Movement Disorders
Hemifacial spasm
Oct. 24, 2024
Worddefinition
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Sydenham chorea …
- Updated 05.20.2024
- Released 03.24.1994
- Expires For CME 05.20.2027
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”) was 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 (116; 76; 91; 120).
For many years, chorea was the term applied to any hyperkinetic syndrome (91; 120). 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) (91; 120).
Historical reviews are available concerning the various choreic disorders (100; 118; 119; 120; 91; 123; 149) and the “dancing mania” (16; 116; 07; 90; 120; 122; 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 (181; 92; 120; 121).
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; 92; 120; 121). 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 (185). |
Few illustrations exist of Syndenham chorea before the late 19th century.
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" (105). 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 (202).
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) (123). He made the fundamental deduction that Sydenham chorea is an “infectious disorder” frequently associated with endocarditis, particularly affecting the mitral valve.
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 (160; 161; 162; 163).
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 (186).
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).
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; 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 (146). 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; 169; 147; 113).
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 (169; 35; 46; 50), albeit without convincing success.
Clinical manifestations
Presentation and course
Streptococcal pharyngitis. Acute rheumatic fever (and its major clinical manifestations of carditis, arthritis, and Sydenham chorea) are the result of an autoimmune process triggered by streptococcal pharyngitis (or scarlet fever) with Group A beta-hemolytic Streptococci (GAS). Even before color photography was available, artistic renditions of streptococcal pharyngitis and the microscopic appearance of the responsible organism were fairly accurate in medical textbooks.
These early artistic depictions of streptococcal pharyngitis from over a century ago compare favorably to modern color photography.
Common features include erythema and edema of the oropharynx, a typical tonsillar exudate, and petechiae on the soft palate.
Group A Streptococcus (group A strep, Streptococcus pyogenes) can cause both noninvasive and invasive disease as well as nonsuppurative sequelae. The wide range of clinical disorders caused by Streptococcus pyogenes includes, in addition to acute rheumatic fever, pharyngitis (Strep throat), cellulitis, impetigo, type II necrotizing fasciitis, scarlet fever, streptococcal toxic shock syndrome, and post-streptococcal glomerulonephritis.
Streptococcus pyogenes is a species of Gram-positive, aerotolerant bacteria in the genus Streptococcus. These bacteria are extracellular and are comprised of nonmotile and non-sporing cocci (round cells) that tend to link in chains.
-
Group of Gram-positive, Streptococcus pyogenes (group A Streptococcus) bacteria
The three-dimensional, computer-generated artistic recreation was based on scanning electron microscopic (SEM) imagery. (Courtesy of the Centers for Disease Control and Prevention Public Health Image Library. Image 22884. Image...
Streptococcus pyogenes is the predominant streptococcal species harboring the Lancefield group A antigen and is often called Group A Streptococcus (GAS). Group A streptococci, when grown on blood agar, typically produce small (2 to 3 mm) zones of beta-hemolysis, a complete destruction of red blood cells.
Culture of Streptococcus pyogenes (Group A beta-hemolytic Streptococcus) bacteria on soy agar containing 5% defibrinated sheep's blood
Petri dish with Streptococcus pyogenes-inoculated trypticase soy agar containing 5% defibrinated sheep's blood that had been streaked and stabbed with a wire loop, which had been dipped into primary culture medium. The...
Because of this feature, the name Group A beta-hemolytic Streptococcus (GABHS) is also used. The characteristic color changes, including a light-colored halo surrounding each colony in which the red blood cells in the blood agar medium had been destroyed or hemolyzed, indicate that the bacteria are indeed beta-hemolytic in nature. In contrast, when grown on blood agar, alpha-hemolytic organisms are surrounded by a hazy, indistinct zone of partial red blood cell hemolysis.
Jones criteria. The entire clinical spectrum of acute rheumatic fever (from tonsillitis to carditis) was first described by English pediatrician William Butler Cheadle (1836-1910) in "Harveian lectures on the various manifestations of the rheumatic state as exemplified in childhood and early life" in 1889 (55).
It was not until World War II that criteria rheumatic fever diagnosis were established by American cardiologist Thomas Duckett Jones (1899-1954) (108). During World War II, rheumatic fever was one of the major causes of lost man-days due to sickness in the Navy and Marine Corps (165), so the disorder achieved national and international importance.
Rheumatic fever diagnosis continues to be based on the Jones criteria, developed in 1944 and then revised twice by the American Heart Association in 1992 and 2015 (108; 179; 86). The Jones criteria divide clinical manifestations into major and minor categories and then set a minimum threshold for features that must be present for a diagnosis of rheumatic fever. The last revision of the Jones criteria supplements the major criteria with echocardiographic examination, introduces a concept of subclinical carditis, and specifies low-, medium-, and high-risk populations.
Although qualifying features now differ somewhat in low-risk and moderate-to-high-risk populations, the conditions specified as major manifestations have not changed: carditis, arthritis, (Sydenham) chorea, erythema marginatum, and subcutaneous nodules. The American Heart Association recommends that all patients with suspected rheumatic fever have Doppler echocardiography after the Jones criteria have been verified, even if no clinical signs of carditis are present.
In an investigation from New Zealand, before the 2015 revision of the criteria, the authors employed slightly modified Jones criteria, allowing as major criteria subclinical carditis (ie, solely based on echocardiography), carditis, and monoarthritis if the patient is on anti-inflammatory drugs; this led to a 16% increase of the number of diagnoses of acute rheumatic fever (211). These issues were, in large measure, incorporated into the 2015 revision.
One feature of the Jones criteria, even in the most recent 2015 incarnation, is the absence of any criteria for clinical or laboratory evidence of antecedent streptococcal pharyngitis (acute pustular pharyngitis, rapid antigen testing or culture-positive throat culture for Group A beta-hemolytic Streptococci (GAS), antistreptolysin O antibody titers).
Carditis. By the end of the 19th century, Osler, based on his clinicopathologic studies in Philadelphia in the late 1880s, made the fundamental deduction that Sydenham chorea is an “infectious disorder,” frequently associated with endocarditis, particularly affecting the mitral valve (123); Cheadle provided an overall synthesis of the most important clinical features of acute rheumatic fever, including the carditis (55).
Section of aortic valve in ulcerative endocarditis in a child with acute rheumatic fever
Proliferation and cell infiltration of subendothelial fibrous tissue, resembling the histologic features of subcutaneous nodules. (Source: Cheadle WB. The acute rheumatism of childhood. In: Albutt TC, editor. A System of Medici...
Indeed, Cheadle illustrated a photomicrograph of a section of the aortic valve from a child with ulcerative endocarditis due to acute rheumatic fever; this showed proliferation and cell infiltration of the subendothelial fibrous tissue, which he noted resembled the histologic features of subcutaneous nodules. But as Osler had recognized, the cardiac valvulopathy most commonly affected the mitral valve, sometimes in conjunction with involvement of other valves, findings that are generally evident on gross examination.
Experimental studies attempting to reproduce carditis in an animal model led to greater scrutiny of the pathologic features of human cases (160; 161; 162; 163). Sections of vegetations in simple rheumatic endocarditis often showed much necrotic tissue but no diplococci, sometimes with evidence of reparative changes, but in other cases, the necrotic tissue contained diplococci.
Sections through affected valves could demonstrate separate identifiable zones of swollen connective tissue of the valve, cellular exudation, and necrosis in the vegetation.
Sections through the left ventricle showed a range of findings, including fatty change in the cardiac muscle fibers, cellular exudates, and, in more chronic cases, fibrosis.
-
Section through the left ventricle of a case of rheumatic carditis to show fatty change in the muscular fibers in the neighborhood of a capillary
(Source: Poynton FJ. Clinical lectures on rheumatic fever. II. Clinical evidences of myocardial damage in rheumatic fever. Int Clin 1903;3[13th series]:226-41.)
-
Section through the left ventricle of a case of rheumatic carditis to show cellular exudation in the interstitial tissues
(A) Cellular exudation. (Source: Poynton FJ. Clinical lectures on rheumatic fever. II. Clinical evidences of myocardial damage in rheumatic fever. Int Clin 1903;3[13th series]:226-41.)
With rheumatic pericarditis, there were identifiable zones of swollen connective tissue, cellular exudation, and necrosis with fibrino-cellular exudation.
Arthritis. Symptoms of acute rheumatic fever can include arthritis, which is usually symmetrical and involves large joints (eg, knees, ankles, elbows, and wrists). Arthritis occurs in approximately 75% of first attacks of acute rheumatic fever, but the likelihood increases with the age of the patient. Arthritis is a major manifestation of acute rheumatic fever in 92% of adults meeting the Jones criteria (in a prior incarnation of the criteria) (208). The arthritis is typically polyarticular, but monoarthritis may serve as sufficient to meet the criteria for a major manifestation according to the 2015 revision of the Jones criteria. Histologic sections through affected joint capsules may show separate identifiable zones of swollen connective tissue, cellular exudate, and necrosis and plastic exudation, which may take the form of very irregular granulations.
Tenosynovitis is common in adults and may suggest a diagnosis of disseminated gonococcal disease (208). The polyarthritis evolves over weeks but overlaps across individual joints, so it is not strictly migratory (208). Arthritis due to acute rheumatic fever generally subsides within 4 to 6 weeks without residual damage (208). If the arthritis does not resolve over this period, an alternate diagnosis should be considered.
Sydenham chorea. Sydenham chorea is a major manifestation of rheumatic fever. Sixty percent to 80% of patients display cardiac involvement, particularly mitral valve dysfunction, in Sydenham chorea, whereas the association with arthritis is less common, seen in 30% of patients; however, in approximately 20% of patients, chorea is the sole finding (51; 78). A prospective follow-up of patients with Sydenham chorea with and without cardiac involvement in the first episode of chorea suggests that the heart remains spared in those without lesions at the onset of the rheumatic fever (154). Sydenham chorea may be associated with other autoimmune disorders such as Takayasu arteritis (203; 12).
Please see further discussion of the clinical features of Sydenham chorea in a separate section below. This material was separated because its inclusion here would have overwhelmed the discussion of the Jones criteria and the various components.
Erythema marginatum. Although a "major" manifestation of rheumatic fever, erythema marginatum is uncommonly reported in some modern series, so it cannot be considered a sensitive sign of the disorder, only one that is fairly specific if present after streptococcal pharyngitis, especially when other manifestations of rheumatic fever are present. The very low frequency reported in some modern series of rheumatic fever may reflect limitations of observation and reporting.
Erythema marginatum is an evanescent, serpiginous, non-pruritic rash of the arm, generally on the trunk and extremities and typically more prominent in a warm bath.
Subcutaneous nodules. Although a "major" manifestation of rheumatic fever, subcutaneous nodules are uncommonly reported in some modern series, so they cannot be considered a sensitive sign of the disorder, only one that is fairly specific if present after streptococcal pharyngitis, especially when other manifestations of rheumatic fever are present. The very low frequency reported in some modern series of rheumatic fever may reflect limitations of observation and reporting.
It has often been assumed that subcutaneous nodules are rare, evanescent, and invariably associated with carditis. In a prospective study of acute rheumatic fever, 42 cases (13%) with subcutaneous nodules occurred among a series of 336 consecutive cases (25). Other major criteria associated with subcutaneous nodules were carditis in 90%, arthritis in 79%, and chorea in 5% (25). The average number of nodules found in the group in which nodules were present was 18 (range four to 49); 31% had less than 10 nodules, and 12% had only four to five nodules (25). Subcutaneous nodules disappeared within 4 weeks in 69%, within 5 to 8 weeks in 19%, and within 9 to 12 weeks in 7% (25). In two cases (5%), multiple nodules were observed 12 weeks later when all other evidence of activity had disappeared (25).
Nineteenth-century artistic renderings graphically show the appearance and extent of these subcutaneous or "rheumatoid" nodules.
-
Acute rheumatic fever, grave form, with numerous large subcutaneous nodules, fatal
Boy, aged 4 years and 3 months. Clinical features included rheumatic nodules, erythema marginatum, chorea, a "double mitral murmur," and arthritis. From the Hospital for Sick Children, Great Ormond St., London. Under the care o...
The histology of these lesions was recorded from the late 19th century as showing active proliferation and infiltration of fibrous tissues.
In most modern reports, such lesions are present in only a minority of cases, are few in number when present, and are often somewhat subtle (101).
Subcutaneous nodules on the left anterior shoulder and chest with faint overlying erythema in an 18-year-old man with Sydenham chorea
(Source: Heard MA, Green MC, Royer M. Acute rheumatic fever: a review of essential cutaneous and histological findings. Cureus 2021;13[1]:e12577. Creative Commons Attribution [CC-BY 4.0] License, https://creativecommons.org/lic...
Histologically, these may show mixed acute and chronic, superficial and deep, perivascular lymphohistiocytic inflammation, extending into the subcutis.
-
Subcutaneous nodule with superficial and deep perivascular lymphohistiocytic inflammation, extending into the subcutis from an 18-year-old man with Sy...
Hematoxylin and eosin, 2x magnification. (Source: Heard MA, Green MC, Royer M. Acute rheumatic fever: a review of essential cutaneous and histological findings. Cureus 2021;13[1]:e12577. Creative Commons Attribution [CC-BY 4.0]...
-
Subcutaneous nodule with subcutaneous mixed acute and chronic inflammation from an 18-year-old man with Sydenham chorea
Hematoxylin and eosin, 10x magnification. (Source: Heard MA, Green MC, Royer M. Acute rheumatic fever: a review of essential cutaneous and histological findings. Cureus 2021;13[1]:e12577. Creative Commons Attribution [CC-BY 4.0...
There were poorly formed granulomas with central coagulative necrosis and peripheral acute inflammation with conspicuous leukocytoclastic vasculitis (101).
Poorly formed perieccrine granuloma with peripheral leukocytoclasis from an 18-year-old man with Sydenham chorea
Hematoxylin and eosin, 10x magnification. (Source: Heard MA, Green MC, Royer M. Acute rheumatic fever: a review of essential cutaneous and histological findings. Cureus 2021;13[1]:e12577. Creative Commons Attribution [CC-BY 4.0...
Subcutaneous nodules are found in approximately one third of patients with rheumatic fever (markedly lower rates in some series may reflect the adequacy of assessment). Typical subcutaneous nodules are firm or hard, usually mobile (ie, not attached to overlying skin or underlying bony structures), and nontender. They may be solitary or multiple, may change in size over time, and may persist for months to years. The lesions are generally small (varying from millimeters to several centimeters in size) and have a tendency to occur over bony prominences such as knuckles, olecranon processes, and humoral epicondyles. The overlying skin may be erythematous. Histologically similar lesions may involve the pleura.
Rheumatoid nodules can also occur in rheumatoid arthritis and systemic lupus erythematosus, and the histologic appearance is identical.
Sydenham chorea. Sydenham chorea is the most common movement disorder associated with bacterial infection. The usual age at onset of Sydenham chorea is 8 to 9 years, but there are reports on patients who developed chorea during the third decade of life. In most series, there is a female preponderance (51; 174). Typically, patients develop this disease 4 to 8 weeks after an episode of group A beta-hemolytic streptococcal pharyngitis. It does not occur after streptococcal infection of the skin.
The chorea spreads rapidly and typically becomes generalized, but 20% of patients remain with hemichorea (146; 51). This movement disorder is characterized by random, brief contractions, particularly affecting distal muscles, and it produces an odd dance-like character to the movements of affected individuals. Patients display motor impersistence, which is particularly noticeable during tongue protrusion and ocular fixation. The muscle tone is usually decreased; in severe and rare cases, this is so pronounced that the patient may become bedridden (chorea paralytica). Some adult patients with a history of Sydenham chorea have residual bradykinesia, which may explain the proclivity of these patients to develop drug-induced parkinsonism when treated with neuroleptics (17).
Other neurologic and neuropsychiatric symptoms and signs.
Among a cohort of 48 subjects with acute rheumatic fever, subjects with Sydenham chorea experienced neuropsychiatric symptoms other than choreic movements at diagnosis significantly more frequently than did those without Sydenham chorea (152).
Rating scale. The Universidade Federal de Minas Gerais Sydenham Chorea Rating Scale was designed to provide a detailed quantitative description of the performance of activities of daily living, behavioral abnormalities, and motor function of patients with Sydenham chorea; it comprises 27 items, and each is scored from 0 (no symptom or sign) to 4 (severe disability or finding) (194).
Speech disorders. Various speech alterations have been observed in Sydenham chorea; during the 19th century, Gowers had already recognized that Sydenham chorea patients present with a “disinclination to speak.” Dysarthria is common, probably of extrapyramidal origin (146). A case-control study of patients described a pattern of decreased verbal fluency that reflected reduced phonetic but not semantic output (65). Sydenham chorea also affects prosody: speech as a decreased range of fundamental frequency, higher intensity, and decreased speed (48; 49; 150).
Attention and executive function. A subset of patients with a history of Sydenham chorea has persistent attention impairment and executive function (44; 19; 53).
Tics. Although there are reports of the common occurrence of tics in Sydenham chorea, it can be extremely difficult to distinguish simple motor tics (sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups) from chorea, and available studies are of low methodological quality (158). Even vocal tics, found in 70% or more of patients with Sydenham chorea in one study, may be difficult to diagnose in patients with hyperkinesias (137). Involuntary vocalizations may result from chorea or dystonia of the pharynx and larynx (106). Under these circumstances, the vocalization lacks the subjective feeling (premonitory urge or sensory tic) so characteristic of idiopathic tic disorders such as Tourette syndrome. Involuntary sounds present in occasional patients with Sydenham chorea probably result from choreic contractions of the upper respiratory tract muscles rather than true tics (191).
Behavior abnormalities (obsessive-compulsive behavior and attention deficit or hyperactivity). Various behavioral abnormalities have been associated with Sydenham chorea, but the data are generally of poor quality to establish a causal relationship (158). Osier mentioned the lability, irritability, and "bizarre behaviors" of the children with Sydenham chorea (123). Obsessive-compulsive behavior was reported to be common in patients with Sydenham chorea (06; 184; 136; 129; 21; 158), although patients with rheumatic fever without chorea also have more obsessive-compulsive behavior and attention deficit or hyperactivity than healthy controls (136; 129). Nevertheless, in a study of behavioral abnormalities in 50 healthy subjects, 50 patients with rheumatic fever without chorea, and 56 patients with Sydenham chorea, the authors found that obsessive-compulsive behavior, obsessive-compulsive disorder, and attention deficit and hyperactivity disorder were significantly more frequent in subjects with Sydenham chorea (19%, 23%, 30%) than in subjects with rheumatic fever without chorea (14%, 6%, 8%) (129). Attention deficit/hyperactivity was reportedly significantly more common in the persistent than acute chorea (50% vs. 16%) (129), but it is not always easy to differentiate restlessness associated with chorea from true hyperactivity of hyperactivity attention deficit disorder.
A study comparing the phenomenology of obsessions and compulsions in subjects with Sydenham chorea and subjects with tic disorders found that the symptoms observed in those with Sydenham chorea differed from those with tic disorders but were similar to those previously reported in pediatric patients with primary obsessive-compulsive disorder (05). The most frequent symptoms observed among subjects with comorbid Sydenham chorea and obsessive-compulsive symptoms were aggressive, contamination, and somatic obsessions and checking, cleaning, and repeating compulsions (05). Obsessive-compulsive behavior in subjects with Sydenham chorea produced little interference in the performance of activities of daily living (129).
There may be a genetic-environment interaction in the development of behavioral problems in Sydenham chorea; obsessive-compulsive spectrum disorders in rheumatic fever probands were associated with an increased risk of obsessive-compulsive spectrum disorders in first-degree relatives (103).
The finding that behavioral problems are common in patients with rheumatic fever and chorea contributed to the notion that Sydenham chorea is a model for childhood autoimmune neuropsychiatric disorders (183). A controversial hypothesis proposes that infection with group A beta-hemolytic streptococci may induce tics, obsessive-compulsive behavior, and other neuropsychiatric disturbances, purported causing "PANDAS" (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) (184). The following working diagnostic criteria for this condition have been proposed: (1) presence of obsessive-compulsive disorder or a tic disorder; (2) prepubertal symptom onset; (3) episodic course of symptom severity; (4) association with group A beta-hemolytic streptococci infections; and (5) association with neurologic abnormalities (184). The same study noted “significant psychiatric comorbidity”: emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, and oppositional behaviors (184). Nevertheless, most had a benign course with mild, if any, persistent motor or behavioral findings, which is better than those previously reported for childhood-onset obsessive-compulsive disorders (125).
A growing list of neurologic symptoms and signs are purportedly associated with streptococcus infection: dementia, dystonia, encephalitis lethargica-like syndrome, motor stereotypies, myoclonus, opsoclonus, parkinsonism, paroxysmal dyskinesia, restless leg syndrome, and tremor (38). There is no conclusive evidence that antibasal ganglia antibodies (ABGA) induced by streptococcus play a significant role in the pathogenesis of tic disorders, although ABGA seropositivity are increased fivefold in primary obsessive-compulsive disorders compared with controls (157). In fact, a population-based epidemiological survey performed in London failed to demonstrate a significant relationship between streptococcal infection and motor or behavioral syndromes (89; 171). A subsequent study similarly failed to find immunologic abnormalities that distinguish controls from patients with Tourette syndrome who meet criteriathe for PANDAS (142). However, a systematic review reiterates that no compelling evidence supports the association of auto-immune disorders with obsessive-compulsive and tic disorders (158).
Psychiatric disorders. Among 50 patients with Sydenham chorea, the most frequent psychiatric disorders observed were major depression (14%), generalized anxiety disorder (16%), social phobia (24%), and obsessive-compulsive disorder (24%) (141); the frequency of psychiatric disorders did not differ between cases with acute chorea in remission and persistent chorea, except for depressive disorders, which were more frequent in the latter. In another study of 32 cases of nonacute Sydenham chorea and age- and gender-matched asymptomatic controls, depressive and anxiety symptoms were not more common in cases than controls (188).
There are rare reports of trichotillomania (117) and psychosis during the acute phase of the illness in cases of Sydenham chorea (196).
Other. Many patients with active chorea have hypometric saccades, and some also show oculogyric crisis.
Migraine is reportedly more frequent in Sydenham chorea than normal controls (197).
The peripheral nervous system is not targeted in Sydenham chorea (38; 204).
Prognosis and complications
Persistent chorea. The older literature describes Sydenham chorea as a rather benign, self-limited condition that remits after several months (146). Although Sydenham chorea is typically self-limited, up to 50% of patients may have persistent chorea (145; 87; 52; 58; 98; 129; 201; 40; 42; 141; 200). Persistence of chorea is highly variable across studies, and some series report few or no cases with persistence of chorea (114; 115; 151). Some of this interstudy variability is due to design flaws in some studies (retrospective record review or inadequate follow-up), whereas studies with prospective follow-up of patients show that chorea persists at least 2 years, and sometimes permanently, in a substantial proportion of cases. Persistent Sydenham chorea is commonly reported in Brazilian cohorts (52; 129; 201; 141; 200; 42).
Recurrent chorea. Despite regular use of secondary prophylaxis, recurrences are frequently observed (130; 52; 114; 140; 177), although many of the recurrences are not associated with either streptococcal infections or anti-basal ganglia antibodies (98; 114; 206). A Turkish study reviewed the outcome of 90 patients with Sydenham chorea (95) and found that 16% experienced recurrence associated with persistence of the first episode for more than 1 year as well as irregular use of antibiotic prophylaxis.
Cardiac valvular disease. The most worrisome problem in patients with Sydenham chorea is the occurrence of cardiac valvular disease and other cardiac complications. In areas where rheumatic fever is endemic, 70% of cardiac surgeries are performed to treat its complications (35). A Slovenian study emphasized the association of Sydenham chorea with carditis, which was found in all patients with chorea (113). A similar outcome was found in a retrospective review of 375 Turkish patients seen at an academic center over 25 years (78).
Although rheumatic fever can affect any heart valve, it predominantly affects the left-sided cardiac valves, particularly of the mitral valve, causing regurgitation, stenosis, or mixed effects (168). The tricuspid valve and (seldomly) the pulmonary valve can be affected, but rarely (if ever) without mitral valve involvement. Similarly, aortic stenosis is rare in isolation. Consequently, neither right-sided valve lesions nor aortic stenosis are included in the criteria for echocardiographic diagnosis of rheumatic heart disease (168). The diagnostic criteria recognize four categories of rheumatic heart disease: Subcategory A--rheumatic heart disease of the mitral valve with regurgitation; Subcategory B--rheumatic heart disease of the mitral valve with stenosis; Subcategory C--rheumatic heart disease of the aortic valve; and Subcategory D--multivalvular rheumatic heart disease (168).
In a large retrospective case series at a tertiary care center in India over a period of 20 years, 10,000 cases were reported in two age groups: group I, aged 18 years or younger (n = 2,910), and group II, aged older than 18 years (n = 7,090) (57). Mitral regurgitation was the single most common lesion (34.6%) in group I, whereas the dominant lesion in group II was mitral stenosis (41.5%). Isolated aortic valve disease was seen in only 4.5% in group I and 2.8% in group II. Tricuspid stenosis was seen in only 0.5% overall, whereas rheumatic involvement of all four cardiac valves was documented in just four cases (0.04%).
Structural and functional consideration. The cardiac cycle involves a complex but stereotyped relationship between the heart sounds, muscle contractions, blood flow, and the position of the valves and apex.
There are two papillary muscles originating from the left ventricular walls. These muscles attach to the mitral valve leaflets via the chordae tendineae and functionally prevent regurgitation of ventricular blood by preventing prolapse or inversion of the valves during systole.
Mitral murmurs have their point of maximum intensity at the apex of the left ventricle, whereas aortic murmurs are heard best at the right second intercostal space.
Mitral murmurs may be systolic (mitral regurgitation), diastolic (mitral stenosis), or both (combined mitral stenosis and regurgitation).
Jugular venous pressure characteristically has three wave peaks.
The jugular venous pressure is usually assessed at the bedside by observing the right side of the patient's neck. Normal mean jugular venous pressure, determined as the vertical distance above the midpoint of the right atrium, is 6 to 8 cm H2O.
Mitral regurgitation (subcategory A). Mitral regurgitation is the most common manifestation of rheumatic heart disease in the young (168). In mitral regurgitation, blood flows bidirectionally during systole: retrograde into the left atrium through the abnormal mitral valve and anterograde into the aorta through the aortic valve.
Comparison of blood flow during systole in a normal heart and a heart with mitral regurgitation
Comparison of blood flow during systole in a normal heart (top) and a heart with mitral regurgitation (bottom). In the normal heart, the mitral valve is closed during systole, and blood flows through the open aortic valve into ...
The retrograde flow through the abnormal mitral valve during systole produces a decrescendo systolic murmur with somewhat variable characteristics depending on the severity of the regurgitation.
The murmur can be pansystolic. It can be heard over a wide area but is loudest over the apex on expiration, and it radiates to the back in an area around the point of the scapula.
The murmur is transmitted to the chest wall as an "apical thrill" (palpable murmur). The first heart sound (S1) is often soft or absent. As rheumatic mitral regurgitation changes from acute to chronic, the atrium dilates, potentially resulting in atrial fibrillation and systemic embolization, and the ventricle thickens and may dilate.
Chronic or acute left ventricular dilatation displaces the papillary muscles and increases leaflet tethering due to tension on the chordae tendineae as well as annular dilatation, resulting in aggravation of the mitral regurgitation (axiom: “mitral regurgitation begets mitral regurgitation”).
Mitral stenosis (subcategory B). Mitral stenosis is almost always caused by rheumatic valvular heart disease. Worldwide, rheumatic heart disease is still responsible for at least 95% of all mitral valve stenoses in individuals aged younger than 50 years (subcategory B), with only a small minority due to congenital mitral valve stenosis, a condition readily distinguishable by associated abnormal papillary muscle arrangements and the very high proportion with concomitant cardiac abnormalities (168). In older individuals, nonrheumatic mitral annular calcification should be considered in the differential diagnosis of mitral valve stenosis (168).
Normally, the mitral valve orifice is about 4 to 6 cm2 during diastole; mitral stenosis is likely to be symptomatic with any decrease in area below 2 to 2.5 cm2, at which point moderate exercise may result in exertional dyspnea. Mitral stenosis is considered severe with a valve area of less than 1 cm2. As the valve progressively narrows, left atrial pressure and the resting diastolic mitral valve gradient increase, causing transudation of fluid into the pulmonary interstitium and alveoli, with resultant dyspnea at rest or with minimal exertion.
Left atrial dilatation increases the risk of atrial fibrillation and subsequent systemic embolization. Hemoptysis may occur if bronchial veins rupture. As pulmonary arterial pressure increases, right ventricular dilation and tricuspid regurgitation may develop, leading to right heart failure.
Manifestations of mitral stenosis include the following: fatigue or weakness, congestive heart failure (dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and, if right-side heart failure develops, jugular venous distention, hepatomegaly, ascites, and edema), pulmonary hypertension, atrial fibrillation (and resultant systemic embolization), palpitations, chest pain, and hemoptysis. Fatigue and weakness increase with exercise and pregnancy.
The mitral valve opens in ventricular diastole (after closure of the aortic valve) when the pressure in the ventricle precipitously drops below left atrial pressure. In individuals with mitral stenosis, the pressure in the left atrium correlates with the severity of the mitral stenosis. As the severity of the mitral stenosis increases, the pressure in the left atrium increases, and the mitral valve opens earlier in ventricular diastole.
Comparison of blood flow during diastole in a normal heart and a heart with mitral stenosis
Comparison of blood flow during diastole in a normal heart (top) and a heart with mitral stenosis (bottom). In the normal heart, the open mitral valve allows blood to flow from the atrium, and the aortic valve is closed. In the...
Auscultatory findings characteristic of mitral stenosis include a loud first heart sound, an opening snap, and a diastolic rumble. With mitral stenosis, the first heart sound (from the closing of the mitral and tricuspid valves) is usually loud and may be palpable (tapping apex beat) because of increased force in closing the mitral valve and the wide closing excursion of the mitral leaflets. When listening at the apex, a high-pitched opening snap may be heard after the A2 (aortic) component of the second heart sound due to the forceful opening of the mitral valve. With increasing severity, the time shortens between S2 (A2) and the opening snap. If pulmonary hypertension is severe, the P2 (pulmonic) component of the second heart sound is accentuated. A so-called "double-shock" sound describes the cadence of a split second heart sound or of the second sound followed by an opening snap or early third heart sound. Mitral stenosis results in a uniquely shaped, low-pitched diastolic rumble best heard with the patient in a left lateral decubitus position (lying on the left side) while listening with the stethoscope bell positioned at the apex.
-
Diastolic (presystolic) murmur often heard in the second stage of mitral stenosis
The murmur occurs throughout diastole, with a gradual increase in intensity as it approaches the first heart sound (S1). No second sound is audible at the apex. (Source: Cabot RC. Physical Diagnosis of Diseases of the Chest. Se...
Rheumatic heart disease sometimes results in combined mitral stenosis and regurgitation.
Aortic valve (subcategory C). Isolated aortic valve disease is uncommon in rheumatic heart disease.
Combined disease of the aortic and mitral valves (subcategory D). Worldwide, rheumatic heart disease remains the most common etiology of combined disease of the aortic and mitral valves (168).
Clinical vignette
An 8-year-old girl suddenly developed pain and swelling of right wrist, knee, and ankles associated with movement disorder in all limbs. One week later, the patient could not speak and became bedridden due to worsening of the involuntary movements. Twenty days after onset, she was admitted to a hospital. Examination revealed anarthria, severe generalized chorea, decreased muscle tone, and an inability to walk or even sit without assistance. Her medical history was remarkable for repeated episodes of pharyngitis and an episode of rheumatic fever 2 years before the current admission with carditis, arthritis, and Sydenham chorea; the latter was controlled with haloperidol, but the family did not comply with penicillin prophylaxis.
During the admission to treat the episode of chorea paralytica, echocardiography showed mild mitral insufficiency. Lab workup included antistreptolysin titers 336 UI/mL (normal range less than 250), C-reactive protein 7.45 mg/mL (normal range less than 8), and sedimentation rate 35 mm. One week of valproic acid 30 mg/kg per day failed to improve the chorea. Valproic acid was discontinued, and she was started on pimozide 4 mg twice daily. She was discharged 15 days after admission with persistent anarthria, mild chorea, and severely decreased muscle tone, but could sit and walk with assistance. On a follow-up visit 3 weeks later, she could sit and walk unassisted and had no evident chorea but had continued dysarthria, decreased verbal output, and moderately decreased muscle tone. After several additional weeks of pimozide therapy, the pimozide was gradually tapered until it was discontinued 4 months after discharge.
Forty-two months after the episode of chorea paralytica, the patient had no evident neurologic abnormalities and continued on penicillin prophylaxis.
Biological basis
Etiology and pathogenesis
Group A beta-hemolytic streptococci are the causative agents of Sydenham chorea and related disorders.
Italian-American internist Angelo Taranta (1927-2016) and American internist Gene H Stollerman (1920-2014) established the casual relationship between infection with group A beta-hemolytic streptococci and the occurrence of Sydenham chorea (186). Based on the assumption of molecular mimicry between streptococcal and CNS antigens, they proposed that bacterial infection in genetically predisposed subjects leads to the formation of cross-reactive antibodies that disrupt the basal ganglia function. Multiple studies have since demonstrated the presence of such circulating anti-basal ganglia antibodies (ABGA) in 50% to 90% of patients with Sydenham chorea (104; 35). A specific epitope of streptococcal M proteins that cross-reacts with basal ganglia has been identified (30). In one study, all patients with active Sydenham chorea had ABGA by ELISA and Western Blot, whereas ABGA positivity in subjects with persistent Sydenham chorea (duration of disease greater than 2 years despite best medical treatment) was about 60% (58).
Although several groups have since reported binding and other effects of ABGA from Sydenham chorea patients when applied to various cell cultures, the pathological significance of ABGA in vivo still remains to be determined.
|
• One group found that ABGA antibodies from patients with Sydenham chorea bind to neuronal surface proteins in cell culture derived from a neuroblastoma cell line, whereas antibodies from subjects with Tourette syndrome or who met criteria for PANDAS did not (27). | |
|
• In another study, IgM of a patient with Sydenham chorea induced expression of calcium/calmodulin-dependent protein kinase II (CaMKII) in a culture of neuroblastoma cells (112). Although an interesting finding, this study has several limitations: (1) it is an in vitro investigation, employing an artificial paradigm that does not necessarily reflect the situation observed in human patients; (2) the antibody was obtained from a single patient; and (3) the authors studied IgM, whereas all investigations of ABGA in Sydenham chorea have detected IgG. In a more recent study, this same group found circulating serum antibodies in patients with Sydenham chorea targeting tubulin, lysoganglioside GM1, and D1 and D2 dopamine receptors (54). | |
|
• Another group reported a linear correlation between the ABGA titer in the serum from Sydenham chorea patients and the increase of intracellular calcium levels in PC12 cells, further suggesting that these antibodies have a pathogenic importance (193). |
Despite the suggestive findings in cell culture studies, an in vivo study failed to demonstrate that antibodies from Sydenham chorea patients infused in the basal ganglia of rodents induce behavioral changes, although they were found to bind to a ∼50-kDa molecule in the striatum extract (22). One possible explanation is that a low titer of the antibodies prevented the occurrence of detectable behavioral manifestations.
There is growing evidence that the pathogenesis of Sydenham chorea involves changes of dopamine transmission (75):
|
• Infusion of sera from Sydenham chorea patients in rodents with a unilateral 6-OH-dopamine-induced lesion of the nigro-striatal system caused circling behavior similar to apomorphine (75), suggesting that the circulating antibodies act on dopamine receptors. | |
|
• Rats exposed to streptococcal antigens not only developed behavioral abnormalities reminiscent of Sydenham chorea but also had IgG that reacted with tubulin and D1 and D2 receptors, causing elevated calcium/calmodulin-dependent protein kinase II signaling (28). This same group found that injection of these antibodies into the striatum of naive rats led to behavioral and immunologic abnormalities similar to those found in animals exposed to streptococcal antigens: specifically, the antibodies bind to D1 and D2 as well as 5HT-2A and 5HT-2C receptors (126). | |
|
• Monoclonal antibodies derived from Sydenham chorea patients target dopaminergic neurons in transgenic mice and signal D2 receptors (63). | |
|
• There is a positive correlation between scores on the Universidade Federal de Minas Gerais Sydenham Chorea Rating Scale and the ratio between anti-D1 and anti-D2 receptors antibodies (23). | |
|
• A comprehensive review of the molecular mimicry hypothesis of the pathogenesis of Sydenham chorea emphasizes the notion that antibodies targeting lysoganglioside of group A Streptococcus cross-react with dopamine D1 and D2 receptors (64). |
Despite the accumulating evidence for the so-called “dopamine hypothesis” of the pathogenesis of Sydenham chorea, other groups have failed to replicate some of the findings described above (42).
It remains unclear why up to 50% of patients with Sydenham chorea develop persistent chorea (42). In light of the autoreactive antibody-mediated hypothesis for Sydenham chorea pathogenesis, the persistence of chorea might conceivably be associated with increased levels of B1 lymphocytes and other lymphocyte subsets; however, evaluation of lymphocyte subsets, including B1 and T cells, in patients with remitted and persistent Sydenham chorea by flow cytometry showed a difference in neither the frequency of T and B lymphocytes subpopulations nor in their activation and functional states, undermining the view that persistent Sydenham chorea is a sustained cytotoxic cellular-mediated condition (200). In persistent Sydenham chorea, the titers of ABGA are low, whereas serum brain-derived neurotrophic factor (BDNF) levels are high, so it is possible that the acute immune process causes structural brain lesions resulting in permanent dysfunction of the basal ganglia (189).
Although some investigations suggest that susceptibility to rheumatic chorea is linked to human leukocyte antigen (HLA) expression (09), other studies failed to identify any relationship between Sydenham chorea and HLA class I and II alleles (74). However, a subsequent investigation has shown an association between HLA-DRB1*07 and recurrent streptococcal pharyngitis and rheumatic heart disease (99).
A proposed genetic marker for rheumatic fever and related conditions is the B-cell alloantigen D8/17 (81). However, despite repeated reports of the group that developed the assay claiming its high specificity and sensitivity (77; 97), other authors report that the D8/17 marker lacks specificity and sensitivity. For instance, the discriminating power of monoclonal antibody against D8/17 was relatively low among patients of North Indian ethnic origin (110). In a study from the United States, 66% of Caucasian patients with obsessive-compulsive disorder or chronic tic disorder and 8% of controls tested positive for D8/17 (144). In the Netherlands, only a minority of patients with post-group A beta-hemolytic streptococcal arthritis had an elevation of D8/17-positive lymphocytes (107).
Another suggested genetic risk factor for developing acute rheumatic fever but not Sydenham chorea is polymorphisms within the promoter region of the tumor necrosis factor-alpha gene (167).
Due to the difficulties with the molecular mimicry hypothesis to fully account for the pathogenesis of Sydenham chorea, studies have further explored immunologic mechanisms to either support or refute the autoantibody hypothesis.
|
• A study investigating various immune parameters in sera and CSF samples of 14 acute and four persistent Sydenham chorea cases found evidence to support an autoantibody mechanism: (1) serum IL-4, IL-10 and IL-12 were elevated in acute compared to persistent Sydenham chorea; (2) oligoclonal bands were present in 46% of acute Sydenham chorea cases; (3) ABGA were present in 93% of acute Sydenham chorea cases and 50% of persistent Sydenham chorea cases (59). However, the elevated IL-10 and IL-12 levels (ie, Th1-type cytokines) suggest that cell-mediated mechanisms may also be involved in the pathogenesis of this disorder | |
|
• Cell-mediated mechanisms were also supported by other studies that found increased concentrations of chemokines CXCL9 and CXCL10 in the serum of patients with acute Sydenham chorea (192), or documented dysfunction of monocytes (199). |
Some authors have suggested that streptococcal infection induces vasculitis of medium-sized vessels, leading to neuronal dysfunction (an idea that originated in the 1860s). Rheumatic fever shares similar cardiac and neurologic pathologies with the antiphospholipid syndrome, but antiphospholipid antibodies are almost invariably absent in Sydenham chorea. Nevertheless, considerable overlap of humoral immunity in rheumatic fever and antiphospholipid syndrome suggests that some common pathogenic mechanisms may underlie the development of cardiac valve lesions and CNS abnormalities in both diseases (26).
The weight of evidence suggests that the pathogenesis of Sydenham chorea is related to circulating cross-reactive antibodies. Streptococcus-induced antibodies can also be associated with a form of acute disseminated encephalomyelitis characterized by a high frequency of dystonia and other movement disorders as well as basal ganglia lesions on neuroimaging (69). Antineural and antinuclear antibodies have also been found in patients with Tourette syndrome, but their relationship with prior streptococcus infection remains doubtful (143).
It has long been suspected that choreas in general, including Sydenham chorea, are characterized by increased excitability of the motor cortex. However, a study of 16 patients with Sydenham chorea demonstrated that there is reduced excitability of corticospinal output similar to what is found in Huntington disease (111); the reasons for this finding remain to be determined (96; 111).
Epidemiology
Nineteenth-century studies in England identified a clear seasonal pattern to rheumatic fever and Sydenham chorea, although the significance of this was not understood at the time. Beginning in the second half of the 19th century, large clinical series at the newly founded pediatric hospitals (the Hospital for Sick Children, Great Ormond Street, London) provided detailed demographic and clinical features of patients (131). English physician Sir William Selby Church, 1st Baronet, KCB (1837-1928) presented graphs of cases of rheumatic fever in the London Hospital from 1873-1881, and St. Bartholomew's Hospital, London, from 1882-1893.
-
English physician Sir William Selby Church, 1st Baronet, KCB (1837-1928)
Church was a successful physician to St Bartholomew's Hospital in London, president of the Royal College of Physicians from 1899 to 1905, and president of the Royal Society of Medicine from 1907 to 1909 and also in 1893. (Court...
-
Cases of rheumatic fever in St. Bartholomew's Hospital, London, 1882-1893
The y-axis for first attacks is on the right, and the y-axis for all attacks is on the left. Number of first attack = 791. Total number of all cases = 1908. (Source: Church WS. Acute rheumatism, or rheumatic fever. In: Albutt T...
Church's graph of rheumatic fever cases at the London Hospital was based on the earlier work of British pathologist Henry Singer Gabbett (1851-1926) and, in particular, used the summary data from Gabbett's table in his 1883 article in Lancet (82; 83).
Average monthly admissions of acute rheumatism (rheumatic fever) to the London Hospital, 1873-1881
The dotted line represents the average monthly rainfall at Greenwich. The y-axis for rainfall is on the right, and the y-axis for admissions is on the left. (Source: Gabbett HS. On the seasons of the year and the prevalence of ...
The incidence of rheumatic fever and Sydenham chorea in the United States and Western Europe has declined since World War II as result of improved health care, increased antibiotic usage, and lower virulence of streptococcal strains (166).
The international decline of rheumatic fever, with incidence data from Denmark (1862-1963) and mortality data from the United States (1921-1970)
Correlation: r = 0.928, r2 = 0.81. Penicillin was introduced in 1943, in the United States and in Denmark. Both graphs changed from logarithmic to a linear scale. Note: Because of a discontinuity in the US data between 1948 and...
This fall is demonstrated by the finding that the annual age-adjusted incidence rate of initial attacks of rheumatic fever per 100,000 children declined from 3.0 in 1970 to 0.5 in 1980 in Fairfax County Virginia, United States (172). Sydenham chorea accounted for 0.9% of pediatric admissions to hospitals in Chicago before 1940, whereas this number dropped to 0.2% between 1950 and 1980 (146).
Despite the fall in the incidence, Sydenham chorea remains the most common cause of acute chorea in children. Since the 1990s, outbreaks of rheumatic fever with the occurrence of chorea have been identified in the United States and Australia (08; 169). A study performed in the pediatrics unit of a university hospital in Pennsylvania showed Sydenham chorea accounted for 96% of all patients with chorea seen during the 1980 to 2004 period (215).
Studies from Australia confirm that Sydenham chorea is a relatively common cause of acute chorea in children (70; 176). Australian Aboriginals are reported to be at high risk of developing rheumatic fever (33). In the Northern Territory of Australia, an area predominantly inhabited by Aboriginal people, the point prevalence of rheumatic fever was 9.6 per 1000 people aged 5 to 14 years in 1995 (34). A national survey of all cases of rheumatic fever in Australia identified 151 children with this condition in a 3-year period. Not surprisingly, most (87%) were Indigenous Australians. Sydenham chorea was diagnosed in 19%. However, the authors identified 10 cases in non-Indigenous Australians, of whom three had atypical presentations. The authors concluded that rheumatic fever may be more common than previously thought among low-risk children (147).
The incidence of acute rheumatic fever in Slovenia has increased more recently, with an annual incidence of 1.25 cases per 100,000 children during the period from 2008 through 2014 (113); carditis was present in all patients, arthritis in 37%, and Sydenham chorea in 32%.
Retrospective analysis of the medical records of 377 patients with acute rheumatic fever admitted to the pediatric cardiology department at a university hospital in southern Turkey suggested that admissions for this disorder decreased significantly over the interval from 1993 to 2017, presumably reflecting a corresponding decline in the population incidence of rheumatic fever (78). The most common manifestations were carditis 84%, arthritis 74%, and Sydenham chorea at 14%; only two patients (0.5%) had erythema marginatum, and two patients (0.5%) had subcutaneous nodules. Of the patients with carditis, 49% had mild or subclinical carditis, 20% had moderate carditis, and 32% had severe carditis. The cardiac valves most commonly affected were the mitral valve alone (55%), followed by both mitral and aortic valves (34%), and the aortic valve alone (6%).
Although population-based studies are lacking, rheumatic fever has remained a significant public health problem in developing areas, such as Brazil, particularly within the low-income population.
Prevention
Prompt treatment of streptococcal pharyngitis with appropriate antibiotics has lowered the incidence of Sydenham chorea. Once the diagnosis of rheumatic chorea is established, the patient must receive secondary prophylaxis with penicillin or, for patients with a penicillin allergy, sulpha drugs. This has been shown to effectively decrease the risk of neurologic or cardiac problems with additional streptococcal infections (132). Patients with a history of Sydenham chorea should be informed of the possible reemergence of chorea during pregnancy or with the use of oral contraceptives.
Differential diagnosis
Confusing conditions
Sydenham chorea is the most common cause of acute chorea in children worldwide, but several other conditions can cause present with chorea in this age range (11). Several conditions may present with clinical manifestations similar to Sydenham chorea (Table 1) (37).
The most important differential diagnosis is systemic lupus erythematosus (SLE), where up to 2% of patients may develop chorea. Most subjects with systemic lupus erythematosus have other nonneurologic manifestations such as arthritis, pericarditis, and other serositis as well as skin abnormalities. Moreover, the neurologic picture of systemic lupus erythematosus tends to be more complex and may include psychosis, seizures, other movement disorders, and even changes in mental status and level of consciousness (10). Only in rare instances will chorea, with a tendency for spontaneous remissions and recurrences, be an isolated manifestation of systemic lupus erythematosus. The difficulty in distinguishing these two conditions is increased by the finding that up to 20% of patients with Sydenham chorea display recurrence of the movement disorder. Eventually, patients with isolated chorea due to systemic lupus erythematosus develop other features, meeting diagnostic criteria for this condition (14).
Primary antiphospholipid antibody syndrome is differentiated from Sydenham chorea by the absence of other clinical and laboratory features of rheumatic fever as well as the usual association with repeated spontaneous abortions, venous thrombosis, other vascular events, and the presence of typical laboratory abnormalities.
In children and adolescents, anti-NMDA receptor encephalitis is usually a paraneoplastic disorder related to ovarian teratoma. Patients present with a combination of psychiatric problems and a mixed movement disorder that may include chorea. However, the severe and proteiform clinical presentation readily distinguishes this condition from Sydenham chorea (13).
Encephalitides, either as a result of direct viral invasion or by means of an immune-mediated postinfectious process, can cause chorea (164). This usually happens, however, in younger children; the clinical picture is more diverse (eg seizures, pyramidal signs, and impaired psychomotor development), and there are laboratory abnormalities suggestive of the underlying condition.
Drug-induced choreas are readily distinguished by careful history demonstrating a temporal relationship between the onset of the movement disorder and exposure to the agent.
Although vascular disease is uncommon in the first 2 decades of life, it can occur and cause chorea (134). This may happen in 3% of patients with moyamoya disease (02).
Benign hereditary chorea is a genetic syndrome associated with multiple mutations, most commonly a mutation of NKX2-1. It is an autosomal dominant disorder but may remain unrecognized due to the variable expression or possible de novo mutation. These patients display chorea, other movement disorders (ie, tics, myoclonus), as well as behavioral disorders (41). It usually starts in early childhood and progresses until the second decade, after which time it remains static or even spontaneously improves. Patients may have a slight hypotonia and motor delay because of chorea; they may also have mild gait ataxia, dystonia, tics, handwriting impairment, and drop attacks. However, the disorder is self-limiting after adolescence in most cases, although it may persist as a mild chorea beyond 60 years of age. Benign hereditary chorea has been linked to mutations in the NKX2-1 (previously called TITF1) gene on chromosome 14q13, coding for a protein called homeobox protein Nkx-2.1, which is a member of the homeobox protein family of transcription factors essential for organogenesis of the lung, thyroid, and basal ganglia (155). Benign hereditary chorea should be considered in children and adults with chorea, mental retardation, congenital hypothyroidism, and chronic lung disease; hence, the term brain-thyroid-lung syndrome has been proposed for this disease. About half of the patients spontaneously improve in adulthood, but levodopa can also be beneficial. Reports suggest that thyroid hormone replacement therapy and methylphenidate may be effective (84; 173).
Another form of “benign” chorea with relatively intact cognitive function is an autosomal dominant syndrome associated with ACDY5 mutation, but the phenotype of this disorder is expanding, and it may include dystonia, myoclonus, axial hypotonia, and episodic and fluctuating painful spasms associated with falls, sleep disturbance, and other manifestations (135).
More rare mutations of the genes PDE10A and PDE2A may also result in a clinical picture resembling benign hereditary chorea. However, these are autosomal recessive conditions, often associated with a seizure disorder and bilateral striatal necrosis (138; 170). Other genes to be considered in this scenario are FOXG1, GNAO1, GPR88, SLC2A1, SQSTM1, ATP8A2, or SYT-1. One review describes the differential diagnosis of autoimmune choreas in detail (42), and a more recent article addresses the differential diagnosis of chorea in children (11).
Psychogenic chorea or pseudochorea (ie, a somatoform disorder resembling chorea) and, indeed, epidemic psychogenic chorea have been recognized since the 19th century. In his Handbook of Geographical and Historical Pathology (1886), German physician and medical historian August Hirsch (1817-1894) noted that:
|
Not unfrequently, the disease spreads by way of mimicry. Small epidemics, even, have been seen to arise under that influence in various kinds of institutions for girls; one person with chorea having been admitted, the malady has quickly extended to the larger part of the inmates (102). |
Table 1. Differential Diagnoses for Sydenham Chorea
|
Inherited | |
|
• Neuroacanthocytosis | |
|
Immunologic | |
|
• Systemic lupus erythematosus | |
|
Infections | |
|
Bacterial | |
|
• Subacute bacterial endocarditis | |
|
Viral | |
|
• Measles | |
|
Drug-related | |
|
• Tardive dyskinesia | |
|
Miscellaneous | |
|
• Anoxic encephalopathy | |
Diagnostic workup
The aim of the diagnostic workup in patients suspected to have rheumatic chorea is 3-fold: (1) to identify evidence of recent streptococcal infection or acute phase reaction; (2) to search for cardiac injury associated with rheumatic fever; and (3) to rule out alternative causes.
Without a clear diagnosis of rheumatic fever, children and young adults with chorea should undergo complete neurologic examination and diagnostic testing to assess the various causes of chorea because there is no specific biological marker of Sydenham chorea.
Supporting evidence of preceding streptococcal infection (eg, increased antistreptolysin-O, antiDNAse-B, or other antistreptococcal antibodies; positive throat culture for group A Streptococcus; or recent scarlet fever) and tests of the acute-phase response are often less helpful in Sydenham chorea than in other forms of rheumatic fever due to the usual long latency between the infection and onset of the movement disorder.
Antistreptolysin O titer. Elevated antistreptolysin O titer may be found in populations with a high prevalence of streptococcal infection. Furthermore, the antistreptolysin O titer declines if the interval between infection and rheumatic fever is longer than 2 months. Anti-DNase-B titers, however, may remain elevated up to 1 year after strep pharyngitis. Heart evaluation (ie, Doppler echocardiography) is mandatory because Sydenham chorea is associated with carditis in up to 80% of patients. Cardiac lesions are the main source of serious morbidity in Sydenham chorea. Serologic studies for systemic lupus erythematosus and primary antiphospholipid antibody syndrome must be ordered to rule out these conditions. EEG may show generalized slowing acutely or after clinical recovery. Spinal fluid analysis is usually normal but may show a slightly increased lymphocyte count. It is important to highlight that although autoantibodies are important for the pathogenesis of Sydenham chorea, they have no role in establishing the diagnosis in clinical practice. This is related to their lack of specificity (43).
Acute phase reactants. The acute-phase response is considered part of the innate immune system, and acute-phase reactants play a role in mediating such systemic effects as fever, leukocytosis, and increased cortisol. Acute phase reactants are inflammation markers that exhibit significant changes in serum concentration during inflammation. Acute phase reactants can be classified as positive or negative, depending on their serum concentrations during inflammation. Positive acute phase reactants are upregulated, and their concentrations increase during inflammation; examples include procalcitonin, C-reactive protein, ferritin, fibrinogen, hepcidin, and serum amyloid A. The erythrocyte sedimentation rate (ESR), an indirect acute phase reactant, reflects plasma viscosity and the presence of acute phase proteins, especially fibrinogen. Negative acute-phase reactants are downregulated, and their concentrations decrease during inflammation; examples include albumin, prealbumin, transferrin, retinol-binding protein, and antithrombin.
Structural neuroimaging. CT scan of the brain invariably fails to display abnormalities in Sydenham chorea. Head MRI is also often normal, although there are case reports of reversible hyperintensity in the basal ganglia. In an 8-year-old girl with Sydenham chorea, brain MRI revealed bilateral symmetrical T2/FLAIR hyperintense signals in the thalami and corpus striatum and altered signal intensity in the left frontal lobe (with a normal echocardiogram and no evidence of carditis) (03).
-
Hyperintense signals in the left frontal lobe of a girl with Sydenham chorea (MRI)
Axial FLAIR T-2 weighted images of the brain showing hyperintense signals in the left frontal lobe in an 8-year-old girl with Sydenham chorea. (Source: Ali A, Anugwom GO, Rehman U, Khalid MZ, Saeeduddin MO. Sydenham chorea mana...
-
Bilateral hyperintense signals in the thalami and corpus striatum a girl with Sydenham chorea (MRI)
Axial FLAIR T-2 weighted images of the brain showing bilateral hyperintense signals in the thalami and corpus striatum in an 8-year-old girl with Sydenham chorea. (Source: Ali A, Anugwom GO, Rehman U, Khalid MZ, Saeeduddin MO. ...
One study noted increased signal intensity in just two of 24 patients (88). Volumetric studies showed that the striatum and putamen are significantly enlarged in the acute phase of Sydenham chorea compared with controls, although extensive overlap between cases and controls makes this of little practical use for clinical diagnosis (88; 109). Very rarely, patients may develop necrotic basal ganglia lesions (32).
Functional neuroimaging. PET and SPECT imaging may prove to be useful tools in the evaluation, revealing transient alterations in striatal metabolism in some patients (94; 210; 124; 18; 61; 153; 20; 93). Most of these studies found transient increases in striatal metabolism, which contrasts with other choreic disorders (eg, Huntington disease) that are associated with hypometabolism; however, one study found hyperperfusion in two patients with Sydenham chorea, whereas the remaining five had hypometabolism (61). Subjects with acute generalized Sydenham chorea may have symmetric or asymmetric increases in basal ganglia perfusion or may have normal basal ganglia perfusion, whereas those with acute hemichorea invariably have asymmetrically increased basal ganglia perfusion (93). Some subjects with Sydenham chorea in motor remission have persistent hyperperfusion of the left putamen on SPECT (20).
Management
Care for patients with Sydenham chorea should be targeted at primary treatment (penicillin, bed rest, aspirin), palliation (symptomatic medication), and prophylaxis.
Antibiotic treatment and prophylaxis. Even though most patients with Sydenham chorea do not have an active infection when chorea appears, most published treatment recommendations include a 10-day course of oral penicillin or a single intramuscular dose of penicillin (205; 72). Sulfa drugs are commonly used for individuals with a penicillin allergy.
The most important measure in treating patients with Sydenham chorea is antibiotic prophylaxis with long-acting penicillin G or, if there is a penicillin allergy, sulfa drugs. Secondary prevention aims to prevent colonization or infection of the upper respiratory tract with group A beta-hemolytic streptococci and the development of recurrent attacks of rheumatic fever (214). Monthly injections of a new long-acting formulation of penicillin, benzathine penicillin G, can prevent recurrences of rheumatic fever in children (182). Secondary prophylaxis is mandatory for all patients who have had an attack of rheumatic fever, regardless of whether they have residual rheumatic valvular heart disease (214). Penicillin prophylaxis appears to reduce the likelihood of further cardiac complications and the recurrence rate of chorea (Gebremariam 1999; 72).
Penicillin remains the antibiotic of choice (67; 214). Intramuscular injection of benzathine benzylpenicillin 1.2 million units every three weeks (every four weeks in low-risk areas or in low-risk patients) is the most effective strategy for preventing recurrent attacks of rheumatic fever (127; 213; 214). Oral penicillin is an alternative, but a serious concern with oral administration is noncompliance because patients often find it difficult to adhere to a daily regimen of antibiotics for many years (68; 214). Even for patients who strictly adhere to an oral penicillin regimen, serum penicillin levels are less predictable, and rheumatic fever recurs more frequently than in comparable patients receiving intramuscular benzathine benzylpenicillin (212; 214). For patients who are allergic to penicillin (or suspected to be allergic), oral sulfadiazine or oral sulfasoxazole represent optimal second choices (213; 214). Although sulfa drugs should not be used for primary prophylaxis, they are acceptable for secondary prophylaxis (214). In rare circumstances where patients are allergic to both penicillin and sulfa drugs, or if these drugs are not available, oral erythromycin may be used (213; 214).
The duration of treatment depends on the severity of cardiac involvement. Patients with no carditis may stop prophylaxis after 5 years or age 18 (whichever is longer), those with mild carditis should continue for 10 years or age 21, and those with moderate to severe carditis should receive lifelong prophylaxis (214). In instances where the diagnosis of Sydenham chorea is made after age 21 years, the policy is less clear; because of the potential seriousness of causing or aggravating cardiac pathology, some have recommended maintaining prophylaxis indefinitely (36).
Unfortunately, there is significant diversity of antibiotic treatment or reporting across prior studies (72). Studies that reported penicillin use varied in terms of its method of administration (eg, either oral or intramuscular primary penicillin therapy preceding intramuscular prophylaxis) or in the substitution of amoxicillin followed by prophylaxis with feneticillin (72). Long-term compliance and logistical problems are also problems with protracted prophylaxis (71; 72).
Although secondary antibiotic prophylaxis has been shown to reduce the risk of new cardiac lesions associated with recurrent rheumatic fever, the effect of prophylaxis on the recurrence of chorea is less clear. Available data suggest that prophylaxis likely reduces the rate of recurrence, but it does not completely prevent it (24; 198; 114; 95; 72).
Symptomatic treatment of acute chorea. There are few controlled studies of the symptomatic treatment of Sydenham chorea, and available information is of limited methodological quality (39; 207; 72; 139). Treatment remains largely empirical and is less than optimal (207; 72). There are no large, well-conducted, randomized controlled trials. Consequently, recommendations for optimal management remain inconsistent and are hampered by the side effects of pharmacotherapy (207; 72). Treatment decisions are based on the treating physician’s clinical experience, the desire to avoid side effects, and the availability of limited scientific evidence (72). Chorea often improves with symptomatic therapy using antiepileptic medications, dopamine-blocking neuroleptics, or dopamine-depleting agents (72). Immunotherapy is typically reserved for those who fail to respond (72); corticosteroids are beneficial, but data using intravenous immunoglobulins and plasmapheresis are very limited (72).
Antiepileptic medications. Open-label trials and anecdotal experience have supported using antiepileptic medications for Sydenham chorea. Valproic acid has been used with an initial dosage of 250 mg per day that is increased during a 2-week period to 250 mg three times a day; if the response is not satisfactory, the dosage can be gradually increased to 1500 mg per day. As this drug has a rather slow onset of action, it is prudent to wait 2 weeks before concluding that a regimen is ineffective. Carbamazepine and levetiracetam have also been reported to effectively control chorea in uncontrolled open-label studies (73). Based on a comparative trial, carbamazepine (15 mg/kg per day) and valproic acid (20 to 25 mg/kg per day) are equally effective and safe drugs in the treatment of choreiform movements in Sydenham chorea (85).
Neuroleptics. If the patient fails to respond to antiepileptic medications, the next option is to prescribe dopamine-blocking or dopamine-depleting therapies. However, although some have advocated dopamine D2 receptor blockers (eg, haloperidol) as a first-line agent in preference to antiepileptic medications (187), this is not a prevailing view. These agents must be used with great caution in patients with Sydenham chorea, given the observation of the development of parkinsonism, dystonia, or both in patients treated with neuroleptics and the potential risk of developing tardive dyskinesia. In one case-control study comparing the response to neuroleptics in patients with Sydenham chorea and Tourette syndrome, 5% of 100 patients with chorea developed extrapyramidal complications, whereas such complications were not observed among patients with tics matched for age and neuroleptic dosage (190).
Risperidone, a relatively potent dopamine D2 receptor blocker, is usually effective in controlling the chorea. The usual initial regimen is 1 mg twice a day. If, 2 weeks later, the chorea is still troublesome, the dosage can be increased to 2 mg twice a day. Haloperidol and pimozide are also occasionally used to manage chorea in Sydenham chorea, although they are less well tolerated.
Because neuroleptics act by blocking dopamine receptors and, therefore, may cause tardive dyskinesia, many clinicians use tetrabenazine, a dopamine-depleting drug, for the symptomatic treatment of Sydenham chorea as this drug has a very low risk of tardive dyskinesia.
Discontinuation of antichoreic agents. There are no published guidelines concerning the discontinuation of antichoreic agents. One approach is to attempt a gradual dosage decrease (eg, 25% reduction every 2 weeks) after the patient remains free of chorea for at least 1 month.
Immunosuppressive therapies. Some controversy exists as to the role of immunosuppression in the management of Sydenham chorea due to the poor methodological quality of supporting data, potential complications, and the high cost of some of the therapies.
Corticosteroids are generally reserved for cases with severe carditis, severe chorea (chorea paralytica), or persistent disabling chorea refractory to antichoreic agents. A placebo-controlled study showed that oral prednisone shortened the time to clinical remission of chorea but did not affect remission and recurrence rates (156; 79). An observational, retrospective, multicentric study involving 30 subjects with Sydenham chorea (of whom 15 were treated with prednisone, and 15 received symptomatic drugs or no treatment) reported that oral prednisone (2 mg/kg for 14 days followed by gradual tapering) shortened both the median time for improvement and the time to achieve clinical remission (80). Methylprednisolone 25 mg/kg per day in children and 1 g/day in adults for 5 days followed by 1 mg/kg per day of prednisone appears to be an effective and well-tolerated treatment for patients with Sydenham chorea refractory to conventional treatment with antichoreic drugs and penicillin (47; 15; 195). A meta-analysis found that patients receiving at least 1 month of corticosteroids had significantly lower odds of a relapsing course (79).
Few reports describe the usefulness of plasma exchange or intravenous immunoglobulin in Sydenham chorea; these options are not usually recommended because of the efficacy of other therapeutic agents, potential complications, and the high cost of the latter treatment modalities. In a randomized open-label study, the authors compared outcomes for 10 children treated with standard management alone and 10 who received additional intravenous immunoglobulin (205); outcomes were better for the intravenous immunoglobulin group based on a clinical rating scale, brain single-photon emission computed tomography, and the duration of symptomatic treatment.
Recurrent chorea. In a significant subgroup of patients, recurrence of Sydenham chorea is not attributable to a true relapse of rheumatic fever (114; 115); instead, apparent recurrences may represent either a primary underlying increased susceptibility or the outcome of permanent subclinical damage to the basal ganglia following the initial choreic episode (114). In a longitudinal study of 24 patients with Sydenham chorea, 10 patients (42%) developed 11 recurrent episodes of chorea from 3 months to 10 years after the initial episode (114). Association of recurrent chorea with rheumatic fever could be suspected in only six of the 11 episodes of recurrence (55%) due to cessation of prophylactic antibiotic treatment or poor compliance in four patients and a rise in anti-streptolysin O titers in two. In an 18-year-old woman, chorea recurred during her first pregnancy. At recurrence, chorea was the sole rheumatic sign in all nine patients who had a single recurrent episode. In a patient with two recurrent episodes, mitral regurgitation developed into mitral stenosis. No statistical differences in previous rheumatic fever activity and rheumatic cardiac involvement were found between subjects with a single episode and those with recurrent episodes.
Special considerations
Pregnancy
Patients with a history of Sydenham chorea may develop chorea gravidarum as manifest by a recurrence of the movement disorder during pregnancy (128), although it is important to emphasize that there are other causes of chorea gravidarum such as systemic lupus erythematosus (35). The onset of chorea gravidarum is usually in the first trimester, with spontaneous improvement or even remission in the third semester. If the movement disorder is not severe, no treatment is advisable. However, if necessary, low doses of neuroleptics can be considered and are safe for mother and child (01; 209).
Early diagnosis of rheumatic mitral stenosis in pregnancy is very important because the heart often cannot tolerate the cardiac output demand of pregnancy with a stenotic mitral valve (the situation that led to the death of my grandmother).
Media
References
- 01
- ACOG Committee on Practice Bulletins--Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008. Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol 2008;111(4):1001-20. PMID 18378767
- 02
- Ahn ES, Scott RM, Robertson RL Jr, Smith ER. Chorea in the clinical presentation of moyamoya disease: results of surgical revascularization and a proposed clinicopathological correlation. J Neurosurg Pediatr 2013;11(3):313-9. PMID 23289915
- 03
- Ali A, Anugwom GO, Rehman U, Khalid MZ, Saeeduddin MO. Sydenham chorea managed with immunoglobulin in acute rheumatic fever. Cureus 2021;13(5):e14990. PMID 34131535
- 04
- Alm PA. Streptococcal infection as a major historical cause of stuttering: data, mechanisms, and current importance. Front Hum Neurosci 2020;14:569519. PMID 33304252
- 05
- Asbahr FR, Garvey MA, Snider LA, Zanetta DM, Elkis H, Swedo SE. Obsessive-compulsive symptoms among patients with Sydenham chorea. Biol Psychiatry 2005;57:1073-6. PMID 15860349
- 06
- Asbahr FR, Negrao AB, Gentil V, et al. Obsessive-compulsive and related symptoms in children and adolescents with rheumatic fever with and without chorea: a prospective 6-month study. Am J Psychiatry 1998;155:1122-4. PMID 9699708
- 07
- Aubert G. Charcot revisited: the case of Bruegel's chorea. Arch Neurol 2005;62(1):155-61.** PMID 15642865
- 08
- Ayoub EM. Resurgence of rheumatic fever in the United States. The changing picture of a preventable illness. Postgrad Med 1992;92:133-42. PMID 1518750
- 09
- Ayoub EM, Barrett DJ, Maclaren NK, Krischer JP. Association of class II human histocompatibility leukocyte antigens with rheumatic fever. J Clin Invest 1986;77:2019-26. PMID 3486889
- 10
- Baizabal-Carvallo JF, Bonnet C, Jankovic J. Movement disorders in systemic lupus erythematosus and the antiphospholipid syndrome. J Neural Transm 2013a;120(11):1579-89. PMID 23580159
- 11
- Baizabal-Carvallo JF, Cardoso F. Chorea in children: etiology, diagnostic approach and management. J Neural Transm (Vienna) 2020;127(10):1323-42. PMID 32776155
- 12
- Baizabal-Carvallo JF, Jankovic J. Movement disorders in autoimmune diseases. Mov Disord 2012;27(8):935-46. PMID 22555904
- 13
- Baizabal-Carvallo JF, Stocco A, Muscal E, Jankovic J. The spectrum of movement disorders in children with anti-NMDA receptor encephalitis. Mov Disord 2013b;28(4):543-7. PMID 23400857
- 14
- Bakdash T, Goetz CG, Singer HS, Cardoso F. A child with recurrent episodes of involuntary movements. Mov Disord 1999;14:146-54. PMID 9918359
- 15
- Barash J, Margalith D, Matitiau A. Corticosteroid treatment in patients with Sydenham's chorea. Pediatr Neurol 2005;32:205-7. PMID 15730904
- 16
- Bartholomew RE. Tarantism, dancing mania and demonopathy: the anthropolitical aspects of 'mass psychogenic illness.' Psychol Med 1994;24(2):281-306. PMID 8084927
- 17
- Barreto LB, Maciel RO, Maia DP, Teixeira AL, Cardoso F. Parkinsonian signs and symptoms in adults with a history of Sydenham's chorea. Parkinsonism Relat Disord 2012;18(5):595-7. PMID 22104009
- 18
- Barsottini OG, Ferraz HB, Seviliano MM, Barbieri A. Brain SPECT imaging in Sydenham's chorea. Braz J Med Biol Res 2002;35:431-6. PMID 11960191
- 19
- Beato R, Maia DP, Teixeira AL Jr, Cardoso F. Executive functioning in adult patients with Sydenham's chorea. Mov Disord 2010;25(7):853-7. PMID 20461802
- 20
- Beato R, Siqueira CF, Marroni BJ, et al. Brain SPECT in Sydenham's chorea in remission. Mov Disord 2014;29(2):256-8. PMID 24591171
- 21
- Ben-Pazi H, Jaworowski S, Shalev RS. Cognitive and psychiatric phenotypes of movement disorders in children: a systematic review. Dev Med Child Neurol 2011;53:1077-84. PMID 21950517
- 22
- Ben-Pazi H, Sadan O, Offen D. Striatal microinjection of Sydenham chorea antibodies: using a rat model to examine the dopamine hypothesis. J Mol Neurosci. 2012;46:162-6. PMID 21647711
- 23
- Ben-Pazi H, Stoner JA, Cunningham MW. Dopamine receptor autoantibodies correlate with symptoms in Sydenham's chorea. PLoS One 2013;8(9):e73516. PMID 24073196
- 24
- Berrios X, Quesney F, Morales A, Blazquez J, Bisno AL. Are all recurrences of "pure" Sydenham chorea true recurrences of acute rheumatic fever? J Pediatr 1985;107(6):867-72. PMID 3906071
- 25
- Behera M. Subcutaneous nodules in acute rheumatic fever--an analysis of age old dictums. Indian Heart J 1993;45(6):463-7. PMID 8070822
- 26
- Blank M, Krause I, Magrini L, et al. Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome. Rheumatology (Oxford) 2006;45:833-41. PMID 16705050
- 27
- Brilot F, Merheb V, Ding A, Murphy T, Dale RC. Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome. Neurology 2011;76:1508-13. PMID 21411742
- 28
- Brimberg L, Benhar I, Mascaro-Blanco A, et al. Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology 2012;37(9):2076-87. PMID 22534626
- 29
- Broadbent WH. On the pathology of chorea. British Medical Journal 1869;86:345-7, 369-71.
- 30
- Bronze MS, Dale JB. Epitopes of streptococcal M proteins that evoke antibodies that cross-react with human brain. J Immunol 1993;151:2820-8. PMID 7689617
- 31
- Cabot RC. Physical Diagnosis of Diseases of the Chest. Second edition. New York: William Wood and Company, 1903.
- 32
- Canavese C, Davico C, Casabianca M, et al. Bilateral striatal necrosis after Sydenham's chorea in a 7-year-old boy: a 2-year follow-up. Neuropediatrics 2018;49(3):209-12. PMID 29471551
- 33
- Carapetis JR, Currie BJ. Rheumatic chorea in northern Australia: a clinical and epidemiological study. Arch Dis Child 1999;80:353-8. PMID 10086943
- 34
- Carapetis JR, Wolff DR, Currie BJ. Acute rheumatic fever and rheumatic heart disease in the top end of Australia's Northern Territory. Med J Aust 1996;164:146-9. PMID 8628132
- 35
- Cardoso F. Chorea gravidarum. Arch Neurol 2002a;59(5):868-70. PMID 12020275
- 36
- Cardoso F. Infectious and transmissible movement disorders. In: Jankovic J, Tolosa E, editors. Parkinson's Disease and Movement Disorders. 4th ed. Baltimore: Williams and Wilkins, 2002b:930-40.
- 37
- Cardoso F. Chorea: non-genetic causes. Curr Opin Neurol 2004;17:433-6. PMID 15247538
- 38
- Cardoso F. Tourette syndrome: autoimmune mechanism. In: Fernández-Alvarez E, Arzimanoglou A, Tolosa E, editors. Pediatric Movement Disorders. Progress in understanding. Montrouge: John Libbey Eurotext, 2005:23-46.
- 39
- Cardoso F. Sydenham’s chorea. Curr Treat Options Neurol 2008;10(3):230-5. PMID 18579027
- 40
- Cardoso F. Sydenham's chorea. Handb Clin Neurol 2011;100:221-9.** PMID 21496581
- 41
- Cardoso F. Movement disorders in childhood. Parkinsonism Relat Disord 2014;20 Suppl 1:S13-6. PMID 24262164
- 42
- Cardoso F. Autoimmune choreas. J Neurol Neurosurg Psychiatry 2017;88(5):412-7. PMID 27919056
- 43
- Cardoso F. Are antibody panels under-utilized in movement disorders diagnosis? No. Mov Disord Clin Pract 2021;8(3):347-9. PMID 33816661
- 44
- Cardoso F, Beato R, Siqueira CF, Lima CF. Neuropsychological performance and brain SPECT Imaging in adult patients with Sydenham's chorea. Neurology 2005a;64 (Suppl 1):A76.
- 45
- Cardoso F, Lees AJ. Did Gustav Mahler have Sydenham's chorea. Mov Disord 2006;1:289-92. PMID 16437586
- 46
- Cardoso F, Maia DP, Cunningham MC, Valenca G. Corticosteroids in the treatment of Sydenham chorea. Mov Disord 2002c;17(Suppl):S113.
- 47
- Cardoso F, Maia D, Cunningham MC, Valenca G. Treatment of Sydenham chorea with corticosteroids. Mov Disord 2003;18(11):1374-7. PMID 14639684
- 48
- Cardoso F, Oliveira PM, Reis CC, et al. Prosody in Sydenham chorea – I: Tessitura. Mov Disord 2006a;21:S359-60.
- 49
- Cardoso F, Oliveira PM, Reis CC, et al. Prosody in Sydenham chorea – II: Duration. f statements. Mov Disord 2006b;21:S360.
- 50
- Cardoso F, Seppi K, Mair KJ, Wenning GK, Poewe W. Seminar on choreas. Lancet Neurol 2006c;5(7):589-602. PMID 16781989
- 51
- Cardoso F, Silva CE, Mota CC. Sydenham’s chorea in 50 consecutive patients with rheumatic fever. Mov Disord 1997;12:701-3. PMID 9380051
- 52
- Cardoso F, Vargas AP, Oliveira LD, Guerra AA, Amaral SV. Persistent Sydenham’s chorea. Mov Disord 1999;14:805-7. PMID 10495042
- 53
- Cavalcanti A, Hilário MO, dos Santos FH, Bolognani SA, Bueno OF, Len CA. Subtle cognitive deficits in adults with a previous history of Sydenham's chorea during childhood. Arthritis Care Res (Hoboken) 2010;62(8):1065-71. PMID 20235195
- 54
- Chain JL, Alvarez K, Mascaro-Blanco A, et al. Autoantibody biomarkers for basal ganglia encephalitis in Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections. Front Psychiatry 2020;11:564. PMID 32670106
- 55
- Cheadle WB. Harveian lectures on the various manifestations of the rheumatic state as exemplified in childhood and early life. Lancet 1889;133:821-7.
- 56
- Cheadle WB. The acute rheumatism of childhood. In: Albutt TC, editor. A system of medicine, by many writers. New York: The MacMillan Co, 1898;4:38-55.
- 57
- Chockalingam A, Gnanavelu G, Elangovan S, Chockalingam V. Clinical spectrum of chronic rheumatic heart disease in India. J Heart Valve Dis 2003;12(5):577-81. PMID 14565709
- 58
- Church AJ, Cardoso F, Dale RC, et al. Anti-basal ganglia antibodies in acute and persistent Sydenham's chorea. Neurology 2002;59:227-31. PMID 12136062
- 59
- Church AJ, Dale RC, Cardoso F, et al. CSF and serum immune parameters in Sydenham's chorea: evidence of an autoimmune syndrome. J Neuroimmunol 2003;136(1-2):149-53. PMID 12620654
- 60
- Church WS. Acute rheumatism, or rheumatic fever. In: Albutt TC, editor. A system of medicine, by many writers. New York: The MacMillan Co 1898;4:1-37.
- 61
- Citak EC, Gukuyener K, Karabacak NI, et al. Functional brain imaging in Sydenham’s chorea and streptococcal tic disorders. J Child Neurol 2004;19:387-90. PMID 15224712
- 62
- Corral-Corral I, Corral-Corral C. El tarantismo en España en el siglo XVIII: latrodectismo y sugestion [Tarantism in Spain in the eighteen century: latrodectism and suggestion]. Rev Neurol 2016;63(8):370-9. PMID 27699754
- 63
- Cox CJ, Sharma M, Leckman JF, et al. Brain human monoclonal autoantibody from sydenham chorea targets dopaminergic neurons in transgenic mice and signals dopamine D2 receptor: implications in human disease. J Immunol 2013;191(11):5524-41. PMID 24184556
- 64
- Cunningham MW. Molecular mimicry, autoimmunity, and infection: the cross-reactive antigens of group A Streptococci and their sequelae. Microbiol Spectr 2019;7(4).** PMID 31373269
- 65
- Cunningham MC, Maia DP, Teixeira AL Jr, Cardoso F. Sydenham's chorea is associated with decreased verbal fluency. Parkinsonism Relat Disord 2006;12(3):165-7. PMID 16460985
- 66
- DaCosta JC Jr. Principles and practice of physical diagnosis. Third edition. Philadelphia: W.B. Saunders Company, 1915.
- 67
- Dajani A, Taubert K, Ferrieri P, Peter G, Shulman S. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics 1995;96(4 Pt 1):758-64. PMID 7567345
- 68
- Dajani AS. Adherence to physicians' instructions as a factor in managing streptococcal pharyngitis. Pediatrics 1996;97(6 Pt 2):976-80. PMID 8637785
- 69
- Dale RC, Church AJ, Cardoso F, et al. Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies. Ann Neurol 2001;50:588-95. PMID 11706964
- 70
- Dale RC, Singh H, Troedson C, Pillai S, Gaikiwari S, Kozlowska K. A prospective study of acute movement disorders in children. Dev Med Child Neurol 2010;52(8):739-48. PMID 20163436
- 71
- Davutoglu V, Kilinc M, Dinckal H, Soydinc S, Sezen Y. Sydenham's chorea-clinical characteristics of nine patients. Int J Cardiol 2004;96(3):483-4. PMID 15301906
- 72
- Dean SL, Singer HS. Treatment of Sydenham's chorea: a review of the current evidence. Tremor Other Hyperkinet Mov (N Y) 2017;7:456. PMID 28589057
- 73
- Direk M, Epcacan S, Epcacan Z, Yildirim DD, Okuyaz C. Efficacy of levetiracetam in the treatment of Sydenham chorea. Pediatr Int 2020;62(11):1264-8. PMID 32445412
- 74
- Donadi EA, Smith AG, Louzada-Junior P, Voltarelli JC, Nepom GT. HLA class I and class II profiles of patients presenting with Sydenham's chorea. J Neurol 2000;247:122-8. PMID 10751115
- 75
- Doyle F, Cardoso F, Lopes L, et al. Infusion of Sydenham's chorea antibodies in striatum with up-regulated dopaminergic receptors: a pilot study to investigate the potential of SC antibodies to increase dopaminergic activity. Neurosci Lett 2012;15;523(2):186-9. PMID 22781496
- 76
- Eftychiadis AC, Chen TS. Saint Vitus and his dance. J Neurol Neurosurg Psychiatry 2001;70:14. PMID 11118241
- 77
- Eisen JL, Leonard HL, Swedo SE, et al. The use of antibody D8/17 to identify B cells in adults with obsessive-compulsive disorder. Psychiatry Res 2001;104:221-5. PMID 11728611
- 78
- Erdem S, Demir F, Ayana M, et al. Acute rheumatic fever in south-east of Turkey: clinical features and epidemiological evaluation of the patients over the last 25 years. Cardiol Young 2020;30(8):1086-94. PMID 32611460
- 79
- Eyre M, Thomas T, Ferrarin E, et al. Treatments and outcomes among patients with sydenham chorea: a meta-analysis. JAMA Netw Open 2024;7(4):e246792. PMID 38625703
- 80
- Favaretto E, Gortani G, Simonini G, et al. Preliminary data on prednisone effectiveness in children with Sydenham chorea. Eur J Pediatr 2020;179(6):993-7. PMID 31965299
- 81
- Feldman BM, Zabriskie JB, Silverman ED, Laxer RM. Diagnostic use of B-cell alloantigen D8/17 in rheumatic chorea. J Pediatr 1993;123:84-6. PMID 8320631
- 82
- Gabbett HS. On the seasons of the year and the prevalence of acute rheumatism. Lancet 1883;2:675-7, 720-2.
- 83
- Gabbett HS. Seasonal variations of rheumatism. Popular Science Monthly 1884;25:429.
- 84
- Gauquelin L, Tran LT, Chouinard S, Bernard G. The movement disorder of brain-lung-thyroid syndrome can be responsive to methylphenidate. Tremor Other Hyperkinet Mov (N Y) 2017;7:508. PMID 29109906
- 85
- Genel F, Arslanoglu S, Uran N, Saylan B. Sydenham's chorea: clinical findings and comparison of the efficacies of sodium valproate and carbamazepine regimens. Brain Dev 2002;24:73-6. PMID 11891095
- 86
- Gewitz M, Baltimore RS, Tani LY, et al. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation 2015;131(20):1806-18. PMID 25908771
- 87
- Gibb WR, Lees AJ, Scadding JW. Persistent rheumatic chorea. Neurology 1985;35(1):101-2. PMID 3965980
- 88
- Giedd JN, Rapoport JL, Kruesi MJ, et al. Sydenham’s chorea: magnetic resonance imaging of the basal ganglia. Neurology 1995;45:2199-202. PMID 8848193
- 89
- Gilbert DL, Kurlan R. PANDAS: horse or zebra. Neurology 2009;73(16):1252-3. PMID 19794126
- 90
- Gimenez-Roldán S, Aubert G. Hysterical chorea: Report of an outbreak and movie documentation by Arthur Van Gehuchten (1861-1914). Mov Disord 2007;22(8):1071-6.** PMID 17230482
- 91
- Goetz CG, Chmura TA, Lanska DJ. History of chorea: Part 3 of the MDS-sponsored History of Movement Disorders Exhibit, Barcelona, Spain, June 2000. Movement Disorders 2001a;16:331-8. PMID 11295790
- 92
- Goetz CG, Chmura TA, Lanska DJ. Seminal figures in the history of movement disorders: Sydenham, Parkinson, and Charcot: part 6 of the MDS-sponsored History of Movement Disorders Exhibit, Barcelona, Spain, June 2000. Mov Disord 2001b;16(3):537-40. PMID 11391755
- 93
- Giorgio SM, Caprio MG, Galante F, et al. Clinical value of perfusion abnormalities of brain on technetium-99m HMPAO single-photon emission computed tomography in children with sydenham chorea. J Child Neurol 2017;32(3):316-21. PMID 27920268
- 94
- Goldman S, Amrom D, Szliwowski HB, et al. Reversible striatal hypermetabolism in a case of Sydenham's chorea. Mov Disord 1993;8(3):355-8. PMID 8341301
- 95
- Gurkas E, Karalok ZS, Taskin BD, et al. Predictors of recurrence in Sydenham’s chorea: clinical observation from a single center. Brain Dev 2016;38(9):827-34. PMID 27209549
- 96
- Hallett M, Obeso J. Where does chorea come from? cortical excitability findings challenge classic pathophysiological concepts. Mov Disord 2015;30(2):169-70. PMID 25546440
- 97
- Harel L, Zeharia A, Kodman Y, et al. Presence of the D8/17 B-cell marker in children with rheumatic fever in Israel. Clin Genet 2002;61:293-8. PMID 12030895
- 98
- Harrison NA, Church A, Nisbet A, Rudge P, Giovannoni G. Late recurrences of Sydenham's chorea are not associated with anti-basal ganglia antibodies. J Neurol Neurosurg Psychiatry 2004;75:1478-9. PMID 15377702
- 99
- Haydardedeoglu FE, Tutkak H, Kose K, Duzgun N. Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis: association with HLA-DR alleles. Tissue Antigens 2006;68:293-6. PMID 17026463
- 100
- Hayden MR. Huntington's chorea. New York: Springer-Verlag, 1981.
- 101
- Heard MA, Green MC, Royer M. Acute rheumatic fever: a review of essential cutaneous and histological findings. Cureus 2021;13(1):e12577. PMID 33575142
- 102
- Hirsch A. Handbook of Geographical and Historical Pathology. Vol. III: Diseases of Organs and Parts. Translated from the second German edition by Charles Creighton MD. London: The New Sydenham Society, 1886:534.
- 103
- Hounie AG, Pauls DL, do Rosario-Campos MC, et al. Obsessive-compulsive spectrum disorders and rheumatic fever: a family study. Biol Psychiatry 2007;61:266-72. PMID 16616727
- 104
- Husby G, Van De Rijn U, Zabriskie JB, Abdin ZH, Williams RC Jr. Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med 1976;144:1094-110. PMID 789810
- 105
- Jackson JH. Observations on the physiology and pathology of hemi-chorea. In: Taylor J, Holmes G, Walshe FMR, editors. John Hughlings Jackson: selected writings. Volume 2. Nijmegen, The Netherlands: Arts and Boeve Publishers, 1996:238-45.
- 106
- Jankovic J. Differential diagnosis and etiology of tics. Adv Neurol 2001;85:15-29. PMID 11530424
- 107
- Jansen TL, Hoekstra PJ, Bijzet J, et al. Elevation of D8/17-positive B lymphocytes in only a minority of Dutch patients with post-streptococcal reactive arthritis (PSRA): a pilot study. Rheumatology 2002;41:1202-3. PMID 12364649
- 108
- Jones TD. The diagnosis of rheumatic fever. JAMA 1944;126:481-4.
- 109
- Karalok ZS, Öztürk Z, Gunes A, Gurkas E. Sydenham chorea: putaminal enlargement. J Child Neurol 2021;36(1):48-53. PMID 32851928
- 110
- Kaur S, Kumar D, Grover A, et al. Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients. Int J Cardiol 1998;64:9-14. PMID 9579811
- 111
- Khedr EM, Ahmed MA, Ali AM, Badry R, Rothwell JC. Changes in motor cortical excitability in patients with Sydenham's chorea. Mov Disord 2015;30(2):259-62. PMID 24909435
- 112
- Kirvan CA, Swedo SE, Heuser JS, Cunningham MW. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 2003;9(7):914-20. PMID 12819778
- 113
- Kocevar U, Toplak N, Kosmač B, et al. Acute rheumatic fever outbreak in southern Central European country. Eur J Pediatr 2017;176(1):23-9. PMID 27815733
- 114
- Korn-Lubetzki I, Brand A, Steiner I. Recurrence of Sydenham chorea: implications for pathogenesis. Arch Neurol 2004;61:1261-4. PMID 15313844
- 115
- Korn-Lubetzki I, Brand A. Sydenham's chorea in Jerusalem: still present. Isr Med Assoc J 2004;6(8):460-2. PMID 15326823
- 116
- Krack P. Relicts of dancing mania: the dancing procession of Echternach. Neurology 1999;53:2169-72.** PMID 10599799
- 117
- Kummer A, Maia DP, Cardoso F, Teixeira AL. Trichotillomania in acute Sydenham’s chorea. Aust NZ J Psychiatry 2007;41(12):1013-4. PMID 17999275
- 118
- Lanska DJ. George Huntington and hereditary chorea. J Child Neurol. 1995;10(1):46-8. PMID 7769178
- 119
- Lanska DJ. George Huntington (1850-1916) and hereditary chorea. J Hist Neurosci 2000;9(1):76-89.** PMID 11232352
- 120
- Lanska DJ. The history of movement disorders. Handb Clin Neurol 2010;95:501-46.** PMID 19892136
- 121
- Lanska DJ. Thomas Sydenham. In: Aminoff MJ, Daroff RB (eds.) Encyclopedia of the Neurological Sciences. 2nd edition. Oxford: Academic Press/Elsevier, 2014;4:366-8.**
- 122
- Lanska DJ. The dancing manias: psychogenic illness as a social phenomenon. Front Neurol Neurosci 2018;42:132-41.** PMID 29151097
- 123
- Lanska DJ, Goetz CG, Chmura TA. Seminal figures in the History of Movement Disorders: Hammond, Osler, and Huntington. Part 11 of the MDS-Sponsored History of Movement Disorders Exhibit, Barcelona, June 2000. Mov Disord 2001;16(4):749-53. PMID 11481703
- 124
- Lee PH, Nam HS, Lee KY, Lee BI, Lee JD. Serial brain SPECT images in a case of Sydenham chorea. Arch Neurol 1999;56:237-40. PMID 10025430
- 125
- Leon J, Hommer R, Grant P, et al. Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). Eur Child Adolesc Psychiatry 2018;27(5):637-43. PMID 29119300
- 126
- Lotan D, Benhar I, Alvarez K, et al. Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats. Brain Behav Immun 2014;38:249-62. PMID 24561489
- 127
- Lue HC, Wu MH, Hsieh KH, Lin GJ, Hsieh RP, Chiou JF. Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs. J Pediatr 1986;108(2):299-304. PMID 3511209
- 128
- Maia DP, Fonseca PG, Camargos ST, et al. Pregnancy in patients with Sydenham's chorea. Parkinsonism Relat Disord 2012;18(5):458-61. PMID 22236583
- 129
- Maia DP, Teixeira AL Jr, Quintao Cunningham MC, Cardoso F. Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea. Neurology 2005;64(10):1799-801. PMID 15911817
- 130
- Majeed HA, Shaltout A, Yousof AM. Recurrences of acute rheumatic fever: a prospective study of 79 episodes. Am J Dis Child 1984;138(4):341-5. PMID 6702784
- 131
- Martino D, Tanner A, Defazio G, et al. Tracing Sydenham's chorea: historical documents from a British paediatric hospital. Arch Dis Child 2005;90(5):507-11. PMID 15851434
- 132
- Mason T, Fisher M, Kujala G. Acute rheumatic fever in West Virginia: not just a disease of children. Arch Intern Med 1991;151:133-6. PMID 1985588
- 133
- Massell BF. Rheumatic fever and streptococcal infection: unraveling the mysteries of a dread disease. Boston, MA: Harvard University Press, 1997.
- 134
- Mehanna R, Jankovic J. Movement disorders in cerebrovascular disease. Lancet Neurol 2013;12(6):597-608. PMID 23602779
- 135
- Mencacci NE, Erro R, Wiethoff S, et al. ADCY5 mutations are another cause of benign hereditary chorea. Neurology 2015;85(1):80-8. PMID 26085604
- 136
- Mercadante MT, Busatto GF, Lombroso PJ, et al. The psychiatric symptoms of rheumatic fever. Am J Psychiatry 2000;157:2036-8. PMID 11097972
- 137
- Mercadante MT, Campos MC, Marques-Dias MJ, et al. Vocal tics in Sydenham’s chorea. J Am Acad Child Adolesc Psychiatry 1997;36:305-6. PMID 9055509
- 138
- Miyatake S, Koshimizu E, Shirai I, et al. A familial case of PDE10A-associated childhood-onset chorea with bilateral striatal lesions. Mov Disord 2018;33(1):177-9. PMID 29165877
- 139
- Mohammad SS, Dale RC. Principles and approaches to the treatment of immune-mediated movement disorders. Eur J Paediatr Neurol 2018;22(2):292-300. PMID 29289523
- 140
- Moreau C, Devos D, Delmaire C, Gervais C, Defebvre L, Destée A. Progressive MRI abnormalities in late recurrence of Sydenham's chorea. J Neurol 2005;252(11):1341-4. PMID 15981082
- 141
- Moreira J, Kummer A, Harsányi E, Cardoso F, Teixeira AL. Psychiatric disorders in persistent and remitted Sydenham's chorea. Parkinsonism Relat Disord 2014;20(2):233-6. PMID 24268384
- 142
- Morris-Berry CM, Pollard M, Gao S, Thompson C, Tourette Syndrome Study Group, Singer HS. Anti-streptococcal, tubulin, and dopamine receptor 2 antibodies in children with PANDAS and Tourette syndrome: single-point and longitudinal assessments. J Neuroimmunol 2013;264(1-2):106-13. PMID 24080310
- 143
- Morshed SA, Parveen S, Leckman JF, et al. Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders. Biol Psychiatry 2001;50:566-77. PMID 11690591
- 144
- Murphy TK, Benson N, Zaytoun A, et al. Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder. J Neuroimmunol 2001;120:146-51. PMID 25314807
- 145
- Nausieda PA, Bieliauskas LA, Bacon LD, Hagerty M, Koller WC, Glantz RN. Chronic dopaminergic sensitivity after Sydenham's chorea. Neurology 1983;33(6):750-4. PMID 6188998
- 146
- Nausieda PA, Grossman BJ, Koller WC, Weiner WJ, Klawans HL. Sydenham's chorea: an update. Neurology 1980;30:331-4. PMID 7189038
- 147
- Noonan S, Zurynski YA, Currie BJ, et al. A national prospective surveillance study of acute rheumatic fever in Australian children. Pediatr Infect Dis J 2013;32(1):e26-32. PMID 22926211
- 148
- Norris GW. Studies in cardiac pathology. Philadelphia and London: W.B. Saunders Company, 1911.
- 149
- Okun MS, Thommi N. Americo Negrette (1924 to 2003): diagnosing Huntington disease in Venezuela. Neurology 2004;63(2):340-3. PMID 15277631
- 150
- Oliveira PM, Cardoso F, Maia DP, Cunningham MC, Teixeira AL Jr, Reis C. Acoustic analysis of prosody in Sydenham’s chorea. Arq Neuropsiquiatr 2010;68(5):744-8. PMID 21049186
- 151
- Orsini A, Foiadelli T, Magistrali M, et al. A nationwide study on Sydenham's chorea: clinical features, treatment and prognostic factors. Eur J Paediatr Neurol 2022a;36:1-6. PMID 34768201
- 152
- Orsini A, Foiadelli T, Sica A, et al. Psychopathological impact in patients with history of rheumatic fever with or without Sydenham's chorea: a multicenter prospective study. Int J Environ Res Public Health 2022b;19(17):10586. PMID 36078300
- 153
- Paghera B, Caobelli F, Giubbini R, Premi E, Padovani A. Reversible striatal hypermetabolism in a case of rare adult-onset Sydenham chorea on two sequential 18F-FDG PET studies. J Neuroradiol 2011;38(5):325-6. PMID 21215457
- 154
- Panamonta M, Chaikitpinyo A, Auvichayapat N, et al. Evolution of valve damage in Sydenham's chorea during recurrence of rheumatic fever. Int J Cardiol 2007;119(1):73-9. PMID 17049647
- 155
- Patel NJ, Jankovic J. NKX2-1-Related Disorders. In: Pagon RA, Adam MP, Bird TD, et al, editors. GeneReviews™ [Internet]. Seattle: University of Washington, 2014.
- 156
- Paz JA, Silva CA, Marques-Dias MJ. Randomized double-blind study with prednisone in Sydenham's chorea. Pediatr Neurol 2006;34:264-9. PMID 16638499
- 157
- Pearlman DM, Vora HS, Marquis BG, Najjar S, Dudley LA. Anti-basal ganglia antibodies in primary obsessive-compulsive disorder: systematic review and meta-analysis. Br J Psychiatry 2014;205(1):8-16. PMID 24986387
- 158
- Perez-Vigil A, Fernández de la Cruz L, Brander G, Isomura K, Gromark C, Mataix-Cois D. The link between autoimmune diseases and obsessive-compulsive and tic disorders: a systematic review. Neurosci Biobehav Rev 2016;71:542-62. PMID 27687817
- 159
- Pineles F. Hyperkinetic diseases: infectious chorea. 811-816. In: Burr CW, editor. Text-book on nervous diseases. Philadelphia: P. Blakiston's Son & Co 1915:811-6.
- 160
- Poynton FJ. Clinical lectures on rheumatic fever. I. Endocarditis in childhood considered as a symptom of infective diseases. Internat Clin 1903a;2(13):181-94.
- 161
- Poynton FJ. Clinical lectures on rheumatic fever. II. Clinical evidences of myocardial damage in rheumatic fever. Internat Clin 1903b;3(13):226-41.
- 162
- Poynton FJ. Clinical lectures on rheumatic fever. III. The parallelism between the clinical symptoms and the pathological lesions of rheumatic fever. Internat Clin 1904;4(13):95-111.
- 163
- Poynton F, Paine A. Researches on rheumatism. London: Churchill Livingstone, 1913.
- 164
- Pulickal AS, Ramachandran S, Rizek P, Narula P, Schubert R. Chorea and developmental regression associated with human herpes virus-6 encephalitis. Pediatr Neurol 2013;48(3):249-51. PMID 23419479
- 165
- Quinn RW. Epidemiologic study of seven hundred and fifty-seven cases of rheumatic fever. Arch Intern Med (Chic) 1947;80(6):709-27.
- 166
- Quinn RW. Comprehensive review of morbidity and mortality trends for rheumatic fever, streptococcal disease, and scarlet fever: the decline of rheumatic fever. Rev Infect Dis 1989;11:928-53. PMID 2690288
- 167
- Ramasawmy R, Fae KC, Spina G, et al. Association of polymorphisms within the promoter region of the tumor necrosis factor-alpha with clinical outcomes of rheumatic fever. Mol Immunol 2007;44:1873-8. PMID 17079017
- 168
- Remenyi B, Wilson N, Steer A, et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease--an evidence-based guideline. Nat Rev Cardiol 2012;9(5):297-309. PMID 22371105
- 169
- Ryan M, Antony JH, Grattan-Smith PJ. Sydenham chorea: a resurgence of the 1990s. J Pediatr Child Health 2000;36:95-6. PMID 17023704
- 170
- Salpietro V, Perez-Dueñas B, Nakashima K, et al. A homozygous loss-of-function mutation in PDE2A associated to early-onset hereditary chorea. Mov Disord 2018;33(3):482-8. PMID 29392776
- 171
- Schrag A, Gilbert R, Giovannoni G, et al. Streptococcal infection, Tourette syndrome, and OCD: is there a connection. Neurology 2009;73(16):1256-63. PMID 19794128
- 172
- Schwartz RH, Hepner SI, Ziai M. Incidence of acute rheumatic fever. A suburban community hospital experience during the 1970s. Clin Pediatr (Phila) 1983;22(12):798-801. PMID 6627812
- 173
- Shiohama T, Ohashi H, Shimizu K, et al. l-thyroxine-responsive drop attacks in childhood benign hereditary chorea: a case report. Brain Dev 2018;40(4):353-6. PMID 29289388
- 174
- Singer HS. Autoantibody-associated movement disorders in children: proven and proposed. Semin Pediatr Neurol 2017;24(3):168-79. PMID 29103424
- 175
- Slade CB. Physical Examination and Diagnostic Anatomy. Philadelphia and London: W.B. Saunders Company, 1910.
- 176
- Smith MT, Lester-Smith D, Zurynski Y, Noonan S, Carapetis JR, Elliott EJ. Persistence of acute rheumatic fever in a tertiary children's hospital. J Paediatr Child Health 2011;47(4):198-203. PMID 21199062
- 177
- Solela G, Fedlu M. Rare recurrence of Sydenham chorea in an adult: a case report. Int Med Case Rep J 2023;16:265-8. PMID 37193054
- 178
- Somers LS. The diagnosis and treatment of membranous tonsillitis. Internat Clin 1906;1(16):41-56.
- 179
- Special Writing Group of the Committee of Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardio-Vascular Disease of the Young of the American Heart Association. Guidelines for diagnosis of rheumatic fever, Jones criteria, 1992 update. Guidelines for the diagnosis of rheumatic fever. JAMA 1992;268:2069-73.
- 180
- Steer AC. Historical aspects of rheumatic fever. J Paediatr Child Health 2015;51(1):21-7. PMID 25586841
- 181
- Stewart JS. A claim to fame: Thomas Sydenham. Postgrad Med J 1953;29(335):465-7. PMID 13088511
- 182
- Stollerman GH, Rusoff JH. Prophylaxis against group A streptococcal infections in rheumatic fever patients; use of new repository penicillin preparation. J Am Med Assoc 1952;150(16):1571-5. PMID 12990472
- 183
- Swedo SE. Sydenham's chorea. A model for childhood autoimmune neuropsychiatric disorders. JAMA 1994;272:1788-91. PMID 7661914
- 184
- Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998;155:264-71. PMID 9464208
- 185
- Sydenham T. On St. Vitus’s dance. In: Sydenham T. The Entire Works of Thomas Sydenham [Translated by Latham RG]. London: Sydenham Society, 1848;2:257-9.
- 186
- Taranta A, Stollerman GH. The relationship of Sydenham’s chorea to infection with group A streptococci. Am J Med 1956;20:1970. PMID 13282936
- 187
- Tariq S, Niaz F, Waseem S, et al. Managing and treating Sydenham chorea: a systematic review. Brain Behav 2023;13(6):e3035. PMID 37150977
- 188
- Teixeira AL, Athayde GR, Sacramento DR, Maia DP, Cardoso F. Depressive and anxiety symptoms in Sydenham's chorea. Mov Disord 2007a;22(6):905-6. PMID 17343271
- 189
- Teixeira AL, Bretas TL, Kummer A, et al. Serum levels of brain-derived neurotrophic factor in Sydenham's chorea. Neurol Sci 2010;31(3):399-401. PMID 20112124
- 190
- Teixeira AL, Cardoso F, Maia DP, Cunningham MC. Sydenham’s chorea may be a risk factor for drug induced parkinsonism. J Neurol Neurosurg Psychiatry 2003;74(9):1350-1. PMID 12933958
- 191
- Teixeira AL, Cardoso F, Maia DP, et al. Frequency and significance of vocalizations in Sydenham’s chorea. Parkinsonism Relat Disord 2009;15(1):62-3. PMID 18343182
- 192
- Teixeira AL, Cardoso F, Souza AL, Teixeira MM. Increased serum concentrations of monokine induced by interferon-gamma/CXCL9 and interferon-gamma-inducible protein 10/CXCL-10 in Sydenham's chorea patients. J Neuroimmunol 2004;150(1-2):157-62. PMID 15081261
- 193
- Teixeira AL, Guimaraes MM, Romano-Silva MA, Cardoso F. Serum from Sydenham's chorea patients modifies intracellular calcium levels in PC12 cells by a complement-independent mechanism. Mov Disord 2005a;20(7):843-5. PMID 15747354
- 194
- Teixeira AL, Maia DP, Cardoso F. UFMG Sydenham's chorea rating scale (USCRS): reliability and consistency. Mov Disord 2005b;20(5):585-91. PMID 15648075
- 195
- Teixeira AL, Maia DP, Cardoso F. Treatment of acute Sydenham's chorea with methyl-prednisolone pulse-therapy. Parkinsonism Relat Disord 2005c;11(5):327-30. PMID 15878690
- 196
- Teixeira AL, Maia DP, Cardoso F. Psychosis following acute Sydenham's chorea. Eur Child Adolesc Psychiatry 2007b;16(1):67-9. PMID 16791540
- 197
- Teixeira AL, Meira FC, Maia DP, Cunningham MC, Cardoso F. Migraine headache in patients with Sydenham's chorea. Cephalalgia 2005d;25(7):542-4. PMID 15955042
- 198
- Terreri MT, Roja SC, Len CA, Faustino PC, Roberto AM, Hilário MO. Sydenham's chorea--clinical and evolutive characteristics. Sao Paulo Med J 2002;120(1):16-9. PMID 11836548
- 199
- Torres KC, Dutra WO, de Rezende VB, Cardoso F, Gollob KJ, Teixeira AL. Monocyte dysfunction in Sydenham's chorea patients. Hum Immunol 2010;71(4):351-4. PMID 20080141
- 200
- Torres KC, Rocha NP, Rezende VB, et al. Persistent Sydenham's chorea is not associated with sustained lymphocyte dysfunction. Arq Neuropsiquiatr 2016;74(1):5-9. PMID 26486494
- 201
- Tumas V, Caldas CT, Santos AC, Nobre A, Fernandes RM. Sydenham's chorea: clinical observations from a Brazilian movement disorder clinic. Parkinsonism Relat Disord 2007;13(5):276-83. PMID 17240185
- 202
- Vale TC, Glass PG, Lees A, Cardoso F. Gowers' Queen Square case notes on chorea: a 21st century re-appraisal. Eur Neurol 2013;69(1):48-52. PMID 23128056
- 203
- Vale TC, Maciel RO, Maia D, Beato R, Cardoso F. Takayasu's arteritis in a patient with Sydenham's chorea: is there an association. Tremor Other Hyperkinet Mov (N Y) 2012;2. PMID 23439787
- 204
- Vijayalakshmi IB, Mithravinda J, Deva AN. The role of echocardiography in diagnosing carditis in the setting of acute rheumatic fever. Cardiol Young 2005;15:583-8. PMID 16297251
- 205
- Walker K, Brink A, Lawrenson J, Mathiassen W, Wilmshurst JM. Treatment of Sydenham chorea with intravenous immunoglobulin. J Child Neurol 2012;27(2):147-55. PMID 21868369
- 206
- Walker KG, Lawrenson J, Wilmshurst JM. Neuropsychiatric movement disorders following streptococcal infection. Dev Med Child Neurol 2005;47:771-5. PMID 16225742
- 207
- 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;3(5):301-9. PMID 21179620
- 208
- Wallace MR, Garst PD, Papadimos TJ, Oldfield EC 3rd. The return of acute rheumatic fever in young adults. JAMA 1989;262(18):2557-61. PMID 2681847
- 209
- Wang Z, Chan AYL, Coghill D, et al. Association between prenatal exposure to antipsychotics and attention-deficit/hyperactivity disorder, autism spectrum disorder, preterm birth, and small for gestational age. JAMA Intern Med 2021;181(10):1332-40. PMID 34398171
- 210
- Weindl A, Kuwert T, Leenders KL, et al. Increased striatal glucose consumption in Sydenham's chorea. Mov Disord 1993;8:437-44. PMID 8232353
- 211
- Wilson NJ, Voss L, Morreau J, Stewart J, Lennon D. New Zealand guidelines for the diagnosis of acute rheumatic fever: small increase in the incidence of definite cases compared to the American Heart Association Jones criteria. N Z Med J 2013;126(1279):50-9. PMID 24045352
- 212
- Wood HF, Feinstein AR, Taranta A, Epstein HA, Simpson R. Rheumatic fever in children and adolescents. A long term epidemiological study of subsequent prophylaxis, streptococcal infections, and clinical sequelae. III. Comparative effectiveness of three prophylaxis regimens in preventing streptococcal infections and rheumatic recurrences. Ann Intern Med 1964;60(2):5:31-46.
- 213
- World Health Organization. WHO Model Prescribing Information: Drugs used in the Treatment of Streptococcal Pharyngitis and Prevention of Rheumatic Fever. Geneva: World Health Organization, 1999.
- 214
- World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO expert consultation: Geneva, 29 October--1 November 2001. WHO Technical Report Series. Geneva: World Health Organization, 2004:923.**
- 215
- Zomorrodi A, Wald ER. Sydenham's chorea in western Pennsylvania. Pediatrics 2006;117:e675-9. PMID 16533893
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Douglas J Lanska MD MS MSPH
Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile
Former Authors
- Christopher F O'Brien MD
- Joseph Jankovic MD
- Francisco Cardoso MD PhD
- Robert Fekete MD
Patient Profile
- Age range of presentation
-
- 6 to 44 years
- Sex preponderance
-
- female>male, >1:1
- Heredity
-
- none
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-10
-
- Rheumatic chorea with heart involvement: I02.0
- Rheumatic chorea without heart involvement: I02.9
- ICD-11
-
- Rheumatic chorea: 1B42
This is an article preview.
Start a Free Account
to access the full version.
-
Nearly 3,000 illustrations, including video clips of neurologic disorders.
-
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
-
Full spectrum of neurology in 1,200 comprehensive articles.
-
Listen to MedLink on the go with Audio versions of each article.
Questions or Comment?
MedLink®, LLC
3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122
Toll Free (U.S. + Canada): 800-452-2400
US Number: +1-619-640-4660
Support: service@medlink.com
Editor: editor@medlink.com
ISSN: 2831-9125
Also in This Category
-
-
Neurogenetic Disorders
Wilson disease
Oct. 23, 2024
-
Peripheral Neuropathies
Neuroacanthocytosis
Aug. 22, 2024
-
Movement Disorders
Restless legs syndrome
Aug. 22, 2024
-
Neurobehavioral & Cognitive Disorders
Dementia in Parkinson disease
Aug. 16, 2024
-
General Neurology
ALS-like disorders of the Western Pacific
Aug. 14, 2024
-
Sleep Disorders
Sleep-related leg cramps
Aug. 09, 2024
-
Sleep Disorders
Sleep and cerebral degenerative disorders
Jul. 13, 2024
