Chorea in Adults Clinical Presentation

Updated: Jul 01, 2019
  • Author: Pradeep C Bollu, MD; Chief Editor: Selim R Benbadis, MD  more...
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Presentation

History

Patients with chorea may not initially be aware of the abnormal movements because they may be subtle. Patients can suppress the chorea temporarily and frequently camouflage some of the movements by incorporating them into semipurposeful activities (ie, parakinesia). The inability to maintain voluntary contraction (ie, motor impersistence), as is seen during manual grip (milkmaid grip) tests or tongue protrusion, is a characteristic feature of chorea and results in the dropping of objects and clumsiness. Muscle stretch reflexes are often hung-up and pendular. In severely affected patients, a peculiar dancelike gait may be noted. Depending on the underlying cause of the chorea, other motor symptoms include dysarthria, dysphagia, postural instability, ataxia, dystonia, and myoclonus. A brief discussion of the clinical manifestations of the most common choreatic diseases is presented.

Huntington disease

Penetrance of HD is 100%. Expression is highly variable, both with respect to clinical manifestations and age of onset. When the disorder emerges early, particularly in patients younger than 20 years, it is most likely to run a rapid course with grave disability due to cognitive decline. [45, 1, 42]

The Westphal variant, a rigid dystonic disorder, may be accompanied by seizures and even myoclonus. It is encountered principally among those with childhood onset. In contrast, when the disorder appears late in life, the cardinal manifestation is chorea.

The insidious onset of clumsiness and adventitious movements may be wrongly attributed to simple nervousness. Although chorea and other motor disabilities are the most readily recognized manifestations of HD, they may be neither the earliest to appear nor the most disabling manifestations of the disease.

Psychological disturbances and personality change are the initial manifestations in greater than 50% of affected persons. Symptoms consistent with a depressive state are the most frequent psychological disturbances.

Despite the challenge in defining the onset of the disease due to the subjective nature of initial symptoms, the inverse correlation between age at motor onset and CAG repeat expansion accounts for approximately 50–70% of the variance in the onset. The remaining difference in age of onset is likely to be genetically encoded. [104]

The duration of illness from onset to death is approximately 15 years in the case of adult HD and 8-10 years for the juvenile variant.

Wilson disease

The clinical features are age-dependent. In children, the disease is manifested initially by progressive dystonia, rigidity and dysarthria, and hepatic dysfunction, whereas in adults, psychiatric symptoms, tremor, and dysarthria usually predominate. [27, 28, 46]

Because Kayser-Fleischer rings are almost always present when neurological symptoms are present, slit-lamp examination of the cornea must be performed to be certain that Wilson disease is excluded in a patient with chorea beginning in childhood or young adulthood. In patients with chorea and negative findings from a slit-lamp examination, serum copper and ceruloplasmin analysis along with a 24-hour copper urine excretion test need to be performed.

Neuroacanthocytosis

Symptoms usually begin in young adulthood with lip and tongue biting (often causing self-injury), orolingual dystonia, motor and phonic tics, generalized chorea, parkinsonism, and seizures. Patients with neuroacanthocytosis may report an inability to feed themselves because of dystonic tongue protrusion every time they try to eat. Although chorea is the typical manifestation, some patients may also present with a parkinsonian picture with rigidity and bradykinesia. [105, 1, 43, 47]

Other features include cognitive and personality changes, dysphagia, dysarthria, amyotrophy, areflexia, evidence of axonal neuropathy with absent deep ankle tendon stretch reflexes, and elevated serum creatine kinase levels without evidence of myopathy.

Senile chorea

This clinical entity is characterized by a gradual onset of generalized and symmetric chorea with slow progression and specifically excluding mental deterioration, emotional disturbances, or family history. [48, 49, 50]

To rule out the possibility of HD, genetic testing is recommended because family history can be inaccurate and distinguishing age-related mental changes from early features of HD in an elderly person may be difficult.

Sydenham chorea

Sydenham chorea is a major manifestation of acute rheumatic fever. With the 1992 modifications of the Jones criteria (see the Jones Criteria for Diagnosis of Rheumatic Fever calculator), it alone is sufficient to enable the physician to make the diagnosis of the first attack of acute rheumatic fever. Sydenham chorea is considered a disease of childhood; however, it also may be seen in adults. Rheumatic chorea is characterized by muscle weakness and the presence of chorea. The patients have the milkmaid grip sign, clumsy gait, and explosive bursts of dysarthric speech. Often, harlequin tongue, which pops in and out when the patient tries to hold it out, can be prominently demonstrated. [51, 52, 53]

Psychological symptoms are equally prominent and typically precede the appearance of even the most subtle choreiform movements. Emotional lability is the most common symptom; decreased attention span, obsessive-compulsive symptoms, and separation anxiety disorder also are seen. Symptoms can lag behind the etiologic streptococcal infection by 1-6 months. In adults, generalized poststreptococcal chorea may complicate birth control or pregnancy (chorea gravidarum).

Benign hereditary chorea

This is a rare autosomal dominant genetic disorder characterized by nonprogressive choreiform movements that appear in childhood, without intellectual impairment. It is further distinguished clinically from juvenile HD by the absence of seizures, rigidity, or cerebellar features. [1, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41]

Benign hereditary chorea is caused by a mutation in the TITF1 gene. Interestingly, this gene contains the code for a transcription factor essential for the organogenesis of the basal ganglia, the lungs, and the thyroid.

It does not shorten the life span of affected patients, but severely affected patients can be markedly disabled by the chorea.

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Physical

Because Huntington disease (HD) is the most clearly defined choreatic disease, its physical findings are described here.

HD is caused by an expansion repeat (CAG) mutation in the IT15 ("interesting transcript 15") gene (which codes for the protein called huntingtin) on chromosome 4. Initial signs of chorea generally are flickers in the fingers and ticlike grimaces of the face. Over time, higher-amplitude dancelike movements disrupt voluntary actions of the extremities and interfere with gait. Speech becomes dysrhythmic. In later stages, chorea involves the pharynx, diaphragm, and larynx presenting as dysarthria and dysphagia. This progressive loss of voluntary motor control leads to a picture of a Parkinson-like rigid and akinetic state. [1, 54, 42]

Characteristically, the patient is hypotonic, although reflexes may be augmented and clonus may be noted.

Voluntary gaze is disturbed early. In particular, saccades may be irregular or of prolonged latency and may require an initial blink for their initiation with preserved pursuit movements. Advanced stages of the disease may have impairment of smooth pursuit, saccades, and refixation.

Loss of optokinetic nystagmus is common after a decade of progressive disease but sometimes can be seen as an early manifestation of the disease too. [114]

Cognitive changes are manifested early as loss of recent memory and impaired judgment. Apraxia is also present. Ultimately, the patient becomes severely demented.

Neurobehavioral changes typically consist of personality changes, apathy, social withdrawal, agitation, impulsiveness, depression, mania, paranoia, delusions, hostility, hallucinations, or psychosis.

The Westphal variant is dominated by rigidity, bradykinesia, and dystonic postures. Generalized seizures and myoclonus may be seen. Ataxia and dementia are also present.

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Causes

See the list below:

  • Idiopathic - Physiological chorea of infancy, buccal-oral-lingual dyskinesia, senile chorea [48, 49, 50]

  • Hereditary - HD, hereditary nonprogressive chorea (benign hereditary chorea) [1, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41] , benign recessively inherited choreoathetosis of early onset [55] , familial inverted chorea [56] , neuroacanthocytosis [43] , familial remitting chorea nystagmus and cataracts [57] , ataxia-telangiectasia, tuberous sclerosis [58] , familial calcification of basal ganglia, pantothenate kinase associated neurodegeneration (PKAN) or pantothenate kinase 2 (PANK2) deficiency (previously termed Hallervorden-Spatz disease), Friedreich ataxia, dentatorubro-pallidoluysian atrophy [59] . ADCY5 mutation, PDE10A mutations, C9ORF72 mutations can also cause chorea.

  • Hereditary (metabolic) - Wilson disease [27, 28] , glutaric aciduria, Lesch-Nyhan disease, phenylketonuria, acute intermittent porphyria, propionic acidemia [60] , abetalipoproteinemia, hypobetalipoproteinemia, lipid storage diseases

  • Other metabolic and endocrine disorders -Kernicterus, hyperthyroidism, hypoparathyroidism, hypoglycemia [61] , nonketotic hyperglycemia [62] , chorea gravidarum, hypomagnesemia, chronic nonfamilial hepatic encephalopathy [63] , anoxic encephalopathy (including postcardiac transplantation) [64] , cardiac surgery [65] , postportocaval anastomosis for portal hypertension

  • Paroxysmal - Paroxysmal kinesogenic choreoathetosis, paroxysmal dystonic choreoathetosis

  • Infectious - Sydenham chorea, encephalitides [66] , subacute sclerosing panencephalitis, syphilis, enteric cytopathogenic human orphan (ECHO) virus infection [66] , Lyme disease, HIV infection [7, 67] , cerebral toxoplasmosis, Creutzfeldt-Jakob disease, subacute bacterial endocarditis

  • Drug induced - Neuroleptics, levodopa, anticholinergics, oral contraceptives, antihistamines, amphetamines, cocaine, phenytoin, tricyclics

  • Toxins - Alcohol intoxication and withdrawal, carbon monoxide [68, 69] , manganese, mercury

  • Vascular - Cerebrovascular disease (ischemic or hemorrhagic) [70, 5, 24, 71, 72, 73] , chronic subdural hematoma [74] , Moyamoya disease [75] , migraine/hemicrania choreatica [76] , Churg-Strauss syndrome [77] , polycythemia vera

  • Immunologic -Systemic lupus erythematosus, Behçet disease [78] , primary antiphospholipid antibody syndrome [79, 80] , multiple sclerosis, postcardiac transplantation [64] , postvaccination and other autoimmune causes [110]

  • Tumors - Primary, metastatic

  • Paraneoplastic [113] - CRMP-5 autoantibodies in testicular cancer can be associated with limbic encephalitis [111] and choreiform dyskinesias. Morvan's fibrillary chorea can be a manifestation of thymoma. [112]

  • Miscellaneous - Mitochondrial cytopathies, ventriculoperitoneal shunts [81] , cardiac sugery [65]

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