The psychiatric symptoms of rheumatic fever

OBJECTIVE: This study examined the frequency and age at onset of psychiatric disorders among children with rheumatic fever, Sydenham's chorea, or both and a comparison group. METHOD: Twenty children with rheumatic fever, 22 with Sydenham's chorea, and 20 comparison children were assessed by means of a semistructured interview and rating scales for tic disorders and obsessive-compulsive disorder. RESULTS: Obsessive-compulsive symptoms were more frequent in both the Sydenham's chorea and rheumatic fever groups than in the comparison group. The Sydenham's chorea group had a higher frequency of major depressive disorder, tic disorders, and attention deficit hyperactivity disorder (ADHD) than both the comparison and rheumatic fever groups. ADHD symptoms were associated with a higher risk of developing Sydenham's chorea. CONCLUSIONS: Both the rheumatic fever and Sydenham's chorea groups were associated with a higher risk of developing neuropsychiatric disorders than the comparison group. ADHD appears to be a risk factor for Sydenham's chorea in children with rheumatic fever.     

Corticosteroid treatment in patients with Sydenham's chorea

Sydenham's chorea occurs in approximately 10% of acute rheumatic fever and is one of its major manifestations. The disease may last for weeks or months, with a high risk of recurrence; usually only supportive treatment is recommended. This report describes five children diagnosed with Sydenham's chorea and treated with a short course of corticosteroids. Marked improvement of the involuntary movements was observed within 24-48 hours, with complete resolution within 7-12 days after commencement of treatment; there were no relapses. Larger, possibly comparative studies are necessary, but in the meantime treatment with corticosteroids in patients with Sydenham's chorea should be considered.     

High prevalence of obsessive-compulsive symptoms in patients with Sydenham's chorea

The 20-item Leyton Obsessional Inventory--Child Version was completed by children and adolescents who had had Sydenham's chorea (N = 23) or rheumatic fever without chorea (N = 14). The Sydenham's chorea subjects had significantly more obsessive thoughts and compulsive behaviors and significantly greater interference from these behaviors. Three Sydenham's chorea patients but no rheumatic fever patients had substantial obsessional interference and met criteria for obsessive-compulsive disorder when interviewed by telephone. This suggests that obsessive-compulsive disorder, at least in some patients, may be due to basal ganglia dysfunction.     

Is Sydenham's chorea an antiphospholipid syndrome?

In 1686, Thomas Sydenham described a syndrome of chorea occurring in youth which was subsequently shown to be a complication of rheumatic fever. An association between chorea and antiphospholipid antibodies has been reported since 1985. We report two females presenting with chorea, aged 17 and 22, who fulfilled the Jones' criteria for rheumatic fever and concurrently had antiphospholipid antibodies detected in serum. A third patient presented at the age of 16 with two bouts of Sydenham's chorea; no assays for antiphospholipid antibodies were performed at the time but 13 years later she was found to have high titres of anticardiolipin antibodies. No patient had abnormalities in the basal ganglia detected on magnetic resonance imaging. Sydenham's chorea may be part of the spectrum of antiphospholipid-associated neurological disease.     

Comparison of the efficacy of carbamazepine,haloperidol and valproic acid in the treatment of children with Sydenham's chorea: clinical follow-up of 18 patients

In order to compare and contrast the efficacy of haloperidol, carbamazepine, and valproic acid in the treatment of Sydenham's chorea a prospective study including 18 cases of this disorder was undertaken. Age of patients ranged from 7 to 15 years. Ten children were female and 8 were male. All but one had generalized, either symmetric or asymmetric chorea. The patients were divided in three equal groups, and were given a standardized dose of each of the drugs built-up over a week. Following therapy, the six children receiving valproic acid showed remarkable improvement, without side effects. Five patients receiving carbamazepine showed improvement without side effects. Only three of the patients that received haloperidol improved. In the 4 cases that did not show clinical improvement after one week of treatment, therapy with valproic acid led to disappearance of the symptoms in a lapse that ranged from 4 to 7 days. Recurrence related to discontinuation of treatment was observed in two patients. In view of the present results we recommend valproic acid as the first choice drug to treat Sydenham chorea.     

Sydenham's chorea: not gone and not forgotten

Sydenham's chorea is an ancient disease that continues to afflict large numbers of children throughout the world. A major manifestation of rheumatic fever, Sydenham's chorea is commonly manifested by movement disorder and psychiatric problems, and also may be a marker for a life-threatening carditis. Because Sydenham's chorea is triggered by streptococcal pharyngitis, the most important component of its therapy is antibiotic prophylaxis against further streptococcal infections. Because the pathogenesis of Sydenham's chorea includes the production of anti-basal ganglia antibodies, therapies that modulate immune function or that restore neurotransmitter balance within the basal ganglia may be effective for Sydenham's chorea. Recent reports have suggested that Sydenham's chorea may be part of a spectrum of neuropsychiatric syndromes induced by streptococcal infection.     

Brain magnetic resonance spectroscopy in Sydenham's chorea and ADHD

This report presents clinical, laboratory, and neuroimaging findings in a 7-year-old male with Sydenham's chorea associated with attention-deficit hyperactivity disorder. Western immunoblotting revealed serum anti-human basal ganglia tissue antibodies. Magnetic resonance imaging results were normal. Proton magnetic resonance spectroscopic imaging disclosed increased choline/creatine ratio in basal ganglia, frontal, and parieto-occipital areas, and decreased N-acetyl aspartate/creatine ratio in both basal ganglia and frontal areas. Moreover magnetic resonance spectroscopy revealed a peak between 3.6-4.2 ppm of unclear significance. The findings of this study are compared with the previous magnetic resonance spectroscopic studies reported on Sydenham's chorea and attention-deficit hyperactivity disorder. Magnetic spectroscopic imaging suggests an autoimmune basal ganglia damage in the pathogenesis of Sydenham's chorea and fronto-striatal impairment in attention-deficit hyperactivity disorder. In the present case, the previous history of an attention-deficit hyperactivity disorder suggests that this neurobehavioral disorder could be a risk factor for Sydenham's chorea in children with rheumatic fever.     

Persistent Sydenham's chorea.

BACKGROUND: Sydenham's chorea (SC) occurs in 26% of patients with rheumatic fever (RF). Despite usually being described as a self-limited condition, few reports indicate that SC may persist in rare subjects. OBJECTIVE: To investigate the proportion of subjects with SC lasting more than 2 years and if clinical features differentiate patients with SC with a duration of less than 2 years (Group 1) from those with SC lasting more than 2 years (Group 2). METHODS: Prospective assessment of all patients with SC seen at our service from July 1993 through March 1998 analyzing the following: gender; age at onset; frequency of arthritis, carditis, family history of RF and SC; topographic distribution; and chorea severity on a 0-4 scale. RESULTS: Thirty-two patients (19 female, 13 male) were studied. In Group 1 (16 subjects, 50%) the follow-up period was 36.2 +/- 20.0 months; 50% were female; age at onset was 10.9 +/- 2.6 years; arthritis and carditis were present in 37.5% and 31.2%, respectively; family history of SC was reported by 18.7%; hemichorea was seen in 25.8% of subjects; and the mean intensity of chorea was 2.6 +/- 0.8. In Group 2, with a follow-up period of 34.1 +/- 18.9 months, 68.8% were female; age at onset was 9.3 +/- 3.9 years; arthritis and carditis were diagnosed in 18.7% and 50%, respectively; no patient reported a family history of SC; hemichorea was observed in 6.2% of subjects; and the mean intensity of chorea was 2.8 +/- 0.5. No difference was statistically significant. CONCLUSIONS: SC persists in half of our patients. Female gender, possibly related to endocrine factors, as well as the presence of carditis, indicating a more severe disease, may be risk factors for a longer duration of SC.     

Sydenham's chorea and psychopathology

Sydenham's chorea is a movement disorder seen in rheumatic fever with basal ganglia pathology. This disorder has been associated with an increased frequency of psychopathology in both the acute choreiform stage and later in life. We conducted a prospective study of 29 subjects with Sydenham's chorea and 29 age- and sex-matched controls. The total number of psychiatric symptoms 10 years after the initial contact was much greater in the study group than in controls (p less than 0.001). Similarly, schizophrenia was more common in the study group compared to controls (p less than 0.01). Possible neuropathological associations and treatment are discussed.     

A possible association of recurrent streptococcal infections and acute onset of obsessive-compulsive disorder

Rheumatic fever is an immunologically mediated disease that follows infection by group A beta-hemolytic Streptococcus (GABHS). In rheumatic fever, antibodies generated against GABHS cross-react with the heart, joints, skin, and other sites, inducing an inflammatory, multisystem disease. Brain tissue-specific antibodies have been demonstrated in a subset of children with Sydenham chorea (a component of the Jones criteria for the diagnosis of rheumatic fever), and most Sydenham chorea patients manifest obsessive-compulsive symptoms very similar to those in traditional obsessive-compulsive disorder. The parallels drawn from the paradigm of Sydenham's chorea to Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is an area of active controversy. Newly emerging information on the role of GABHS superantigens in the pathogenesis of rheumatic fever is of particular interest. In this article, we review the microbial characteristics of GABHS and the subsequent immune responses to GABHS as a possible etiology of PANDAS.     

Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies.

Antibasal ganglia antibodies (ABGA) are associated with Sydenham's chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. We present 10 patients with acute disseminated encephalomyelitis (ADEM) associated with Group A beta hemolytic streptococcal infection. The clinical phenotype was novel, with 50% having a dystonic extrapyramidal movement disorder, and 70% a behavioral syndrome. None of the patients had rheumatic fever or Sydenham's chorea. Enzyme-linked immunosorbent assay, Western immunoblotting, and immunohistochemistry were used to detect ABGA. Neurological (n = 40) and streptococcal (n = 40) controls were used for comparison. Enzyme-linked immunosorbent assay results showed significantly elevated ABGA in the patients with poststreptococcal ADEM. Western immunoblotting demonstrated ABGA reactivity to three dominant protein bands of 60, 67, or 80 kDa; a finding not reproduced in controls. Fluorescent immunohistochemistry demonstrated specific binding to large striatal neurones, which was not seen in controls. Streptococcal serology was also significantly elevated in the poststreptococcal ADEM group compared with neurological controls. Magnetic resonance imaging studies showed hyperintense basal ganglia in 80% of patients with poststreptococcal ADEM, compared to 18% of patients with nonstreptococcal ADEM. These findings support a new subgroup of postinfectious autoimmune inflammatory disorders associated with Group A beta hemolytic streptococcus, abnormal basal ganglia imaging, and elevated ABGA.     

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

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

Sydenham's chorea, and its complications affecting the nervous system

The well-known symptoms of rheumatic fever and Sydenham's chorea are briefly discussed. Then the associated psychiatric and neurological disorders are considered, especially the obsessive-compulsive and the attention deficit hyperactivity disorders; all linked to previous haemolytic streptococcal infections. Dystonic syndromes, and acute disseminated encephalopathies, also show such links; and may be part of the clinical spectrum of the post-infectious streptococcal illnesses. The causes of Sydenham's chorea are considered, especially an immune reactivity against the basal ganglia, supported by the finding of antibodies reactive against the neurons of the caudate nucleus. The resulting imbalance between dopaminergic and cholinergic systems may cause the involuntary choreiform movements, and account for the beneficial effects of certain drugs. The differential diagnosis of Sydenham's chorea is discussed, and the role of tests such as special imaging techniques. The possible treatments include prophylaxis with penicillin and the use of drugs like sodium valproate, carbamazapine and haloperidol. Immune therapy occupies a special role in selected patients, There is still a need for research into the links between these conditions.     

Neuropsychiatric movement disorders following streptococcal infection

The aim of this study was to describe post-streptococcal movement disorders that form part of the acute rheumatic fever complex. The clinical records of patients diagnosed with Sydenham's chorea were analyzed retrospectively to investigate epidemiology, the significance of socioeconomic deprivation, clinical manifestations, treatments, outcomes, long-term morbidity, and disease evolution. Forty-two patients (21 males, 21 females) were diagnosed with Sydenham's chorea. The median presentation age was 9 years 8 months (range 3y 5mo to 13y 2mo). Nineteen patients were of indigenous African ancestry; 23 were of mixed ancestry. All patients lived in poverty and had poor access to medical care. Twelve of the total group had disabling symptoms for longer than 2 years; six of these patients developed paediatric autoimmune neuropsychiatric disorder associated with Streptococcus (Paediatric autoimmune neuropsychiatric disorder associated with Streptococcus [PANDAS]), five Tourette syndrome (TS), and one learning difficulties. Poor outcome was significantly more prevalent in patients of mixed ancestry, in those with a positive family history, previous behavioural problems, or a failure to complete 10 days of penicillin and 'bed-rest'/hospitalization. Sydenham's chorea is one manifestation of post-streptococcal neuropsychiatric movement disorders. This study demonstrates that patients can present with one diagnosis and evolve other neuropsychiatric conditions such as TS and PANDAS. In the South African context, it is important to delineate neuropsychiatric movement disorders associated with streptococcal infections. The potential genetic susceptibility should be explored.     

Recurrence of Sydenham chorea: implications for pathogenesis

BACKGROUND: Sydenham chorea (SC), a major sign of rheumatic fever (RF), is related to systemic streptococcal infection and is treated with antibiotics. Recurrence usually occurs within a short interval following the initial event and is considered part of RF. OBJECTIVE: To evaluate the rate, nature, and course of recurrent SC during an extended follow-up period. DESIGN: Prospective assessment of a cohort of patients with SC who were admitted between 1985 and 2002. SETTING: General community hospital. METHODS: Diagnosis of RF was based on the revised Jones criteria. Other causes of chorea were excluded. Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were observed from 1 to 14 years following the initial SC episode and for at least 1 year after recurrence. At recurrence, patients were assessed for RF clinical and laboratory activity, including change in cardiac involvement. RESULTS: Twenty-four patients had SC. In 19 patients (79%), the chorea was associated with other RF signs, and 5 suffered from pure chorea. Ten patients (42%, 7 women) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. Association of recurrent chorea with RF could be suspected in only 6 episodes: cessation of prophylactic antibiotic treatment or poor compliance in 4 patients and rise in antistreptolysin O titers in 2. In an 18-year-old woman, chorea recurred during her first pregnancy. At recurrence, chorea was the sole rheumatic sign in all 9 patients who had 1 recurrent episode. In the patient with 2 recurrent episodes, mitral regurgitation developed into mitral stenosis. No statistical differences in previous RF activity and rheumatic cardiac involvement between patients with recurrent SC and patients with a single episode could be found. CONCLUSIONS: In a significant subgroup of patients, SC recurrence might not be a true relapse of rheumatic fever. It might represent either a primary underlying abnormality that renders patients susceptible to developing such a movement disorder or the outcome of permanent subclinical damage to the basal ganglia following the initial SC episode.     

Sydenham's chorea: clinical observations from a Brazilian movement disorder clinic

We retrospectively evaluated the clinical and epidemiological characteristics of 100 patients suffering from Sydenham's chorea (SC). Our analysis revealed a recent, progressive decline in the number of new cases. Onset of SC was frequently reported between 7 and 12 years of age, being more frequent in females. Patients with generalized or severe chorea showed a higher risk of presenting gait abnormalities and behavioral symptoms. Chorea was transitory and remitted within the first 6 months in about 50% of patients but was persistent in 40%. Almost all patients with persistent chorea remitted after a protracted course of the disease.     

Sporadic choreas: analysis of a general hospital series

The incidence of sporadic chorea among general hospital admissions is unknown, and the relation of clinical manifestations and etiological factors to neuroimaging findings has been little investigated in this condition. We reviewed the 7,829 cases admitted to the neurology departments of two general hospitals over 3.25 years and identified 23 (8 male and 15 female) cases of apparently sporadic chorea. Analysis of the records of these patients permitted etiological classification as follows: drug-induced chorea (5 patients), vascular chorea (6 patients), chorea-vasculitis (1 patient), Sydenham's chorea (1 patient), AIDS-related chorea (5 patients) and in 4 patients neither etiological factors nor neuroradiological alterations were found. Finally in 1 patient, the genetic test for Huntington's disease was positive. Thirteen patients had pathological neuroimaging findings; however, in only 3 were basal ganglia lesions considered to be the cause of the chorea. We conclude that sporadic chorea is not rare among neurological department admissions (we found 2.94 cases per 1,000 admissions) and only in a minority of cases is the symptomatology attributable to gross basal ganglia lesions; HIV infection is an emerging cause of chorea.     

Did Gustav Mahler have Sydenham's chorea?

Sydenham's chorea (SC), a major manifestation of acute rheumatic fever (RF), is characterized by chorea and other motor and non-motor features. Among the latter are behavioral symptoms, including obsessive-compulsive disorder. Although SC is typically a self-limited condition, up to 50% of patients may evolve with persistent chorea. There is evidence that Gustav Mahler had a movement disorder, but its nature remains undetermined. There are witnesses describing him as having facial dyskinesia and a gait disorder consistent with chorea. His conducting performance was notorious for obsessive attention to details of the staging and musical production. Mahler was diagnosed with a valvulopathy in 1907 and died of subacute bacterial endocarditis in 1911. It is possible that the composer suffered from RF in childhood with carditis and SC, which may left him with valvulopathy, obsessive-compulsive disorder, and persistent chorea.     

Sydenham's chorea: clinical findings and comparison of the efficacies of sodium valproate and carbamazepine regimens

BACKGROUND: Sydenham's chorea is still the most frequently seen form of acquired chorea in childhood in developing world despite the use of antibiotics. It is a debilitating illness lasting for weeks or months and requires drug therapy. OBJECTIVE: To evaluate and compare the efficacies of sodium valproate and carbamazepine in the treatment of the choreiform movements in Sydenham's chorea. DESIGN: A prospective trial carried out with 24 children with Sydenham's chorea. Patients: Twenty-four patients were divided into two groups having similar demographic and clinical properties. One group (n = 17) was given carbamazepine (15 mg/kg per day) and the other (n = 7) was given sodium valproate (20-25 mg/kg per day). As soon as the symptoms were taken under control, doses of the drugs were tapered slowly. The duration of the drug use was recorded. The time of response to therapy was compared between the groups and the patients were monitored for the adverse effects. RESULTS: There was no significant difference between the groups with respect to the time of clinical improvement and time of complete remission, duration of the therapy and the recurrence rates. Clinical improvement began by 8.0 +/- 4.0 days in sodium valproate and 7.4 +/- 8.2 days in carbamazepine group (P = 0.88). In the whole group no adverse effect was seen due to the drugs. CONCLUSION: Carbamazepine and valproic acid are equally effective and safe drugs in the treatment of choreiform movements in Sydenham chorea.     

Obsessive compulsive behavior, hyperactivity, and attention deficit disorder in Sydenham chorea

The authors investigated obsessive-compulsive behavior, obsessive-compulsive disorder (OCD), and attention deficit and hyperactivity disorder (ADHD) in 50 healthy subjects, 50 patients with rheumatic fever without chorea, and 56 patients with Sydenham chorea. Obsessive-compulsive behavior, OCD, and ADHD were more frequent in the Sydenham chorea group (19%, 23.2%, 30.4%) than in the healthy subjects (11%, 4%, 8%) and in the rheumatic fever without chorea group (14%, 6%, 8%). ADHD was more common in persistent Sydenham chorea.