Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 31;8(3):352-360.
doi: 10.1002/mdc3.13148. eCollection 2021 Apr.

Disease Onset in Huntington's Disease: When Is the Conversion?

Mayke Oosterloo  1   2 , Bianca T A de Greef  1   3 , Emilia K Bijlsma  4 , Alexandra Durr  5 , Sarah J Tabrizi  6 , Carlos Estevez-Fraga  6 , Christine E M de Die-Smulders  7   8 , Raymund A C Roos  2
Affiliations

Disease Onset in Huntington's Disease: When Is the Conversion?

Mayke Oosterloo et al. Mov Disord Clin Pract. .

Abstract

Background: Determination of disease onset in Huntington's disease is made by clinical experience. The diagnostic confidence level is an assessment regarding the certainty about the clinical diagnosis based on motor signs. A level of 4 means the rater has ≥99% confidence motor abnormalities are unequivocal signs of disease. However, it does not state which motor abnormalities are signs of disease and how many must be present.

Objective: Our aim is to explore how accurate the diagnostic confidence level is in estimating disease onset using the Enroll-HD data set. For clinical disease onset we use a cut-off total motor score >5 of the Unified Huntington's Disease Rating Scale. This score is used in the TRACK-HD study, with ≤5 indicating no substantial motor signs in premanifests.

Methods: At baseline premanifest participants who converted to manifest (converters) and non-converters were compared for clinical symptoms and diagnostic confidence level. Clinical symptoms and diagnostic confidence levels were longitudinally displayed in converters.

Results: Of 3731 eligible participants, 455 were converters and 3276 non-converters. Baseline diagnostic confidence levels were significantly higher in converters compared to non-converters (P < 0.001). 232 (51%) converters displayed a baseline motor score >5 (mean = 6.7). Converters had significantly more baseline clinical symptoms, and higher disease burden compared to non-converters (P < 0.001). Diagnostic confidence level before disease onset ranged between 1 and 3 in converters.

Conclusions: According to this data the diagnostic confidence level is not an accurate instrument to determine phenoconversion. With trials evaluating disease modifying therapies it is important to develop more reliable diagnostic criteria.

Keywords: Huntington's disease; diagnostic confidence interval; disease onset; unified Huntington's disease rating scale.

PubMed Disclaimer

Conflict of interest statement

No specific funding was received for this research. The authors declare that there is no conflict of interest.

Figures

FIG. 1
FIG. 1
Flow chart of inclusion. DCL, diagnostic confidence interval.
FIG. 2
FIG. 2
Unified Huntington Disease Rating Scale. Total motor score compared to diagnostic level of confidence at baseline in premanifest and converted HD patients; UHDRS, Unified Huntington's Disease Rating Scale.
FIG. 3
FIG. 3
Unified Huntington Disease Rating Scale. Total motor score (A), apathy (B), perseverative/obsessive–compulsive behavior, (C) and diagnostic confidence level (D) in time in converted group. UHDRS, Unified Huntington's Disease Rating Scale; OCB, obsessive–compulsive behavior.
FIG. 4
FIG. 4
Stroop interference test total correct (A), Symbol Digit Modality Test total correct (B) in time in the converted group.
FIG. 5
FIG. 5
Total motor score (A) and diagnostic confidence level (B) in years of follow‐up in converted and non‐converted group.
See this image and copyright information in PMC

References

    1. The Huntington's Disease Collaborative Research Group . A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993;72(6):971–983. - PubMed
    1. Bruyn GW. Huntington's chorea. Historical, clinical and laboratory synopsis. In: Vinken PJ, Bruyn GW, eds. Handbook of Clinical Neurology. Amsterdam: Elsevier; 1968.
    1. Huntington Study Group . Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11(2):136–142. - PubMed
    1. Tabrizi SJ, Langbehn DR, Leavitt BR, et al. Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK‐HD study: cross‐sectional analysis of baseline data. Lancet Neurol 2009;8(9):791–801. - PMC - PubMed
    1. de Boo G, Tibben A, Hermans J, Maat A, Roos RA. Subtle involuntary movements are not reliable indicators of incipient Huntington's disease. Mov Disord 1998;13(1):96–99. - PubMed

LinkOut - more resources