Medical Condition

Sydenham chorea (SC) is a key model for understanding post-infectious autoimmune neurological disorders, with important implications for both movement and psychiatric symptoms such as OCD. There are strong historical and mechanistic links between Group A Streptococcal infections, basal ganglia inflammation, and autoimmune interference with dopamine signaling—insights that may inform broader strategies for diagnosing and treating similar neuropsychiatric conditions.

Sydenham chorea (SC), historically known as St. Vitus’ Dance, is a neurological disorder characterized by continuous, irregular, and unpredictable involuntary movements, primarily affecting the face, hands, and feet. These movements are non-repetitive, non-rhythmic, and lack a specific pattern, often described as a “dance-like” flow. SC is easily distinguished from tic disorders and seldom confused. One hallmark feature of SC is motor impersistence, where patients struggle to sustain muscle contractions, leading to signs such as a fluctuating “milkmaid’s grip.”

Prior to antibiotics, population-wide studies placed the annual incidence of ARF at 100-200 cases per 100,000 people per year with high variability by age and geography. (Acheson, 1965) SC represented approximately 20-40% of those cases (Cardoso 2010). Exposure to strep was highest in school-aged children where nearly all children are exposed to Group A Streptococcus (GAS). However,not all strains of GAS are linked to ARF or SC.

A landmark paper in 1950 demonstrated that ARF (and SC) became rare when children were treated with antibiotics (Denny et al., 1950). These findings, along with subsequent research, reinforce three key points: (1) there is a genetic predisposition, (2) only certain GAS strains trigger ARF or SC, and (3) ARF and SC arise primarily when infections are left untreated.

Today, the incidence rate of SC in the US is ~1 in 200,000 (or about 200 cases per year), reflecting a dramatic reduction in ARF/SC cases due to the introduction of antibiotics. The residual cases are difficult to pin down as often the strep infection is long gone by the time of the movement disorder and there may be no record of prior pharyngitis.

Neuropsychiatric manifestations are frequently observed in SC and can precede, coincide with, or follow motor symptoms. Common features include emotional lability, irritability, anxiety, depression, and attentional deficits. These symptoms are thought to arise from inflammation or dysfunction in corticostriatal circuits. In some cases, neuropsychiatric disturbances may persist even after resolution of choreiform movements, suggesting a lasting impact on neural circuitry.

Two interrelated theories have emerged. One centers on inflammation of the basal ganglia (particularly in the caudate and thalamus) (Dale 2003), and the other on dopamine dysregulation caused by autoantibodies found in serum and cerebrospinal fluid (Kirvan 2006). These autoantibodies have been shown to target D1 and D2 dopamine receptors, and molecular studies indicate elevated CAM Kinase II activation and interaction with lysoganglioside receptors, supporting an autoimmune mechanism. The connection between basal ganglia inflammation and antibody action suggests a compounding effect on motor and psychiatric symptoms. The blood-brain barrier may mediate the delay between streptococcal infection, antibody production, and symptom onset.

SC is often described as a self-limiting disorder because the movement symptoms typically resolve within months. However, psychiatric symptoms, including OCD and emotional dysregulation, frequently persist long after the chorea has resolved, suggesting ongoing neuroinflammatory or autoimmune activity. Treatment primarily involves antibiotics (both to treat an initial infection and as prophylaxis to minimize the chance of recurrence in susceptible individuals).

Anecdotal case studies and cohort studies have indicated improvement of post-infection OCD symptoms with immunotherapies (such as steroids and IVIG), with two recent clinical trials showing >60% reduction in symptoms, though these trials were small.

Despite over two centuries of clinical observation linking SC to untreated streptococcal infections, the precise mechanisms underlying its pathogenesis remain incompletely understood.

This underscores the importance of ongoing research into post-infectious autoimmune neuropsychiatric disorders. While SC has long been accepted as an immune-mediated condition, other post-streptococcal syndromes, such as PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections), has some disagreement despite being better characterized in some respects. The persistence of OCD symptoms in SC patients further reinforces the potential link between infections and neuropsychiatric dysfunction, warranting continued investigation and refinement of therapeutic approaches.

1. Osler, W. (1894). On chorea and choreiform affections. London: H.K. Lewis.
2. Cardoso, F. (2011). Sydenham’s chorea. Handbook of Clinical Neurology, 100, 221–229.
3. Asbahr, F. R., et al. (1994). Obsessive-compulsive symptoms in Sydenham’s chorea. American Journal of Psychiatry, 151(5), 627–630.
4. Swedo, S. E., et al. (1989). High prevalence of obsessive-compulsive symptoms in patients with Sydenham’s chorea. American Journal of Psychiatry, 146(2), 246–249.
5. Denny, F. W., Wannamaker, L. W., Brink, W. R., Rammelkamp, C. H., Jr., & Custer, E. A. (1950). Prevention of rheumatic fever: Treatment of the preceding streptococcic infection. JAMA, 254(4), 534–537. https://doi.org/10.1001/jama.254.4.534
6. Garvey, M. A., et al. (2005). Treatment of Sydenham’s chorea with intravenous immunoglobulin, plasma exchange, or prednisone. Journal of Child Neurology, 20(5), 424–429.
7. Cunningham, M. W. (2006). Molecular mimicry, autoimmunity, and infection: The cross-reactive antigens of group A streptococci and their sequelae. Microbiology Spectrum, 7(4).
8. Paz, J. A., et al. (2006). Randomized double-blind study with prednisone in Sydenham’s chorea. Pediatric Neurology, 34(4), 264–269.
9. Barash, J., et al. (2005). Corticosteroids for the treatment of Sydenham’s chorea. Pediatric Neurology, 32(3), 205–207.
10. World Health Organization. (2010). Rheumatic fever and rheumatic heart disease: Report of a WHO expert consultation. Geneva: WHO.
11. Dale, R. C. (2003). Autoimmunity and the basal ganglia: New insights into old diseases. QJM: An International Journal of Medicine, 96(3), 183–191. https://doi.org/10.1093/qjmed/hcg026