Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2015 Dec;262(12):2691-8.
doi: 10.1007/s00415-015-7900-7. Epub 2015 Sep 26.

Motor Onset and Diagnosis in Huntington Disease Using the Diagnostic Confidence Level

Collaborators, Affiliations
Free PMC article
Observational Study

Motor Onset and Diagnosis in Huntington Disease Using the Diagnostic Confidence Level

Dawei Liu et al. J Neurol. .
Free PMC article


Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI 27-69%). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models.

Keywords: Diagnosis; Diagnostic confidence level; Hidden Markov model; Huntington disease; Onset; Prediction.


Fig 1
Fig 1
Examples of observed data from two participants in the PREDICT-HD study. HD Huntington disease

Similar articles

  • Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study.
    Paulsen JS, Long JD, Ross CA, Harrington DL, Erwin CJ, Williams JK, Westervelt HJ, Johnson HJ, Aylward EH, Zhang Y, Bockholt HJ, Barker RA; PREDICT-HD Investigators and Coordinators of the Huntington Study Group. Paulsen JS, et al. Lancet Neurol. 2014 Dec;13(12):1193-201. doi: 10.1016/S1474-4422(14)70238-8. Epub 2014 Nov 3. Lancet Neurol. 2014. PMID: 25453459 Free PMC article. Clinical Trial.
  • Clinical-Genetic Associations in the Prospective Huntington at Risk Observational Study (PHAROS): Implications for Clinical Trials.
    Huntington Study Group PHAROS Investigators, Biglan KM, Shoulson I, Kieburtz K, Oakes D, Kayson E, Shinaman MA, Zhao H, Romer M, Young A, Hersch S, Penney J, Marder K, Paulsen J, Quaid K, Siemers E, Tanner C, Mallonee W, Suter G, Dubinsky R, Gray C, Nance M, Bundlie S, Radtke D, Kostyk S, Baic C, Caress J, Walker F, Hunt V, O'Neill C, Chouinard S, Factor S, Greenamyre T, Wood-Siverio C, Corey-Bloom J, Song D, Peavy G, Moskowitz C, Wesson M, Samii A, Bird T, Lipe H, Blindauer K, Marshall F, Zimmerman C, Goldstein J, Rosas D, Novak P, Caviness J, Adler C, Duffy A, Wheelock V, Tempkin T, Richman D, Seeberger L, Albin R, Chou KL, Racette B, Perlmutter JS, Perlman S, Bordelon Y, Martin W, Wieler M, Leavitt B, Raymond L, Decolongon J, Clarke L, Jankovic J, Hunter C, Hauser RA, Sanchez-Ramos J, Furtado S, Suchowersky O, Klimek ML, Guttman M, Sethna R, Feigin A, Cox M, Shannon B, Percy A, Dure L, Harrison M, Johnson W, Higgins D, Molho E, Nickerson C, Evans S, Hobson D, Singer C, Galvez-Jimenez N, Shannon K, Comella C, Ross C, Saint-Hilaire MH, Testa C, Rosenblatt A, Hogarth P, Weiner W, Como P, Kumar R, Cotto C, Stout J, Brocht A, Watts A, Eberly S, Weaver C, Foroud T, Gusella J, MacDonald M, Myers R, Fahn S, Shults C. Huntington Study Group PHAROS Investigators, et al. JAMA Neurol. 2016 Jan;73(1):102-10. doi: 10.1001/jamaneurol.2015.2736. JAMA Neurol. 2016. PMID: 26569098 Clinical Trial.
  • Multivariate prediction of motor diagnosis in Huntington's disease: 12 years of PREDICT-HD.
    Long JD, Paulsen JS; PREDICT-HD Investigators and Coordinators of the Huntington Study Group. Long JD, et al. Version 2. Mov Disord. 2015 Oct;30(12):1664-72. doi: 10.1002/mds.26364. Epub 2015 Sep 4. Mov Disord. 2015. PMID: 26340420 Free PMC article.
  • Risk factors for the onset and progression of Huntington disease.
    Chao TK, Hu J, Pringsheim T. Chao TK, et al. Neurotoxicology. 2017 Jul;61:79-99. doi: 10.1016/j.neuro.2017.01.005. Epub 2017 Jan 20. Neurotoxicology. 2017. PMID: 28111121 Review.
  • Exploring the correlates of intermediate CAG repeats in Huntington disease.
    Ha AD, Jankovic J. Ha AD, et al. Postgrad Med. 2011 Sep;123(5):116-21. doi: 10.3810/pgm.2011.09.2466. Postgrad Med. 2011. PMID: 21904093 Review.
See all similar articles

Cited by 2 articles

Publication types