PATIENT 1: SYDENHAM'S CHOREA
Look at this patient.
· Ask about sore throats il' the patient is an adolescent, particularly if female: suspect Sydenham's chorea (St Vitus' dance) inrheumatic fever.· Take a family history (especially in the middle-aged adult) for Huntington's disease.· Take a history of oral contraceptive use in a young woman or recent pregnancy (chorea gravidorum).
· 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 beendescribed 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 assess mental status (to exclude pre-mature dementia seen in Huntington's disease).
This young patient has Sydenham's chorea (lesion) secondary to streptococcal sore throat (aetiology); this condition is usuallyself-limiting.
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 I month; a few may have relapses. A small proportion may develop valvular heart disease and henceshould receive penicillin prophylaxis to prevent recurrence of rheumatic fever.
Is there any haematological disorder associated with chorea?
· Polycythaemia vera.· Neuroacanthocytosis or 'chorea-acanthocystosis' where more than 15% of the red blood cells are acanthocytes (Brain 1991;114: 13).Thomas Sydenham (1624-1689) was a Puritan from Dorset, and in 1666 published his first work on fevers which he dedicated toRobert Boyle.Chorea in Greek means 'dance'.
PATIENT 2: HUNTINGTON'S DISEASE
Look at this patient and ask him a few questions.
HistoryTell 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.
This patient has chorea (lesion) due to Huntington's disease, and is severely limited by the disease and chorea.
What do you know about Huntington's disease?
It is an autosomal dominant disorder with full penetrance characterized by pro-gressive chorea and dementia in middle life. Thesecharacteristic findings result from severe neuronal loss, initially in the neostriatum and later in the cerebral cortex. The defect is onthe small arm of chromosome 4. There is associated random repetition of a sequence of trinucleotides (viz. CAG; normalchromosomes contain about 11-34 copies of this repeat). In Huntington's disease, the greater the number of CAG repeats, theearlier the onset of disease (Cell 1993; 72: 971). The protein product for the gene has been termed 'huntingtin'. It has beenproposed that the huntingtin protein is cleaved to fragments which are conjugated with ubiquitin and carried to the proteasomecomplex. Components of both huntingtin and the proteasome then translocate to the nucleus to form intranuclear inclusions, andover time this process leads to cell death.There is a marked reduction in acetylcholine, substance P and T-aminobutyric acid (GABA) activity in the 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 result from additional damage in projections of the medial globus pallidus.
What is the advantage of assessing CAG expansion in persons at risk for Huntington's disease?
It is a direct test that allows more accurate assessment of genetic risk without the need to obtain DNA from family members. Thisalso allows privacy and confiden-tiality to be maintained because of the reduced need for blood samples from relatives. However,since the misdiagnosis of other illnesses as Huntington's disease may occur, the testing of DNA from at least one affected relative isrecommended to confirm that CAG expansion is present in other affected persons in the family. This finding will allow the correctinterpretation of a normal number of CAG repeats in a person at risk.
Are any other diseases known to be associated with increased numbers of triplet repeats?
Yes; these include myotonic muscular dystrophy, spinocerebellar ataxia type l, FRAXE mental retardation (a variant of fragile Xsyndrome) and hereditary dentatorubral pallidoluysian atrophy (DRPLA).
How would you manage this patient?
A combination of valproate and olanzapine may help in relieving the psychosis and movement disorders associated withHuntington's disease (N Engl J Med 2000; 343: 973).George Summer Huntington (1851-1916) first documented (in 1909) the clinical and hereditary features of this condition in a familyfrom Suffolk settled in Long Island in New York.