Chorea

Chorea is an irregular, often jerky, flowing movement that moves between different body parts. Chorea can often be observed throughout the examination at rest and posture and can be exacerbated by action and while walking.

A.

There are a few specific clinical events that can precipitate chorea. Hemichorea can arise as a presentation of acute stroke but can also occur in the subsequent weeks during recovery. ‘Post-pump’ chorea occurs rarely after extracorporeal membrane oxygenation (ECMO). Chorea has also been described after global hypoxic-ischemic injury.
B.

Uptitration of dopaminergic medications in patients with Parkinsonism can cause choreiform movements abruptly, both in Parkinson disease and the atypical Parkinsonian syndromes. Tardive dyskinesia from dopamine blockade causes orobuccal choreiform movements. Illicit drugs including cocaine, methamphetamine, synthetic cannabinoids, and others can cause acute chorea as part of their toxidromes.
C.

Many of the metabolic causes of chorea are treatable, so a thorough workup is essential. Hyperglycemia can cause chorea and is associated with bilateral basal ganglia hyperintensities on magnetic resonance imaging (MRI) T1 sequences. Liver failure of any cause can lead to hepatocerebral degeneration because of inability to metabolize certain heavy metals. Wilson disease is a specific metabolic disorder due to inability to excrete copper that results in chorea and also liver failure. Polycythemia vera is known to cause chorea, presumably due to “sludging” in lenticulostriate vessels leading to hypoxia in the basal ganglia.
D.

Sydenham chorea after streptococcal infection is likely the most common cause of chorea in children. Immune-mediated vasculitides that cause chorea include lupus and antiphospholipid antibody syndrome. Several paraneoplastic syndromes can include chorea as part of their neurologic phenotype.
E.

Toxic exposure causing chorea is rare but has been ascribed to manganese, mercury, and carbon monoxide toxicity. Creutzfeldt-Jakob disease can cause a subacute progressive chorea. Other cerebral infections have also been described.
F.

If investigations for acquired causes of chorea have been unrevealing, genetic causes should be considered. Sporadic mutations, anticipation, and nonpaternity can all lead to a presentation of genetic chorea without a significant family history. Huntington disease (HD) is by far the most likely entity given population carrier rates of intermediate length huntingtin expansions.
G.

Chorea with an autosomal dominant inheritance pattern is highly likely to be due to HD and therefore testing for this entity should occur first. If negative, there are several HD phenocopies. C9orf72 hexameric repeat expansions have emerged as a cause of hereditary chorea. The same repeat expansion is also a common cause of familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia. A brain MRI with iron deposition is highly suggestive of neuroferritonopathy, the only autosomal dominant neurodegeneration with brain iron accumulation (NBIA) syndrome. HD-like 2 (HDL 2 due to expansion mutations in JPH3 ) is common in African populations. Further testing may be guided by associated symptoms and signs. Dementia and epilepsy are described in Huntington disease-like 1 (HDL 1 due to mutations in the PRNP gene), dentatorubral-pallidoluysian atrophy (DRPLA due to expansion mutations in ATN1 ) and spinocerebellar ataxia type 17 (SCA-17). Otherwise, SCA 1–3 have been described as causing chorea. ADCY5 mutations have recently been associated with childhood onset chorea, facial myokymia, and other movement disorders. Patients with mild, minimally progressive chorea with childhood onset without other neurologic features may have a mutation in the TITF-1 gene leading to benign hereditary chorea (BHC).
H.

The majority of NBIAs are inherited in an autosomal recessive fashion (e.g., those due to mutations in PANK2 , PLA2G6 , C19orf12 , FA2H , ATP13A2 , COASY , CP , and DCAF17) . Aceruloplasminemia can also cause iron deposition on MRI, and also has the additional features of low ceruloplasmin, copper, and iron. Acanthocytosis can be seen in chorea acanthocytosis. Wilson disease should be ruled out if not done already. Lastly, chorea has been described in ataxia telangiectasia and Friedrich ataxia. X-linked inherited genetic choreas are rare. One of the NBIAs is X-linked inherited beta-propeller protein-associated neurodegeneration (BPAN) due to mutations in WDR45. McCleod syndrome is another of the core neuroacanthocytosis syndromes. Chorea is a less common manifestation of Lubag disease (DYT3: X-linked dystonia Parkinsonism due to mutations in TAF1 ) and has been described in female carriers of the mutation.