Chorea-Athetosis: Causes, Workup, and Treatment
Overview
Chorea-athetosis is characterized by irregular, flowing, non-stereotyped involuntary movements (chorea) combined with slower, writhing movements (athetosis), requiring systematic evaluation to identify treatable causes before considering symptomatic management. 1, 2
Causes and Differential Diagnosis
Primary Etiologies
Genetic/Hereditary Causes:
- Huntington's disease - most common cause of adult-onset chorea, caused by CAG repeat expansions in the huntingtin gene 1, 2
- Benign hereditary chorea - caused by NKX2-1/TITF1 gene mutations on chromosome 14q13.3 3
- Ataxia-telangiectasia - presents with cerebellar ataxia, choreoathetosis, oculomotor apraxia, and immunodeficiency 4
Acquired Causes:
- Sydenham's chorea - most common childhood chorea, post-streptococcal autoimmune disorder 2, 5
- Drug-induced - accounts for majority of adult cases alongside Huntington's disease; particularly neuroleptics causing tardive dyskinesia 1, 6, 2
- Cerebrovascular disease - including carbon monoxide poisoning causing bilateral basal ganglia infarction 7
- Autoimmune disorders - systemic lupus erythematosus, antiphospholipid syndrome 1
- Metabolic disorders - hyperthyroidism, hypoparathyroidism, hypoglycemia, kernicterus 4
- Infectious/post-infectious - encephalitis 5
Diagnostic Workup
Imaging Studies
Brain MRI without contrast is the optimal imaging modality to identify structural causes, assess neurodegenerative patterns, and detect basal ganglia lesions, though it may be normal early in disease. 1, 6
Laboratory Evaluation
Essential blood tests to exclude secondary causes:
- Thyroid function (T3/FT3, T4/FT4, TSH) for hyperthyroidism 4
- Serum calcium, phosphorus, parathyroid hormone for calcium-phosphate metabolism disorders 4
- Blood glucose for hypoglycemia 4
- Serum ceruloplasmin for Wilson's disease 4
- Alpha-fetoprotein (elevated in ataxia-telangiectasia) 4
- Complete blood count and lactate dehydrogenase 4
Genetic Testing
Genetic testing is recommended for suspected Huntington's disease to detect CAG repeat expansions in the huntingtin gene. 1, 6
For suspected ataxia-telangiectasia: Confirm diagnosis with genetic testing to identify ATM gene mutations and measure ATM protein kinase levels 4
Additional Studies
- EEG - to exclude epileptic disorders 4
- Neuropsychological assessment - particularly for neurodegenerative causes 4
- Autoimmune panel - antiphospholipid antibodies, lupus serologies when autoimmune etiology suspected 1
Treatment Approach
Treat Underlying Cause First
Autoimmune Chorea:
- For antiphospholipid antibody syndrome: Antiplatelet and/or anticoagulation therapy in addition to symptomatic treatment 1
- For systemic lupus erythematosus: Glucocorticoids alone or combined with immunosuppressive therapy (azathioprine, cyclophosphamide) 1
- For refractory cases with generalized autoimmune activity: Pulse intravenous methylprednisolone with intravenous cyclophosphamide 1
Drug-Induced Chorea:
- Discontinue offending agent (particularly neuroleptics) 2
- Monitor patients on long-term neuroleptics periodically to detect tardive dyskinesia development 6, 3
Metabolic Causes:
- Correct thyroid dysfunction, calcium-phosphate abnormalities, or glucose disturbances 4
Symptomatic Pharmacological Management
For paroxysmal dystonic choreoathetosis:
- Benzodiazepines (oxazepam) using alternate-day dosing schedule may minimize receptor down-regulation and sustain therapeutic effect 8
Non-Pharmacological Interventions
Supportive therapies are essential for functional improvement:
- Speech therapy for patients with orofacial chorea affecting speech and swallowing 1, 3
- Occupational therapy to assist with activities of daily living impacted by choreiform movements 1, 3
Important Clinical Considerations
Key distinguishing features:
- Chorea consists of irregular, rapid, non-stereotyped movements appearing as "dance-like" 6, 2
- Athetosis involves slower, more twisted movements 6
- Ballism represents proximal, large-amplitude chorea 2
- Movements worsen with anxiety/stress and subside during sleep 2
Critical pitfall: Patients often attempt to disguise chorea by incorporating it into purposeful activities, which can delay diagnosis 2
For ataxia-telangiectasia patients: Avoid ionizing radiation and x-rays due to increased radiosensitivity; adjust cancer treatment regimens accordingly 4