Treatments and Outcomes Among Patients with Sydenham Chorea: A Meta-Analysis.

Importance: Sydenham chorea is the most common acquired chorea of childhood worldwide; however, treatment is limited by a lack of high-quality evidence. Objectives: To evaluate historical changes in the clinical characteristics of Sydenham chorea and identify clinical and treatment factors at disease onset associated with chorea duration, relapsing disease course, and functional outcome. Data Sources: The systematic search for this meta-analysis was conducted in PubMed, Embase, CINAHL, Cochrane Library, and LILACS databases and registers of clinical trials from inception to November 1, 2022 (search terms: [Sydenham OR Sydenham's OR rheumatic OR minor] AND chorea). Study Selection: Published articles that included patients with a final diagnosis of Sydenham chorea (in selected languages). Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Individual patient data on clinical characteristics, treatments, chorea duration, relapse, and final outcome were extracted. Data from patients in the modern era (1945 through 2022) were entered into multivariable models and stratified by corticosteroid duration for survival analysis of chorea duration. Main Outcomes and Measures: The planned study outcomes were chorea duration at onset, monophasic course (absence of relapse after ≥24 months), and functional outcome (poor: modified Rankin Scale score 2-6 or persisting chorea, psychiatric, or behavioral symptoms at final follow-up after ≥6 months; good: modified Rankin Scale score 0-1 and no chorea, psychiatric, or behavioral symptoms at final follow-up). Results: In total, 1479 patients were included (from 307 articles), 1325 since 1945 (median [IQR] age at onset, 10 [8-13] years; 875 of 1272 female [68.8%]). Immunotherapy was associated with shorter chorea duration (hazard ratio for chorea resolution, 1.51 [95% CI, 1.05-2.19]; P = .03). The median chorea duration in patients receiving 1 or more months of corticosteroids was 1.2 months (95% CI, 1.2-2.0) vs 2.8 months (95% CI, 2.0-3.0) for patients receiving none (P = .004). Treatment factors associated with monophasic disease course were antibiotics (odds ratio [OR] for relapse, 0.28 [95% CI, 0.09-0.85]; P = .02), corticosteroids (OR, 0.32 [95% CI, 0.15-0.67]; P = .003), and sodium valproate (OR, 0.33 [95% CI, 0.15-0.71]; P = .004). Patients receiving at least 1 month of corticosteroids had significantly lower odds of relapsing course (OR, 0.10 [95% CI, 0.04-0.25]; P < .001). No treatment factor was associated with good functional outcome. Conclusions and Relevance: In this meta-analysis of treatments and outcomes in patients with Sydenham chorea, immunotherapy, in particular corticosteroid treatment, was associated with faster resolution of chorea. Antibiotics, corticosteroids and sodium valproate were associated with a monophasic disease course. This synthesis of retrospective data should support the development of evidence-based treatment guidelines for patients with Sydenham chorea.

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

Background: Acute to subacute pediatric movement disorders require prompt diagnosis to identify potentially treatable diseases. Case Report: We present a 6-year-old male with a three-week history of generalized chorea transitioning to predominantly right-sided hemichorea and then to left hemiplegia. Discussion: We review the mechanisms in tuberculous meningitis underlying his movement abnormalities.

Genetic testing for non-parkinsonian movement disorders: Navigating the diagnostic maze.

Genetic testing has become a valuable diagnostic tool for movement disorders due to substantial advancements in understanding their genetic basis. However, the heterogeneity of movement disorders poses a significant challenge, with many genes implicated in different subtypes. This paper aims to provide a neurologist's perspective on approaching patients with hereditary hyperkinetic disorders with a focus on select forms of dystonia, paroxysmal dyskinesia, chorea, and ataxia. Age at onset, initial symptoms, and their severity, as well as the presence of any concurrent neurological and non-neurological features, contribute to the individual clinical profiles of hereditary non-parkinsonian movement disorders, aiding in the selection of appropriate genetic testing strategies. There are also more specific diagnostic clues that may facilitate the decision-making process and may be highly specific for certain conditions, such as diurnal fluctuations and l-dopa response in dopa-responsive dystonia, and triggering factors, duration and frequency of attacks in paroxysmal dyskinesia. While the genetic and mutational spectrum across non-parkinsonian movement disorders is broad, certain groups of diseases tend to be associated with specific types of pathogenic variants, such as repeat expansions in many of the ataxias. Some of these pathogenic variants cannot be detected by standard methods, such as panel or exome sequencing, but require the investigation of intronic regions for repeat expansions, such as Friedreich's or FGF14-linked ataxia. With our advancing knowledge of the genetic underpinnings of movement disorders, the incorporation of precise and personalized diagnostic strategies can enhance patient care, prognosis, and the application and development of targeted therapeutic interventions.

Hyperglycemia-induced hemichorea-hemiballismus syndrome - a systematic review.

Nonketotic hyperglycemia may occur as a cause of chorea in patients with chronic decompensated diabetes. Because it is rare and consequently poorly studied, diagnosis and treatment can be delayed. Therefore, our objective was to summarize clinical and radiological features, as well as treatments performed, from previously reported cases to facilitate adequate management in clinical practice. We searched MEDLINE/PubMed, EMBASE, Cochrane, CINAHL, Web of Science, Scopus, and LILACS databases for studies published before April 23, 2021. We included case reports and case series of adults (aged ≥ 18 years) that described hyperglycemic chorea with measurement ofglycated hemoglobin (HbA1c) and cranial magnetic resonance imaging (MRI). Studies were excluded if participants were pregnant women, aged < 18 years, and had no description of chorea and/or physical examination. We found 121 studies that met the inclusion criteria, for a total of 214 cases. The majority of the included studies were published in Asia (67.3%). Most patients were women(65.3%) aged > 65 years (67.3%). Almost all patients had decompensated diabetes upon arrival at the emergency department (97.2%). The most common MRI finding was abnormalities of the basal ganglia (89.2%). There was no difference in patient recovery between treatment with insulin alone and in combination with other medications. Although rare, hyperglycemic chorea is a reversible cause of this syndrome; therefore, hyperglycemia should always be considered in these cases.

[The value of re-evaluation and thorough family history taking for the diagnostic work-up of chorea]. / Het diagnostisch proces bij chorea: het belang van heroverwegen en de familieanamnese.

The differential diagnosis of chorea encompasses a broad range of disorders. In psychiatry, tardive dyskinesia may be difficult to discern from other causes, particularly when the family history is negative. A 59-year-old man with an unclear medical history had been using risperidone for over a decade when we first saw him. He presented with severe dyskinesia in all extremities. The family history for neuropsychiatric disorders was negative. We interpreted the movement disorder as tardive dyskinesia, but later he turned out to suffer from Huntington’s disease. To improve diagnostic accuracy, we should have more frequently re-evaluated the differential diagnosis and our family history should have been more thorough. We outline the diagnostic considerations in patients presenting with chorea. Finally, we highlight the value of diagnostic re-evaluation and thorough family history taking to optimize diagnostic accuracy in neuropsychiatry.

Chorea as an initial and solitary manifestation of systemic lupus erythematosus with antiphospholipid syndrome in an elderly man.

Chorea can be an initial manifestation of systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). It has been mostly described in younger female adults in association with other manifestations of SLE. When chorea appears as an initial and only manifestation in SLE/APS patients, the establishment of the correct diagnosis is difficult, and it may be initially attributed to a more common aetiology. Here we report an elderly man who presented with a new onset of right-sided chorea without other clinical manifestations of SLE/APS. He started on steroids a year later, however, there was no improvement. His chorea was symptomatically managed along with aspirin, and hydroxychloroquine as he refused to be on additional immunosuppression. Anticoagulation was relatively contraindicated, and also not favoured by this patient; therefore, aspirin was initiated. Even in elderly patients, once the common etiologies of chorea have been worked up, we suggest doing a rheumatological evaluation. Early diagnosis and prompt treatment can prevent persistent neurological abnormality.

Footloose (footloose), footloose.

A 78-year-old woman without past relevant medical history presented to the emergency department for acute transient dysarthria. NIHSS was 0/42. Neurological examination revealed chorea-like movements over the left limbs, especially the foot. No other neurological signs were present. CT perfusion showed right cortical hypoperfusion due to right M2 occlusion, basal-ganglia perfusion was normal. Brain MRI revealed a small focus of restricted diffusion in the right insula, sparing basal ganglia. Based on the neuroimaging features and clinical correlation, despite the NIHSS score, we decided to treat the patient with alteplase, after iv-thrombolysis hyperkinetic movements ceased completely. Brain-MRI performed 72 h after symptom onset confirmed a confined insular ischemic lesion without the involvement of deep gray matter structures. Hyperkinetic movement disorders, such as hemichorea hemiballismus, are rare presentations of stroke, basal ganglia are mainly involved even if the insular cortex has been described too. Clinical decision on whether to treat ischemic stroke does not include movement disorders. Our case underscores NIHSS limitations in clinical practice.

Recurrent hemichorea in an adolescent with systemic lupus erythematosus and previous ipsilateral cerebral infarction.

Systemic lupus erythematosus (SLE) can present with movement disorders, among which chorea is closely associated with antiphospholipid (aPL) antibodies. Brain imaging results obtained in patients with chorea are generally inconsistent with the clinical manifestation of chorea; moreover, medical tests for hemichorea, which are expected to reveal distinct localization, may show negative findings. Herein, we present a case of a 15-year-old girl with SLE who had a history of left cerebral infarction; tests revealed elevated aPL levels, and she developed recurrent left hemichorea 2 years later. Brain magnetic resonance imaging (MRI) results revealed no acute lesions during each episode of involuntary movements, and an MRI perfusion scan failed to provide an explanation for the asymmetric presentation. Although various hypotheses have been proposed regarding the mechanism underlying the occurrence of chorea, some scenarios still remain unexplained. Further investigation on the pathophysiology of chorea in SLE may be warranted to clarify its prognosis.

Resolving the Dance: A Case Study on Non-Ketotic Hyperglycemic Hemichorea-Hemiballismus in a Patient with Long-Standing Type 2 Diabetes.

BACKGROUND Non-ketotic hyperglycemic hemichorea-hemiballism (HCHB) is a rare complication of diabetes, which is mainly described in case reports. This condition occurs more commonly in older women and is known to be associated with T1 hyperintensity basal ganglia lesions on magnetic resonance imaging (MRI). The pathophysiology of non-ketotic hyperglycemic HCHB is not well defined, although a combination of regional metabolic failure and ischemia due to hyperglycemia is suspected to occur. Treatment entails tight blood glucose control, although antipsychotic medications such as risperidone may be helpful in refractory cases. CASE REPORT We describe a case of a middle-aged man with long-standing type 2 diabetes who experienced 3 weeks of progressive unilateral arm, leg, and face choreiform movements. Laboratory testing performed just prior to symptom onset was notable for a hemoglobin A1C of >15% and a serum blood glucose of 566 mg/dl. MRI revealed diffuse T1 hyperintensity in the left lentiform nucleus. Our patient's insulin regimen was adjusted, resulting in improvement in average serum glucose (A1C of 9.4%). However, his symptoms did not improve significantly. A trial of benzodiazepine was attempted, without success. When risperidone was started, the patient experienced resolution of symptoms. Recurrence of non-ketotic hyperglycemic HCHB while off risperidone has not occurred to date. CONCLUSIONS Non-ketotic hyperglycemic HCHB is a rare but important diagnosis to consider in patients with hyperglycemia and new-onset choreiform movements. Patients with long-standing type 2 diabetes may be affected, especially when glycemic control worsens. When tight blood glucose control does not resolve symptoms, a short course of antipsychotic agents may provide relief.

Chorea in the Elderly: A Differential Diagnosis and Case Report of Late-Onset Huntington's Disease in an Octogenarian.

The term "senile chorea" was previously used to describe cases of insidious onset chorea in elderly patients who lacked family history of chorea. However, many of these patients have an identifiable etiology for their chorea. In this article, we discuss a case of generalized, insidious onset chorea in an 89-year-old man and apply a systematic diagnostic approach to chorea in the elderly to arrive at a diagnosis of late-onset Huntington's disease. He is to our knowledge the second oldest case of late-onset Huntington's disease reported in the literature and his case lends support to the expanding phenotype of Huntington's disease.

[A case of a pathological variant of the PRRT2 gene in twins with paroxysmal kinesiogenic dyskinesia]. / Sluchai patologicheskogo varianta gena PRRT2 u bliznetsov s paroksizmal'noi kineziogennoi diskineziei.

Paroxysmal dyskinesia is a clinically and etiologically polymorphic group of diseases, the main clinical manifestation of which is transient attacks of extrapyramidal movements, with different conditions of occurrence. Paroxysmal kinesigenic dyskinesia belongs to the group of primary dyskinesias, which also includes paroxysmal non-kinesigenic dyskinesia and exercise-induced paroxysmal dyskinesia. The most common cause of paroxysmal kinesiogenic dyskinesia is mutations in the PRRT2 gene; in cases of non-kinesiogenic dyskinesia, a mutation in the MR1 gene is detected. The diagnosis of primary dyskinesias causes significant difficulty for clinicians due to the rarity of occurrence, as well as the large spectrum of conditions occurring with paroxysmal motor disorders in childhood. The article describes the clinical observation of 16-year-old twin brothers with transient attacks of dystonic, choreic and ballistic hyperkinesis that suddenly arose during movement. Patients were treated for tics and epilepsy for 12 years. Taking into account the clinical picture - transient attacks of hyperkinesis, their connection with movement, as well as data from video-electroencephalographic monitoring, a diagnosis of paroxysmal kinesiogenic dyskinesia was established, which in a further diagnostic search was confirmed by targeted sequencing of the pathological variant of the PRRT2 gene previously described in patients with kinesiogenic dyskinesia. The administration of carbamazepine, which is the drug of choice in the treatment of this category of patients, has achieved significant control over hyperkinesis in twins. Thus, molecular genetic diagnosis helps confirm the diagnosis of paroxysmal dyskinesias, but careful analysis of the clinical picture, considering the provoking factor, remains the basis of diagnosis.

Unilateral chorea linked to cavernous haemangioma involving the putamen improved by surgery.

Unilateral chorea movements caused by cavernous haemangioma in the putamen are extremely rare. We report a case with chorea movements linked to cavernous haemangioma, localised to an area including the putamen in which pharmacotherapy was found to be ineffective. Symptoms were, however, improved by resection of the cavernous haemangioma. In cases where chorea movements linked to cavernous haemangioma, involving the putamen, prove intractable with watchful waiting or pharmacotherapy, improvement can be expected with surgical removal of the cavernous haemangioma. It is also possible to reduce the risk of complications through the use of intraoperative navigation and monitoring.

Narcolepsy type 1 and Sydenham chorea - Report of 3 cases and review of the literature.

OBJECTIVES/BACKGROUND: Narcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1. Sydenham chorea (SC) results from a post-streptococcal autoimmune process targeting basal ganglia neurons. Despite this common trigger, SC has been interpreted as a misdiagnosis in a few described cases of patients who were first diagnosed with SC and later with NT1. Our goal was to analyze the association between SC and NT1. PATIENTS/METHODS: We reviewed the literature and report three patients from three European sleep centers who were diagnosed with both SC and NT1 within a few months. RESULTS: We describe the cases of one male (age 10) and two female (age 22 and 10) patients. CONCLUSIONS: We argue that in those cases both diagnoses are justified, unlike reports of previous cases in which SC was considered a misdiagnosis in patients with NT1. It remains, however, unclear if the conditions occur independently or if there is an overlap disorder- an SC-like subtype of narcolepsy with a particular sequence of symptoms. Further studies need to clarify the causality of the relationship and the pathophysiology of the reported rare association.

Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism.

Background: Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this context, comprehensive descriptions of movement disorders are limited and primarily derived from single cases or small patient series, highlighting the need for increased awareness and additional research in this field. Methods: A systematic review was conducted using the MEDLINE database and GeneReviews. The search included studies on inborn errors of metabolism associated with chorea, athetosis, or ballismus. The review adhered to PRISMA guidelines. Results: The systematic review analyzed 76 studies out of 2350 records, encompassing the period from 1964 to 2022. Chorea was observed in 90.1% of the 173 patients, followed by athetosis in 5.7%. Various inborn errors of metabolism showed an association with chorea, with trace elements and metals being the most frequent. Cognitive and developmental abnormalities were common in the cohort. Frequent neurological features included seizures, dysarthria, and optic atrophy, whereas non-neurological features included, among others, facial dysmorphia and failure to thrive. Neuroimaging and biochemical testing played crucial roles in aiding diagnosis, revealing abnormal findings in 34.1% and 47.9% of patients, respectively. However, symptomatic treatment efficacy for movement disorders was limited. Discussion: This study emphasizes the complexities of chorea in inborn errors of metabolism. A systematic approach with red flags, biochemical testing, and neuroimaging is required for diagnosis. Collaboration between neurologists, geneticists, and metabolic specialists is crucial for improving early detection and individualized treatment. Utilizing genetic testing technologies and potential therapeutic avenues can aid in the improvement of patient outcomes.

The enduring enigma of sporadic chorea: A single center case series.

Chorea can have a wide variety of causes including neurodegenerative, pharmacological, structural, metabolic, infectious, immunologic and paraneoplastic processes. We reviewed the clinical records of patients with apparently sporadic choreic movements and no relevant family history, who presented to our neurology department (Hospital Fundación Jimenez Diaz) between 1991 and 2022. We detected 38 cases of apparent sporadic chorea (ASC); Our analysis revealed 5 cases of genetic chorea (including 3 cases with Huntington's disease) while 6 cases were autoimmune/hematological; 6 drug-related chorea, 5 metabolic-vascular, 5 due to miscellaneous conditions and 4 were of mixed etiology. No clear etiology was identified in 8 cases. The differential diagnosis of ASC is extensive and challenging. Highlights: Chorea can have a wide variety of genetic and sporadic causesWe reviewed the clinical records of patients with apparently sporadic chorea (ASC), who presented to our neurology department over the last 30 yearsWe detected 38 cases of apparent ASC; Our analysis revealed a wide array of different sporadic conditions and 5 cases of genetic choreaThe differential diagnosis of ASC is extensive and challenging.

Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder.

Postinfectious neuroinflammation has been implicated in multiple models of acute-onset obsessive-compulsive disorder including Sydenham chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.

Paroxysmal movement disorders: Paroxysmal dyskinesia and episodic ataxia.

Paroxysmal movement disorders have traditionally been classified into paroxysmal dyskinesia (PxD), which consists in attacks of involuntary movements (mainly dystonia and/or chorea) without loss of consciousness, and episodic ataxia (EA), which features spells of cerebellar dysfunction with or without interictal neurological manifestations. In this chapter, PxD will be discussed first according to the trigger-based classification, thus reviewing clinical, genetic, and molecular features of paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia, and paroxysmal exercise-induced dyskinesia. EA will be presented thereafter according to their designated gene or genetic locus. Clinicogenetic similarities among paroxysmal movement disorders have progressively emerged, which are herein highlighted along with growing evidence that their pathomechanisms overlap those of epilepsy and migraine. Advances in our comprehension of the biological pathways underlying paroxysmal movement disorders, which involve ion channels as well as proteins associated with the vesical synaptic cycle or implicated in neuronal energy metabolism, may represent the cornerstone for defining a shared pathophysiologic framework and developing target-specific therapies.

Dystonic head tremor in paroxysmal dyskinesia in 17 dogs (2021-2023).

BACKGROUND: Dystonia is a common component of the movement disorder paroxysmal dyskinesia (PD) in dogs. However, the incidence of dystonic head tremor (DHT) in these dogs has not previously been evaluated. METHODS: The medical records of dogs presenting with PD between 2021 and 2023 were retrospectively reviewed, and those with available video footage and the presence of a head tremor were selected for further analysis. RESULTS: Seventeen of the 39 (43.6%) dogs diagnosed with PD that had video footage available manifested DHT. Poodle or Poodle-cross was the most commonly affected breed (7/17). DHTs were described as fine irregular head tremors accompanied by cervical dystonia (17/17), truncal (11/17) or head (10/17) sway, shifting limb (10/17) or single limb (6/17) dystonia, freezing (8/17), ataxia (6/17), ptyalism (5/17), falling (5/17), kyphosis (4/17) and prayer posture (4/17). Neurological examination and advanced imaging, when available, were within normal limits. LIMITATIONS: The limitations of the study include its retrospective nature, the lack of video recordings for all PD patients and the lack of electrophysiological evaluation of tremors and electroencephalography. CONCLUSIONS: DHT exists in dogs with PD; it has characteristic features, and it should be considered in differential diagnoses for dogs with head tremors.

Sydenham chorea in the top end of Australia's Northern Territory: A 20-year retrospective case series.

AIM: Sydenham chorea is an immune-mediated neuropsychiatric condition, and a major criterion for diagnosis of acute rheumatic fever (ARF). Children in remote Northern Australia experience disproportionately high rates of ARF, yet studies looking at the epidemiology, clinical presentation and management of Sydenham chorea are limited in this population. METHODS: We conducted a retrospective case series from January 2002 to April 2022 of all paediatric patients aged ≤18 years admitted to Royal Darwin Hospital with Sydenham chorea. Cases were identified using the hospital's clinical coding system (ICD10). Medical records were reviewed and data on demographics, clinical presentation, investigation results, treatment and outcome were extracted, deidentified and analysed. RESULTS: One hundred ten presentations of Sydenham chorea occurred between 2002 and 2022, 109 (99%) of these were in First Nations children, with 85% residing in very remote locations. Most commonly, chorea presented as a generalised movement disorder affecting all four limbs (49%). Neuropsychiatric symptoms were reported in 33 (30%), and there was evidence of rheumatic heart disease on echocardiogram in 86 (78%) at presentation. All patients received benzathine penicillin, but there was significant variation in management of chorea, ranging from supportive management, to symptomatic management with anticonvulsants, to immunomodulatory medications including corticosteroids. CONCLUSION: This case series highlights the significant burden of Sydenham chorea among First Nations children living in Northern Australia and demonstrates wide variation in treatment approaches. High-quality clinical trials are required to determine the best treatment for this disabling condition.