Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis.
Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis.
复制标题
DOI：
10.1007/s00401-018-1818-y
复制
发表时间：
2018-04
影响因子：
12.7
通讯作者：
Huitinga I
中科院分区：
文献类型：
--
作者：
Luchetti S;Fransen NL;van Eden CG;Ramaglia V;Mason M;Huitinga I
多发性硬化症（MS）是一种高度异质性疾病，在病程中具有很大的个体间差异。MS病变病理学显示患者之间在定位、细胞含量和脱髓鞘程度方面存在相当大的异质性。在这项研究中，我们调查了病理相关的疾病过程中MS使用尸检队列的荷兰脑银行（NBB），包含182 MS脑捐助者。使用标准化尸检程序，包括从标准位置进行系统解剖，解剖了包含7562个MS病变的3188个组织块。使用来自标准位置的组织进行损伤载荷的无偏测量。病变脱髓鞘和先天性炎症活性通过蛋白脂质蛋白和人类白细胞抗原的免疫组织化学观察。病变分为活动性、混合活动/非活动性（也称为慢性活动性）、非活动性或髓鞘再生，而小胶质细胞/巨噬细胞形态分为分枝状、变形虫状或泡沫状。严重程度评分从首次出现症状至EDSS-6的时间计算。分析病变类型患病率和小胶质细胞/巨噬细胞形态与临床病程、疾病严重程度、病变负荷和性别的关系以及相互关系。该分析首次显示：（1）在平均病程为28.6 ± 13.3年（平均值± SD）的进展性MS中，至死亡时存在大量炎性病变活动。57%的病变为活动性或混合活动性/非活动性，78%的患者存在混合活动性/非活动性病变;（2）病程较严重的患者表现出较高比例的活动性/非活动性病变（p = 6 e −06）和较高的损伤负荷（p = 2 e −04）死亡时，（3）病程进展的患者显示出更高的病变负荷（p = 0.001），以及较低比例的髓鞘再生病变（p = 0.03）与复发性病程的患者相比，（4）在整个队列中，与女性相比，男性具有更高的皮质灰质病变发生率（p = 0.027）和更高比例的混合活性/非活性病变（p = 0.007）。我们证实，与复发性疾病相比，进展性MS中混合活动/非活动性病变的比例更高（p = 0.006）。在MRI上识别混合的活动/非活动病变是必要的，以确定它们是否可以用作MS患者的预后工具。本文的在线版本（10.1007/s 00401 -018-1818-y）包含补充材料，可供授权用户使用。
Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in disease course. MS lesion pathology shows considerable heterogeneity in localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates of disease course in MS using the autopsy cohort of the Netherlands Brain Bank (NBB), containing 182 MS brain donors. Using a standardized autopsy procedure including systematic dissection from standard locations, 3188 tissue blocks containing 7562 MS lesions were dissected. Unbiased measurements of lesion load were made using the tissue from standard locations. Lesion demyelinating and innate inflammatory activity were visualized by immunohistochemistry for proteolipid protein and human leukocyte antigen. Lesions were classified into active, mixed active/inactive (also known as chronic active), inactive or remyelinated, while microglia/macrophage morphology was classified as ramified, amoeboid or foamy. The severity score was calculated from the time from first symptoms to EDSS-6. Lesion type prevalence and microglia/macrophage morphology were analyzed in relation to clinical course, disease severity, lesion load and sex, and in relation to each other. This analysis shows for the first time that (1) in progressive MS, with a mean disease duration of 28.6 ± 13.3 years (mean ± SD), there is substantial inflammatory lesion activity at time to death. 57% of all lesions were either active or mixed active/inactive and 78% of all patients had a mixed active/inactive lesion present; (2) patients that had a more severe disease course show a higher proportion of mixed active/inactive lesions (p = 6e−06) and a higher lesion load (p = 2e−04) at the time of death, (3) patients with a progressive disease course show a higher lesion load (p = 0.001), and a lower proportion of remyelinated lesions (p = 0.03) compared to patients with a relapsing disease course, (4) males have a higher incidence of cortical grey matter lesions (p = 0.027) and a higher proportion of mixed active/inactive lesions compared to females across the whole cohort (p = 0.007). We confirm that there is a higher proportion of mixed active/inactive lesions (p = 0.006) in progressive MS compared to relapsing disease. Identification of mixed active/inactive lesions on MRI is necessary to determine whether they can be used as a prognostic tool in living MS patients. The online version of this article (10.1007/s00401-018-1818-y) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
11.2
作者：
Herranz, Elena;Gianni, Costanza;Louapre, Celine;Treaba, Constantina A.;Govindarajan, Sindhuja T.;Ouellette, Russell;Loggia, Marco L.;Sloane, Jacob A.;Madigan, Nancy;Izquierdo-Garcia, David;Ward, Noreen;Mangeat, Gabriel;Granberg, Tobias;Klawiter, Eric C.;Catana, Ciprian;Hooker, Jacob M.;Taylor, Norman;Ionete, Carolina;Kinkel, Revere P.;Mainero, Caterina
通讯作者：
Mainero, Caterina
DOI：
10.3174/ajnr.a4726
发表时间：
2016-08
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Harrison DM;Li X;Liu H;Jones CK;Caffo B;Calabresi PA;van Zijl P
通讯作者：
van Zijl P
影响因子：
6.4
作者：
Dziedzic, Tomasz;Metz, Imke;Brueck, Wolfgang
通讯作者：
Brueck, Wolfgang
影响因子：
11.2
作者：
Breij, Esther C. W.;Brink, Bianca P.;Boe, Lars
通讯作者：
Boe, Lars
影响因子：
3.3
作者：
Hendrickx, Debbie A. E.;van Eden, Corbert G.;Huitinga, Inge
通讯作者：
Huitinga, Inge