Chorea: Treatment Update

1. Chorea: Treatment Update
Ade Wijaya, MD – November 2019

2. Introduction
 Chorea is a hyperkinetic movement disorder consisting of rapid dance-like
involuntary movements that flow from one area of the body to another
 Dysfunction of the basal ganglia is a core feature of the pathophysiology of
chorea
Hermann A, Walker RH. Diagnosis and treatment of chorea syndromes. Curr Neurol Neurosci Rep. 2015;15
Mink JW. The basal ganglia and involuntary movements: impaired inhibition of competing motor patterns. Arch Neurol. 2003;60:1365–8

3. Mink JW. The basal ganglia and involuntary movements: impaired inhibition of competing motor patterns. Arch Neurol. 2003;60:1365–8

4. Dopamine-depleting Agents
 Tetrabenazine
- Start with a daily dose of 12.5 mg, increased weekly as tolerated to three to
four doses a day
- Adverse events: parkinsonism, weight loss, dysphagia, and depression
- Effective for chorea due to a variety of etiologies and can be especially useful
if dystonia is an additional feature
Feinstein E, Walker R. An Update on the Treatment of Chorea. Current treatment options in neurology. 2018 Oct 1;20(10):44.

5. Dopamine-depleting Agents
 Deutetrabenazine
- Initiated at a dose of 6 mg/ day and increased to approximately 40 mg/day
- Adverse events: sedation, dry mouth, anxiety, depression
- Less potential for developing the side effects related to Tetrabenazine
Frank S, Testa CM, Stamler D, et al. Effect of Deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016;316:40–50.
Fernandez HH, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, et al. Randomized controlled trial of deutetrabenazine for tardive dyskinesia: the ARM-TD study. Neurology. 2017;88:2003–10.
Anderson KE, Stamler D, Davis MD, Factor SA, Hauser RA, Isojärvi J, et al. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebocontrolled, phase
3 trial. The lancet Psychiatry. 2017;4:595–604.

6. Dopamine-depleting Agents
 Valbenazine
- 40-80 mg / day
- Adverse events: somnolence, akathisia, and dry mouth
- Less side effecs
Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic characterization of Valbenazine (NBI-98854) and its metabolites. J Pharmacol Exp Ther. 2017;361:454–61.
Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jimenez R, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of Valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174:476–84.
Factor SA, Remington G, Comella CL, Correll CU, Burke J, Jimenez R, et al. The effects of Valbenazine in participants with tardive dyskinesia. J Clin Psychiatry. 2017;78:1344–50.

7. Dopamine D2 receptor-blocking agents
 Neuroleptics: typical
- Haloperidol
- Adverse events: somnolence, parkinsonism, and the potential to cause tardive
dyskinesia
 Neuroleptics: atypical
- Clozapine 150 mg / day
- Olanzapine 10-30 mg / day
Feinstein E, Walker R. An Update on the Treatment of Chorea. Current treatment options in neurology. 2018 Oct 1;20(10):44.

8. Anticonvulsants
 Valproic acid: Sydenham’s chorea (15 to 20 mg/kg/day, divided two to three
times daily)
 Carbamazepine: Sydenham’s chorea (15–20 mg/kg/day twice daily)
 Benzodiazepines: clonazepam 2–4.5 mg significantly reduced dyskinesia in
schizophrenics with tardive dyskinesia
 Levetiracetam: Huntington disease / tardive dyskinesia (500–3000 mg/day)
Feinstein E, Walker R. An Update on the Treatment of Chorea. Current treatment options in neurology. 2018 Oct 1;20(10):44.

9. Anti-glutamatergic Agents
 Amantadine
- 100 mg / day
- Adverse events: hallucinations, confusion, forgetfulness, anxiety/agitation,
morbid thoughts, diarrhea, and nausea
 Riluzole: 200 mg/day
Feinstein E, Walker R. An Update on the Treatment of Chorea. Current treatment options in neurology. 2018 Oct 1;20(10):44.

10. Deep Brain Stimulation (DBS)
 Is a reasonable option for patients with hyperkinetic movement disorders that
cannot be adequately controlled with oral medications
 However, the surgery can worsen some disease features, such as dysarthria,
dysphagia, and gait impairment
 Risks and benefits should be carefully weighed in individual cases, but the
procedure is most likely to benefit patients with non-degenerative disorders
Feinstein E, Walker R. An Update on the Treatment of Chorea. Current treatment options in neurology. 2018 Oct 1;20(10):44.

11. Summary
 Symptomatic chorea from infections, structural lesions, or metabolic causes is
often self-limited, may resolve with treatment of the primary condition, and
does not typically require treatment.
 Treatment: medications and DBS
 Multidisciplinary approach

12. THANK YOU