Progression of regional grey matter atrophy in multiple sclerosis
Eshaghi, Arman (University College London. Department of Computer Science)
Marinescu, Razvan V (University College London. Department of Computer Science)
Young, Alexandra L. (University College London. Department of Computer Science)
Firth, Nicholas C. (University College London. Department of Computer Science)
Prados Carrasco, Ferran (University College London. Department of Medical Physics and Bioengineering)
Jorge Cardoso, M. (University College London. Department of Medical Physics and Bioengineering)
Tur, Carmen (University College London. Faculty of Brain Sciences)
De Angelis, Floriana (University College London. Faculty of Brain Sciences)
Cawley, Niamh (University College London. Faculty of Brain Sciences)
Brownlee, Wallace J. (University College London. Faculty of Brain Sciences)
De Stefano, Nicola (University of Siena (Itàlia). Department of Medicine, Surgery and Neuroscience)
Laura Stromillo, M. (University of Siena (Itàlia). Department of Medicine, Surgery and Neuroscience)
Battaglini, Marco (University of Siena (Itàlia). Department of Medicine, Surgery and Neuroscience)
Ruggieri, Serena (University of Rome Sapienza. Department of Neurology and Psychiatry)
Gasperini, Claudio (San Camillo Forlanini Hospital)
Filippi, Massimo (Vita-Salute San Raffaele University (Milà, Itàlia))
Rocca, Maria A. (Vita-Salute San Raffaele University (Milà, Itàlia))
Rovira, Alex (Hospital Universitari Vall d'Hebron)
Sastre-Garriga, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Geurts, Jeroen J. G. (Amsterdam UMC. University Medical Center)
Vrenken, Hugo (MS Center Amsterdam. Department of Radiology and Nuclear Medicine)
Wottschel, Viktor (MS Center Amsterdam. Department of Radiology and Nuclear Medicine)
Leurs, Cyra E. (MS Center Amsterdam. Department of Radiology and Nuclear Medicine)
Uitdehaag, Bernard (MS Center Amsterdam. Department of Radiology and Nuclear Medicine)
Pirpamer, Lukas (Medical University of Graz (Graz, Àustria))
Enzinger, Christian (Medical University of Graz (Graz, Àustria))
Ourselin, Sebastien (University College London Hospitals)
Gandini Wheeler-Kingshott, Claudia A. M (IRCCS Mondino Foundation (Pavia, Itàlia))
Chard, Declan (University College London Hospitals)
Thompson, Alan J. (University College London. Faculty of Brain Sciences)
Barkhof, Frederik (MS Center Amsterdam. Department of Radiology and Nuclear Medicine)
Alexander, Daniel C.. (University College London. Department of Computer Science)
Ciccarelli, Olga (University College London Hospitals)
Universitat Autònoma de Barcelona

Data:	2018
Resum:	See Stankoff and Louapre (doi:) for a scientific commentary on this article. Grey matter atrophy in multiple sclerosis affects certain areas preferentially. Eshaghi et al. use a data-driven computational model to predict the order in which regions atrophy, and use this sequence to stage patients. Atrophy begins in deep grey matter nuclei and posterior cortical regions, before spreading to other cortical areas. See Stankoff and Louapre (doi:) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2. 41 years (standard deviation = 1. 97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0. 001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0. 0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.
Ajuts:	European Commission 634541 European Commission 666992
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Multiple sclerosis ; Atrophy ; Grey matter ; Probabilistic modelling ; Disability accumulation
Publicat a:	Brain, Vol. 141 (may 2018) , p. 1665-1677, ISSN 1460-2156

DOI: 10.1093/brain/awy088
PMID: 29741648

13 p, 1.2 MB

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