and jitteriness at birth; at 6-18 mo, progressive hyperkinetic movements (dystonia, choreoathetosis); may have seizures
Alternating hemiplegia of childhood	AR	ATP1A-3	Neonate to <18 mo	Transient episodes of alternating hemiplegia/hemiparesis, dystonic attacks, paroxysmal abnormal ocular movements, seizures, episodes of autonomic dysfunction; between attacks, may have ataxia, dystonia, and/or choreoathetosis; most have intellectual disability
Succinate semialdehyde dehydrogenase deficiency	AR	ALDH5A	Infancy to early childhood	Intellectual disability, pronounced language dysfunction, autistic traits, hypotonia, aggression, ataxia, anxiety, hallucinations, can have choreoathetosis

AD, Autosomal dominant; AR, autosomal recessive; CK, creatine kinase; MRI, magnetic resonance imaging.

Acquired Causes of Chorea

From Kliegman RM: Nelson textbook of pediatrics, ed 21, Philadelphia, 2020, Elsevier.

Structural-Basal Ganglia Lesions
StrokeMoyamoya diseaseVascular malformationsHemorrhageChoreoathetoid cerebral palsyPostcardiac transplant (postpump chorea)Mass lesions (CNS lymphoma, metastatic brain tumors)Multiple sclerosis plaqueExtrapontine myelinolysisTrauma
Parainfectious And Autoimmune Disorders
Poststreptococcal Sydenham choreaChorea secondary to systemic lupus erythematosusChorea secondary to antiphospholipid antibody syndromeAcute disseminated encephalomyelitisAnti-NMDA receptor encephalitisRasmussen encephalitisChorea gravidarumPostinfectious or postvaccinal encephalitisParaneoplastic choreas
Infectious Disorders
HIV encephalopathyToxoplasmosisCysticercosisDiphtheriaBacterial endocarditisNeurosyphilisScarlet feverViral encephalitis (mumps, measles, varicella)
Metabolic Or Toxic Disorders
Acute intermittent porphyriaHyponatremia/hypernatremiaHypocalcemiaHyperthyroidismHypoparathyroidismHepatic/renal failureCarbon monoxide poisoning	Methyl alcoholTolueneManganese poisoningMercury poisoningOrganophosphate poisoningPheochromocytoma
Psychogenic Disorders
Drug-Induced Disorders
Dopamine-Blocking Agents (upon withdrawal or as a tardive syndrome)	PhenothiazinesButyrophenonesBenzamides
Antiparkinsonian Drugs	L-DOPADopamine agonistsAnticholinergics
Antiepileptic Drugs	PhenytoinCarbamazepineValproic acid
Psychostimulants	AmphetaminesMethylphenidateCocaine
Calcium Channel Blockers	CinnarizineFlunarizineVerapamil
Others	LithiumBaclofenDigoxinTricyclic antidepressantsCyclosporineSteroids/oral contraceptivesTheophyllinePropofol

CNS, Central nervous system; HIV, human immunodeficiency virus; L-DOPA, levodopa; NMDA, N-methyl-D-aspartate.

Differential Diagnosis

• •Huntington disease
• •Tardive dyskinesia
• •Dystonia
• •Tic disorders
• •Stroke
• •Prion disease
• •Rheumatic fever
• •Conversion disorder

Laboratory Tests

• •Complete metabolic panel, including liver function tests
• •CBC with peripheral smear looking for acanthocytes
• •Serum copper and ceruloplasmin levels
• •Thyroid function tests
• •Antistreptolysin O antibodies
• •Genetic testing for Huntington disease should be done at a comprehensive center involving neurology, psychology, and genetics; complete team support is required before genetic testing is undertaken

Imaging Studies

• •MRI of the brain with and without contrast
• •Echocardiogram if rheumatic fever is suspected

 Treatment

• •Depending on the cause, treatment must be tailored.
• •Chorea related to Huntington disease can be treated with tetrabenazine or deutetrabenazine (recently approved by the FDA). Caution must be exercised because the medication puts the patient at significant risk for depression.
• •Withdrawing the offending drug can treat drug-induced chorea.
• •Some conditions such as SCA3 or neuroacanthocytosis and Huntington disease have a strong neuropsychiatric component and may need to be comanaged with behavioral health specialists.

Nonpharmacologic Therapy

• •Rehabilitative services such as physical therapy, occupational therapy, and speech therapy are important for genetic forms of chorea.
• •Cognitive therapy is now becoming more important in maintaining quality of life in most of these disorders.

Acute General Treatment

• •Sudden-onset chorea warrants brain imaging to evaluate for stroke.
• •MRI of the brain is important for full evaluation of chorea, as it allows for the evaluation of basal ganglia structure. Huntington disease is associated with atrophy of the head of the caudate.
• •Subacute onset chorea may represent autoimmune or paraneoplastic syndromes due to a host of autoantibodies including anti-NMDA, anti-Hu, and anti-CRMP-5, anti-Yo, anti-LGI1, anti-CASPR2, anti-GAD65, and anti-IgLON5.

Chronic Treatment

• •Tetrabenazine and deutetrabenazine are the only medications currently approved by the FDA to treat the chorea of Huntington disease. These medications reduce the chorea but do not halt the underlying neurodegenerative process of Huntington disease.
• •Deutetrabenazine and valbenazine are the only medications currently approved by the FDA for treating tardive dyskinesia.
• •A multidisciplinary approach is useful for treating Huntington disease.

Complementary Medicine

There are case reports showing some efficacy in acupuncture for the treatment of temporomandibular chorea in a patient with Sydenham chorea.

Disposition

• •Sydenham chorea and chorea gravidarum tend to resolve in a few weeks.
• •Huntington disease is a progressive neurodegenerative disorder.
• •Tardive dyskinesia due to neuroleptics may be treated medically, and offending agents should be withdrawn, but comanagement with a psychiatrist is imperative to avoid destabilization of the patient and to monitor for depression using TD-specific therapy.

Referral

Refer to a neurologist.

Pearls & Considerations

Chorea is a symptom of an underlying disorder. Investigations are targeted to identify reversible causes.

Prevention

• •Treat streptococcal throat infection early to prevent future complications.
• •Weigh risk-benefit in using medications known to cause tardive dyskinesia.

Patient & Family Education

For Huntington disease and other genetic forms of chorea, it is important to provide support and refer to support groups.

Seek Additional Information

• Bansil S., et al.: Movement disorders after stroke in adults: a review. Tremor Other Hyperkinet Mov 2012; 2:
• Cardoso F., Vale T.: Chorea: a journey through history. Tremor Other Hyperkinetic Mov 2015; 28 (5):
• Termsarasab P.: Chorea. Continuum (Minneap Minn) 2019; 25 (4, Movement Disorders): pp. 1001-1035.
• Waln O., et al.: An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov 2013; 12 (3):