Chorea in Adults

Back

Background

"Chorea" is a borrowed Latin word that derives from the Greek khoreia, a choral dance. The basic Greek word for dance (written with the Roman alphabet) is khoros.[1, 2]

The ad hoc Committee on Classification of the World Federation of Neurology has defined chorea as "a state of excessive, spontaneous movements, irregularly timed, non-repetitive, 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, unstable dance-like gait to a continuous flow of disabling, violent movements."[3]

Patients with chorea exhibit motor impersistence (ie, they cannot maintain a sustained posture). When attempting to grip an object, they alternately squeeze and release ("milkmaid's grip"). When they attempt to protrude the tongue, the tongue often pops in and out ("harlequin's tongue"). Patients often drop objects involuntarily. Also common are attempts by patients to mask the chorea by voluntarily augmenting the choreiform movements with semipurposeful movements.[1]

Chorea involves both proximal and distal muscles. In most patients, normal tone is noted, but, in some instances, hypotonia is present. In a busy movement disorder center, levodopa-induced chorea is the most common movement disorder, followed by Huntington disease (HD).[1]

Any discussion of chorea must also address the related terms athetosis, choreoathetosis, and ballism (also known as ballismus).

The term athetosis comes from the Greek word athetos (not fixed).[1, 2] It is a slow form of chorea. Because of the slowness, the movements have a writhing (ie, squirming, twisting, or snakelike) appearance. Choreoathetosis is essentially an intermediate form (ie, a bit more rapid than the usual athetosis, slower than the usual chorea, or a mingling of chorea and athetosis within the same patient at different times or in different limbs). Given that the only difference between chorea, choreoathetosis, and athetosis is the speed of movement, some neurologists argue that the term athetosis is unnecessary and even confusing. They argue a simpler nomenclature would delineate fast, intermediate, and slow chorea. While the authors of this article understand the basis of that argument, they also believe that in some cases, the writhing movements are extremely prominent, even apart from the speed of the movement. Thus, the authors of this article advocate retaining this descriptive term.

Ballism or ballismus is considered a very severe form of chorea in which the movements have a violent, flinging quality. In Greek, ballismos means "a jumping about or dancing."[2] Ballism has been defined as "continuous, violent, coordinated involuntary activity involving the axial and proximal appendicular musculature such that the limbs are flung about." This movement disorder most often involves only one side of the body (ie, hemiballism or hemiballismus). Occasionally, bilateral movements occur (ie, biballism or paraballism). Many patients with hemiballism have choreiform movements and vice versa, and hemiballism often evolves into hemichorea. Currently, ballism should be viewed as a severe form of chorea.[1, 4, 5, 6, 7, 8]

Pathophysiology

A simple model of basal ganglia function states that dopaminergic and GABAergic impulses from the substantia nigra and motor cortex, respectively, are funneled through the pallidum into the motor thalamus and motor cortex. These impulses are modulated in the striatum via two segregated, parallel, direct and indirect loops through the medial pallidum and lateral pallidum/subthalamic nucleus. Subthalamic nucleus activity drives the medial pallidum to inhibit cortex-mediated impulses, thereby inducing parkinsonism. Absent subthalamic nucleus inhibition enhances motor activity through the motor thalamus, resulting in abnormal involuntary movements such as dystonia, chorea, and tics. A classic example of loss of subthalamic inhibitory drive is ballism.[1]

The most well-studied choreatic syndrome is Huntington chorea; therefore, the pathophysiology of HD as it applies to chorea is the focus of the discussion that follows.

Huntington disease is caused by an expanded CAG trinucleotide repeat in the gene that encodes the protein huntingtin. Mutant huntingtin is thought to cause neuronal degeneration through transcription dysregulation as well as mitochondrial impairment.[9, 10, 11, 12]

Dopaminergic mechanism

In Huntington chorea, the content of striatal dopamine is normal, indicating that the major pathological alterations lay in the surviving — but diseased — medium-sized, spiny, striatal dopaminergic neurons. Pharmacologic agents that either deplete dopamine (eg, reserpine and tetrabenazine) or block dopamine receptors (eg, neuroleptic medications) improve chorea, which gives further support to this observation. Given that drugs that decrease the striatal content of dopamine improve chorea, increasing the amount of dopamine worsens chorea, such as in the levodopa-induced chorea seen in persons with Parkinson disease (PD).[13, 14]

Cholinergic mechanism[15]

The concept that a critical striatal balance between acetylcholine (Ach) and dopamine is essential for normal striatal function received its greatest acceptance in the understanding of PD. In the early days of PD therapy, anticholinergic medications were used frequently, especially when tremor was the predominant symptom. Other PD symptoms, such as bradykinesia and rigidity, often improved as well.

The development of chorea in patients treated with anticholinergic medications, such as trihexyphenidyl, is a common clinical observation. Furthermore, the intravenous administration of physostigmine (a centrally acting anticholinesterase) can temporarily reduce chorea. The same treatment can also promptly overcome anticholinergic-induced chorea.

Patients with HD have a patchy reduction of choline acetyltransferase in the basal ganglia. This enzyme catalyzes the synthesis of ACh. A marked reduction of muscarinic cholinergic receptor sites has also been reported. These two observations could explain the variability of patients' response to physostigmine and the limited efficacy of Ach precursors such as choline and lecithin.

Serotonergic mechanism

Fluctuations in striatal serotonin may play a role in the genesis of many abnormal movements. Selective serotonin reuptake inhibitors, such as fluoxetine, may induce or aggravate parkinsonism, akinesia, myoclonus, or tremor. The role of serotonin (5-hydroxytryptamine [5-HT]) in choreiform movements is less clear since the striatum has a relatively high concentration of serotonin. Pharmacologic attempts to either stimulate or inhibit serotonin receptors in persons with Huntington chorea have shown no effect, indicating that serotonin's contribution to the pathogenesis of chorea is limited.

GABAergic mechanism

The most consistent biochemical lesion in patients with Huntington chorea appears to be a loss of neurons in the basal ganglia that synthesize and contain GABA.[16] The significance of this remains unknown. A variety of pharmacologic techniques have been attempted to increase CNS GABA levels. Valproic acid, which acts in part via a GABAergic mechanism, has, in a limited number of uncontrolled cases, ameliorated not only the agitation sometimes seen in persons with HD but also the movement problem.[17] However, no systematic studies have been conducted on the use of GABAergic agents to treat HD.

Substance P and somatostatin

Substance P levels have been shown to be markedly lower in persons with Huntington disease (HD), while somatostatin levels are higher. The significance of this remains unknown as well.

Cannabinoids

Endocannabinoids are thought to play a role in HD. Loss of the cannabinoid CB1 receptor from the medium spiny neurons is one of the earliest neurochemical changes seen in HD. Reuptake inhibition of anandamine, an endogenous cannabinoid, has been shown to alleviate motor symptoms in animal models of HD and other neurodegenerative disorders such as PD and MS.[18, 19, 16]

Ballism

This movement disorder usually involves only one side of the body (ie, hemiballism). Hemiballism is usually attributed to lesions of the contralateral subthalamic nucleus, although infarction in the caudate, striatum, lenticular nucleus, or thalamus has also been associated with hemiballism.[1, 4]

Lesions of the subthalamic nucleus can cause contralateral hemiballism-hemichorea by reducing the normal excitatory drive from the subthalamic nucleus to the internal segment of the globus pallidus. This reduces the inhibitory output of the globus pallidus on the thalamus, and this disinhibition gives rise to excessive excitatory drive to the cortex, which is expressed as contralateral hyperkinetic movements. Confusingly, however, this disorder often appears in the absence of a lesion in the subthalamic nucleus.[1, 20]

Klawans[21, 22] suggested that increased dopaminergic transmission might play a role in the pathophysiology of this disorder. This hypothesis is supported by the observation that dopamine-receptor blockers and catecholamine-depleting agents often improve hemiballism. While hemiballism and hemichorea are distinguishable on the basis of the type and distribution of movements, they represent two different symptoms on a spectrum of the same disease process. Why one patient with basal ganglia dysfunction develops hemiballism and another with similar pathologic changes develops hemichorea is not understood. On the cellular and molecular level, ballism can be caused by multiple pathologies including ischemia, infection, demyelination, and tumor.[5, 6, 23, 24, 25, 26, 7, 8]

Epidemiology

Frequency

United States

Although no data are available regarding the incidence of chorea, the incidences of several disorders in which chorea is the main clinical feature are well known.

Race

Age

Chorea can commence at any age. In children, postpump chorea and infectious, inflammatory, and striatal lesions may account for many cases.

History

Patients with chorea may not initially be aware of the abnormal movements because they may be subtle. Patients can suppress the chorea temporarily and frequently camouflage some of the movements by incorporating them into semipurposeful activities (ie, parakinesia). The inability to maintain voluntary contraction (ie, motor impersistence), as is seen during manual grip (milkmaid grip) tests or tongue protrusion, is a characteristic feature of chorea and results in the dropping of objects and clumsiness. Muscle stretch reflexes are often hung-up and pendular. In severely affected patients, a peculiar dancelike gait may be noted. Depending on the underlying cause of the chorea, other motor symptoms include dysarthria, dysphagia, postural instability, ataxia, dystonia, and myoclonus. A brief discussion of the clinical manifestations of the most common choreatic diseases is presented.

Physical

Because Huntington disease (HD) is the most clearly defined choreatic disease, its physical findings are described here.

Causes

Laboratory Studies

Imaging Studies

Medical Care

Surgical Care

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Haloperidol (Haldol)

Clinical Context:  Useful in treatment of irregular spasmodic movements of limbs or facial muscles.

Fluphenazine (Prolixin)

Clinical Context:  Blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in brain. Exhibits strong alpha-adrenergic and anticholinergic effects. May depress reticular activating system.

Clozapine (Clozaril)

Clinical Context:  New atypical neuroleptic medication available in 25- and 100-mg tab. Blocks norepinephrine, serotonergic, cholinergic, histamine, and dopaminergic receptors. Mechanism of action still unclear. Affinity for mesolimbic D4 dopamine receptor accounts for striking effects in control of behavioral and psychiatric symptoms with low incidence of extrapyramidal symptoms. Histamine receptor blockade accounts for increased incidence of sleep disturbances.

Olanzapine (Zyprexa)

Clinical Context:  May inhibit serotonin, muscarinic, and dopamine effects.

Risperidone (Risperdal)

Clinical Context:  Binds to dopamine D2-receptor with 20 times lower affinity than for 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of extrapyramidal adverse effects.

Quetiapine (Seroquel)

Clinical Context:  May act by antagonizing dopamine and serotonin effects.

Class Summary

Block dopamine receptors and appear to have antispasmodic effects.

Reserpine

Clinical Context:  Depletes norepinephrine and epinephrine, which, in turn, depress sympathetic nerve functions.

Tetrabenazine (Xenazine)

Clinical Context:  Depletes neurotransmitter stores of dopamine, serotonin, and noradrenaline within nerve cells in the brain, thereby altering transmission of electric signals from the brain that control movement by reversibly inhibiting vesicular monoamine transporter 2 (VMAT2).

Efficacy and safety established in a randomized, double-blind, placebo-controlled, multicenter study. Patients treated with tetrabenazine had significant improvement in chorea compared with those treated with placebo. Additional studies support this effect. Indicated for chorea associated with Huntington disease.

Class Summary

Deplete CNS of dopamine, thereby reducing chorea.

Clonazepam (Klonopin, Rivotril)

Clinical Context:  Developed as antiepileptic, hypnotic, and anxiolytic used as adjunct for treatment of chorea. Belongs to benzodiazepine group, increasing GABAergic transmission in CNS. Reaches peak plasma concentration at 2-4 h after oral or rectal administration.

Class Summary

Demonstrated to reduce GABA concentrations in the caudate, putamen, substantia nigra, and globus pallidus. By analogy, increased GABA activity might ameliorate chorea.

Valproic acid (Depacon, Depakote, Depakote ER)

Clinical Context:  Off-label therapy sometimes helpful in reducing choreiform movements and ameliorating disruptive behavior (eg, behavior induced by anger) in patients with HD. Dosages and other information mentioned is taken from dosages used for epilepsy because dosages for HD are not clearly established. Chemically unrelated to other drugs used to treat seizure disorders. Although mechanism of action not established, its activity may be related to increased brain levels of GABA or enhanced GABA action. Also may potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect.

For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% q2wk. This reduction may be started at initiation of therapy or delayed by 1-2 wk if concern that seizures are likely to occur with reduction. Monitor patients closely for increased seizure frequency during this period.

As adjunctive therapy, divalproex sodium may be added to patient's regimen at 10-15 mg/kg/d. Dosage may be increased by 5-10 mg/kg/d qwk to achieve optimal clinical response. Ordinarily, optimal clinical response achieved at daily doses of < 60 mg/kg/d.

Depakote Sprinkle Capsules (daily doses >250 mg should be divided bid/tid) and Depakote ER (once-daily formulation) are convenient dosage forms used in adults and children >10 y.

Carbamazepine (Carbatrol, Tegretol, Epitol)

Clinical Context:  Has been of symptomatic help in chorea, particularly in Sydenham chorea and chorea gravidarum, but also in other types. Dosage recommendations and cautions are essentially the same in this off-label use as for the more common indication of seizures.

When used as an anticonvulsant, mechanism of action may involve depressing activity in nucleus ventralis anterior of thalamus, resulting in reduction of polysynaptic responses and blocking posttetanic potentiation. Reduces sustained high-frequency repetitive neural firing. Potent enzyme inducer that can induce own metabolism. Due to potentially serious blood dyscrasias, undertake benefit-to-risk evaluation before drug instituted. Therapeutic plasma levels are 4-12 mcg/mL for analgesic and antiseizure response. Peak serum levels in 4-5 h. Half-life (serum) in 12-17 h with repeated doses. Metabolized in liver to active metabolite (ie, epoxide derivative) with half-life of 5-8 h. Metabolites excreted through feces and urine.

Class Summary

May help by various neuropharmacological mechanisms. Valproate is a GABAergic agent and thus it may help in the same way as benzodiazepines. Main mechanism of action of carbamazepine appears to be stabilization of inactivated state of voltage-gated sodium channels. This may reduce neuronal firing in many systems and therefore may nonspecifically reduce abnormal movements in some patients.

Complications

Prognosis

Prognosis depends on the cause of the chorea. Huntington disease (HD) has a poor prognosis, because all patients will die of complications of the disease. Similarly, patients with neuroacanthocytosis may develop aspiration pneumonia, which can cause early death.

Author

Stephanie M Vertrees, MD, Fellow in Public Health, Weill Cornell Medical College-Hospital for Special Surgery Fellowship in Medical Ethics; Fellow in Neuromuscular Medicine, Hospital for Special Surgery

Disclosure: Nothing to disclose.

Coauthor(s)

Stephen A Berman, MD, PhD, MBA, Professor of Neurology, University of Central Florida College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Stephen T Gancher, MD, Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Sunovion Consulting fee None; Supernus Honoraria Speaking, consulting; Upsher-Smith None; Eisai Honoraria Speaking and teaching

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Eric Dinnerstein, MD, Maria Alejandra Herrera, MD, and Nestor Galvez-Jimenez, MD, MSc, MHA, to the development and writing of this article.

References

  1. Berman SA. Chorea. In: Joseph AB, Young RR, eds. Movement Disorders in Neurology and Neuropsychiatry. 2nd ed. Malden, Mass: Blackwell Science; 1999:481-94.
  2. Dorland WA, ed. Dorlands Illustrated Medical Dictionary. 30th ed. Philadelphia, Pa: WB Saunders; 2003.
  3. Barbeau A, Duvoisin RC, Gerstenbrand F, Lakke JP, Marsden CD, Stern G. Classification of extrapyramidal disorders. Proposal for an international classification and glossary of terms. J Neurol Sci. Aug 1981;51(2):311-27. [View Abstract]
  4. Dewey RB Jr, Jankovic J. Hemiballism-hemichorea. Clinical and pharmacologic findings in 21 patients. Arch Neurol. Aug 1989;46(8):862-7. [View Abstract]
  5. Fukui T, Hasegawa Y, Seriyama S, et al. Hemiballism-hemichorea induced by subcortical ischemia. Can J Neurol Sci. Nov 1993;20(4):324-8. [View Abstract]
  6. Glass JP, Jankovic J, Borit A. Hemiballism and metastatic brain tumor. Neurology. Feb 1984;34(2):204-7. [View Abstract]
  7. Sanchez-Ramos JR, Factor SA, Weiner WJ, Marquez J. Hemichorea-hemiballismus associated with acquired immune deficiency syndrome and cerebral toxoplasmosis. Mov Disord. 1989;4(3):266-73. [View Abstract]
  8. Vidakovic A, Dragasevic N, Kostic VS. Hemiballism: report of 25 cases. J Neurol Neurosurg Psychiatry. Aug 1994;57(8):945-9. [View Abstract]
  9. Chen-Plotkin AS, Sadri-Vakili G, Yohrling GJ, Braveman MW, Benn CL, Glajch KE, et al. Decreased association of the transcription factor Sp1 with genes downregulated in Huntingtons disease. Neurobiol Dis. May 2006;22(2):233-41. [View Abstract]
  10. Smith KM, Matson S, Matson WR, Cormier K, Del Signore SJ, Hagerty SW. Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntingtons disease mice. Biochim Biophys Acta. Jun 2006;1762(6):616-26. [View Abstract]
  11. Stack EC, Smith KM, Ryu H, Cormier K, Chen M, Hagerty SW, et al. Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntingtons disease mice. Biochim Biophys Acta. Mar 2006;1762(3):373-80. [View Abstract]
  12. Zuccato C, Belyaev N, Conforti P, Ooi L, Tartari M, Papadimou E, et al. Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntingtons disease. J Neurosci. Jun 27 2007;27(26):6972-83. [View Abstract]
  13. Leavitt BR, Hayden MR. Is tetrabenazine safe and effective for suppressing chorea in Huntingtons disease?. Nat Clin Pract Neurol. Oct 2006;2(10):536-7. [View Abstract]
  14. Savani AA, Login IS. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. Mar 6 2007;68(10):797; author reply 797. [View Abstract]
  15. Gomez-Anson B, Alegret M, Munoz E, Sainz A, Monte GC, Tolosa E. Decreased frontal choline and neuropsychological performance in preclinical Huntington disease. Neurology. Mar 20 2007;68(12):906-10. [View Abstract]
  16. Glass M, Dragunow M, Faull RL. The pattern of neurodegeneration in Huntingtons disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntingtons disease. Neuroscience. 2000;97(3):505-19. [View Abstract]
  17. Saft C, Lauter T, Kraus PH, Przuntek H, Andrich JE. Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntingtons Disease patients: a case series. BMC Neurol. Feb 28 2006;6:11. [View Abstract]
  18. Curtis MA, Faull RL, Glass M. A novel population of progenitor cells expressing cannabinoid receptors in the subependymal layer of the adult normal and Huntingtons disease human brain. J Chem Neuroanat. Apr 2006;31(3):210-5. [View Abstract]
  19. de Lago E, Fernandez-Ruiz J, Ortega-Gutierrez S, Cabranes A, Pryce G, Baker D, et al. UCM707, an inhibitor of the anandamide uptake, behaves as a symptom control agent in models of Huntingtons disease and multiple sclerosis, but fails to delay/arrest the progression of different motor-related disorders. Eur Neuropsychopharmacol. Jan 2006;16(1):7-18. [View Abstract]
  20. Dubinsky RM, Greenberg M, Di Chiro G, et al. Hemiballismus: study of a case using positron emission tomography with 18fluoro-2-deoxyglucose. Mov Disord. 1989;4(4):310-9. [View Abstract]
  21. Klawans HL. Chorea. Can J Neurol Sci. Aug 1987;14(3 Suppl):536-40. [View Abstract]
  22. Evidente VG, Gwinn-Hardy K, Caviness JN, Alder CH. Risperidone is effective in severe hemichorea/hemiballismus. Mov Disord. Mar 1999;14(2):377-9. [View Abstract]
  23. Inzelberg R, Korczyn AD. Persistent hemiballism in Parkinsons disease. J Neurol Neurosurg Psychiatry. Aug 1994;57(8):1013-4. [View Abstract]
  24. Johnson WG, Fahn S. Treatment of vascular hemiballism and hemichorea. Neurology. Jul 1977;27(7):634-6. [View Abstract]
  25. Martinez-Martin P. Hemichorea-hemiballism in AIDS. Mov Disord. 1990;5(2):180. [View Abstract]
  26. Riley D, Lang AE. Hemiballism in multiple sclerosis. Mov Disord. 1988;3(1):88-94. [View Abstract]
  27. Jankovic J. Huntingtons disease, Wilsons disease, and neuroacanthocytosis. A Comprehensive Review of Movement Disorders for the Clinical Practitioner. 2nd Annual Course. New York, NY: Columbia University; 1992:261-78.
  28. Petrukhin K, Lutsenko S, Chernov I, et al. Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions. Hum Mol Genet. Sep 1994;3(9):1647-56. [View Abstract]
  29. Bird TD, Carlson CB, Hall JG. Familial essential (benign) chorea. J Med Genet. Oct 1976;13(5):357-62. [View Abstract]
  30. Breedveld GJ, van Dongen JW, Danesino C, et al. Mutations in TITF-1 are associated with benign hereditary chorea. Hum Mol Genet. Apr 15 2002;11(8):971-9. [View Abstract]
  31. Burns J, Neuhauser G, Tomasi L. Benign hereditary non-progressive chorea of early onset. Clinical genetics of the syndrome and report of a new family. Neuropadiatrie. Nov 1976;7(4):431-8. [View Abstract]
  32. Chun RW, Daly RF, Mansheim BJ Jr, Wolcott GJ. Benign familial chorea with onset in childhood. JAMA. Sep 24 1973;225(13):1603-7. [View Abstract]
  33. Damasio H, Antunes L, Damasio AR. Familial nonprogressive involuntary movements of childhood. Ann Neurol. Jun 1977;1(6):602-3. [View Abstract]
  34. Haerer AF, Currier RD, Jackson JF. Hereditary nonprogressive chorea of early onset. N Engl J Med. Jun 1 1967;276(22):1220-4. [View Abstract]
  35. Kuwert T, Lange HW, Langen KJ, et al. Normal striatal glucose consumption in two patients with benign hereditary chorea as measured by positron emission tomography. J Neurol. Apr 1990;237(2):80-4. [View Abstract]
  36. MacMillan JC, Morrison PJ, Nevin NC, Shaw DJ, Harper PS, Quarrell OW, et al. Identification of an expanded CAG repeat in the Huntington's disease gene (IT15) in a family reported to have benign hereditary chorea. J Med Genet. Dec 1993;30(12):1012-3. [View Abstract]
  37. Rice E, Terrence C. Computerized tomography in hereditary nonprogressive chorea. Arch Neurol. Apr 1979;36(4):249-50. [View Abstract]
  38. Robinson RO, Thornett CE. Benign hereditary chorea--response to steroids. Dev Med Child Neurol. Dec 1985;27(6):814-6. [View Abstract]
  39. Suchowersky O, Hayden MR, Martin WR, et al. Cerebral metabolism of glucose in benign hereditary chorea. Mov Disord. 1986;1(1):33-44. [View Abstract]
  40. Wheeler PG, Weaver DD, Dobyns WB. Benign hereditary chorea. Pediatr Neurol. Sep-Oct 1993;9(5):337-40. [View Abstract]
  41. Yapijakis C, Kapaki E, Zournas C, Rentzos M, Loukopoulos D, Papageorgiou C. Exclusion mapping of the benign hereditary chorea gene from the Huntingtons disease locus: report of a family. Clin Genet. Mar 1995;47(3):133-8. [View Abstract]
  42. McKusick V. Huntington disease; HD. OMIM ID #143100. Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov/omim/143100. Accessed March 17, 2009.
  43. McKusick V. Choreoacanthocytosis; CHAC. OMIM ID #200150. Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov/omim/200150. Accessed March 17, 2009.
  44. McKusick V. Chorea, benign hereditary; BHC. OMIM ID #118700. Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov/omim/118700. Accessed March 17, 2009.
  45. Jones R, Stout JC, Labuschagne I, Say M, Justo D, Coleman A, et al. The potential of composite cognitive scores for tracking progression in Huntington's disease. J Huntingtons Dis. 2014;3(2):197-207. [View Abstract]
  46. Klein C. The Wilson films--Huntington's chorea. Mov Disord. Dec 2011;26(14):2464-6. [View Abstract]
  47. Kobal J, Dobson-Stone C, Danek A, Fidler V, Zvan B, Zaletel M. Chorea-acanthocytosis presenting as dystonia. Acta Clin Croat. Mar 2014;53(1):107-12. [View Abstract]
  48. Alcock, NS. A note of the pathology of senile chorea (non-hereditary). Brain. 1936;59:376-87.
  49. Friedman JH, Ambler M. A case of senile chorea. Mov Disord. 1990;5(3):251-3. [View Abstract]
  50. Galvez-Jimenez N, Friedman J, Lang A. A consistent MRI pattern in three cases of senile chorea. Neurology. 1995;45 (Supplement 4):A185.
  51. Giedd JN, Rapoport JL, Kruesi MJ, Parker C, Schapiro MB, Allen AJ, et al. Sydenhams chorea: magnetic resonance imaging of the basal ganglia. Neurology. Dec 1995;45(12):2199-202. [View Abstract]
  52. Swedo SE. Sydenhams chorea. A model for childhood autoimmune neuropsychiatric disorders. JAMA. Dec 14 1994;272(22):1788-91. [View Abstract]
  53. Beato R, Maia DP, Teixeira AL Jr, Cardoso F. Executive functioning in adult patients with Sydenham's chorea. Mov Disord. May 15 2010;25(7):853-7. [View Abstract]
  54. Gusella JF, MacDonald ME. Huntingtons disease: seeing the pathogenic process through a genetic lens. Trends Biochem Sci. July 2006;31(pt 9):533-40.
  55. Nutting PA, Cole BR, Schimke RN. Benign, recessively inherited choreo-athetosis of early onset. J Med Genet. Dec 1969;6(4):408-10. [View Abstract]
  56. Fisher M, Sargent J, Drachman D. Familial inverted choreoathetosis. Neurology. Dec 1979;29(12):1627-31. [View Abstract]
  57. Wheeler PG, Dobyns WB, Plager DA, Ellis FD. Familial remitting chorea, nystagmus, and cataracts. Am J Med Genet. Dec 1 1993;47(8):1215-7. [View Abstract]
  58. Evans BK, Jankovic J. Tuberous sclerosis and chorea. Ann Neurol. Jan 1983;13(1):106-7. [View Abstract]
  59. Ross CA, Margolis RL, Rosenblatt A, et al. Huntington disease and the related disorder, dentatorubral-pallidoluysian atrophy (DRPLA). Medicine (Baltimore). Sep 1997;76(5):305-38. [View Abstract]
  60. Sethi KD, Ray R, Roesel RA, et al. Adult-onset chorea and dementia with propionic acidemia. Neurology. Oct 1989;39(10):1343-5. [View Abstract]
  61. Hefter H, Mayer P, Benecke R. Persistent chorea after recurrent hypoglycemia. A case report. Eur Neurol. 1993;33(3):244-7. [View Abstract]
  62. Linazasoro G, Urtasun M, Poza JJ, et al. Generalized chorea induced by nonketotic hyperglycemia. Mov Disord. 1993;8(1):119-20. [View Abstract]
  63. Toghill PJ, Johnston AW, Smith JF. Choreoathetosis in porto-systemic encephalopathy. J Neurol Neurosurg Psychiatry. Aug 1967;30(4):358-63. [View Abstract]
  64. Blunt SB, Brooks DJ, Kennard C. Steroid-responsive chorea in childhood following cardiac transplantation. Mov Disord. Jan 1994;9(1):112-4. [View Abstract]
  65. Curless RG, Katz DA, Perryman RA, et al. Choreoathetosis after surgery for congenital heart disease. J Pediatr. May 1994;124(5 Pt 1):737-9. [View Abstract]
  66. Peters AC, Vielvoye GJ, Versteeg J, et al. ECHO 25 focal encephalitis and subacute hemichorea. Neurology. May 1979;29(5):676-81. [View Abstract]
  67. Sweeney BJ, Edgecombe J, Churchill DR, et al. Choreoathetosis/ballismus associated with pentamidine-induced hypoglycemia in a patient with the acquired immunodeficiency syndrome. Arch Neurol. Jul 1994;51(7):723-5. [View Abstract]
  68. Davous P, Rondot P, Marion MH, Gueguen B. Severe chorea after acute carbon monoxide poisoning. J Neurol Neurosurg Psychiatry. Feb 1986;49(2):206-8. [View Abstract]
  69. Schwartz A, Hennerici M, Wegener OH. Delayed choreoathetosis following acute carbon monoxide poisoning. Neurology. Jan 1985;35(1):98-9. [View Abstract]
  70. Abbruzzese G, Brusa G, DallAgata D, Morena M, Spadavecchia L, Favale E. Electrophysiological analysis of motor control in patients with vascular hemichorea. Ital J Neurol Sci. Aug 1987;8(4):357-62. [View Abstract]
  71. Jones HR Jr, Baker RA, Kott HS. Hypertensive putaminal hemorrhage presenting with hemichorea. Stroke. Jan-Feb 1985;16(1):130-1. [View Abstract]
  72. Margolin DI, Marsden CD. Episodic dyskinesias and transient cerebral ischemia. Neurology. Dec 1982;32(12):1379-80. [View Abstract]
  73. Tabaton M, Mancardi G, Loeb C. Generalized chorea due to bilateral small, deep cerebral infarcts. Neurology. Apr 1985;35(4):588-9. [View Abstract]
  74. Bae SH, Vates TS Jr, Kenton EJ 3d. Generalized chorea associated with chronic subdural hematomas. Ann Neurol. Oct 1980;8(4):449-50. [View Abstract]
  75. Pavlakis SG, Schneider S, Black K, Gould RJ. Steroid-responsive chorea in moyamoya disease. Mov Disord. 1991;6(4):347-9. [View Abstract]
  76. Bruyn GW, Ferrari MD. Chorea and migraine: Hemicrania choreatica?. Cephalalgia. Jun 1984;4(2):119-24. [View Abstract]
  77. Kok J, Bosseray A, Brion JP, et al. Chorea in a child with Churg-Strauss syndrome. Stroke. Aug 1993;24(8):1263-4. [View Abstract]
  78. Kimura N, Sugihara R, Kimura A, Kumamoto T, Tsuda T. [A case of neuro-Behcets disease presenting with chorea]. Rinsho Shinkeigaku. Jan 2001;41(1):45-9. [View Abstract]
  79. Caviness VS Jr. Huntingtons disease. Dev Med Child Neurol. Dec 1985;27(6):826-9. [View Abstract]
  80. Cervera R, Asherson RA, Font J, et al. Chorea in the antiphospholipid syndrome. Clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature. Medicine (Baltimore). May 1997;76(3):203-12. [View Abstract]
  81. Walker FO, Hunt VP. Ballism: an association with ventriculoperitoneal shunting. Neurology. Jun 1990;40(6):1004. [View Abstract]
  82. Rosenblatt A, Liang KY, Zhou H, Abbott MH, Gourley LM, Margolis RL. The association of CAG repeat length with clinical progression in Huntington disease. Neurology. Apr 11 2006;66(7):1016-20. [View Abstract]
  83. Burton PD. Magnetic resonance imaging and brain iron: implications in the diagnosis and pathochemistry of movement disorders and dementia. Barrow Neurological Institute Quarterly. 1987;3, No. 4:15-29.
  84. Rutledge JN, Hilal SK, Silver AJ, et al. Study of movement disorders and brain iron by MR. Am J Neuroradiol. 1987;8:397-411.
  85. Montoya A, Price BH, Menear M, Lepage M. Brain imaging and cognitive dysfunctions in Huntingtons disease. J Psychiatry Neurosci. Jan 2006;31(1):21-9. [View Abstract]
  86. Hosokawa S, Ichiya Y, Kuwabara Y, et al. Positron emission tomography in cases of chorea with different underlying diseases. J Neurol Neurosurg Psychiatry. Oct 1987;50(10):1284-7. [View Abstract]
  87. Otsuka M, Ichiya Y, Kuwabara Y, et al. Cerebral glucose metabolism and striatal 18F-dopa uptake by PET in cases of chorea with or without dementia. J Neurol Sci. Apr 1993;115(2):153-7. [View Abstract]
  88. Tanaka M, Hirai S, Kondo S, et al. Cerebral hypoperfusion and hypometabolism with altered striatal signal intensity in chorea-acanthocytosis: a combined PET and MRI study. Mov Disord. Jan 1998;13(1):100-7. [View Abstract]
  89. Grove VE Jr, Quintanilla J, DeVaney GT. Improvement of Huntingtons disease with olanzapine and valproate. N Engl J Med. Sep 28 2000;343(13):973-4. [View Abstract]
  90. Shannon KM. Hemiballismus. Clin Neuropharmacol. Oct 1990;13(5):413-25. [View Abstract]
  91. Thompson TP, Kondziolka D, Albright AL. Thalamic stimulation for choreiform movement disorders in children. Report of two cases. J Neurosurg. Apr 2000;92(4):718-21. [View Abstract]
  92. Krauss JK, Loher TJ, Weigel R, et al. Chronic stimulation of the globus pallidus internus for treatment of non-dYT1 generalized dystonia and choreoathetosis: 2-year follow up. J Neurosurg. Apr 2003;98(4):785-92. [View Abstract]
  93. Moro E, Lang AE, Strafella AP, et al. Bilateral globus pallidus stimulation for Huntingtons disease. Ann Neurol. Aug 2004;56(2):290-4. [View Abstract]
  94. Bachoud-Levi AC, Gaura V, Brugieres P, Lefaucheur JP, Boisse MF, Maison P, et al. Effect of fetal neural transplants in patients with Huntingtons disease 6 years after surgery: a long-term follow-up study. Lancet Neurol. Apr 2006;5(4):303-9. [View Abstract]
  95. Keene CD, Sonnen JA, Swanson PD, Kopyov O, Leverenz JB, Bird TD, et al. Neural transplantation in Huntington disease: long-term grafts in two patients. Neurology. Jun 12 2007;68(24):2093-8. [View Abstract]
  96. Souza Ad, Moloi MW. Involuntary movements due to vitamin B12 deficiency. Neurol Res. Dec 2014;36(12):1121-8. [View Abstract]