Sydenham chorea in a 5-year-old Saudi patient

Despite improvements in socio-economic status and the standard of health care services, rheumatic fever continuous to occur in Saudi Arabia, although with decreasing frequency. The disease is most commonly observed in school-aged children, but can also occur in a younger age group. Carditis and arthritis are the major clinical symptoms on presentation of acute rheumatic fever in young children. Rheumatic chorea is infrequently reported in young children. Here, a case of Sydenham chorea, in a 5-year-old boy, is presented. Although rare, the diagnosis of Sydenham chorea should always be considered in young children with choreiform movements.Acute rheumatic fever (ARF) is most frequently seen in school-aged children. The disease and its neurological manifestation, Sydenham chorea, are considered rare in preschool aged children (<5 years of age). As the most common cause of acquired chorea, Sydenham chorea must be included in the deferential diagnosis of choreiform movements among young children. Failure to recognize this disease may increase the risk of recurrence of ARF as well as rheumatic heart disease. We present a case of Sydenham chorea in a 5-year-old boy. The objective in presenting this particular case is to highlight the need to raise awareness of the possibility of Sydenham chorea in young children.     

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.     

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.     

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.     

Autoimmune neurological disorders associated with group-A beta-hemolytic streptococcal infection

Although central nervous system (CNS) disorders associated with group-A beta-hemolytic streptococcal (GABHS) infection occur only rarely, Sydenham’s chorea is a well-recognized disease that can arise following infection. Children may develop a tic, obsessive compulsive disorder (OCD), and extrapyramidal movement subsequent to GABHS infection. These disorders have been termed pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). Herein we report one case each of acute disseminated encephalomyelitis (ADEM), PANDAS and subacute encephalitis associated with GABHS infection. To evaluate the pathogenesis of the CNS disorders associated with GABHS infection, we measured levels of neurotransmitters, cytokines, anti-neuronal autoantibodies, and performed immunohistochemistry using patient sera to stain human brain sections. All three cases showed psychiatric behavioral disorders. Immunotherapy was effective, and homovanillic acid levels in the cerebrospinal fluid (CSF) were elevated at the acute stage in all three cases. In each case of ADEM and PANDAS, immunohistochemistry demonstrated neuronal impairment in the basal ganglia during the acute stage. Neuronal immunoreactivity was visualized in the cerebral cortex at the acute stage in the case of subacute encephalitis. There was no direct correlation between immunoreactivity of patient sera on the brain sections and positivity of anti-neuronal autoantibodies or CSF biomarkers. The results suggest that autoimmune responses may modulate neurotransmission, and the use of patient serum for immunohistochemistry is a sensitive screening method for the detection of anti-neuronal autoantibodies in CNS disorders associated with GABHS infection.     

Autoimmune neuropsychiatric disorders associated with streptococcal infection: Sydenham chorea, PANDAS, and PANDAS variants

Streptococcal infection in children is usually benign and self-limited. In a small percentage of children, prominent neurologic and/or psychiatric sequelae can occur. Sydenham chorea is the best defined and best recognized. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a group A beta-hemolytic streptococcal infection. PANDAS constitutes a subset of children with tics, Tourette syndrome, and obsessive-compulsive disorder. In addition to strictly defined PANDAS, we and others have recognized several PANDAS variants, including adult-onset variant, a dystonic variant, a myoclonic variant, and a "chronic" PANDAS variant. The nosology and classification of these entities are rapidly evolving. The recognition that some pediatric neurobehavioral syndromes have infectious and/or immunologic triggers points to important new avenues of disease treatment. In this review, we summarize this complex and rapidly evolving area of clinical research.     

Obsessive-compulsive disorder and immunology: a review

Interest in the possibility of an immune-mediated pathophysiology of obsessive-compulsive disorder and related disorders has increased. In the late 1980s, the National Institute of Mental Health reported an increase in obsessive-compulsive symptoms (OCS) in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCS but no chorea led to the coining of PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection). This association has furthered interest in biological measures for immune and genetic susceptibility in non-PANDAS obsessive-compulsive disorder patients (OCD). Furthermore, some studies are trying to demonstrate alterations of immune parameters in OCD patients, with few positive results. In this narrative review, our objective was to describe the immunologic findings in OCD, PANDAS, and their association with SC.     

Obsessive compulsive disorder: is there an association with childhood streptococcal infections and altered immune function?

During the last few years, an increased interest in the possibility of immune mediated pathophysiology of obsessive compulsive disorder (OCD) and related disorders has been seen. In the late 1980s, the National Institute of Mental Health reported an increase of obsessive compulsive symptoms in patients with Sydenham chorea (SC). Subsequently, a precipitating streptococcal infection in children with sudden onset of OCD symptoms but no chorea led to the coining of PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus).This association has furthered interest in studying immune parameters in non-PANDAS OCD as well. This article will review the neuropsychiatric findings in OCD and Tourette syndrome (TS) with emphasis placed on PANDAS, and its association with SC, and a review of the existing studies that have assessed immunologic measures in patients with OCD and TS.     

Sydenham舞蹈病

Sydenham舞蹈病是风湿热在神经系统的特征性表现,是临床最为常见的儿童获得性舞蹈病.本文通过对近年来与该病相关国内外文献的系统回顾,对其病因、发病机制、临床表现、辅助检查、诊断与治疗,以及最新研究进展等进行归纳总结,以期临床医师在诊断与治疗过程中能够综合患者临床症状、体征及辅助检查结果,做到早诊断、早治疗,从而有效控制临床症状、缩短病程,达到改善患者预后之目的.     

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.     

PANDAS: a commentary

PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection. As defined, the criteria include prepubertal children with either a tic or obsessive-compulsive disorder in whom a Group A beta-hemolytic streptococcal infection (GABHS) triggers the abrupt onset or exacerbation of tics/obsessive-compulsive behaviors. Pathophysiologically, it is proposed that antibodies produced against GABHS cross-react with neuronal cells, in a process involving molecular mimicry. Although PANDAS has received widespread notoriety, the existence of this condition has been questioned. This commentary reviews clinical and laboratory issues pertinent to the diagnosis of this entity. We conclude that PANDAS is an intriguing hypothesis that requires further confirmation.     

Infection-triggered anorexia nervosa in children: clinical description of four cases

BACKGROUND: Anorexia nervosa (AN) is a serious illness with no definitive treatment. Clinical and research evidence led to the hypothesis that some children with AN may have a pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), similar in pathogenesis to other hypothesized PANDAS disorders. METHODS: Four youngsters (ages, 11-15 years) with PANDAS AN were treated with an open trial of antibiotics, in addition to conventional treatment. They were evaluated for eating disorder and obsessive-compulsive symptoms, and for weight gain. Evidence of streptococcal infection came from clinical evaluation, throat cultures, and two serological tests: anti-deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers. The "rheumatic" marker D8/17 was also measured. This B-cell alloantigen is associated, in several publications, with poststreptococcal autoimmunity: Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive compulsive disorder (OCD) and tic disorders. RESULTS: There was clinical evidence of possible antecedent streptococcal infection in all four patients, two of whom had comorbid OCD, with possible infection-triggered AN. All four had the rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean of 33% (12% or more is considered positive for the marker). The patients responded to conventional treatment plus antibiotics with weight restoration and decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain weight and did so. CONCLUSIONS: There may be a link between infectious disease and some cases of AN, which raises the possibility of new treatment.     

Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.     

Acute postinfectious movement and psychiatric disorders in children and adolescents

The authors report 4 children and adolescents who had the acute onset of a movement and psychiatric disorder after a febrile illness. The differential diagnosis includes poststreptococcal syndromes (Sydenham chorea, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection [PANDAS], acute disseminated encephalomyelitis) and other postinfectious conditions. Their cases illustrate difficulties in making an accurate diagnosis and determining proper therapy and they recommend a standard diagnostic approach. More research is needed to clarify the nature, causes, and appropriate treatment of these types of disorders.     

A case of adult-onset Sydenham chorea accompanied with psychiatric symptoms]

We report a 56-year-old man with adult-onset Sydenham chorea. Since January 2003, he had often troubled other persons, and in October 2003, following an episode of fever in August of the same year, he noticed left shoulder joint pain and involuntary movements of his limbs, especially on the left side. These involuntary movements gradually worsened and he became unable to converse due to psychiatric symptoms. On admission, neurological examination revealed dementia, emotional incontinence, abnormal behavior and chorea in four limbs. Brain MRI disclosed swelling of bilateral caudate heads that was more marked on the right side. Hypermetabolism in bilateral caudate nuclei, especially on the right, was found on FDG-PET study, which was compatible with his left side-dominant chorea and might reflect inflammation as a nature. A gallium scintigram demonstrated excess accumulations in the plural joints of his extremities, which gradually decreased in parallel with joint pain relief. The present case was diagnosed as Sydenham chorea, because of the presence of arthritis, chorea, fever, increased erythrocyte sedimentation rate and elevated CRP. We believe that this is a first report of adult-onset Sydenham chorea accompanied with psychiatric symptoms.     

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.     

The PANDAS subgroup of tic disorders and childhood-onset obsessive–compulsive disorder

Diagnosis and treatment of the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) variant of Gilles de la Tourette syndrome (GTS) and childhood-onset obsessive–compulsive disorder (OCD) are still controversial issues. Most cross-sectional studies confirm a significant association between GTS and the development of an immune response against group A β-hemolytic streptococcus (GABHS). Moreover, longitudinal retrospective studies suggest that a recent exposure to GABHS might be a risk factor for the onset of tics and obsessive–compulsive symptoms. However, further evidence from longitudinal prospective research is needed to verify whether a temporal association between GABHS infections and symptom exacerbations is a useful and reliable criterion for the diagnosis of PANDAS. In addition, preliminary results suggest that the PANDAS spectrum might be enlarged to include attention deficit/hyperactivity disorder.Although a number of immunological biomarkers have been proposed as markers of the PANDAS variant, at present, none of these has been conclusively proved useful to diagnose and monitor disease course in children with a suspicion of PANDAS.Finally, despite their empirical use in community settings, we still lack conclusive, evidence-based data regarding the usefulness of antibiotic and immunomodulatory treatments in children with PANDAS. Given the relevance of this topic for general pediatric health, additional research efforts to solve all the pending issues and the hottest points of debate are warranted.     

A preliminary study of the frequency of anti-basal ganglia antibodies and streptococcal infection in attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is often present in patients with post-streptococcal neuropsychiatric disorders such as Sydenham’s chorea and PANDAS, in which anti-basal ganglia antibodies (ABGA) have been frequently found. Our study investigates the hypothesis that pharyngeal group A β-hemolytic streptococcus (GABHS) infections and serum ABGA are more frequent in children with ADHD non-comorbid (nc-ADHD) with obsessive-compulsive disorder or tics than in controls. We compared 22 children with nc-ADHD (DSM-IV-TR) and 22 healthy controls matched by age, gender and season of sample collection, for the frequency of recent GABHS infection and the presence of ABGA. Eleven out of 22 children (51%) with nc-ADHD showed evidence of GABHS infection compared to three out of 22 (14%) controls (P = 0.007). We found positive ABGA in one ADHD subject (4%) and in one control (4%). This preliminary study indicates that frequency of ABGA in children with nc-ADHD does not differ from that in matched controls, despite the fact that our ADHD patients had had more recent GABHS infections than the controls. This suggests that ABGA do not have a role in the pathogenesis of nc-ADHD.     

Parkinsonian signs and symptoms in adults with a history of Sydenham's chorea

BackgroundSydenham’s chorea is associated with dysfunction of fronto-striatal circuits induced by cross-reactive antibodies to group A β-hemolytic streptococcus. High susceptibility of extrapyramidal effects of neuroleptics in patients with Sydenham’s chorea suggests underlying nigro-striatal dysfunction.ObjectiveTo study the presence of parkinsonism in patients with a history of Sydenham’s Chorea.MethodsWe used the UFMG Sydenham’s Chorea Rating Scale (USCRS) and the Unified Parkinson’s Disease Rating Scale (UPDRS) part III, respectively, to determine the presence of chorea and parkinsonian symptoms and signs in 25 adults with a history of previous Sydenham’s Chorea currently without chorea or use of anti-choreic drugs.ResultsBradykinesia was found in 64% of subjects. There was a statistically significant correlation between bradykinesia and hemichorea (?0.412; p = 0.036) and bradykinesia and generalized chorea (0.412; p = 0.036). There was no correlation between bradykinesia and use of anti-choreic drugs.ConclusionsBradykinesia is common in patients with Sydenham’s Chorea in remission. This finding suggests an immune-mediated dysfunction of the nigro-striatal system.