eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Huntington Disease: Differential Diagnoses & Workup

Author: Fredy J Revilla, MD, Assistant Professor of Neurology, Head of Division of Movement Disorders, Department of Neurology, University of Cincinnati College of Medicine, Cincinnati Veterans Affairs Medical Center
Coauthor(s): Jaime Grutzendler, MD, Assistant Professor, Department of Neurology and Physiology, Northwestern University School of Medicine
Contributor Information and Disclosures

Updated: Sep 4, 2008

Differential Diagnoses

Chorea Gravidarum
Multiple Sclerosis
Neuroacanthocytosis
Systemic Lupus Erythematosus

Other Problems to Be Considered

Sydenham chorea
Antiphospholipid antibody syndrome
Benign hereditary chorea
Dentatorubropallidoluysian atrophy (DRPLA)
Senile chorea
Vascular chorea, hemichorea, and hemiballismus
Hyperthyroidism
Polycythemia vera
Paroxysmal dyskinesias
Drug effects

See Medscape CME activity The Huntington's Disease-Like Syndromes: What to Consider in Patients With a Negative Huntington's Disease Gene Test.

Workup

Imaging Studies

  • No single imaging technique is necessary or sufficient for diagnosis of Huntington disease (HD). Measurement of the bicaudate diameter (ie, the distance between the heads of the 2 caudate nuclei) by CT scan or MRI is a reliable marker of HD.14
  • Abnormalities in positron emission tomography (PET) scanning and proton MR spectroscopy have been reported; however, their use in clinical practice is limited.

Other Tests

  • Genetic testing (reported as the CAG repeat number for each allele) is now commercially available.
    • Genetic testing may not be necessary in a patient with a typical clinical picture and a genetically proven family history of HD.
    • In the absence of a family history of HD, patients with a suggestive clinical presentation should undergo genetic testing to exclude or confirm HD.
    • Persons at risk for HD who request presymptomatic testing should undergo extensive genetic counseling and neurologic and psychiatric evaluation, given the implications of receiving a positive (or negative) result for an untreatable, familial, progressive, neurodegenerative disease. Most testing centers follow strict protocols, such as the one put forth by the Huntington's Disease Society of America (HDSA).15
  • If the genetic test is negative for HD, then testing for systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome, thyroid disease, neuroacanthocytosis, DRPLA, Wilson disease, and other less common causes of chorea may be reasonable, depending on the individual case.

Staging

The extent of gross striatal pathology, neuronal loss, and gliosis provides a basis for grading the severity of HD pathology (grades 0-4). See Pathophysiology.

More on Huntington Disease

Overview: Huntington Disease
Differential Diagnoses & Workup: Huntington Disease
Treatment & Medication: Huntington Disease
Follow-up: Huntington Disease
References
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References

  1. Huntington G. On chorea. Med Surg Report. 1872;26:320.

  2. Folstein SE. Huntington's Disease: A Disorder of Families. The Johns Hopkins University Press;1989.

  3. Vonsattel JP, DiFiglia M. Huntington disease. J Neuropathol Exp Neurol. May 1998;57(5):369-84. [Medline].

  4. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr. Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol. Nov 1985;44(6):559-77. [Medline].

  5. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. Mar 26 1993;72(6):971-83. [Medline].

  6. Cooper JK, Schilling G, Peters MF, et al. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet. May 1998;7(5):783-90. [Medline].

  7. Davies SW, Turmaine M, Cozens BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. Aug 8 1997;90(3):537-48. [Medline].

  8. Klement IA, Skinner PJ, Kaytor MD, et al. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell. Oct 2 1998;95(1):41-53. [Medline].

  9. Saudou F, Finkbeiner S, Devys D, et al. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell. Oct 2 1998;95(1):55-66. [Medline].

  10. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci U S A. Mar 9 2004;101(10):3498-503. [Medline].

  11. Wexler NS, Young AB, Tanzi RE, Travers H, Starosta-Rubinstein S, Penney JB, et al. Homozygotes for Huntington's disease. Nature. Mar 12-18 1987;326(6109):194-7. [Medline].

  12. Nucifora FC Jr, Sasaki M, Peters MF, et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science. Mar 23 2001;291(5512):2423-8. [Medline].

  13. Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, Lu G. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell. Jun 16 2006;125(6):1179-91. [Medline].

  14. Stober T, Wussow W, Schimrigk K. Bicaudate diameter--the most specific and simple CT parameter in the diagnosis of Huntington's disease. Neuroradiology. 1984;26(1):25-8. [Medline].

  15. Quaid KA. Presymptomatic testing for Huntington disease in the United States. Am J Hum Genet. Sep 1993;53(3):785-7. [Medline].

  16. Ondo WG, Tintner R, Thomas M, Jankovic J. Tetrabenazine treatment for Huntington's disease-associated chorea. Clin Neuropharmacol. Nov-Dec 2002;25(6):300-2. [Medline].

  17. Racette BA, Perlmutter JS. Levodopa responsive parkinsonism in an adult with Huntington's disease. J Neurol Neurosurg Psychiatry. Oct 1998;65(4):577-9. [Medline].

  18. Barbeau A, Duvoisin RC, Gerstenbrand F, et al. Classification of extrapyramidal disorders. Proposal for an international classification and glossary of terms. J Neurol Sci. Aug 1981;51(2):311-27. [Medline].

  19. Bruyn G, Bots G, Dom R. Huntington's chorea. Current neuropathological status. Adv Neurol. 1979;1:83-93.

  20. DiFiglia M, Sapp E, Chase K, et al. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron. May 1995;14(5):1075-81. [Medline].

  21. DiFiglia M, Sapp E, Chase KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. Sep 26 1997;277(5334):1990-3. [Medline].

  22. Fahn S. Concept and classification of dystonia. Adv Neurol. 1988;50:1-8. [Medline].

  23. Folstein SE, Chase GA, Wahl WE, et al. Huntington disease in Maryland: clinical aspects of racial variation. Am J Hum Genet. Aug 1987;41(2):168-79. [Medline].

  24. Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, et al. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J Neurosci. Apr 1 1999;19(7):2522-34. [Medline].

  25. Gutekunst CA, Norflus F, Hersch SM. Recent advances in Huntington's disease. Curr Opin Neurol. Aug 2000;13(4):445-50. [Medline].

  26. Harper PS. Huntington's Disease. 2nd ed. Philadelphia: WB Saunders Company Ltd; 1996.

  27. Hersch S, Ferrante R. Neuropathology and pathophysiology of Huntington's disease. In: Watts RL, Koller WC, eds. Movement Disorders: Neurologic Principles and Practice. New York: McGraw-Hill; 1997:503-526.

  28. Jenkins JB, Conneally PM. The paradigm of Huntington disease. Am J Hum Genet. Jul 1989;45(1):169-75. [Medline].

  29. Kim M, Lee HS, LaForet G, et al. Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion formation and neuronal survival by caspase inhibition. J Neurosci. Feb 1 1999;19(3):964-73. [Medline].

  30. Kuemmerle S, Gutekunst CA, Klein AM, Li XJ, Li SH, Beal MF, et al. Huntington aggregates may not predict neuronal death in Huntington's disease. Ann Neurol. Dec 1999;46(6):842-9. [Medline].

  31. Lasker AG, Zee DS, Hain TC, Folstein SE, Singer HS. Saccades in Huntington's disease: initiation defects and distractibility. Neurology. Mar 1987;37(3):364-70. [Medline].

  32. Marshall FJ, Shoulson I. Clinical features and treatment of Huntington's disease. In: Watts RL, Koller WC, eds. Movement Disorders: Neurologic Principles and Practice. New York: McGraw-Hill; 1997.

  33. PEARSON JS, PETERSEN MC, LAZARTE JA, BLODGETT HE, KLEY IB. An educational approach to the social problem of Huntington's chorea. Proc Staff Meet Mayo Clin. Aug 10 1955;30(16):349-57. [Medline].

  34. Penney JB, Young AB. Huntington's disease. In: Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders. 3rd ed. Baltimore: Williams & Wilkins; 1998.

  35. Petersén A, Mani K, Brundin P. Recent advances on the pathogenesis of Huntington's disease. Exp Neurol. May 1999;157(1):1-18. [Medline].

  36. REED TE, CHANDLER JH. Huntington's chorea in Michigan. I. Demography and genetics. Am J Hum Genet. Jun 1958;10(2):201-25. [Medline].

  37. Shokeir MH. Investigations on Huntington's disease in the Canadian Prairies. I. Prevalence. Clin Genet. Apr 1975;7(4):345-8. [Medline].

  38. Sørensen SA, Fenger K. Causes of death in patients with Huntington's disease and in unaffected first degree relatives. J Med Genet. Dec 1992;29(12):911-4. [Medline].

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Further Reading

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Keywords

Huntington's disease, HD, Huntington chorea, hereditary chorea, huntingtin, involuntary movements, dementia, Huntington disease, behavior changes, juvenile HD, juvenile Huntington disease, autosomal dominant disorder, movement disorder, cognitive disorder, behavior disorder, chorea, neuronal dysfunction, neuronal loss

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Contributor Information and Disclosures

Author

Fredy J Revilla, MD, Assistant Professor of Neurology, Head of Division of Movement Disorders, Department of Neurology, University of Cincinnati College of Medicine, Cincinnati Veterans Affairs Medical Center
Fredy J Revilla, MD is a member of the following medical societies: American Academy of Neurology and Movement Disorders Society
Disclosure: Nothing to disclose.

Coauthor(s)

Jaime Grutzendler, MD, Assistant Professor, Department of Neurology and Physiology, Northwestern University School of Medicine
Jaime Grutzendler, MD is a member of the following medical societies: American Academy of Neurology and Society for Neuroscience
Disclosure: Nothing to disclose.

Medical Editor

Robert A Hauser, MD, MBA, Professor of Neurology, Molecular Pharmacology and Physiology, Director, Parkinson's Disease and Movement Disorders Center, University of South Florida; Clinical Chair, Signature Interdisciplinary Program in Neuroscience
Robert A Hauser, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Academy of Neurology, American Medical Association, American Society of Neuroimaging, and Movement Disorders Society
Disclosure: Allergan Sales, LLC Honoraria Speaking and teaching; Bayer Shering Pharma AG Honoraria Consulting; Boehringer Ingelheim France Honoraria Consulting; Centapharm Honoraria Speaking and teaching; Genzyme Corporation Honoraria Consulting; GlaxoSmithKline Honoraria Consulting; IMPAX Laboratories, Inc.  Consulting; Kyowa Pharmaceuticals, Inc. Honoraria Consulting; Novartis Pharmaceuticals Corp. Honoraria Consulting; Prestwick Pharmaceuticals, Inc. Honoraria Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

 
 
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