Cause Of Chorea Research Articles

Sleep Disorders in Patients with Choreic Syndromes.

Patients with different types of choreic syndromes, specially those with Huntington's (HD) and Wilson's (WD) diseases, report frequent sleep complaints. This review focuses on the main findings of studies addressing the sleep features in these diseases, and other less frequent causes of chorea associated with sleep disorders, including a new syndrome described in the last decade associated with IgLON5 antibodies. Patients with HD and WD showed a bad quality of sleep and high frequency of insomnia and excessive daytime somnolence. WD patients also showed high scores on a specific scale for rapid eye movement sleep behavior disorders. HD and WD share decreased sleep efficiency and increased REM sleep latencies, percentage of sleep stage N1, and wake after sleep onset (WASO) among their polysomnographic features. Patients with HD and WD showed a high prevalence of different sleep disorders. Patients with other causes of chorea, including neuroacanthocytosis, parasomnia with sleep breathing disorder associated with antibodies to IgLON5, Sydenham's chorea, and choreic syndromes associated to certain genetic mutations show sleep disorders as well.

POLG-Related Ataxia and Ophthalmoplegia: A Case Report (P9-11.008)

<h3>Objective:</h3> Not applicable <h3>Background:</h3> Genetic variants of the POLG gene result in mitochondrial DNA defects and account for a large proportion of mitochondrial diseases. These disorders encompass a spectrum of phenotypes, with onset ranging from infancy to late adulthood. In addition to hepatic dysfunction and myopathy in younger populations, and hormone derangements with cataracts in older patients, patients may also present with prominent neurologic symptoms, including ataxia, parkinsonism, epilepsy, and ophthalmoplegia. More than 300 pathogenic mutations of POLG have been reported and there are no clear genotype-phenotype correlations. Given the rarity of these syndromes and wide range of clinical phenotypes, there is often delay in diagnosis. <h3>Design/Methods:</h3> Not applicable <h3>Results:</h3> We present a 47-year old woman with symptoms of difficulty speaking and development of tremor, vision loss, dizziness, and gait difficulty progressing over several months. Initial exam was significant for ataxia and choreiform movements. Extraocular movement (EOM) testing revealed delayed initiation of saccades and slow, saccadic pursuits with nystagmus. Bloodwork, which included extensive workup for causes of chorea and ataxia, electromyography/nerve conduction studies, and imaging (MRI brain and malignancy work-up) were unremarkable. She continued to decline with development of ophthalmoplegia, ptosis, numbness, weakness, and pain, severely limiting her functional capacity. Whole exome sequencing was performed and showed a heterozygous variant of uncertain significance (VUS) in the POLG gene, which may explain her presentation. <h3>Conclusions:</h3> This case adds to a growing collection of case reports describing the various phenotypes of POLG-related disorders. Early detection of POLG variants and phenotype/genotype characterization may help guide development of future treatments for patients with similar conditions. <b>Disclosure:</b> Dr. Peabody has nothing to disclose. An immediate family member of Dr. Shpiner has received personal compensation for serving as an employee of University of Miami.

Teaching Video NeuroImages: A treatable rare cause of chorea

A 72-year-old woman developed progressive choreic movements involving the right hemibody and the orofacial muscles (video 1). Her examination was otherwise unremarkable, without ataxia. Brain MRI, blood glucose, thyroid function, and rheumatologic panel were unremarkable. Genetic testing for Huntington disease and C9orf72 expansions were negative. Initial hematocrit and hemoglobin levels were normal, but increased to abnormal values (56% and 18.5 g/dL) 1 year after chorea onset. The JAK2V617F mutation was positive, suggesting a diagnosis of chorea due to polycythemia vera. Chorea disappeared with phlebotomy and hydroxyurea. Neurologists should suspect this rare treatable entity in elderly patients with chorea even with initially normal hematocrit levels.1

Diagnostic Uncertainties: Chorea.

Chorea is a hyperkinetic movement disorder with a multitude of potential etiologies, both acquired and inherited. Although the differential diagnosis for new-onset chorea is extensive, there are often clues in the history, exam, and basic testing that can help to narrow the options. Evaluation for treatable or reversible causes should take priority, as rapid diagnosis can lead to more favorable outcomes. While Huntington's disease is most common genetic cause of chorea, multiple phenocopies also exist and should be considered if Huntington gene testing is negative. The decision of what additional genetic testing to pursue should be based on both clinical and epidemiological factors. The following review provides an overview of the many possible etiologies as well as a practical approach for a patient presenting with new-onset chorea.

Chorea.

This article provides an overview of the diagnostic and therapeutic approach to a patient with chorea. The phenomenology of chorea is described in addition to other common hyperkinetic movements that may be mistaken for or coexist with chorea. Chorea can be acquired or hereditary. Key historical and clinical features that can aid in determining the etiology are reviewed, and pharmacologic and nonpharmacologic treatment strategies are discussed. Clinical investigations are under way to target transcription and translation of the mutant huntingtin protein as a potential disease-modifying strategy in Huntington disease (HD). Additional heritable factors have been revealed through genome-wide association studies. Symptom-focused treatments for HD are are being studied, including a third vesicular monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and drugs to target irritability and cognitive impairment. Increased availability of genetic testing has led to increased awareness of HD mimics (eg, C9orf72 and IgLON5). Chorea is a relatively common hyperkinetic disorder with a broad differential. The first step in the approach to a patient with chorea is accurately defining the phenomenology. Once it has been determined that the patient has chorea, the investigation into determining an etiology can begin. Factors such as age of onset, time course, family history, unique clinical features, and imaging and laboratory findings can guide the diagnosis. Treatments for most causes of chorea are purely symptomatic, although it is important to recognize causes that are reversible or have disease-modifying interventions.

Sydenham Chorea On Indonesian 10 Years Old Boy Caused By Rheumatic Heart Disease : Case Report And Literature Review

Sydenham's chorea (SC) is one of the manifestations of rheumatic fever, and is the most common cause of chorea in childrens. Sydenham chorea is characterized by involuntary movements such as jerking of the arms, legs, and face. The following case is a 10-year-old boy with complaints of moving his right arm and leg on its own. On physical examination, there was a grade 4/5 systolic murmur at ICS 5 2 cm lateral to the left MCL blowing radiating to the left arm. ASTO examination there is an increase. CT scan of the head without contrast showed no abnormalities. The results of echocardiography showed severe mitral regurgitation. The patient was diagnosed with Sydenham Chorea and Rheumatic Heart Disease. The patient refused hospitalization and was treated as an outpatient with given therapy erythromycin 250 mg four times daily for 10 days followed by a twice daily dose for the next two months, symptomatic haloperidol 1 mg and trihexyphenidyl 0.5 mg twice a day, aspirin 300 mg four times a day for one month. From this treatment, the complaints improved slowly, and the chorea disappeared within 10 days of the start of treatment.

HD like presentation of HIV in adult: Rare case report

Movement disorders including parkinsonism, tremor, myoclonus, and dystonia have been reported in patients with HIV (human immunodeficiency virus) encephalopathy. Chorea and ballismus have been reported in AIDS (acquired immune deficiency syndrome) complicated by CNS toxoplasmosis infection. Huntington disease (HD) is common cause of chorea in adult with chronic history. Generalised chorea as a presenting symptom of HIV rare. We are reporting this HD like presentation of HIV in adult as it is probably the rare case report after thorough review of literature.

Corticostriatal Hypermetabolism in Moyamoya Disease-Induced Hemichorea: Two Case Reports and a Literature Review

Moyamoya disease (MMD) is a rare cause of chorea, and its pathophysiological mechanism remains unclear. We explore the use of cerebral positron emission tomography (PET) to study brain functional connectivity in 2 patients with MMD-induced hemichorea. Abnormal metabolism of brain was analyzed by 18F-fluorodeoxyglucose (18F-FDG) PET images. Dopamine transporters (DAT) PET evaluated the integrity of the cerebral dopamine system. A comprehensive systemic literature search of the PubMed database was also conducted. The 18F-FDG imaging of our patients showed no responsible hypometabolism in affected brain areas, while hypermetabolism in the affected caudate nucleus, putamen and fronto-parietal areas could be seen. DAT PET imaging was normal in patient 1 (a 23-year-old woman), while remarkably reduced DAT binding was seen in the left striatum of patient 2 (a 48-year-old woman). The literature review of 9 publications revealed that 11 patients who underwent single photon emission computed tomography (SPECT) showed cerebral hypoperfusion in the cortex and subcortical area; 18F-FDG PET was performed in 3 cases, which revealed hypermetabolism in the affected striatum in 2 cases. These findings suggest that the striatal and cortical hypermetabolism in the first patient result from underactivity in indirect pathway from basal ganglia-thalamocortical circuits, causing increased activity of excitatory glutamatergic thalamostriatal and thalamocortical projection neurons. The collateral vessels in the basal ganglia might lead to disruption of normal basal ganglia signaling. A dominant left hemisphere with corpus callosal connections to the right basal ganglia resulting into left hemichorea is the most probable explanation for the second patient. We have identified abnormal functional connectivity in basal ganglia-thalamocortical circuits in patients with MMD-induced chorea highlighting the corticostriatal pathway plays an important role in the pathogenesis of MMD-induced chorea.

Differential Diagnosis of Chorea-HIV Infection Delays Diagnosis of Huntington's Disease by Years.

Background: There is a broad range of potential differential diagnoses for chorea. Besides rare, inherited neurodegenerative diseases such as Huntington’s disease (HD) chorea can accompany basal ganglia disorders due to vasculitis or infections, e.g., with the human immunodeficiency virus (HIV). The clinical picture is complicated by the rare occurrence of HIV infection and HD. Methods: First, we present a case suffering simultaneously from HIV and HD (HIV/HD) focusing on clinical manifestation and disease onset. We investigated cross-sectional data regarding molecular genetic, motoric, cognitive, functional, and psychiatric disease manifestation of HIV/HD in comparison to motor-manifest HD patients without HIV infection (nonHIV/HD) in the largest cohort of HD patients worldwide using the registry study ENROLL-HD. Data were analyzed using ANCOVA analyses controlling for covariates of age and CAG repeat length between groups in IBM SPSS Statistics V.25. Results: The HD diagnosis in our case report was delayed by approximately nine years due to the false assumption that the HIV infection might have been the cause of chorea. Out of n = 21,116 participants in ENROLL-HD, we identified n = 10,125 motor-manifest HD patients. n = 23 male participants were classified as suffering from HIV infection as a comorbidity, compared to n = 4898 male non-HIV/HD patients. Except for age, with HIV/HD being significantly younger (p < 0.050), we observed no group differences regarding sociodemographic, genetic, educational, motoric, functional, and cognitive parameters. Male HIV/HD patients reported about a 5.3-year-earlier onset of HD symptoms noticed by themselves compared to non-HIV/HD (p < 0.050). Moreover, patients in the HIV/HD group had a longer diagnostic delay of 1.8 years between onset of symptoms and HD diagnosis and a longer time regarding assessment of first symptoms by the rater and judgement of the patient (all p < 0.050). Unexpectedly, HIV/HD patients showed less irritability in the Hospital Anxiety and Depression Scale (all p < 0.05). Conclusions: The HD diagnosis in HIV-infected male patients is secured with a diagnostic delay between first symptoms noticed by the patient and final diagnosis. Treating physicians therefore should be sensitized to think of potential alternative diagnoses in HIV-infected patients also afflicted by movement disorders, especially if there is evidence of subcortical atrophy and a history of hyperkinesia, even without a clear HD-family history. Those patients should be transferred for early genetic testing to avoid further unnecessary diagnostics and improve sociomedical care.

Phenytoin induced Chorea: commonly used antiepileptic drug causing a rare movement disorder

Background: Phenytoin, a commonly prescribed antiepileptic drug, causes side effects like ataxia, tremor, hirsutism, gum hyperplasia, insomnia, confusion, headache and vertigo when used for longer duration. However, chorea is a rarely reported side effect of phenytoin and is completely reversible on stopping treatment. Case presentation: A twenty-one-year-old Indian male patient, who had generalized epilepsy and had been on sodium valproate for 2 years, presented with acute onset chorea four days after starting phenytoin sodium. He had normal serum phenytoin levels. A thorough evaluation was done, which suggested phenytoin as a possible cause of chorea. Phenytoin was withdrawn, resulting in a dramatic subsiding of chorea. A rechallenge with the drug resulted in reappearance of choreiform movements. These disappeared again after drug withdrawal, implicating phenytoin as the possible etiological agent for chorea. Conclusion: Phenytoin rarely induces involuntary movements as an adverse effect. During phenytoin therapy, if a patient develops involuntary movements, phenytoin toxicity should be suspected even with normal drug levels. This is important as drug withdrawal leads to complete symptomatic improvement thereby avoiding extensive workup for other secondary causes.

Review of Hereditary and Acquired Rare Choreas.

Background:Movement disorders are often a prominent part of the phenotype of many neurologic rare diseases. In order to promote awareness and diagnosis of these rare diseases, the International Parkinson’s and Movement Disorders Society Rare Movement Disorders Study Group provides updates on rare movement disorders.Methods:In this narrative review, we discuss the differential diagnosis of the rare disorders that can cause chorea.Results:Although the most common causes of chorea are hereditary, it is critical to identify acquired or symptomatic choreas since these are potentially treatable conditions. Disorders of metabolism and mitochondrial cytopathies can also be associated with chorea.Discussion:The present review discusses clues to the diagnosis of chorea of various etiologies. Authors propose algorithms to help the clinician in the diagnosis of these rare disorders.

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.

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.

Chorea, Pruritus and Polycythemia: Looking for Clues.

Chorea is a movement disorder usually due to vascular, hereditary, metabolic or drug-induced causes, and has rarely been reported in association with polycythemia vera (PV). Polycythemic chorea is an uncommon clinical entity that occurs more often in elderly women. PV is a treatable cause of chorea and must be considered during the diagnostic approach. We report the case of a 75-year-old woman with involuntary movements of the mouth and face with subsequent involvement of the trunk and limbs who was admitted for investigation of the chorea. The patient had the haematological attributes of PV and a positive mutation in the janus kinase 2 (JAK2) gene, and was therefore treated with hydroxyurea which led to a marked reduction in the chorea and improvement in haematological parameters. Various aetiologies of chorea must be considered in the elderly. The present case illustrates the importance of considering PV in the differential diagnosis, since its treatment leads to chorea resolution, thus avoiding serious complications.LEARNING POINTSPolycythemia vera is a sporadic myeloproliferative disorder of the haematopoietic stem cells and is a treatable cause of chorea.Chorea is a movement disorder with various aetiologies that is difficult to diagnose.Prompt treatment of polycythemia vera will lead to resolution of the chorea, with aspirin and phlebotomy being recommended in low-risk cases and hydroxyurea in high-risk cases.

An Update on the Treatment of Chorea.

There are many causes for chorea, including genetic, autoimmune, pharmacological, and structural lesions. Where appropriate, treatment is based on reversing the underlying cause of chorea; many cases are self-limited, resolving when the primary disorder is treated. This review focuses on the management of chorea due to untreatable causes. There are a limited number of double-blind randomized control trials assessing the efficacy of specific chorea treatments. Most therapeutic recommendations are based on small open-label studies, case reports, and expert opinion. This is in part due to the heterogeneity of chorea and chorea-associated syndromes and the variety of neurodegenerative phenotypes with variable progression rates. Chorea can be treated with a variety of medications ranging from antiepileptics to antipsychotics. The recent development of selective vesicular monoamine transporter blocking agents has allowed for targeted chorea management with minimal side effects. Neurosurgical interventions such as deep brain surgery (DBS) and pallidotomy are reserved for medication-refractory chorea. As a symptom of neurodegenerative disease, chorea is only one aspect of the basal ganglia syndromes, and often, a multidisciplinary approach tailored to individual patient needs provides the best management.

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.

Réponse spectaculaire au valproate de sodium d’une chorée de Sydenham récurrente

La chorée du Sydenham est la première cause de chorée acquise dans le tiers monde. Nous rapportons le cas d'une Chorée récurrente traitée avec succès par le valproate du sodium. Mlle A.C âgée de 16 ans ayant comme antécédents des angines à répétition et un épisode de mouvement choréique il y a 2 ans, pour lequel elle a été mise sous Halopéridol et sous prévention du rhumatisme articulaire aigu. La patiente a interrompue le traitement et quelques mois plus tard elle a présenté le même tableau neurologique. L'IRM cérébrale et l'échographie transthoracique étaient normales. La prévention par Extencilline a été réinstaurée ainsi que l'halopéridol sans aucune amélioration, d'où la mise en route sous valproate de sodium. La réponse était spectaculaire après 2 mois de traitement sans récidive après 3ans de recul. Le traitement de la chorée du Sydenham était les neuroleptiques. Des études récentes préconisent d'autres molécules efficaces et mieux tolérées.

De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions

Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very similar and unique clinical presentation of childhood-onset chorea and characteristic brain MRI showing symmetrical bilateral striatal lesions. All individuals were identified to carry a de novo heterozygous mutation in PDE10A (c.898T>C [p.Phe300Leu] in two individuals and c.1000T>C [p.Phe334Leu] in one individual), encoding a phosphodiesterase highly and selectively present in MSNs. PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. In silico modeling showed that the altered residues are located deep in the binding pocket, where they are likely to alter cAMP binding properties. In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. The identification of PDE10A mutations as a cause of chorea further motivates the study of cAMP signaling in MSNs and highlights the crucial role of striatal cAMP signaling in the regulation of basal ganglia circuitry. Pharmacological modulation of this pathway could offer promising etiologically targeted treatments for chorea and other hyperkinetic movement disorders.

The non-Huntington disease choreas: Five new things.

Chorea can be due to a wide variety of causes. In this review, I provide updates on several recently identified genetic and autoimmune causes of chorea, and review evidence supporting the use of deep brain stimulation in chorea. New genes that may cause chorea include ADCY5 (encoding for adenylate cyclase 5) C9ORF72 (in addition to amyotrophic lateral sclerosis and frontotemporal dementia), and those responsible for the neurodegeneration with brain iron accumulation disorders. Novel autoantibodies are increasingly being identified as associated with a variety of neurologic syndromes, including chorea, in both paraneoplastic and non-paraneoplastic settings. Deep brain stimulation can be a useful intervention in patients with chorea who do not respond to oral medications, whether due to neurodegenerative or nondegenerative causes. New causes of chorea continue to be identified. Correct diagnosis is essential for prognostication and treatment.

Apenas mais um acidente de trabalho? Relato de um caso clínico de coreia de Huntington

Introduction: Abnormal involuntary movements, also known as dyskinesias, may manifest as chorea, athetosis, tremor, myoclonus, asterixis, spasticity, dystonia and tics. Huntington disease is the most common cause of hereditary chorea and is a cause of morbidity and premature death. Relatives and others living with the patient are often the first to notice chorea in a patient. Family physicians have a special opportunity to diagnose movement disorders. Case description: We present the case of a 41 year-old married Caucasian male living in a nuclear family. He was a construction worker but had been unemployed for one year. There was no relevant previous medical history. His father died at age 56 with “Parkinson disease”, according to one family member. He was the father of two healthy 5 year-old twin boys. A relative of the patient went to the family physician in January 2014, stating that the health of the patient had changed in the past three years. He noted ‘uncoordinated and clumsy movements’ of the limbs, memory changes, and speech difficulties. These changes were similar to the abnormal movements that the patient’s father had shown. The relative also highlighted the history of a work accident he suffered in construction work in 2012, in which he a cut his right hand on a grinding wheel, with permanent loss of function. Due to the concerns of the family, the patient visited the family physician one month later. He was referred for consultation with a neurologist and Huntington disease was diagnosed as the cause of the chorea. Comment: Movement disorders are diagnosed by taking a good clinical history (including obtaining information from family members and others living with the patient) and careful physical examination. Chorea may include the inability to maintain movement during motor tasks and this may predispose to accidents, as in this case.