F Sampedro1,2,3, S Martínez-Horta1,2,3,4, J Perez-Perez1,2,3,4, A Horta-Barba1,2,3, J Martin-Lahoz1,2,3,4, A Alonso-Solís2, I Corripio5,2,6, B Gomez-Anson7,8, J Kulisevsky9,2,3,8. 1. From the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department. 2. Biomedical 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. 3. Centro de Investigación en Red-Enfermedades Neurodegenerativas (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Madrid, Spain. 4. Universitat Autónoma de Barcelona (S.M.-H., J.P.-P., J.M.-L., B.G.-A., J.K.), Barcelona, Spain. 5. Psychiatry Department (I.C.), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6. Centro de Investigación Biomédica en Red-Salud Mental (I.C.), Madrid, Spain. 7. Neuroradiology, Radiology Department (B.G.-A.). 8. European Huntington's Disease Network (S.M.-H., J.P.-P., A.H.-B., J.K.), Ulm, Germany. 9. From the Movement Disorders Unit (F.S., S.M.-H., J.P.-P., A.H.-B., J.M.-L., J.K.), Neurology Department jkulisevsky@santpau.cat.
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.
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.
Authors: E H Aylward; A Rosenblatt; K Field; V Yallapragada; K Kieburtz; M McDermott; L A Raymond; E W Almqvist; M Hayden; C A Ross Journal: Brain Res Bull Date: 2003-12-15 Impact factor: 4.077
Authors: Victor Montal; Eduard Vilaplana; Daniel Alcolea; Jordi Pegueroles; Ofer Pasternak; Sofia González-Ortiz; Jordi Clarimón; María Carmona-Iragui; Ignacio Illán-Gala; Estrella Morenas-Rodríguez; Roser Ribosa-Nogué; Isabel Sala; María-Belén Sánchez-Saudinós; Maite García-Sebastian; Jorge Villanúa; Andrea Izagirre; Ainara Estanga; Mirian Ecay-Torres; Ane Iriondo; Montserrat Clerigue; Mikel Tainta; Ana Pozueta; Andrea González; Eloy Martínez-Heras; Sara Llufriu; Rafael Blesa; Pascual Sanchez-Juan; Pablo Martínez-Lage; Alberto Lleó; Juan Fortea Journal: Alzheimers Dement Date: 2017-10-31 Impact factor: 21.566
Authors: N Z Hobbs; J Barnes; C Frost; S M D Henley; E J Wild; K Macdonald; R A Barker; R I Scahill; N C Fox; S J Tabrizi Journal: AJNR Am J Neuroradiol Date: 2010-02-11 Impact factor: 3.825
Authors: Stefan Klöppel; Cynthia M Stonnington; Predrag Petrovic; Dean Mobbs; Oliver Tüscher; David Craufurd; Sarah J Tabrizi; Richard S J Frackowiak Journal: Neuropsychologia Date: 2009-10-28 Impact factor: 3.139
Authors: Anastasia Yendiki; Patricia Panneck; Priti Srinivasan; Allison Stevens; Lilla Zöllei; Jean Augustinack; Ruopeng Wang; David Salat; Stefan Ehrlich; Tim Behrens; Saad Jbabdi; Randy Gollub; Bruce Fischl Journal: Front Neuroinform Date: 2011-10-14 Impact factor: 4.081
Authors: Philip S J Weston; Ivor J A Simpson; Natalie S Ryan; Sebastien Ourselin; Nick C Fox Journal: Alzheimers Res Ther Date: 2015-07-01 Impact factor: 6.982