Frederic Sampedro1,2,3, Saul Martínez-Horta1,2,3,4, Jesús Perez-Perez1,2,3,4,5, Andrea Horta-Barba1,2,4, Diego Alfonso Lopez-Mora6, Valle Camacho6, Alejandro Fernández-León6, Beatriz Gomez-Anson5,7, Ignasi Carrió5,6, Jaime Kulisevsky8,9,10,11,12. 1. Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, 08041, Barcelona, Spain. 2. Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain. 3. Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. 4. European Huntington's Disease Network (EHDN), Ulm, Germany. 5. Autonomous University of Barcelona, Barcelona, Spain. 6. Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 7. Neuroradiology, Radiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 8. Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, 08041, Barcelona, Spain. jkulisevsky@santpau.cat. 9. Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain. jkulisevsky@santpau.cat. 10. Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. jkulisevsky@santpau.cat. 11. European Huntington's Disease Network (EHDN), Ulm, Germany. jkulisevsky@santpau.cat. 12. Autonomous University of Barcelona, Barcelona, Spain. jkulisevsky@santpau.cat.
Abstract
PURPOSE: Huntington's disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient's functional independence. Our objective was to characterize cortical structural and metabolic neurodegeneration in the transition from premanifest to early-stage Huntington's disease (HD). METHODS: Using a surface-based neuroimaging approach, we compared cortical thickness and intracortical FDG-PET uptake in 19 early-symptomatic HD patients with respect to 21 premanifest HD individuals. RESULTS: Early-HD patients showed significant cortical atrophy and intracortical hypometabolism when compared to premanifest subjects (p < 0.05, corrected for multiple comparisons). However, whereas the atrophy pattern was restricted to precentral and parieto-occipital regions, a pronounced frontotemporal hypometabolism was observed. Importantly, structural changes correlated with motor and cognitive performance, and metabolic changes were associated with the presence and severity of apathy in this population, a core neuropsychiatric feature of this disorder. CONCLUSION: Our findings reveal an asynchronous neuronal loss and metabolic compromise across the cerebral cortex in early HD. Hence, the use of structural and metabolic imaging indicators to characterize disease progression in this population should take into consideration the dissociation which occurs between cortical atrophy and hypometabolism.
PURPOSE:Huntington's disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient's functional independence. Our objective was to characterize cortical structural and metabolic neurodegeneration in the transition from premanifest to early-stage Huntington's disease (HD). METHODS: Using a surface-based neuroimaging approach, we compared cortical thickness and intracortical FDG-PET uptake in 19 early-symptomatic HDpatients with respect to 21 premanifest HD individuals. RESULTS: Early-HDpatients showed significant cortical atrophy and intracortical hypometabolism when compared to premanifest subjects (p < 0.05, corrected for multiple comparisons). However, whereas the atrophy pattern was restricted to precentral and parieto-occipital regions, a pronounced frontotemporal hypometabolism was observed. Importantly, structural changes correlated with motor and cognitive performance, and metabolic changes were associated with the presence and severity of apathy in this population, a core neuropsychiatric feature of this disorder. CONCLUSION: Our findings reveal an asynchronous neuronal loss and metabolic compromise across the cerebral cortex in early HD. Hence, the use of structural and metabolic imaging indicators to characterize disease progression in this population should take into consideration the dissociation which occurs between cortical atrophy and hypometabolism.
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