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Improved Turnaround Times | Median time to first decision: 12 days

Research ArticleAdult Brain
Open Access

Widespread Increased Diffusivity Reveals Early Cortical Degeneration in Huntington Disease

F. Sampedro, S. Martínez-Horta, J. Perez-Perez, A. Horta-Barba, J. Martin-Lahoz, A. Alonso-Solís, I. Corripio, B. Gomez-Anson and J. Kulisevsky
American Journal of Neuroradiology September 2019, 40 (9) 1464-1468; DOI: https://doi.org/10.3174/ajnr.A6168
F. Sampedro
aFrom the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
eCentro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain
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S. Martínez-Horta
aFrom the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
eCentro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain
fUniversitat Autónoma de Barcelona (S.M.-H., J.P.-P., J.M.-L., B.G.-A., J.K.), Barcelona, Spain
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J. Perez-Perez
aFrom the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
eCentro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain
fUniversitat Autónoma de Barcelona (S.M.-H., J.P.-P., J.M.-L., B.G.-A., J.K.), Barcelona, Spain
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A. Horta-Barba
aFrom the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
eCentro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain
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J. Martin-Lahoz
aFrom the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
eCentro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain
fUniversitat Autónoma de Barcelona (S.M.-H., J.P.-P., J.M.-L., B.G.-A., J.K.), Barcelona, Spain
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A. Alonso-Solís
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
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I. Corripio
cPsychiatry Department (I.C.), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
hCentro de Investigación Biomédica en Red-Salud Mental (I.C.), Madrid, Spain.
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B. Gomez-Anson
bNeuroradiology, Radiology Department (B.G.-A.)
gEuropean Huntington's Disease Network (S.M.-H., J.P.-P., A.H.-B., J.K.), Ulm, Germany
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J. Kulisevsky
aFrom the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department
dBiomedical Research Institute (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., A.A.-S., I.C., J.K.), Barcelona, Spain
eCentro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain
gEuropean Huntington's Disease Network (S.M.-H., J.P.-P., A.H.-B., J.K.), Ulm, Germany
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Abstract

BACKGROUND AND PURPOSE: Huntington disease is a devastating genetic neurodegenerative disorder for which no effective treatment is yet available. Although progressive striatal atrophy is its pathologic hallmark, concomitant cortical deterioration is assumed to occur, but it is poorly characterized. Our objective was to study the loss of cortical integrity and its association with clinical indicators throughout the course of the disease.

MATERIALS AND METHODS: Using a cohort of 39 patients with Huntington disease and 25 controls with available MR imaging (T1WI and DTI), we compared cortical atrophy and intracortical diffusivity across disease stages. Intracortical diffusivity is a DTI-derived metric that has recently been suggested to detect incipient neuronal death because water can diffuse more freely in cortical regions with reduced neural density.

RESULTS: We observed progressive thinning and increasing diffusivity within the cerebral cortex of patients with Huntington disease (P < .05, corrected for multiple comparisons). Most important, in the absence of pronounced atrophy, widespread increased diffusivity was already present in individuals with premanifest Huntington disease, correlating, in turn, with clinical and disease-specific progression markers.

CONCLUSIONS: Intracortical diffusivity may be more sensitive than cortical thinning for tracking early neurodegeneration in Huntington disease. Moreover, our findings provide further evidence of an early cortical compromise in Huntington disease, which contributes to our understanding of its clinical phenotype and could have important therapeutic implications.

ABBREVIATIONS:

CAG
cytosine-adenine-guanine
CN
healthy controls
Cth
cortical thickness
DBS
disease burden score
earlyHD
early-symptomatic HD
HD
Huntington disease
MD
mean diffusivity
midadvHD
middle-advanced HD
preHD
premanifest HD
SDMT
Symbol Digit Modalities Test
TMT
Trail-Making Test
UHDRS
Unified Huntington's Disease Rating Scale
  • © 2019 by American Journal of Neuroradiology

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Cite this article
F. Sampedro, S. Martínez-Horta, J. Perez-Perez, A. Horta-Barba, J. Martin-Lahoz, A. Alonso-Solís, I. Corripio, B. Gomez-Anson, J. Kulisevsky
Widespread Increased Diffusivity Reveals Early Cortical Degeneration in Huntington Disease
American Journal of Neuroradiology Sep 2019, 40 (9) 1464-1468; DOI: 10.3174/ajnr.A6168

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Widespread Increased Diffusivity Reveals Early Cortical Degeneration in Huntington Disease
F. Sampedro, S. Martínez-Horta, J. Perez-Perez, A. Horta-Barba, J. Martin-Lahoz, A. Alonso-Solís, I. Corripio, B. Gomez-Anson, J. Kulisevsky
American Journal of Neuroradiology Sep 2019, 40 (9) 1464-1468; DOI: 10.3174/ajnr.A6168
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