Review
On defining Sydenham’s chorea: where do we draw the line?

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Abstract

Sydenham’s chorea (SC) is a major manifestation of rheumatic fever characterized by an array of neuropsychiatric symptoms that vary in severity, timing, and character. Some of the same symptoms are seen in Tourette’s syndrome and childhood-onset obsessive–compulsive disorder. Genetic vulnerability appears to play a role in all three conditions. The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) has been introduced to describe a putative subset of obsessive–compulsive disorder and Tourette’s syndrome that bears some resemblance to Sydenham’s chorea. This article discusses whether PANDAS should be subsumed under Sydenham’s chorea, thus expanding the diagnostic boundaries of Sydenham’s chorea to include primarily neuropsychiatric presentations now classified as cases of obsessive–compulsive disorder or Tourette’s syndrome. We conclude that PANDAS is a useful construct, but that it would be premature to view it as a subset of Sydenham’s chorea—whether defined narrowly or broadly.

Introduction

Bouteille’s quote about Sydenham’s chorea (SC) in Bouteille 1810 still largely applies to this illness today: “Every thing about this disease is unusual, its name is ridiculous, its symptoms are peculiar, its character is equivocal, its cause is unknown, its treatment is problematic.” It is known that SC is a major manifestation of rheumatic fever (RF). Sydenham’s chorea is thought to occur when antibodies directed against group A beta hemolytic streptococcus (GABHS) cross-react with epitopes on neurons of the basal ganglia (and other brain areas) causing motoric and behavioral disturbances (Husby et al 1976). Sydenham’s chorea has been described extensively in historic scientific literature, much of these descriptions predating laboratory tests for streptococcal exposure. Interest in this illness has recently been renewed with the proposal that some cases of childhood-onset obsessive–compulsive disorder (OCD) may be related to an infection-triggered autoimmune process similar to that of SC (Swedo 1994). Swedo has coined the term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) to describe cases of childhood-onset OCD that resemble SC with respect to acute onset following a GABHS infection, accompanying neurologic signs, and an episodic course (Swedo 1994). Clinically, the possibility of an infection-induced neuropsychiatric disorder has raised concern among clinicians and researchers as to appropriate diagnostic and treatment options for this group of young patients.

Section snippets

Rheumatic fever

Starting in 1987, an unexpected resurgence of RF was reported in geographically diverse parts of the United States, including Utah and Pennsylvania (Ayoub 1992). Recent observations suggest that the strains of GABHS associated with the resurgence of RF in this country appear less likely to cause symptomatic pharyngitis—thus, easily escaping detection and appropriate treatment—but are more virulent with respect to the autoimmune complications of those infections, particularly SC.

Only 2–3%

Sydenham’s chorea

Thomas Sydenham originally described the childhood-onset chorea later classified as rheumatic chorea in 1686 (Sydenham 1848). The relationship between SC and RF was first suggested in 1780, although this association was not widely accepted until much later. During the 1800s there was much debate as to which type of abnormal movements were to be labeled SC versus other movement disorders such as Tourette’s syndrome (TS; Kushner and Kiessling 1996). In 1931, Taranta and Stollerman delineated the

SC pathology

Available postmortem data (Colony and Malamud 1956) and recent neuroimaging studies in patients with SC are consistent with involvement of basal ganglia and cortical structures Giedd et al 1995, Kienzle et al 1991. In a report on two patients with SC, galadinium-enhanced magnetic resonance imaging (MRI) scans were suggestive of disruptions in the blood–brain barrier (Kienzle et al 1991). Magnetic resonance imaging scans performed both during and after acute episodes of SC within the same

PANDAS

The criteria for PANDAS developed by Swedo include 1) presence of OCD and/or tic disorder, 2) pediatric onset (generally prepubertal), 3) episodic course of symptom severity characterized by abrupt onset or dramatic symptom exacerbation interspersed with episodes of partial or complete remission, 4) temporal association with GABHS infection, and 5) association with neurologic abnormalities during symptom exacerbations (e.g., “choreiform” movements, tics and hyperactivity; Swedo et al 1998).

Relationship between SC and PANDAS

A central question before us is should the definition of SC be broadened to include PANDAS (i.e., some forms of TS and childhood-onset OCD)? In other words, is it possible for some instances of SC to have a predominantly psychiatric presentation (as in OCD) or atypical presentation of motor symptoms (as in TS)? We discuss critical issues pertaining to the PANDAS–SC interface, indicating what additional evidence is needed to elucidate the nature of the interrelationship (Table 1).

Acknowledgements

This work was supported in part by National Institute of Mental Health Grant No. RO1-MH56597 (WKG), the University of Florida Brain Institute, and the State of Florida.

The authors thank Micheal S. Okun, Nathan A. Shapira, and Mark H. Lewis for their critical review of the manuscript.

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