Deep grey matter volume loss drives disability worsening in multiple sclerosis

Arman Eshaghi; Ferrán Prados; Wallace J. Brownlee; Daniel R. Altmann; Carmen Tur; M. Jorge Cardoso; Floriana De Angelis; Steven H. van de Pavert; Niamh Cawley; Nicola De Stefano; ML Stromillo; Marco Battaglini; Serena Ruggieri; Claudio Gasperini; Massimo Filippi; Maria Assunta Rocca; Àlex Rovira; Jaume Sastre‐Garriga; Hugo Vrenken; Cyra E Leurs; Joep Killestein; Lukas Pirpamer; Christian Enzinger; Sebastien Ourselin A; Claudia A. M. Gandini Wheeler‐Kingshott; Declan Chard; Alan J. Thompson; Daniel C. Alexander; Frederik Barkhof; Olga Ciccarelli

doi:10.1002/ana.25145

NeuroscienceAnnals of NeurologyJan 13, 2018

Peer-reviewed journal article

Deep grey matter volume loss drives disability worsening in multiple sclerosis

Arman Eshaghi iD, Ferrán Prados iD, Wallace J. Brownlee iD, Daniel R. Altmann iD, Carmen Tur iD, M. Jorge Cardoso iD, Floriana De Angelis iD, Steven H. van de Pavert, Niamh Cawley, Nicola De Stefano iD, ML Stromillo, Marco Battaglini iD, Serena Ruggieri iD, Claudio Gasperini iD, Massimo Filippi iD, Maria Assunta Rocca iD, Àlex Rovira iD, Jaume Sastre‐Garriga iD, Hugo Vrenken iD, Cyra E Leurs iD, Joep Killestein iD, Lukas Pirpamer iD, Christian Enzinger iD, Sebastien Ourselin A iD, Claudia A. M. Gandini Wheeler‐Kingshott iD, , Jacqueline A. Palace iD

Abstract

ObjectiveGrey matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.\n\nMethodsWe analysed 3,604 brain high-resolution T1-weighted MRI scans from 1,417 participants: 1,214 MS patients (253 clinically-isolated syndrome[CIS], 708 relapsingremitting[RRMS], 128 secondary-progressive[SPMS], 125 primary-progressive[PPMS]), over an average follow-up of 2.41 years (standard deviation[SD]=1.97), and 203 healthy controls (HCs) [average follow-up=1.83 year, SD=1.77], attending 7 European centres. Disability was assessed with the Expanded-Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem and cerebral white matter. Hierarchical mixed-models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression.\n\nResultsSPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio=0.73, 95% CIs 0.65, 0.82; p<0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%)[p<0.01]. The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%) (all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta=0.04, p<0.001).\n\nInterpretationThis large multi-centre and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions.

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