Chorea

Published on 05/05/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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78 Chorea

Patient 1: Sydenham’s chorea

Instruction

Look at this patient.

Salient features

History

• Ask about sore throats if the patient is an adolescent, particularly if female; suspect Syndenham’s chorea (St Vitus dance) in rheumatic fever.

• Take a family history (especially in the middle-aged adult) for Huntington disease.

• Take a history of oral contraceptive use in a young woman or recent pregnancy (chorea gravidorum).

Examination

• Irregular, jerking, ill-sustained, unpredictable, quasipurposive movements of the upper limbs

• The patient is clumsy and keeps dropping objects. Patients with mild disease may show increased fidgeting or restlessness.

Proceed as follows:

• Check the grip of the hands: ask the patient to squeeze your fingers. A squeezing and relaxing motion occurs, which has been described as a ‘milkmaid’s grip’.

• Look at the tongue for any involuntary movements: known as ‘jack-in-the box’ tongue or ‘bag of worms’.

• Test deep tendon reflexes (‘pendular’ or ‘hung-up’ reflexes).

• Tell the examiner that you would like to make enquiries to assess mental status (to exclude premature dementia seen in Huntington disease).

Diagnosis

This young patient has Sydenham’s chorea (lesion) secondary to streptococcal sore throat (aetiology); this condition is usually self-limiting.

Advanced-level questions

Mention a few more causes of chorea

• SLE

• Polycythaemia vera

• Chorea gravidorum, seen in pregnancy

• Idiopathic hypoparathyroidism

• Following a stroke

• Kernicterus.

What is the prognosis of patients with Sydenham’s chorea?

Most patients recover within 1 month; a few may have relapses. A small proportion may develop valvular heart disease and hence should receive penicillin prophylaxis to prevent recurrence of rheumatic fever.

Is there any haematological disorder associated with chorea?

• Polycythaemia vera

• Neuroacanthocytosis or ‘chorea–acanthocystosis’, where >15% of the red blood cells are acanthocytes (Brain 1991;114:13).

Patient 2: Huntington disease

Instruction

Look at this patient and ask him a few questions.

Salient features

History

• Tell the examiner that you would like to take a family history of dementia and chorea.

Examination

• Young adult (aged 30–50 years)

• Chorea

• Patient has dementia.

Diagnosis

This patient has chorea (lesion) caused by Huntington disease, and is severely limited by the disease and chorea.

Advanced-level questions

What do you know about Huntington disease?

It is an autosomal dominant disorder with a full penetrance characterized by progressive chorea and dementia in middle life. These characteristic findings are the result of severe neuronal loss, initially in the neostriatum and later in the cerebral cortex. The defect is on the small arm of chromosome 4. There is associated random repetition of a sequence of trinucleotides (CAG; normal chromosomes contain about 11–34 copies of this repeat). In Huntington disease, the greater the number of CAG repeats, the earlier the onset of disease (Cell 1993;72:971). The protein product for the gene has been termed huntingtin. It has been proposed that the huntingtin protein is cleaved to fragments that are conjugated with ubiquitin and carried to the proteasome complex. This huntingtin and proteasome component then translocates to the nucleus where it forms intranuclear inclusions; over time this process leads to cell death.

There is a marked reduction in acetylcholine, substance P and γ-aminobutyric acid (GABA) activity in corpus striatum, whereas dopamine activity is normal and somatostatin is increased (Ann Neurol 1990;27:357).

Using neuropeptide immunochemistry, the chorea has been shown to be associated with damage to the lateral globus pallidus, whereas the parkinsonian signs are caused by additional damage in projections of the medial globus pallidus.

What is the advantage of assessing CAG expansion in persons at risk for Huntington disease?

It is a direct test allowing more accurate assessment of genetic risk, without the need to obtain DNA from family members. This also allows privacy and confidentiality to be maintained because of the reduced need for blood samples from relatives. However, since the misdiagnosis of other illnesses as Huntington disease may occur, the testing of DNA from at least one affected relative is recommended to confirm that CAG expansion is present in other affected persons in the family. This finding will allow the correct interpretation of a normal number of CAG repeats in a person at risk.

Notes

Transcriptional dysregulation and mitochondrial impairment are two important mechanisms in Huntingtons’s disease and these are related (N Engl J Med 2007;356:518).

Transcriptional dysregulation. Mutant huntingtin may alter the complement of proteins that are synthesized in a cell, a change that may lead to the pattern of neurodegeneration that characterizes Huntington disease (it binds and sequesters the binding protein for cyclic AMP response-element-binding protein (CREB), which alters the expression of genes regulated by the transcription factor CREB. In a similar way, mutant huntingtin interferes with Sp1-mediated gene transcription.

Mitochondrial impairment. Activities of mitochondrial electron transport complexes II, III and IV are reduced in Huntington disease. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a transcriptional coactivator that controls many metabolic processes, including mitochondrial biogenesis, oxidative phosphorylation and adaptive thermogenesis (the body’s response to cold temperatures). PGC-1α-regulated gene transcription is defective. As a result, there is reduced expression of mitochondrial and antioxidant genes regulated by PGC-1α.

Are any other diseases known to be associated with increased numbers of triplet repeats?

Yes, these include myotonic muscular dystrophy, spinocerebellar ataxia type 1, FRAXE mental retardation (a variant of fragile X syndrome) and hereditary dentatorubral pallidoluysian atrophy (DRPLA).

How would you manage this patient?

Management progresses from clinical suspicion and genetic testing. Once a diagnosis is confirmed, the treatment is symptomatic plus support for depression. A combination of valporate and olanzapine may help in relieving the psychosis and movements disorders associated with Huntington disease (N Engl J Med 2000;343:973).

Thomas Sydenham (1624–1689) was a Puritan from Dorset, and in 1666 published his first work on fevers, which he dedicated to Robert Boyle. Chorea in Greek means dance.

Gustav Mahler was diagnosed with a cardiac valve anomaly in 1907 and died of subacute bacterial endocarditis in 1911. It is possible that the composer suffered from rheumatic disease in childhood with carditis and Syndenham’s chorea, which may have left him with cardiac valve disorder, obsessive–compulsive personality and persistent chorea.

George Summer Huntington (1851–1916) first documented (in 1909) the clinical and hereditary features of this condition in a family from Suffolk settled in Long Island in New York.

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