Deep gray matter volume loss drives disability worsening in multiple sclerosis.
Deep gray matter volume loss drives disability worsening in multiple sclerosis.
复制标题
DOI：
10.1002/ana.25145
复制
发表时间：
2018-03
影响因子：
11.2
通讯作者：
MAGNIMS study group
中科院分区：
文献类型：
--
作者：
Eshaghi A;Prados F;Brownlee WJ;Altmann DR;Tur C;Cardoso MJ;De Angelis F;van de Pavert SH;Cawley N;De Stefano N;Stromillo ML;Battaglini M;Ruggieri S;Gasperini C;Filippi M;Rocca MA;Rovira A;Sastre-Garriga J;Vrenken H;Leurs CE;Killestein J;Pirpamer L;Enzinger C;Ourselin S;Wheeler-Kingshott CAMG;Chard D;Thompson AJ;Alexander DC;Barkhof F;Ciccarelli O;MAGNIMS study group
灰质(GM)萎缩发生在所有多发性硬化症(MS)表型中。我们分析了来自1,417名参与者的3,604例脑部高分辨率T1加权磁共振成像扫描：1,214名MS患者(253名临床孤立综合征[CIS]，708名复发缓解[RRMS]，128名继发性进展[SPMS]和125名原发进展[PPMS])，平均随访2.41年(标准差[SD]=1.97)，以及203名健康对照组(HCS；平均随访=1.83年；SD=1.77)，参加7个欧洲中心。用扩展的残疾状态量表(EDSS)评定残疾。我们获得了深部GM(DGM)、颞叶、额叶、顶叶、枕叶和小脑GM、脑干和大脑白质的体积。分级混合模型评估了区域组织丢失的年度百分率，并确定了与EDSS进展时间相关的区域体积。SPM显示皮质GM和DGM的基线体积最低。在所有的基线区域容量中，只有DGM预测到EDSS进展的时间(危险比=0.73；95%可信区间0.65，0.82；p<；0.001)：基线DGM容量每减少一个标准差，在随访期间出现EDSS恶化的时间缩短的风险增加27%。在所有纵向指标中，DGM表现出最快的年萎缩速度，SPMS(-1.45%)、PPMS(-1.66%)和RRMS(-1.34%)快于CIS(-0.88%)和HCS(-0.94%；p<；0.01)。SPMS组的颞叶GM萎缩率(-1.21%)明显快于RRMS(-0.76%)、CIS(-0.75%)和HCS(-0.51%)。同样，SPMS组顶叶GM萎缩率(-1.24%)快于CIS组(-0.63%)和HCS组(-0.23%；均P<0.05)。只有DGM患者的萎缩率与残疾累积显著相关(β=0.04；p<；0.001)。这项大型、多中心和纵向研究表明，DGM容量损失推动了MS患者的残疾积累，而颞叶皮质GM显示SPMS患者比RRMS患者萎缩更快。在评估治疗干预措施的治疗效果时，需要考虑表型之间的区域性GM萎缩发展的差异。Ann Neurol 2018；83：210-222
Gray 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. We analyzed 3,604 brain high‐resolution T1‐weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing‐remitting [RRMS], 128 secondary‐progressive [SPMS], and 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 seven European centers. 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. SPMS 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% confidence interval, 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). This large, multicenter 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. Ann Neurol 2018;83:210–222
登录
查看更多内容
影响因子：
2.5
作者：
Healy BC;Engler D;Glanz B;Musallam A;Chitnis T
通讯作者：
Chitnis T
影响因子：
11.2
作者：
Cree, Bruce A. C.;Gourraud, Pierre-Antoine;Hauser, Stephen L.
通讯作者：
Hauser, Stephen L.
影响因子：
10.9
作者：
Cardoso, M. Jorge;Leung, Kelvin;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien
影响因子：
11.2
作者：
Fisher, Elizabeth;Lee, Jar-Chi;Rudick, Richard A.
通讯作者：
Rudick, Richard A.
影响因子：
10.6
作者：
Cardoso, M. Jorge;Modat, Marc;Ourselin, Sebastien
通讯作者：
Ourselin, Sebastien