Chorea In Children Research Articles

Management, treatment, and clinical approach of Sydenham's chorea in children: Italian survey on expert-based experience

Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use. The autoimmune response affecting the basal ganglia, notably against dopamine, underlies the pathophysiology. Clinical management necessitates an integrated approach, potentially involving immunomodulatory therapies.To address discrepancies in SC management, a survey was conducted across Italy, targeting specialists in neurology, pediatrics, child neuropsychiatry, and rheumatology. Of the 51 responding physicians, consensus favored hospitalization for suspected SC, with broad support for laboratory tests and brain MRI. Treatment preferences showed agreement on oral prednisone and IVIG, while opinions varied on duration and plasmapheresis. Haloperidol emerged as the preferred symptomatic therapy. Post-SC penicillin prophylaxis and steroid therapy gained strong support, although opinions differed on duration. Follow-up recommendations included neuropsychological and cardiological assessments.Despite offering valuable insights, broader and more studies are needed in order to guide treatment decisions in this well-known yet challenging complication of acute rheumatic fever, which continues to warrant scientific attention and concerted clinical efforts.

Sydenham's Chorea in Children with Acute Rheumatic Fever: An Echocardiographic Survey of Pediatric Patients in Northwestern Iran.

Although infrequent, Sydenham's chorea (SC) may occur as a result of injury to the basal ganglia in children with acute rheumatic fever (ARF) secondary to group A Streptococcal infection. Certain hallmarks of SC, such as movement disorders, could be utilized as a predictive marker for carditis. The present study aimed to investigate neurologic and cardiologic symptoms in children with suspected SC after ARF. All children aged 5-16 who were admitted at Shahid Madani Pediatric Hospital (Tabriz, Iran), with an initial diagnosis of ARF and SC between 2009 and 2022 were included for echocardiographic assessment and prospective follow-up within 6 and 12 months after the start point. The pattern and severity of valvulopathy, as well as the prevalence of Jones criteria for rheumatic fever, were used to assess the effect. The collected data were analyzed using SPSS Statistics software (version 22.0) using Chi square and Fisher's exact tests. P<0.05 was considered statistically significant. The study enrolled 85 children, 36 girls and 49 boys, with a mean age of 9.7±2.7. On the first echocardiography, 42.4% of patients had mitral valve regurgitation (MR), with a predominance of female patients (P=0.04). Of those diagnosed with SC (12 girls and 6 boys), 66.7% showed cardiac involvement, with a higher prevalence of MR in both sexes (P=0.04). The pattern of cardiac involvement after 6 months was significantly different between the groups (P=0.04). However, no such difference was observed during the one-year follow-up (P=0.07). Female sex was found to have a significant relationship with SC localization (P=0.01). In addition to its neurological manifestations, SC can be associated with clinical or subclinical cardiac valve dysfunction that might last for more than a year. In addition to attempting early detection and appropriate management, a precise cardiac and neurologic assessment during admission and follow-up is recommended.A preprint version of this manuscript is available at DOI: 10.21203/rs.3.rs-772662/v1 (https://www.researchsquare.com/article/rs-772662/v1).

Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment.

Chorea is a hyperkinetic movement disorder frequently observed in the pediatric population, and, due to advancements in genetic techniques, an increasing number of genes have been associated with this disorder. In genetic conditions, chorea may be the primary feature of the disorder, or be part of a more complex phenotype characterized by epileptic encephalopathy or a multisystemic syndrome. Moreover, it can appear as a persistent disorder (chronic chorea) or have an episodic course (paroxysmal chorea). Managing chorea in childhood presents challenges due to its varied clinical presentation, often involving a spectrum of hyperkinetic movement disorders alongside neuropsychiatric and multisystemic manifestations. Furthermore, during infancy and early childhood, transient motor phenomena resembling chorea occurring due to the rapid nervous system development during this period can complicate the diagnosis. This review aims to provide an overview of the main genetic causes of pediatric chorea that may manifest during infancy and early childhood, focusing on peculiarities that can aid in differential diagnosis among different phenotypes and discussing possible treatment options.

Dancing Out of Step: A Case of Tuberculous Meningitis Disguised as Childhood Chorea

Dancing Out of Step: A Case of Tuberculous Meningitis Disguised as Childhood Chorea

PDE10A Mutation as an Emerging Cause of Childhood-Onset Hyperkinetic Movement Disorders: A Review of All Published Cases.

Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which act as intracellular second messengers for signal transduction pathways and modulate various processes in the central nervous system. Recent discoveries that mutations in genes encoding different PDEs, including PDE10A, are responsible for rare forms of chorea in children led to the recognition of an emerging role of PDEs in the field of pediatric movement disorders. A comprehensive literature review of all reported cases of PDE10A mutations in PubMed and Web of Science was performed in English. We included eight studies, describing 31 patients harboring a PDE10A mutation and exhibiting a hyperkinetic movement disorder with onset in infancy or childhood. Mutations in both GAF-A, GAF-B regulatory domains and outside the GAF domains of the PDE10A gene have been reported to cause hyperkinetic movement disorders. In general, patients with homozygous mutations in either GAF-A domain of PDE10A present with a more severe phenotype and at an earlier age but without any extensive abnormalities of the striata compared with patients with dominant variants in GAF-B domain, indicating that dominant and recessive mutations have different pathogenic mechanisms. PDE10A plays a key role in regulating control of striato-cortical movement. Comprehension of the molecular mechanisms within the cAMP and cGMP signaling systems caused by PDE10A mutations may inform novel therapeutic strategies that could alleviate symptoms in young patients affected by these rare movement disorders.

Expanding Knowledge of the Causes of Childhood Chorea

Paolo Claudio M. de Gusmao, Jeff L. Waugh Seminars in Pediatric Neurology Volume 25, April 2018, Pages 42-53 Chorea is a symptom of a broad array of genetic, structural, and metabolic disorders. While chorea can result from systemic illness and damage to diverse brain structures, injury to the basal ganglia, especially the putamen or globus pallidus, appears to be a uniting features of these diverse neuropathologies. The timing of onset, rate of progression, and the associated neurological or systemic symptoms can often narrow the differential diagnosis to a few disorders. Recognizing the correct etiology for childhood chorea is critical, as numerous disorders in this category are potentially curable, or are remediable, with early treatment.

Sydenham Chorea in Sudan; Presentation Panorama.

Sydenham's chorea (SC) is the most common form of acquired chorea in childhood, it is considered a neurological complication of streptococcal pharyngitis. In this study, we aimed to determine the clinical pattern, association of Sydenham's chorea with other manifestations of acute rheumatic fever, and the laboratory findings of Sydenham's chorea among Sudanese patients. A prospective cross-sectional study involving fifty patients of various ages diagnosed with Sydenham's chorea and followed up at The National Center for Neurological Sciences from January 2017 to November 2019. Data were obtained after patients' consent through personal interviews or personal review of patients' records via a structured questionnaire composed of demographic data, symptoms, co-morbid illness, risk factors, physical examination, and related investigations. About 50 patient was enrolled in this study with a median age of 13.7 years. Females were (n=35) (70%) and (30%) (n=15) s were males. Generalized chorea was seen in 33 (66%) and hemichorea in 17 (34%) patients. Weakness (38%) and hypotonia (46%) were common, such as behavior change (44%), dysarthria (70%), gait change (18%), and deterioration of handwriting (12%). Arthritis occurred in (36%), carditis in 30 (60%), both arthritis and carditis in 18 (36%), and pure chorea in 14 (28%). Erythema marginatum and subcutaneous nodules were not observed in our patients. Only 13 patients (26%) gave a history of pharyngitis. Sydenham chorea is more common in young female Sudanese, with a familial predominance and a tendency towards mitral valve disease. All pediatric Patients with chorea should be screened for Sydenham's chorea.

Exploring the Complex Associations Between Prenatal and Early-Life Infections and Obsessive-Compulsive and Tic-Related Disorders

An association between rheumatic fever and chorea was first posited at the beginning of the 19th century, but it was not until the mid–19th century that these observations crystalized into a widely accepted understanding that rheumatism caused Sydenham chorea ( 1 Martino D. Tanner A. Defazio G. Church A.J. Bhatia K.P. Giovannoni G. Dale R.C. Tracing Sydenham’s chorea: Historical documents from a British paediatric hospital. Arch Dis Child. 2005; 90: 507-511 Crossref PubMed Scopus (13) Google Scholar ). Advances in diagnostic methods, including the use of the stethoscope to detect cardiac manifestations of rheumatic fever, partially explain this discovery. However, perhaps an even more significant factor was the gradual shift during this period in the locus of medical care from the home to specialized centers, such as children’s hospitals, which led to case-based registries ( 1 Martino D. Tanner A. Defazio G. Church A.J. Bhatia K.P. Giovannoni G. Dale R.C. Tracing Sydenham’s chorea: Historical documents from a British paediatric hospital. Arch Dis Child. 2005; 90: 507-511 Crossref PubMed Scopus (13) Google Scholar ). It was from examination of these registries that British researchers were initially able to show a temporal relationship between seasonal spikes in rheumatic fever and chorea in children. SEE CORRESPONDING ARTICLE ON PAGE 1023 SEE CORRESPONDING ARTICLE ON PAGE 1023 Prenatal and Early Childhood Infections and Subsequent Risk of Obsessive-Compulsive Disorder and Tic Disorders: A Nationwide, Sibling-Controlled StudyBiological PsychiatryVol. 93Issue 11PreviewPostinfectious autoimmune processes are hypothesized to be causally related to both obsessive-compulsive disorder (OCD) and tic disorders, but current evidence is conflicting. This study examined whether prenatal maternal (and paternal, as an internal control) infections and early childhood infections in the offspring (i.e., during the first 3 years of life) were associated with a subsequent risk of OCD and Tourette syndrome or chronic tic disorder (TS/CTD). Full-Text PDF Open Access

Post-COVID-19 Sydenham Chorea: A Case Report

Background: Sydenham chorea, or rheumatic chorea, is a movement disorder that is more prevalent among young people, with a mean age at symptom onset between 8 and 9 years. The condition is more common in females. Sydenham chorea is associated with rheumatic fever and is considered the most common cause of acute chorea in children. We believe that the present case is worth reporting since the occurrence of Sydenham chorea as a post-COVID-19 sequela has not been described in Brazil. Case Presentation: We report here the case of a 14-year-old girl with symptoms of acute chorea that emerged 15 days after treatment resolution of COVID-19 (SARS-CoV-2 or severe acute respiratory syndrome coronavirus 2). Brain computed tomography (CT) and magnetic resonance imaging scans showed no changes, and the laboratory tests revealed no signs of an active infectious process. In contrast, neurological positron-emission tomography/CT showed mild glycolytic hypometabolism in the bilateral mesial frontal region. Administration of an oral anticonvulsant resulted in a marked improvement in her symptoms. Conclusion: Despite major efforts of the scientific community for discovering treatments, preventive methods, mechanisms of action, and possible sequelae of SARS-CoV-2, there is still a long way to go to better understand this devastating pathological agent that has affected the global population.

Efficacy of Steroid Therapy in Management of Sydenham’s Chorea in Children: A Comparative Prospective Study

Objective: To determine the efficacy of steroid therapy in Sydenham’s chorea in children.&#x0D; Study Design: Comparative prospective study.&#x0D; Place and Duration of Study: Inpatient and Outpatient Department of Pediatric Neurology, Children Hospital and Institute of Child Health, Lahore Pakistan, from Dec 2019 to May 2020.&#x0D; Methodology: Sixty-eight children of Sydenham’s chorea were divided in Group A and B. Each Group was treated with Diazepam (0.3mg-1mg/kg/day) and an injection of Benzathine Penicillin. Group-B was given additional oral prednisolone (2mg/kg/day) for four weeks, with tapering in the next two weeks. Epidemiological data, clinical features and laboratory parameters were collected. The Universiade Federal de Minas Gerais Sydenham’s chorea Rating Scale (USCRS) was applied to both groups at the presentation after two weeks and four weeks.&#x0D; Results: Out of 68 patients, the mean Universidade Federal de Minas Gerais (UFMG) Sydenham's Chorea Rating Scale (USCRS) got progressively better in Group-B (mean score improvement was 25.73±5.56 at two weeks and 41.06±6.89 at four weeks) than in Group-A (mean score improvement was 9.12±3.75 at two weeks and 17.97±3.89 at four weeks) with p-value of &lt;0.05.&#x0D; Conclusion: Steroid therapy significantly improved patients with Sydenham’s chorea compared to those who did not receive any steroid therapy.Keywords: Efficacy, Steroid therapy, Sydenham chorea.

Resistant Chorea Successfully Treated with Intravenous Immunoglobulin: A Case Report

Sydenham’s chorea (SC) is common cause of acquired chorea in childhood. SC occurs mainly in children with untreated streptococcal infections. An effective list of therapeutic options has been used to treat this disorder: antiepileptic drugs (valproic acid, carbamazepine etc.), haloperidol, chlorpromazine, amphetamines, steroids, plasma exchange and intravenous immunoglobulins (IVIG). We report a 12-year-old girl with carditis and severely generalized chorea and successfully treated with IVIG. This case report shows that IVIG is an effective treatment for the chorea cases resistant to anticonvulsants, dopamine antagonists and steroids, although larger studies are needed to confirm this conclusion.

An unexpected cause of chorea in an adolescent girl: systemic lupus erythematosus.

Involuntary movement disorders are rare in childhood. Hyperkinetic movement disorders including chorea stand as the leading cause. Although Sydenham chorea is the major diagnosis in most children and adolescents, appropriate differential diagnosis is fundamental for afinal decision. Adetailed and careful history as well as physical examination is the principal proceeding for accurate diagnosis. Herein, we report on an adolescent girl who was admitted to our hospital with chorea and subsequently diagnosed with systemic lupus erythematosus (SLE). Accompanying joint complaints in the patient's history, including growth retardation noticed during aphysical examination and bicytopenia recognized in laboratory evaluation, increased the suspicion of SLE rather than Sydenham chorea in the patient. Central nervous system involvement defined as neuropsychiatric lupus presents wide clinical findings varying from stroke and seizures to psychosis and cognitive dysfunction. Although disease activity, persistently positive anticardiolipin antibodies, and lupus anticoagulant positivity are reported to be the most important risk factors in neuropsychiatric lupus, they are not always directly correlated. We present this patient in order to draw attention to the importance of physical examination and history in the differential diagnosis of chorea in childhood.

Chorea in children: etiology, diagnostic approach and management.

Chorea is defined by the presence of abnormal, involuntary, continuous, random movements that results from a number of autoimmune, hereditary, vascular, metabolic, drug-induced and functional (psychogenic) causes. Chorea may present at all stages of life, from newborns to elderly individuals. While Huntington disease is the main suspicion in adults presenting with chorea, once a drug-induced or parkinsonian dyskinesia have been ruled out; Huntington disease exceptionally presents with chorea in children. Sydenham chorea is considered the most common cause of acute childhood-onset chorea, but its prevalence has decreased in Western countries. However, in younger children other etiologies such as dyskinetic cerebral palsy, anti-NMDAR receptor encephalitis, other autoimmune conditions, or mutations in NKX2-1, ADCY-5, FOXG1, GNAO1, GPR88, SLC2A1, SQSTM1, ATP8A2, or SYT-1 should be considered. In this manuscript, we review the main causes, diagnosis and management of chorea in children.

Choreic Movements as Manifestation of Hyperthyroidism in an Adolescent at the Onset of Graves’ Disease

Objective; Nervous system dysfunction, including irritability, emotional lability and hyperkinesia are the signs and symptoms frequently observed in hyperthyroidism; chorea and/or choreoathetosis have also been reported in adults and rarely in pediatric age. Case report; We described the case of a 12-year-old boy with bilateral choreiform movements of the arms at the onset of the Graves’ disease. The patient was treated with metimazole and chorea disappeared with euthyroidism. Discussion; Hyperthyroidism is to be considered an unusual cause of chorea in childhood. Every child and adolescent with choreiform movements should be examined also for thyroid function.

Sydenham chorea in a12- year old Saudi girl

Sydenham chorea (SC) is the most common acquired cause of chorea in children.(SC) is the neurological manifestation of rheumatic fever. Rheumatic fever is still reported in Saudi Arabia, although less frequently. According to modified Jones criteria, carditis and arthritis are the major manifestations of acute rheumatic fever (ARF) in children.SC is often seen in isolated form; however, it can occur in association with other clinical manifestations of ARF like carditis. It has been reported that silent, mild valvular regurgitation has been found in patients with pure chorea.SC is characterized by abnormal body movement, associated with behavioral changes. It is an autoimmune disease that occurs following an infection with Group A beta-haemolytic streptococcal infection that is prevalent in Saudi Arabia.Despite recent advances in child health care services, RF continues to occur in Saudi Arabia. We describe a 12-year-old Saudi girl with SC and clinically inaudible, but echocardiographically significant mild valvular regurgitation.The diagnosis of Sydenham chorea should be considered in young children with choreiform movements. Doppler echocardiography may be useful in detecting silent valvular regurgitation and in deciding the duration of penicillin prophylaxis.

Kore Ön Tanılı Hastaların Değerlendirilmesi: Sydenham Koresi ve Ayırıcı Tanılar

Objective: Our aim is to evaluate patients being referred with an initial diagnosis of chorea according to their clinical, laboratory features and final diagnoses while emphasizing cardiological findings of patients with Sydenham chorea. Method: Children aged 4-18 years who were referred to Okmeydanı Research and Training Hospital Pediatric Neurology department with an initial diagnosis of acute, subacute chorea between January 2017-January 2020 were retrospectively included. Chronic chorea and diseases associated with chronic chorea were excluded from the study. Data concerning clinical, laboratory features, cardiological findings, etiologies, treatments, recurrence rates and follow-ups of patients were recorded. Descriptive statistical analysis were performed using SPSS 21.0. Results: Fifteen patients has been referred with the initial diagnosis of chorea. Mean age of the patients was 11.5±2.2 years. Ten (67%) patients were females, 5 (33%) patients were male. After admission, 8 (54%) patients were diagnosed with Sydenham chorea, and 2 (13%) patients with recurrent Sydenham chorea. During physical examination, 5 (33%) patients did not have chorea, and 3 cases had tic disorder. Out of 8 patients with new diagnosis of Sydenham chorea, 3 (37.5%) patients had subclinical carditis, and 5 (62.5%) patients clinical carditis. Chorea had been treated with one of haloperidol/biperiden, valproic acid and prednisolon options. The treatment of 6 patients attending regular follow-up visits was stopped 2-6 months later. Chorea of two patients recurred during our follow-up, and one of our newly diagnosed Sydenham chorea patients had been recognized as antiphospholipid antibody syndrome after recurrence. Conclusion: Sydenham chorea is the most common cause of acquired chorea in childhood. Most of the time it is self limiting. Differential diagnosis of chorea must be kept in mind especially when there is a recurrence.

Inherited and Acquired Choreas

Chorea is a symptom of a broad array of genetic, structural, and metabolic disorders. While chorea can result from systemic illness and damage to diverse brain structures, injury to the basal ganglia, especially the putamen or globus pallidus, appears to be a uniting features of these diverse neuropathologies. The timing of onset, rate of progression, and the associated neurological or systemic symptoms can often narrow the differential diagnosis to a few disorders. Recognizing the correct etiology for childhood chorea is critical, as numerous disorders in this category are potentially curable, or are remediable, with early treatment.

Update on chorea

Chorea is a movement disorder characterized by a continuous flow of unpredictable muscle contractions conveying a dance-like appearance. The aim of this talk is to provide an overview of new developments in the field of chorea. There is an ongoing phase 1 trial of ISIS-HTTRX, an antisense oligonucleotide aiming at reducing the expression of huntingtin in Huntington’s disease (HD). HD is the most common cause of genetic choreas. HD phenocopies are patients with the phenotype of the disease but without the genetic defect of HD. Expansion of the C9orf72 hexanucleotide is the most common cause of phenocopies among Caucasians whereas Huntington disease like-2 mutation is the leading cause in areas with significant African background. Benign hereditary chorea (BHC), the most common etiology of genetic chorea in children, is usually caused by mutations of the NKX2-1 (TITF1). There is growing recognition though that BHC phenotype can be associated with mutations of the ADCY5 gene. The usual clinical features of the later are a variable combination of facial dyskinesia, dystonia, pyramidal signs and cognitive impairment with a characteristic worsening during induction of sleep. Vascular disease remains as the most common cause of acquired chorea in adults whereas Sydenham’s chorea (SC) account for the vast majority of cases in children. There has been a steep decline of the incidence of SC even in the developing world. In contrast, several new auto-immune causes of chorea have been recently described. Anti-NMDAR encephalitis causes a complex movement disorders that can include chorea. A few patients with anti-LGI1 antibody, a condition more commonly seen in elderly people, may have chorea as part of their clinical picture.

Treatment of Sydenham's Chorea: A Review of the Current Evidence.

BackgroundSydenham’s chorea (SC), the neurologic manifestation of rheumatic fever, remains the most prevalent form of chorea in children. Suggested treatments of chorea in SC include prophylactic penicillin, symptomatic (antipsychotic and anticonvulsant) medications, and immunomodulatory therapy (steroids, intravenous immunoglobulin (IVIG), and plasma exchange). In this manuscript, we undertook a systematic review of the published literature to examine the data supporting these therapeutic recommendations.MethodsA search of PubMed, Embase, Psychinfo, and clinicaltrials.gov was conducted for publications pertaining to the treatment of SC/rheumatic chorea from 1956 to 2016.ResultsPenicillin prophylaxis appears to reduce the likelihood of further cardiac complications and the recurrence rate of chorea. Data on symptomatic therapy for chorea are limited to individual case reports or series and rare comparison studies. The efficacy of steroid use is supported by a single placebo-controlled study and several case series. Information on other immunomodulatory therapies such as IVIG and plasmapheresis are limited to a small number of reports and a single comparison study.DiscussionTreatment decisions in SC are currently based on the treating physician’s clinical experience, the desire to avoid side effects, and the existence of only limited scientific evidence. Based on a review of the available literature, chorea often improves with symptomatic therapy and immunotherapy tends to be reserved for those who fail to respond. Steroids are beneficial; however, data using IVIG and plasmapheresis are very limited. Larger, well-controlled studies, using standardized assessment scales, are required if therapeutic decisions for SC are to be based on meaningful information.

Predictors of recurrence in Sydenham’s chorea: Clinical observation from a single center

ObjectiveSydenham’s chorea is the most common cause of acquired chorea in children and is the major manifestation for acute rheumatic fever. Despite being known as a benign, self-limiting condition, recurrences and persistence of symptoms can be seen. In this study, we aimed to evaluate retrospectively the clinical and laboratory features of patients with Sydenham’s chorea and the rate and the course of recurrences, and to assess the risk of recurrences. MethodsThe study was a retrospective study conducted in a tertiary hospital. Patients with Sydenham’s chorea who were admitted to our outpatient clinics between January 2013 and June 2015 were included. Both newly diagnosed and follow-up patients were enrolled during this period. We retrospectively reviewed the medical charts of the patients. ResultsThere were 90 patients with female predominance. The mean age of onset was 11±2.4years. Complete remission was maintained in 77 patients (85.6%) at 1–6months and 4 patients had symptoms at more than 12months. Patients were followed for 6months to 9years. The recurrence rate was 16%. When we compared recurrent patients with the non-recurrent group, complete remission in 6months, the presence of persistent chorea, and regular use of prophylaxis were significantly different between the 2 groups. ConclusionsSydenham’s chorea is still an important health problem and has high morbidity in patients with recurrent and persistent chorea. The irregular usage of antibiotic prophylaxis, failure to achieve remission within 6months, and prolongation of symptoms for more than 1year are risk factors for recurrence of chorea.