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Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype

Expansion mutations in the C9orf72 gene may cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or mixtures of the two clinical phenotypes. Different imaging findings have been described for C9orf72-associated diseases in comparison with sporadic patients with the same phenotyp...

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Autores principales: Floeter, Mary Kay, Bageac, Devin, Danielian, Laura E., Braun, Laura E., Traynor, Bryan J., Kwan, Justin Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153604/
https://www.ncbi.nlm.nih.gov/pubmed/27995069
http://dx.doi.org/10.1016/j.nicl.2016.10.014
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author Floeter, Mary Kay
Bageac, Devin
Danielian, Laura E.
Braun, Laura E.
Traynor, Bryan J.
Kwan, Justin Y.
author_facet Floeter, Mary Kay
Bageac, Devin
Danielian, Laura E.
Braun, Laura E.
Traynor, Bryan J.
Kwan, Justin Y.
author_sort Floeter, Mary Kay
collection PubMed
description Expansion mutations in the C9orf72 gene may cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or mixtures of the two clinical phenotypes. Different imaging findings have been described for C9orf72-associated diseases in comparison with sporadic patients with the same phenotypes, but it is uncertain whether different phenotypes have a common genotype-associated imaging signature. To address this question, 27 unrelated C9orf72 expansion mutation carriers (C9 +) with varied phenotypes, 28 age-matched healthy controls and 22 patients with sporadic ALS (sALS) underwent 3T MRI scanning and clinical phenotyping. Measures of brain volumes and cortical thickness were extracted from T1 images. Compared to healthy controls and sALS patients, symptomatic C9 + subjects had greater ventricular volume loss and thalamic atrophy for age, with diffuse, patchy cortical thinning. Asymptomatic carriers did not differ from controls. C9 + ALS and ALS-FTD patients had less thinning of the motor cortex than sALS patients, but more thinning in extramotor regions, particularly in frontal and temporal lobes. C9 + ALS patients differed from sporadic ALS patients in the thickness of the superior frontal gyrus and lateral orbitofrontal cortex. Thickness of the precentral gyrus was weakly correlated with the revised ALS functional rating scale. Thickness of many cortical regions, including several frontal and temporal regions, was moderately correlated with letter fluency scores. Letter fluency scores were weakly correlated with ventricular and thalamic volume. To better understand how imaging findings are related to disease progression, nineteen C9 + subjects and 23 healthy controls were scanned approximately 6 months later. Ventricular volume increased in C9 + patients with FTD and ALS-FTD phenotypes and remained stable in asymptomatic C9 + subjects. We conclude that diffuse atrophy is a common underlying feature of disease associated with C9orf72 mutations across its clinical phenotypes. Ventricular enlargement can be measured over a 6-month time frame, and appears to be faster in patients with cognitive impairment.
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spelling pubmed-51536042016-12-19 Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype Floeter, Mary Kay Bageac, Devin Danielian, Laura E. Braun, Laura E. Traynor, Bryan J. Kwan, Justin Y. Neuroimage Clin Article Expansion mutations in the C9orf72 gene may cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or mixtures of the two clinical phenotypes. Different imaging findings have been described for C9orf72-associated diseases in comparison with sporadic patients with the same phenotypes, but it is uncertain whether different phenotypes have a common genotype-associated imaging signature. To address this question, 27 unrelated C9orf72 expansion mutation carriers (C9 +) with varied phenotypes, 28 age-matched healthy controls and 22 patients with sporadic ALS (sALS) underwent 3T MRI scanning and clinical phenotyping. Measures of brain volumes and cortical thickness were extracted from T1 images. Compared to healthy controls and sALS patients, symptomatic C9 + subjects had greater ventricular volume loss and thalamic atrophy for age, with diffuse, patchy cortical thinning. Asymptomatic carriers did not differ from controls. C9 + ALS and ALS-FTD patients had less thinning of the motor cortex than sALS patients, but more thinning in extramotor regions, particularly in frontal and temporal lobes. C9 + ALS patients differed from sporadic ALS patients in the thickness of the superior frontal gyrus and lateral orbitofrontal cortex. Thickness of the precentral gyrus was weakly correlated with the revised ALS functional rating scale. Thickness of many cortical regions, including several frontal and temporal regions, was moderately correlated with letter fluency scores. Letter fluency scores were weakly correlated with ventricular and thalamic volume. To better understand how imaging findings are related to disease progression, nineteen C9 + subjects and 23 healthy controls were scanned approximately 6 months later. Ventricular volume increased in C9 + patients with FTD and ALS-FTD phenotypes and remained stable in asymptomatic C9 + subjects. We conclude that diffuse atrophy is a common underlying feature of disease associated with C9orf72 mutations across its clinical phenotypes. Ventricular enlargement can be measured over a 6-month time frame, and appears to be faster in patients with cognitive impairment. Elsevier 2016-10-22 /pmc/articles/PMC5153604/ /pubmed/27995069 http://dx.doi.org/10.1016/j.nicl.2016.10.014 Text en http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Floeter, Mary Kay
Bageac, Devin
Danielian, Laura E.
Braun, Laura E.
Traynor, Bryan J.
Kwan, Justin Y.
Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype
title Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype
title_full Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype
title_fullStr Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype
title_full_unstemmed Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype
title_short Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype
title_sort longitudinal imaging in c9orf72 mutation carriers: relationship to phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153604/
https://www.ncbi.nlm.nih.gov/pubmed/27995069
http://dx.doi.org/10.1016/j.nicl.2016.10.014
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