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Chorea is a hyperkinetic movement disorder with multiple causes or etiologies. According to the Committee on Classification of the World Federation of Neurology, chorea is a state of excessive, spontaneous movements that are irregularly timed, nonrepetitive, randomly distributed, and abrupt in character. These movements may vary in severity from restlessness with mild intermittent exaggeration of gesture and expression, fidgeting movements of the hands, and unstable dance-like gait to a continuous flow of disabling, violent movements. Chorea, similar to choreography, refers to movements that resemble dancing. Chorea is often accompanied by athetosis and, very rarely, ballism. Athetosis is a slower form of chorea. The slowed movements have a writhing or twisting motion. Ballism is a very severe form of chorea where a violent flinging of the extremities is observed. The movements are involuntary and usually involve the limbs. Ballismus is usually unilateral but, rarely, may be bilateral. The causes of chorea are extensive and include hereditary and acquired etiologies. A careful history, detailed examination, and some laboratory tests may narrow the list of differential diagnoses. Management focuses on treating the underlying cause, using medications like dopamine-depleting agents or antipsychotics to reduce involuntary movements. The prognosis depends on the cause. Some cases resolve with treatment, while others, such as Huntington disease, may progress over time. This activity for healthcare professionals is designed to enhance learners' competence in evaluating and managing chorea. Participants gain a deeper understanding of the condition's etiology, pathophysiology, and varied presentations. The differential diagnosis of chorea will be explored, and the best approaches to diagnosis and management will be highlighted. Greater proficiency will equip clinicians to work within an interprofessional team caring for patients with this movement disorder, improving outcomes. Objectives: Differentiate chorea from other movement disorders in terms of the characteristics of the movements, the conditions' underlying causes, and the critical neuroimaging findings. Select the appropriate diagnostic tests for evaluating chorea. Implement personalized, evidence-based interventions to manage chorea.

This activity for healthcare professionals is designed to enhance learners' competence in evaluating and managing chorea. Participants gain a deeper understanding of the condition's etiology, pathophysiology, and varied presentations. The differential diagnosis of chorea will be explored, and the best approaches to diagnosis and management will be highlighted. Greater proficiency will equip clinicians to work within an interprofessional team caring for patients with this movement disorder, improving outcomes. Objectives: Differentiate chorea from other movement disorders in terms of the characteristics of the movements, the conditions' underlying causes, and the critical neuroimaging findings. Select the appropriate diagnostic tests for evaluating chorea. Implement personalized, evidence-based interventions to manage chorea. Collaborate with the interprofessional team to educate, treat, and monitor patients with chorea to improve their quality of life and health outcomes. Access free multiple choice questions on this topic.

Chorea is a hyperkinetic movement disorder that can manifest from a number of diseases. The Committee on Classification of the World Federation of Neurology describes chorea as a state of excessive, spontaneous movements that are irregularly timed, nonrepetitive, randomly distributed, and abrupt in character. These movements may vary in severity from restlessness with mild, intermittent exaggeration of gesture and expression, fidgeting hand motions, and unstable dance-like gait to a continuous flow of disabling, violent movements. Chorea, similar to choreography, refers to movements that resemble dancing. The causes of this symptom are extensive and include hereditary and acquired etiologies. A careful history, detailed examination, and some laboratory tests may narrow the list of differential diagnoses.[1][2][3][4][5][6] Chorea is often accompanied by athetosis and, very rarely, ballism. Athetosis is a slower form of chorea. The slowed movements have a writhing or twisting motion. Chorea and athetosis are caused by lesions of the striatum, particularly the caudate or putamen.[7] Ballism is a very severe form of chorea characterized by violent flinging of the extremities. The movements are involuntary and usually involve the limbs. Ballismus is usually unilateral and rarely bilateral. Hemiballismus classically results from an acute lesion in the contralateral subthalamic nucleus of the basal ganglia.[8][9] Chorea is classified as "primary" when it is a feature of genetic conditions, most notably Huntington disease. The symptom is "secondary" when it is caused by other diseases affecting the basal ganglia, including toxic, metabolic, infectious, pharmacologic, neoplastic, vascular, autoimmune, and paraneoplastic disorders.[10]

Primary Chorea Primary chorea refers to chorea that is the main symptom or presentation of a medical condition. Primary chorea is classically described in Huntington disease. Most disorders giving rise to primary chorea have a genetic etiology. Other primary chorea disorders include Wilson disease, spinocerebellar ataxia subtypes, neurodegeneration with brain iron accumulation disorders (NBIA), X-linked dystonia-parkinsonism, and paroxysmal kinesigenic and nonkinesigenic dyskinesia. The most common chorea disorder is Huntington disease, which is hereditary and comprises one of the trinucleotide repeat disorders. Huntington disease is caused by a cytosine-adenine-guanine (CAG) repeat on chromosome 4 in the Huntington or HTT gene.[11][12][13] Secondary Chorea Secondary chorea generally arises from a basal ganglia pathology, often noted on neuroimaging as lesions in the striatum, typically in the caudate nucleus or putamen. Systemic conditions that may cause secondary chorea include the following: Endocrine and metabolic disorders: Hypoglycemia, nonketotic hyperglycemia, hyperthyroidism, kernicterus, hypomagnesemia, complicated hemodialysis, oral contraceptive use, and pregnancy [14][15] Infectious diseases: Rheumatic fever (Sydenham chorea), syphilis, subacute sclerosing panencephalitis, Lyme disease, toxoplasmosis, HIV, and endocarditis Adverse pharmacologic effects: Levodopa, oral contraceptive, neuroleptics, antihistamines, cocaine, amphetamine, tricyclics Toxic exposures: Carbon monoxide, mercury, excessive alcohol consumption Vascular conditions: Ischemic or hemorrhagic stroke Vasculitis and autoimmune disorders: Polycythemia, Churg-Strauss syndrome, systemic lupus erythematosus (SLE), Behcet disease, multiple sclerosis Malignant and paraneoplastic diseases: Primary brain tumors, metastatic lesions, anti-Hu and anti-CRMP5 antibody formation [16]

Toxic exposures: Carbon monoxide, mercury, excessive alcohol consumption Vascular conditions: Ischemic or hemorrhagic stroke Vasculitis and autoimmune disorders: Polycythemia, Churg-Strauss syndrome, systemic lupus erythematosus (SLE), Behcet disease, multiple sclerosis Malignant and paraneoplastic diseases: Primary brain tumors, metastatic lesions, anti-Hu and anti-CRMP5 antibody formation [16] Note that Sydenham chorea, chorea gravidarum, and chorea associated with oral contraceptive use represent a continuum of conditions related to a prior group A β-hemolytic streptococcal infection. Sydenham chorea is a major criterion in the Jones criteria for diagnosing rheumatic fever. In cases where a child with a history of rheumatic fever or streptococcal infection develops chorea in adulthood, it is frequently triggered by pregnancy (chorea gravidarum) or the use of oral contraceptives.[17] Additionally, chorea gravidarum may be associated with systemic lupus erythematosus and antiphospholipid antibody syndrome.[18]

Information on the global incidence of chorea is lacking, but the incidence of the conditions presenting with this symptom is known. For example, Huntington disease is a neurodegenerative autosomal dominant disorder with a prevalence of about 5 to 10 cases per 100,000 individuals in the U.S. The condition more commonly affects Whites and is now seen in expats settling in South and Central America. Wilson disease is an autosomal recessive, multisystem disorder with a prevalence of about 30 cases per million people. Benign hereditary chorea is a rare, autosomal dominant illness with a prevalence of 1 case per half a million people. Chorea can occur at any age. In young people, the most common causes of chorea are infections, trauma, and inflammatory diseases. Sydenham chorea occurs in 25% of patients diagnosed with acute rheumatic fever, which is the most common cause of acute-onset chorea in pediatric patients and second only to cerebral palsy among all chorea etiologies in children. The symptom occurs in children between the ages of 5 and 15, most commonly around the ages of 8 or 9. Chorea's incidence has steadily declined over the past few decades due to a decrease in the incidence of rheumatic fever and the widespread use of antibiotics.[19] Huntington chorea is progressive and usually presents in the 4th to 5th decade of life and is rarely seen before the 3rd decade of life. Early onset of this condition is often associated with paternal inheritance, while late-onset cases are more likely linked to maternal inheritance.

The basal ganglia, the primary deep gray matter structures of the brain, are responsible for controlling and fine-tuning movements. This control is modulated within the striatum, primarily through impulses mediated by dopamine and γ-aminobutyric acid (GABA) via 2 parallel pathways, with additional input from cholinergic and serotonergic mechanisms. The striatum serves as the main afferent nucleus, receiving input from the cerebral cortex and the substantia nigra. Striatal modulation occurs through the medial pallidum in the direct pathway and the lateral pallidum and subthalamic nuclei in the indirect pathway. Striatal modulation is mainly inhibitory through GABAergic innervation. Consequently, any striatal lesion can disrupt this inhibitory mechanism, resulting in hyperkinetic movement disorders such as chorea or choreoathetosis.[20] Notably, the most consistent biochemical finding in patients with Huntington disease is the loss of GABAergic neurons in the basal ganglia.[21] Huntington disease is an autosomal dominant inherited CAG triplet repeat disorder. The CAG repeats result in a mutated huntingtin protein containing numerous glutamate residues. These mutated huntingtin proteins are believed to aggregate rather than fold into functional proteins, leading to cellular dysfunction. Neurotransmitters involved in chorea include dopamine, acetylcholine, serotonin, GABA, substance P, and cannabinoids.

The most important aspects of the history of patients with chorea are age, mode of onset, and temporal progression. Huntington disease is the most common cause of chronic chorea in adults. Genetic testing is used to confirm the diagnosis. Besides cerebral palsy, various genetic causes must be considered in children with chronic chorea. Other phenotypic features, such as ataxia and hypotonia, may provide clues to the diagnosis. A detailed medical history and medication review are always important to rule out pharmacological and toxic-metabolic causes. A sudden or acute onset of chorea may indicate a vascular or toxic-metabolic cause. An acute or subacute onset may suggest an autoimmune or structural neoplastic disorder. Autoimmune causes must be considered in the appropriate clinical context. The universal feature of chorea is uncontrolled motor persistence, which prevents patients from maintaining a steady posture, position, or movement. For example, when asked to grip an object, patients will alternately release and squeeze, a sign often referred to as a "milkmaid grip." Another characteristic is the frequent dropping of objects. Chorea can affect both distal and proximal muscles. Most patients have normal muscle tone, but some may exhibit hypotonia. Excessive, unintentional movements of body parts are the most common reason for seeking medical consultation. These choreiform movements are clearly visible upon observation. Another frequent finding is motor persistence of the tongue, where patients cannot maintain tongue protrusion when asked to stick it out, causing it to dart in and out of the mouth. Magnetic resonance imaging (MRI) often shows caudate atrophy, characterized by the widening of the lateral ventricles. Cognitive and behavioral symptoms become prominent in later stages.

A detailed history and thorough physical examination are essential for diagnosis. Thyroid function testing and a complete metabolic panel are also vital, as these diagnostic modalities help identify toxic-metabolic causes. Serum glucose testing can easily rule out hypoglycemia or nonketotic hyperglycemia as the underlying cause. Evaluation of patients with Huntington disease may include genetic testing, neuroimaging through computed tomography (CT) or MRI, and performing a psychiatric evaluation to assess deficits in cognitive, behavioral, and functional areas. Inquiry about suicidality is crucial. The classical MRI finding in Huntington disease is caudate atrophy, which results in a boxcar appearance.[22][23][24][25] MRI is the preferred neuroimaging study for patients presenting with acute-onset chorea, as it helps identify underlying pathological lesions in the basal ganglia. Positron emission tomography (PET) is sometimes used to evaluate Huntington chorea and neuroacanthocytosis. Bilateral reductions in metabolism in the putamen and caudate nucleus are frequently observed. However, this metabolic reduction may not be seen in patients with benign hereditary chorea.[26]

Chorea is a symptom or sign, and treatment should focus on addressing the underlying etiology, particularly for secondary causes. Chorea arising from pharmacological, toxic, or metabolic factors often resolves with correction of the underlying cause. For example, correcting glucose and electrolyte disturbances is typically sufficient in cases of hypoglycemia and nonketotic hyperglycemia. Discontinuing offending medications, such as neuroleptics, or lowering the dose of drugs like levodopa can alleviate drug-induced chorea. Oral contraceptive-induced chorea resolves with discontinuation of the hormonal agent. For autoimmune and paraneoplastic causes, treatment of the underlying malignancy or the use of immune modulators like intravenous immunoglobulin may be beneficial. When chorea is secondary to infection, medication, metabolic abnormalities, autoimmune processes, or paraneoplastic illness, the movements usually resolve once the underlying condition is treated. Generally, no cure exists for primary chorea, such as that associated with Huntington disease, though symptoms can be managed. Evaluating and establishing a patient's support system are highly important. Patients often require specialized caregiving as the disease progresses. Nutrition management becomes crucial due to swallowing difficulties. Paroxysmal kinesigenic dyskinesia responds dramatically to treatment with sodium channel-blocking agents, including carbamazepine, oxcarbazepine, lamotrigine, and phenytoin. Vesicular Monoamine Transporter Inhibitors for Symptomatic Treatment of Chorea Monoamine neurotransmitters, including norepinephrine, dopamine, serotonin, and histamine, are packaged by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles for storage and subsequent release in neurons. Hyperkinetic movement disorders like Huntington disease and tardive dyskinesia are believed to result from increased phasic dopaminergic signaling in the striatum.

Monoamine neurotransmitters, including norepinephrine, dopamine, serotonin, and histamine, are packaged by vesicular monoamine transporter 2 (VMAT2) into synaptic vesicles for storage and subsequent release in neurons. Hyperkinetic movement disorders like Huntington disease and tardive dyskinesia are believed to result from increased phasic dopaminergic signaling in the striatum. VMAT2 inhibitors work symptomatically by reducing dopaminergic hyperactivity. Tetrabenazine, the first VMAT2 inhibitor, was approved for Huntington disease in 2008. In 2017, deutetrabenazine was approved for tardive dyskinesia and Huntington disease-associated chorea. Valbenazine and deutetrabenazine have recently been made available in the market as treatment options for hyperkinetic movement disorders. This class of medications has partly revolutionized the symptomatic treatment of primary chorea, leading to improved patient satisfaction.[27][28][29] Other pharmacologic options for chorea target more specific neurotransmitter pathways. These medications include neuroleptics, which block dopamine receptors, and GABAergic agents like valproate, clonazepam, and gabapentin. Surgical Treatment by Deep Brain Stimulation Deep brain stimulation (DBS) has advanced in the past decade. This therapeutic modality may benefit some patients with chorea. Anecdotal reports indicate that the procedure can reduce chorea in selected patients. DBS is performed by placing electrodes in the globus pallidus internus (GPi-DBS). This intervention is effective for controlling medically refractory chorea associated with Huntington disease.[30]

The differential diagnosis of chorea includes all hyperkinetic disorders and their causes. The most important conditions to consider are the following: Huntington disease Lesch-Nyhan disease Lyme disease Multiple system atrophy Neuroacanthocytosis Pediatric torticollis surgery Ramsay Hunt syndrome Striatonigral degeneration Tourette syndrome Viral encephalitis Accurately identifying the cause of chorea requires careful consideration of these potential diagnoses. Proper identification ensures targeted treatment and better patient outcomes.

The prognosis of chorea depends on the underlying cause. The majority of patients with Huntington disease and neuroacanthocytosis have a poor prognosis and die prematurely. Localized trauma or rhabdomyolysis may result from severe involuntary movements. Swallowing may be impaired in patients who have neuroacanthocytosis or develop tongue dystonia, resulting in body weight loss, recurrent aspiration pneumonia episodes, and even death. Patients with the best prognosis are those with secondary chorea disorders due to reversible causes, including medications, oral contraceptives, toxins, and metabolic etiologies.

Complications of chorea extend beyond physical impairments, often impacting patients' quality of life in multiple ways. Difficulty with motor control can affect basic functions such as speaking, eating, and walking, leading to weight loss, aspiration pneumonia, an increased risk of falls, and possibly death. Socially, patients may experience isolation due to embarrassment, inability to engage in social activities, or challenges with communication. Psychosocial complications, such as depression and anxiety, are also common, particularly in patients with chronic conditions like Huntington disease.

Preventive measures for chorea primarily focus on addressing the underlying causes and reducing risk factors. For primary chorea, such as Huntington disease, genetic counseling and early diagnosis can help individuals and families prepare for disease progression and potential treatment options. In secondary chorea, preventive measures include managing conditions that can lead to hyperkinetic movements, such as controlling blood glucose levels in diabetes, discontinuing or adjusting medications that may induce chorea, and monitoring for infections or autoimmune conditions. Additionally, avoiding toxins, ensuring proper nutrition, and treating metabolic disturbances early can help prevent the development of chorea. Regular follow-up with healthcare providers for individuals at risk may also aid in early detection and intervention.

Huntington disease, neuroacanthocytosis, and Wilson disease are genetic disorders. Hence, counseling should be provided to any couple who plans to conceive, especially if one partner has the disorder. Genetic testing should be offered to any family member if they want to know the potential risk of inheriting the disease. All patients must be educated regarding the clinical features of the disease, as well as the treatment options and prognosis. VMAT2 inhibitors are a group of relatively new medications with good efficacy for the symptomatic treatment of chorea and other hyperkinetic disorders. Patients must be offered this option for symptom control whenever appropriate.

The management of primary chorea is challenging due to the absence of a cure, with all current treatments focusing primarily on symptom management. While the neurologist typically oversees treatment, primary care providers and nurse practitioners may assist with follow-up care. A key component of management is establishing a comprehensive support system for the patient. Specialized caregiving becomes necessary as the disease progresses, and nutrition management is critical due to swallowing difficulties. Genetic testing should be offered to family members who wish to understand their potential risk of inheriting the condition. Patients should be educated about the clinical features, treatment options, and prognosis of the disease. The prognosis of primary chorea is generally poor, with a significant decline in quality of life.[31]