The Pathophysiology of Syndeham’s Chorea

By: Neal Shah, Co Editor-In-Chief

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Dyskinesias are abnormal, involuntary movement disorders.  Subsets of dyskinesias include choreas and atheosis.  Chorea is irregular and sporadic contraction of muscles whereas athetosis involves a twisting and writhing of muscles.  These two dyskinesias often occur together and are thus termed choreathetosis.¹  Common conditions which feature choreatheosis are Huntington’s, and Sydenham’s.²   Since chorea involves the dopaminic pathway, first generation antipsychotics, anti-epileptic drugs, and levodopa are among the drugs that trigger this dyskinesia.

Huntington’s is a genetic disease that results from an aberrant elongation of the huntingtin protein leading to overexpression of the dopaminic pathway.³  Considered the pharmacologic antagonists of Parkinson’s disease, first generation antipsychotics like haloperidol and fluphenazine are shown to ameliorate symptoms of Huntington’s disease.⁴  While tetrabenazine remains the only FDA-approved pharmacological treatment for Huntington’s chorea, there is no true cure for the disease.^4,5  Tetrabenazine works in a similar fashion as reserpine: it depletes monoamines such as dopamine by inhibiting their incorporation into vesicles.  Also like reserpine, this agent is linked to depression and suicidal tendencies, and is thus reserved for advanced cases of chorea after other neuroleptic agents have failed.^5.6

Sydenham’s is a lesser-known dyskinesia.  Unlike Huntington’s, it is relatively cureable and those afflicted usually have complete recovery.⁷  Sydenham’s chorea results from an auto-immune reaction against a prolonged S. pyogenes infection, where the body forms antibodies against antigens of the bacteria known as epitopes.  Similar epitopes are found in the basal ganglia, an area in the brain which controls movements.  Antibodies then begin to attack the basal ganglia, causing the dyskinetic movements clinically seen with Sydenham’s chorea.^7,8  Sydenham’s chorea is part of the Rheumatic Fever component of auto-immune reaction against S. pyogenes infection, which includes rheumatic heart disease, strept throat, and polyarthritis.⁹  Sydenham’s chorea mainly effects children aged 5—13 and has a predisposition to effect more females than males in roughly a 2:1 ratio.¹⁰

The treatment for Sydenham’s chorea is empiric against S. pyogenes: penicillin or amoxicillin dosed at 500 mg three-to-four times a day for ten days.  These beta-lactams are relatively inexpensive and show very low resistance rates among S. pyogenes strains.¹¹  For patients with severe Sydenham’s chorea who are admitted inpatients, a single penicillin G benzathine injection of 600,000–1,200,000 units will suffice.  In penicillin-allergic patients, clindamycin or the macrolides are safe to use and provide similar clinical efficacies.  These agents are also given for a duration of ten days.¹¹

Other treatments include valproic acid, immunoglobulins, and corticosteroids.^12-13  The latter two are administered based on the auto-immune component of Sydenham’s chorea.  Valproic acid is an anticonvulsant that is generally reserved as an alternative treatment.

SOURCES:

1. NINDS Chorea Information Page. Available at: http://www.ninds.nih.gov/disorders/chorea/chorea.htm. Accessed June 24, 2012.
2. Chorea. Available at: http://www.movementdisorders.org/disorders/chorea.php. Accessed June 24, 2012.
3. Bonelli RM, Beal MF. Huntington’s disease. Handb Clin Neurol. 2012;106:507—26.
4. Pidgeon C, Rickards H. The pathophysiology and pharmacological treatment of Huntington disease. Behav Neurol. 2012 Epub ahead of print[NS1] .
5. Killoran A, Biglan KM. Therapeutics in Huntington’s Disease. Curr Treat Options Neurol. 2012. [Epub ahead of print].
6. Scott LJ. Tetrabenazine: for chorea associated with Huntington’s disease. CNS Drugs. 2011;25(12):1073—85.
7. NINDS Sydenham Chorea Information Page. Available at: http://www.ninds.nih.gov/disorders/sydenham/sydenham.htm. Accessed June 24, 2012.
8. Cunningham MW. Streptococcus and rheumatic fever. Curr Opin Rheumatol. 2012;24(4):408—16.
9. Rheumatic fever. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004388/. Accessed June 24, 2012.
10. Rheumatic fever. Available at: http://www.uptodate.com/contents/sydenham-chorea. Accessed June 24, 2012.
11. Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis. Available at: http://circ.ahajournals.org/content/119/11/1541.full. Accessed June 24, 2012.
12. Peña J, Mora E, Cardozo J et al. Comparison of the efficacy of carbamazepine, haloperidol and valproic acid in the treatment of children with Sydenham’s chorea: clinical follow-up of 18 patients. Arq Neuropsiquiatr. 2002;60(2-B):374—7.
13. Walker KG, Wilmshurst JM. An update on the treatment of Sydenham’s chorea: the evidence for established and evolving interventions. Ther Adv Neurol Disord. 2010 Sep;3(5):301—9.