Skip to main content
AAN.com

Abstract

Article abstract-Cross-sectional MRI studies demonstrating an association between caudate atrophy and symptom severity and duration of symptoms in patients with Huntington's disease (HD) have been assumed to reflect longitudinal changes in basal ganglia, but such neuropathologic progression has never been directly demonstrated. Subjects in the current study were 23 HD patients at various stages of the disorder who had two MRI images at least 10 months apart (mean interimage interval = 20.8 months). We measured volumes of caudate, putamen, and globus pallidus blind to the order of the images. For each structure, we calculated a change score by subtracting the volume obtained on the follow-up imaging from that obtained on the initial imaging. Results indicated significant decreases over time in caudate, putamen, and total basal ganglia volume. Age at onset and length of trinucleotide repeat correlated significantly with amount of volume change in caudate and total basal ganglia, even after controlling for length of interimage interval, duration of disease, and measures of symptom severity. Amount of change in basal ganglia structures was not significantly correlated with neurologic symptom severity at the time of the initial imaging or duration of symptoms. This is the first longitudinal MRI study to document progressive basal ganglia atrophy in HD, and suggests that quantitative neuroimaging with serial MRI may be useful in monitoring effectiveness of potential treatments. In addition, demonstration of greater rate of basal ganglia atrophy in patients with earlier symptom onset suggests that treatment effects may be more quickly observed in this subgroup of patients than in the general HD population.
NEUROLOGY 1997;48: 394-399

Get full access to this article

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

REFERENCES

1.
Meynert T. Diskussion zu fritsch. Psychiat-CbL 1877;47:7.
2.
De La Monte SM, Vonsattel J, Richardson EP. Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington's disease. J Neuropathol Exp Neurol 1988;47:516-525.
3.
Myers RH, Vonsattel JP, Stevens TJ, et al. Clinical and neuropathologic assessment of severity in Huntington's disease. Neurology 1988;38:341-347.
4.
Young A, Shoulson I, Penney J, et al. Huntington's disease in Venezuela: neurologic features and functional decline. Neurology 1986;36:244-249.
5.
Myers RH, Sax DS, Koroshetz WJ, et al. Factors associated with slow progression in Huntington's disease. Arch Neurol 1991;48:800-804.
6.
Currier RD, Jackson JF, Meydrech EF. Progression rate and age at onset are related in autosomal dominant neurologic diseases. Neurology 1982;32:907-909.
7.
Myers RH, Sax DS, Schoenfeld M, et al. Late onset of Huntington's disease. J Neurol Neurosurg Psychiatry 1985;48:530-534.
8.
Feigin A, Kieburtz K, Bordwell K, et al. Functional decline in Huntington's disease. Mov Disord 1995;10:211-214.
9.
Furtado S, Suchowersky O, Rewcastle N, Graham L, Klimek M, Garber A. Relationship between trinucleotide repeats and neuropathological changes in Huntington's disease. Ann Neurol 1996;39:132-136.
10.
Illarioshkin S, Igarashi S, Onodera O, et al. Trinucleotide repeat length and rate of progression of Huntington's disease. Ann Neurol 1994;36:630-635.
11.
Brandt J, Bylsma FW, Gross R, Stine OC, Ranen N, Ross CA. Trinucleotide repeat length and clinical progression in Huntington's disease. Neurology 1996;46:527-531.
12.
Kieburtz K, MacDonald M, Shih C, et al. Trinucleotide repeat length and progression of illness in Huntington's disease. J Med Genet 1994;31:872-874.
13.
Folstein SE, Leigh RR, Parhad IM, Folstein MF. The diagnosis of Huntington's disease. Neurology 1986;36:1279-1283.
14.
Folstein SE. Huntington's disease: a disorder of families. Baltimore, MD: Johns Hopkins University Press, 1989.
15.
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.
16.
Stine OC, Pleasant N, Franz ML, Abbott MH, Folstein SE, Ross CA. Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum Mol Genet 1993;2:1547-1549.
17.
Folstein SE, Jensen B, Leigh RJ, Folstein M. The measurement of abnormal movement: methods developed for Huntington's disease. Neurobehav Toxicol Teratol 1983;5:605-609.
18.
Aylward EH, Brandt J, Codori A, Mangus R, Barta P, Harris G. Reduced basal ganglia volume associated with the gene for Huntington's disease in asymptomatic at-risk persons. Neurology 1994;44:823-828.
19.
Starkstein S, Folstein S, Brandt J, Pearlson G, McDonnell A, Folstein M. Brain atrophy in Huntington's disease: a CT-scan study. Neuroradiology 1989;31:156-159.
20.
Oepen G, Ostertag C. Diagnostic value of CT in patients with Huntington's chorea and their offspring. J Neurol 1981;225:189-196.
21.
Sax D, Menzer L. Computerized tomography in Huntington disease. Neurology 1977;27:388.
22.
Masucci EF, Borts FT, Kurtzke JF. CT brainstem abnormalities in the differential diagnosis of Huntington's disease. Comput Med Imaging Graph 1990;14:205-212.
23.
Lang C. Is direct CT caudatometry superior to indirect parameters in confirming Huntington's disease? Neuroradiology 1985;27:161-163.
24.
Bamford KA, Caine ED, Kido DK, Plassche WM, Shoulson I. Clinical-pathologic correlation in Huntington's disease: a neuropsychological and computed tomography study. Neurology 1989;39:796-801.
25.
Bamford KA, Caine ED, Kido DK, Cox C, Shoulson I. A prospective evaluation of cognitive decline in early Huntington's disease: functional and radiographic correlates. Neurology 1995;45:1867-1873.
26.
Starkstein S, Brandt J, Folstein S, et al. Neuropsychological and neuroradiological in Huntington's disease. J Neurol Neurosurg Psychiatry 1988;51:1259-1263.
27.
Folstein M, Brandt J, Starkstein S. Cognition in Huntington's disease: characteristics and correlates. In: Franks A, Ironside J, Mindham R, Smith R, Spokes E, Winlow W, eds. Function and dysfunction in the basal ganglia. Manchester, England: Manchester University Press, 1990:224-229.
28.
Sax D, O'Donnell B, Butters N, Menzer L, Montgomery K, Kayne H. Computerized tomographic, neurologic, and neuropsychological correlates of Huntington's disease. Int J Neurosci 1983;18:21-36.
29.
Kuhl D, Phelps M, Markham C, Metter E, Riege W, Winter J. Cerebral metabolism and atrophy in Huntington's disease determined by sup 18 FDG and computed tomographic scan. Ann Neurol 1982;12:425-434.
30.
Starkstein SE, Brandt J, Bylsma F, Peyser C, Folstein M, Folstein SE. Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study. Neuroradiology 1992;34:487-489.
31.
Stober T, Wussow W, Schimrigk K. Bicaudate diameter-the most specific and simple CT parameter in the diagnosis of Huntington's disease. Neuroradiology 1984;26:25-28.
32.
Neophytides A, DiChiro G, Barron S, Chase T. Computed axial tomography in Huntington's disease and persons at-risk for Huntington's disease. Adv Neurol 1979;23:185-191.
33.
Harris GJ, Pearlson GD, Peyser CE, et al. Putamen volume reduction on magnetic resonance imaging exceeds caudate changes in mild Huntington's disease. Ann Neurol 1992;31:69-75.
34.
Aylward EH, Schwartz J, Machlin S, Pearlson G. Bicaudate ratio as a measure of caudate volume on MR images. AJNR Am J Neuroradiol 1991;12:1217-1222.
35.
Ranen NG, Peyser CE, Coyle JT, et al. A controlled trial of idebenone in Huntington's disease. Mov Disord 1996;11:549-554.

Information & Authors

Information

Published In

Neurology®
Volume 48Number 2February 1997
Pages: 394-399
PubMed: 9040728

Publication History

Published online: February 1, 1997
Published in print: February 1997

Permissions

Request permissions for this article.

Authors

Affiliations & Disclosures

From the Division of Psychiatric Neuroimaging (Drs. Aylward, Li, Barta, and Pearlson), the Baltimore Huntington's Disease Center (Drs. Aylward, Li, Stine, Ranen, Bylsma, and Ross, and M. Sherr), and the Department of Neuroscience (Dr. Ross), Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD.
Supported by grants from the NINDS (16375), NIH Division of Research Resources/Johns Hopkins Outpatient Clinical Research Center (RR00722), and the Huntington's Disease Society of America.
Received May 7, 1996. Accepted in final form July 3, 1996.
Address correspondence and reprint requests to Elizabeth H. Aylward, PhD, Meyer 3-166, The Johns Hopkins University School of Medicine, 600 North Wolfe St., Baltimore, MD 21287-7362.

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
  1. Freesurfer Software Update Significantly Impacts Striatal Volumes in the Huntington’s Disease Young Adult Study and Will Influence HD-ISS Staging, Journal of Huntington's Disease, 13, 1, (77-90), (2024).https://doi.org/10.3233/JHD-231512
    Crossref
  2. Huntington's disease: Clinical features, genetic diagnosis, and brain imaging, Huntington's Disease, (1-39), (2024).https://doi.org/10.1016/B978-0-323-95672-7.00010-8
    Crossref
  3. Neuropathology of Neurological Disorders, Mechanism and Genetic Susceptibility of Neurological Disorders, (1-33), (2024).https://doi.org/10.1007/978-981-99-9404-5_1
    Crossref
  4. Applications of fMRI to Neurodegenerative Disease, Functional Neuroradiology, (819-860), (2023).https://doi.org/10.1007/978-3-031-10909-6_36
    Crossref
  5. Longitudinal Imaging of Regional Brain Volumes, SV2A, and Glucose Metabolism In Huntington's Disease , Movement Disorders, 38, 8, (1515-1526), (2023).https://doi.org/10.1002/mds.29501
    Crossref
  6. Altered Spontaneous Brain Activity Patterns of Meibomian Gland Dysfunction in Severely Obese Population Measured Using the Fractional Amplitude of Low-Frequency Fluctuations, Frontiers in Psychiatry, 13, (2022).https://doi.org/10.3389/fpsyt.2022.914039
    Crossref
  7. Huntington disease: a single-gene degenerative disorder of the striatum, Dialogues in Clinical Neuroscience, 18, 1, (91-98), (2022).https://doi.org/10.31887/DCNS.2016.18.1/pnopoulos
    Crossref
  8. Decreased Basal Ganglia Volume in Cerebral Amyloid Angiopathy, Journal of Stroke, 23, 2, (223-233), (2021).https://doi.org/10.5853/jos.2020.04280
    Crossref
  9. Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells, International Journal of Molecular Sciences, 22, 14, (7710), (2021).https://doi.org/10.3390/ijms22147710
    Crossref
  10. Huntingtin silencing delays onset and slows progression of Huntington’s disease: a biomarker study, Brain, 144, 10, (3101-3113), (2021).https://doi.org/10.1093/brain/awab190
    Crossref
  11. See more
Loading...

View Options

Get Access

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

Purchase this article to access the full text.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share