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  • Updated 06.22.2023
  • Released 03.24.1994
  • Expires For CME 06.22.2026

Sydenham chorea

Introduction

Overview

Sydenham chorea is the prototype of chorea resulting from immune mechanisms. Although its incidence has steadily declined in the last decades, it remains the most common cause of acute chorea in childhood worldwide and is still an endemic condition in developing areas of the world. There is still interest related to the possibility that a similar pathogenic mechanism may be responsible for a subset of patients with tics and other movement disorders as well as behavioral abnormalities. The author reviews the clinical features, pathogenesis, and management of this condition.

Key points

• Sydenham chorea is the most common cause of acute chorea in children worldwide although its incidence is declining.

• Vascular chorea is the most important differential diagnosis of Sydenham chorea.

• Evidence suggests that Sydenham chorea results from Streptococcus-induced antibodies that cross-react with central nervous system antigens.

• Neuropsychiatric symptoms, such as obsessions, compulsions, hyperactivity, attention disorder, and depression, are often present in patients with Sydenham chorea.

• Genetic conditions such as mutations of ACDY5, NKX2-1, PDE10A, and PDE2A may mimic Sydenham chorea.

Historical note and terminology

The term chorea (from the Greek word for “dance”) had been used since the Middle Ages to describe both organic and psychological disorders of motor control. Epidemics of a psychosomatic "dancing mania" (or "choreomania” from choros [dance] and mania [madness]) erupted in central Europe coincident with the Black Death, with St. Vitus among the various saints called onto intercede, leading to the terms chorea Sancti Viti and Saint Vitus’ dance (114; 76; 90; 118).

For many years, chorea was the term applied to any hyperkinetic syndrome (90; 118). The itinerant German-Swiss physician, alchemist, astrologer, and philosopher Paracelsus (1493-1541; born Philippus Aureolus Theophrastus Bombastus von Hohenheim) divided chorea into three types: (1) chorea imaginativa (imagination), (2) chorea lasciva (sexual desires), and (3) chorea naturalis (organic disorders) (90; 118).

Swiss physician, alchemist, lay theologian, and philosopher Paracelsus (Theophrastus von Hohenheim; d. 1541)

(Source: Guerini V. A history of dentistry from the most ancient times until the end of the eighteenth century. Philadelphia & New York: Lea & Febiger, 1909.)

Historical reviews are available concerning the various choreic disorders (99; 116; 117; 118; 90; 121; 147) and the “dancing mania” (16; 114; 07; 89; 118; 120; 62).

English physician Thomas Sydenham (1624-1689), “The English Hippocrates," achieved fame during his own lifetime because he emphasized bedside observation, provided vivid clinical descriptions of diseases and their natural history, and adopted a moderate approach to treatment (179; 91; 118; 119).

In 1686, Sydenham confusingly applied the term “Saint Vitus’ dance” to his classic description of childhood chorea. After Sydenham, “Saint Vitus dance” could mean either organic chorea (Sydenham chorea, chorea minor, or chorea anglorum) or psychogenic chorea (chorea major or chorea germanorum) (76; 91; 118; 119). Nevertheless, in 1686 Sydenham did provide a clear and succinct description of some of the clinical features of postinfectious chorea:

There is a kind of convulsion, which attacks boys and girls from the tenth year to the time of puberty. It first shows itself by limping or unsteadiness in one of the legs, which the patient drags. The hand cannot be steady for a moment. It passes from one position to another by a convulsive movement, however much the patient may strive to the contrary. Before he can raise a cup to his lips, he makes as many gesticulations as a mountebank; because he does not move it in a straight line, but has his hand drawn aside by spasms, until by some good fortune he brings it at last to his mouth. He then gulps it off at once, so suddenly and so greedily as to look as if he were trying to amuse the lookers-on (183).

Few illustrations exist of Syndenham chorea before the late 19th century.

La Danse de Saint-Guy (boys with Sydenham chorea)

(Source: La Médecine Illustrée 1880 [December 10.] Public domain. Edited by Dr. Douglas J Lanska.)

Sydenham's description of the irregular nature of choreic movements in children was well captured when sequential photographic images became possible.

Sequential photographs of a girl with Sydenham's chorea ("chorea minor") who was told to "stand still"

Photographs by German internist Friedrich Pineles (1868-1936) at the Medical Clinic in Heidelberg, c 1915. (Source: Pineles F. Hyperkinetic diseases: Infectious chorea. In: Burr CW, editor. Text-Book on Nervous Diseases. Philad...

As early as the 1860s, British neurologists John Hughlings Jackson (1835-1911) and (later Sir) William Henry Broadbent (1835-1907) implicated striatal dysfunction in childhood chorea, a fortuitous conclusion based largely on the longstanding but erroneous assumption that the striatum was the seat of movement. Jackson concluded, "It has long seemed to me that embolism ... of parts in the region of the corpus striatum gives a most satisfactory explanation of the physiology and pathology of cases of chorea" (103). Broadbent agreed that chorea was typically caused by embolism but claimed that some cases may be caused by "a morbid condition of the blood," resulting in a "delirium of the sensori-motor ganglia" (29).

A review of clinical notes of inpatients seen by Sir William Gowers at the National Hospital of London from 1878 to 1911 showed that almost all chorea cases were caused by (or at least attributed to) Sydenham chorea (199).

British Neurologist Sir William Gowers

(Source: Courtesy of the U.S. National Library of Medicine. Public domain.)

In the nineteenth century, some observers recognized a relationship between childhood chorea, rheumatic arthritis, and valvular heart disease. In 1887, Canadian internist William Osler (1849-1919) studied 410 cases of Sydenham chorea and rheumatic heart disease treated at the Infirmary for Nervous Diseases since 1876. In Osler's On Chorea and Choreiform Affections (1887), based in large measure on his studies in the late 1880s in Philadelphia, he provided a new classification of chorea: (1) chorea minor (Sydenham); (2) chorea major (hysterical); (3) pseudo-chorea (eg, tics); and (4) secondary or symptomatic (eg, post-hemiplegic and Huntington) (121). He made the fundamental deduction that Sydenham chorea is an “infectious disorder,” frequently associated with endocarditis, particularly affecting the mitral valve.

Canadian internist William Osler (1849-1919) in 1890

Osler was Professor of Clinical Medicine at the University of Pennsylvania from 1884 to 1888 before becoming the first Chairperson and Physician-in-Chief of the Johns Hopkins Department of Medicine in Baltimore. (Source: Collec...

In 1899, a diplococcus was isolated from the cerebrospinal and pericardial fluids of a child who died with chorea and carditis, suggesting that these disorders were bacterial infection complications. From 1901 to 1903, Frederic John Poynton (1869-1943) and Alexander Paine produced irregular movements, arthritis, and carditis in rabbits injected intravenously with diplococci from affected patients (158; 159; 160; 161).

Development of the antistreptolysin O titer as a marker of antecedent streptococcal pharyngitis in the early 1930s made it possible to demonstrate that all manifestations of rheumatic fever, including Sydenham chorea, which is a sequel to group A streptococcal pharyngitis. The causal relationship of Sydenham chorea with streptococcal infection was firmly established by the mid-20th century (184).

Acute rheumatic fever was quite common in the 19th and early 20th centuries. My own grandmother died in her 20s (in 1939) from cardiac complications of rheumatic fever sustained as a teenager, leaving my mother and her three siblings to be orphans.

Persistent Sydenham chorea has been suggested for the neurologic and medical illness of Austro-Bohemian Romantic composer Gustav Mahler (1860-1911) (45).

Gustav Mahler in the foyer of Vienna's Opera House

(Source: Specht R. Gustav Mahler. Berlin and Leipzig: Schuster and Loeffler, 1913, plate 12. Public domain.)

Mahler had a movement disorder with facial dyskinesia and a gait disorder consistent with chorea. As a conductor, Mahler was notorious for obsessive attention to details of staging and musical production. He was diagnosed with a valvulopathy in 1907 and died of subacute bacterial endocarditis in 1911. Cardoso and Lee suggested that the composer's valvulopathy, obsessive-compulsive disorder, and persistent chorea resulted from rheumatic fever in childhood with carditis and Sydenham chorea (45).

By the late 1930s, sulfonamides were demonstrated to prevent recurrences of rheumatic fever, and in the 1940s, prompt administration of penicillin for group A streptococcal pharyngitis was shown to prevent primary (initial) attacks of rheumatic fever. Antibiotic prophylaxis for its prevention led to a marked drop in the incidence of rheumatic fever and its manifestations, including Sydenham chorea. In particular, the incidence of Sydenham chorea dropped drastically in North America and Western Europe after World War II, in part due to the increasing availability of antibiotics and the ability to diagnose and treat streptococcal infections early (144). Nevertheless, Sydenham chorea and acute rheumatic fever have persisted as important health problems in developing countries. (The cases of Sydenham chorea that I have observed were at hospitals in India and Jamaica in the 1980s and in Ecuador in the 2010s). Since the 1990s, Sydenham chorea has been recognized with increasing frequency in Brazil, Australia, and the United States, and there have more recent outbreaks in Central Europe (08; 167; 145; 111).

In the early twentieth century, the embolic theory was abandoned, and bacterial meningoencephalitis was proposed as an etiological explanation, but bacteria were not consistently cultured from brain tissue or cerebrospinal fluid of affected cases, and the process by which infection would selectively target the corpus striatum was never satisfactorily explained. Sydenham chorea is now understood to result from an antibody cross-reaction to basal ganglia epitopes following infection with group A β-hemolytic streptococci.

Because of the postinfectious immunological basis for Sydenham chorea, multiple studies have attempted to relate other movement disorders (eg, tics) and childhood behavioral abnormalities with Streptococcus-induced autoantibodies targeted at basal ganglia neurons (167; 35; 46; 50), albeit without convincing success.