Skip to main content

AAN.com

Articles

July 19, 2006

Saccades in presymptomatic and early stages of Huntington disease

T. Blekher, PhD, S. A. Johnson, PhD, J. Marshall, BS, K. White, MS, S. Hui, PhD, M. Weaver, MS, J. Gray, BS, R. Yee, MD, J. C. Stout, PhD, X. Beristain, MD, J. Wojcieszek, MD, and T. Foroud, PhDAuthors Info & Affiliations

August 8, 2006 issue

67 (3) 394-399

https://doi.org/10.1212/01.wnl.0000227890.87398.c1

Abstract

Objective: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD).

Methods: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington’s Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks.

Results: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD.

Conclusions: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (blekher.pdf)

Download
1.49 MB

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;72:971–983.

2.

Rosas HD, Hevelone ND, Zaleta AK, Greve DN, Salat DH, Fischl B. Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 2005;65:745–747.

3.

Aylward EH, Sparks BF, Field KM, et al. Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology 2004;63:66–72.

4.

Paulsen JS, Zimbelman JL, Hinton SC, et al. fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington’s disease. Am J Neuroradiol 2004;25:1715–1721.

5.

Reading SA, Dziorny AC, Peroutka LA, et al. Functional brain changes in presymptomatic Huntington’s disease. Ann Neurol 2004;55:879–883.

6.

Paulsen JS, Zhao H, Stout JS, et al. Clinical markers of early disease in persons near onset of Huntington’s disease. Neurology 2001;57:658–662.

7.

Gutekunst CA, Li SH, Yi H, et al. Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J Neurosci 1999;19:2522–2534.

8.

Weeks RA, Piccini P, Harding AE, Brooks DJ. Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington’s disease. Ann Neurol 1996;40:49–54.

9.

Leigh RJ, Newman SA, Folstein SE, Lasker AG, Jensen BA. Abnormal ocular motor control in Huntington’s disease. Neurology 1983;33:1268–1275.

10.

Starr A. A disorder of rapid eye movements in Huntington’s chorea. Brain 1967;90:545–564.

11.

Lasker AG, Zee DS. Ocular motor abnormalities in Huntington’s disease. Vision Res 1997;37:3639–3645.

12.

Tian JR, Zee DS, Lasker AG, Folstein SE. Saccades in Huntington’s disease: predictive tracking and interaction between release of fixation and initiation of saccades. Neurology 1991;41:875–881.

13.

Lasker AG, Zee DS, Hain TC, Folstein SE, Singer HS. Saccades in Huntington’s disease: initiation defects and distractibility. Neurology 1987;37:364–370.

14.

Rothlind JC, Brandt J, Zee D, Codori AM, Folstein S. Unimpaired verbal memory and oculomotor control in asymptomatic adults with the genetic marker for Huntington’s disease. Arch Neurol 1993;50:799–802.

15.

Collewijn H, Went LN, Tamminga EP, Vegter-Van der Vlis M. Oculomotor defects in patients with Huntington’s disease and their offspring. J Neurol Sci 1988;86:307–320.

16.

Kirkwood SC, Siemers E, Hodes ME, Conneally PM, Christian JC, Foroud T. Subtle changes among presymptomatic Huntington’s disease gene carriers. J Neurol Neurosurg Psychiatry 2000;69:773–779.

17.

Siemers E, Foroud T, Bill DJ, et al. Motor changes in presymptomatic Huntington’s disease gene carriers. Arch Neurol 1996;53:487–492.

18.

Blekher TM, Yee RD, Kirkwood SC, et al. Oculomotor control in asymptomatic and recently diagnosed individuals with the genetic marker for Huntington’s disease. Vision Res 2004;44:2729–2736.

19.

The Huntington Study Group. Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136–142.

20.

Lahiri DK, Bye S, Nurnberger JIJr., Hodes ME, Crisp M. A non-organic and non-enzymatic extraction method gives higher yields of genomic DNA from whole-blood samples than do nine other methods tested. J Biochem Biophys Methods 1992;25:193–205.

21.

Bond CE, Hodes ME. Direct amplification of the CAG repeat of huntingtin without amplification of CCG. Clin Chem 1996;42:773–774.

22.

Bahill AT, Clark MR, Stark L. The main sequence, a tool for studying human eye movements. Math Biosci 1975;24:191–204.

23.

Ramchandani VA, O’Connor S, Blekher T, et al. A preliminary study of acute responses to clamped alcohol concentration and family history of alcoholism. Alcohol Clin Exp Res 1999;23:1320–1330.

24.

Roy-Byrne P, Radant A, Wingerson D, Cowley DS. Human oculomotor function: reliability and diurnal variation. Biological Psychiatry 1995;38:92–97.

25.

Munoz DP, Broughton JR, Goldring JE, Armstrong IT. Age-related performance of human subjects on saccadic eye movement tasks. Exp Brain Res 1998;121:391–400.

26.

Leigh RJ, Zee DS. The neurology of eye movements. New York: Oxford Univ Press, 1999.

27.

Rebok GW, Bylsma FW, Keyl PM, Brandt J, Folstein SE. Automobile driving in Huntington’s disease. Mov Disord 1995;10:778–787.

Information & Authors

Information

Published In

Neurology^®

Volume 67 • Number 3 • August 8, 2006

Pages: 394-399

PubMed: 16855205

Copyright

© 2006.

Publication History

Published online: July 19, 2006

Published in print: August 8, 2006

Permissions

Request permissions for this article.

Request Permissions

Authors

Affiliations & Disclosures

T. Blekher, PhD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

S. A. Johnson, PhD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

J. Marshall, BS

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

K. White, MS

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

S. Hui, PhD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

M. Weaver, MS

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

J. Gray, BS

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

R. Yee, MD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

J. C. Stout, PhD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

X. Beristain, MD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

J. Wojcieszek, MD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

T. Foroud, PhD

From the Departments of Ophthalmology (T.B., R.Y.), Medical and Molecular Genetics (J.M., K.W., M.W., J.G., T.F.), Medicine, Division of Biostatistics (S.H.), and Neurology (X.B., J.W.), Indiana University School of Medicine, Indianapolis; and Department of Psychological and Brain Science (S.A.J., J.C.S.), Indiana University, Bloomington.

View all articles by this author

Notes

Address correspondence and reprint requests to Dr. Tanya Blekher, Indiana University School of Medicine, Department of Ophthalmology, 702 Rotary Circle, Indianapolis, IN 46202-5251; e-mail: [email protected]

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By

- Lenka Hapakova,
- Jan Necpal,
- Zuzana Kosutzka,
The antisaccadic paradigm: A complementary neuropsychological tool in basal ganglia disorders, Cortex, 178, (116-140), (2024).https://doi.org/10.1016/j.cortex.2024.06.005
Crossref
- Renana Mertin,
- Cid Diesta,
- Norbert Brüggemann,
- Raymond L. Rosales,
- Henrike Hanssen,
- Ana Westenberger,
- Julia Steinhardt,
- Marcus Heldmann,
- Hans T. S. Manalo,
- Jean Q. Oropilla,
- Christine Klein,
- Christoph Helmchen,
- Andreas Sprenger,
Oculomotor abnormalities indicate early executive dysfunction in prodromal X-linked dystonia-parkinsonism (XDP), Journal of Neurology, 270, 9, (4262-4275), (2023).https://doi.org/10.1007/s00415-023-11761-8
Crossref
- Abera Saeed,
- Peter van Wijngaarden,
Retinal Imaging and Functional Biomarkers of Huntington’s Disease, Biomarkers for Huntington's Disease, (101-125), (2023).https://doi.org/10.1007/978-3-031-32815-2_5
Crossref
- Khushboo Patel,
- Nitish Kamble,
- Vikram V. Holla,
- Pramod K. Pal,
- Ravi Yadav,
Evolution of eye movement abnormalities in Huntington’s disease, Annals of Movement Disorders, 5, 1, (1-11), (2022).https://doi.org/10.4103/AOMD.AOMD_24_21
Crossref
- Adonay S. Nunes,
- Nataliia Kozhemiako,
- Christopher D. Stephen,
- Jeremy D. Schmahmann,
- Sheraz Khan,
- Anoopum S. Gupta,
Automatic Classification and Severity Estimation of Ataxia From Finger Tapping Videos, Frontiers in Neurology, 12, (2022).https://doi.org/10.3389/fneur.2021.795258
Crossref
- Anoopum S. Gupta,
Digital Phenotyping in Clinical Neurology, Seminars in Neurology, 42, 01, (048-059), (2022).https://doi.org/10.1055/s-0041-1741495
Crossref
- Pilar Rojas,
- Rosa de Hoz,
- Manuel Cadena,
- Elena Salobrar-García,
- José A. Fernández-Albarral,
- Inés López-Cuenca,
- Lorena Elvira-Hurtado,
- José L. Urcelay-Segura,
- Juan J. Salazar,
- José M. Ramírez,
- Ana I. Ramírez,
Neuro-Ophthalmological Findings in Friedreich’s Ataxia, Journal of Personalized Medicine, 11, 8, (708), (2021).https://doi.org/10.3390/jpm11080708
Crossref
- Christina Lang,
- Christopher Gries,
- Katrin S. Lindenberg,
- Jan Lewerenz,
- Stefanie Uhl,
- Christian Olsson,
- Jan Samzelius,
- G. Bernhard Landwehrmeyer,
Monitoring the Motor Phenotype in Huntington’s Disease by Analysis of Keyboard Typing During Real Life Computer Use, Journal of Huntington's Disease, 10, 2, (259-268), (2021).https://doi.org/10.3233/JHD-200451
Crossref
- Vassilis Cutsuridis,
- Shouyong Jiang,
- Matt J. Dunn,
- Anne Rosser,
- James Brawn,
- Jonathan T. Erichsen,
Neural modeling of antisaccade performance of healthy controls and early Huntington's disease patients, Chaos: An Interdisciplinary Journal of Nonlinear Science, 31, 1, (2021).https://doi.org/10.1063/5.0021584
Crossref
- Annabell Coors,
- Natascha Merten,
- David D. Ward,
- Matthias Schmid,
- Monique M.B. Breteler,
- Ulrich Ettinger,
Strong age but weak sex effects in eye movement performance in the general adult population: Evidence from the Rhineland Study, Vision Research, 178, (124-133), (2021).https://doi.org/10.1016/j.visres.2020.10.004
Crossref
See more

View Options

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login

Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
[email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

PDF and All Supplements

Download PDF and Supplementary Material

Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

advertisement

Open Review Pilot Project

Explore peer reviews, author responses, and editor comments on selected articles.

Learn More

Letters to the Editor

The Letters section represents an opportunity for ongoing author debate and post-publication peer review. View our submission guidelines for Letters to the Editor before submitting your comment.

Submit a Letter for this article

View full text|Download PDF