Neurology:神经丝蛋白水平,或可反映多发性硬化慢性白质炎症

2021-06-22 Freeman MedSci原创

神经丝蛋白水平,或可反映多发性硬化慢性白质炎症

多发性硬化症是一种慢性神经炎症和神经退行性疾病,以散布在整个中枢神经系统的局灶性脱髓鞘病变为特征。新的活动性多发性硬化症病变以明显的炎症和血脑屏障(BBB)损伤为特征,在MRI上可见钆(Gd)增强的局域。在急性脱髓鞘的第一阶段后。
这些病变的一个子类在边缘保留了慢性炎症(称为 "慢性活动性/折叠性病变")。在过去的十年中,一些MRI-组织病理学验证研究表明,慢性活动性/折叠性病变(尽管可能不是所有的病变)可以在基于易感性的MRI上显示为非钆增强的病变,有一个顺磁性边缘(PRL)。


病变边缘的MRI易感性对比主要与激活的小胶质细胞/巨噬细胞内的铁积累有关,尽管持续的氧化应激也可能起作用。从临床角度来看,PRL在复发缓解型和进展型多发性硬化症中都很常见,并且在临床上与更具侵略性的疾病有关。在MS中,PRL是否与活动着神经轴损伤增加有关,目前尚不清楚。

神经病理学研究表明,在一些慢性多发性硬化症病变的边缘可以发现富含铁的活化小胶质细胞/巨噬细胞和燃烧的脱髓鞘,根据观察到的髓鞘吞噬量,这些病变被分为 "慢性活动性 "或 "燃烧性 "病变。事实上,慢性炎症和髓鞘及轴突的损害是一个谱系,因此有时在组织病理学分析中很难准确区分慢性活动性病变和烟熏病变。轴突缺失和持续的轴突损伤已被描述,分别在这种病变的中心和边缘,在进行性多发性硬化症病例中,轴突损伤与慢性活动性和烟熏性病变( smoldering)的数量有一定的相关性。综上所述,这些结果表明,局灶性慢性炎症可以驱动神经变性。

神经轴突损伤被认为是永久性神经残疾的基质,监测外周血中的神经丝蛋白水平已显示出作为多发性硬化症疾病活动和神经变性的标志物的前景。具体来说,以前的研究表明,sNfL水平不仅反映了弥漫性神经元损失,也反映了多发性硬化症的局灶性炎症损害:当出现急性Gd增强病变时,sNfL水平增加,与这种病变的数量相关。然而,sNfL水平是否反映慢性白质炎症的存在,以PRL的形式,尚未在体内进行调查。

藉此,法国Université catholique de Louvain的çPietro Maggi等人,评估了多发性硬化症患者体内PRL的存在是否与血清NfL水平的增加有关,这基于易感性的MRI检测。我们还旨在证实和扩展以前的知识,表明慢性活动性和烟熏性病变--PRL的组织病理学相关性--表现出大量轴突损失,与慢性炎症细胞共存,导致NfL释放增加。


他们在118名没有钆增强病变或近期复发的多发性硬化症患者中,我们分析了三维亚毫米相位MRI和sNfL水平。对另外20名尸检的多发性硬化症患者的25个多发性硬化症病灶进行了组织病理学评估。

他们发现:在单变量分析中,与PRL≤1的参与者("PRL≥2",n=43)相比,年龄调整后的sNfL百分位数(中位数,91和68;p<0.001)更高,MS疾病严重程度评分(

MS disease severity scale, MSSS中位数,4.3和2.4;p=0.003)更高。

在多变量分析中,PRL≥2的病例sNfL百分位数水平较高,而疾病修饰治疗(DMT)、EDSS和T2病变负荷并不影响sNfL。

在一个类似的模型中,sNfL百分位数水平在PRL≥4的病例中最高。随后的多变量分析显示,PRL≥2的病例的MSSS也较高,而MSSS不受DMT或T2病灶负荷的影响。在组织病理学上,慢性活动性病变和烟熏性病变在病变边缘都表现出比病变中心更严重的急性轴索损伤(边缘与中心:P=0.004和P=0.0002,分别)。

这个研究的重要意义在于发现了,慢性白质炎症与非急性MS患者的sNfL水平和疾病严重程度的增加有关,表明PRL有助于临床上相关的、炎症驱动的神经变性。


原文出处:
Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis
Pietro Maggi, Jens Kuhle, Sabine Schädelin, et al.
Neurology Jun 2021, 10.1212/WNL.0000000000012326; DOI: 10.1212/WNL.0000000000012326

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  5. [GetPortalCommentsPageByObjectIdResponse(id=1765875, encodeId=17011e65875b4, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Mar 01 05:29:24 CST 2022, time=2022-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890265, encodeId=200a18902659c, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Mon Dec 06 21:29:24 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1801682, encodeId=fec9180168237, content=<a href='/topic/show?id=91f1e4142bd' target=_blank style='color:#2F92EE;'>#神经丝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74142, encryptionId=91f1e4142bd, topicName=神经丝)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Wed Jul 07 20:29:24 CST 2021, time=2021-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2033258, encodeId=d053203325828, content=<a href='/topic/show?id=e4d4e414363' target=_blank style='color:#2F92EE;'>#神经丝蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74143, encryptionId=e4d4e414363, topicName=神经丝蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c39f145, createdName=smlt2008, createdTime=Tue Mar 15 00:29:24 CST 2022, time=2022-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2001373, encodeId=163f20013e3b1, content=<a href='/topic/show?id=d5df12695e6' target=_blank style='color:#2F92EE;'>#Neurol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12695, encryptionId=d5df12695e6, topicName=Neurol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Fri Jul 23 06:29:24 CST 2021, time=2021-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=975929, encodeId=3b459e59298d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=51705231149, createdName=1479ea96m27暂无昵称, createdTime=Tue Jun 22 21:19:58 CST 2021, time=2021-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=975731, encodeId=394f9e5731c2, content=👏🏻, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=91315530943, createdName=zhangyating_zoey, createdTime=Tue Jun 22 09:47:17 CST 2021, time=2021-06-22, status=1, ipAttribution=)]
    2021-07-23 yinhl1978
  6. [GetPortalCommentsPageByObjectIdResponse(id=1765875, encodeId=17011e65875b4, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Mar 01 05:29:24 CST 2022, time=2022-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890265, encodeId=200a18902659c, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Mon Dec 06 21:29:24 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1801682, encodeId=fec9180168237, content=<a href='/topic/show?id=91f1e4142bd' target=_blank style='color:#2F92EE;'>#神经丝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74142, encryptionId=91f1e4142bd, topicName=神经丝)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Wed Jul 07 20:29:24 CST 2021, time=2021-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2033258, encodeId=d053203325828, content=<a href='/topic/show?id=e4d4e414363' target=_blank style='color:#2F92EE;'>#神经丝蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74143, encryptionId=e4d4e414363, topicName=神经丝蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c39f145, createdName=smlt2008, createdTime=Tue Mar 15 00:29:24 CST 2022, time=2022-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2001373, encodeId=163f20013e3b1, content=<a href='/topic/show?id=d5df12695e6' target=_blank style='color:#2F92EE;'>#Neurol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12695, encryptionId=d5df12695e6, topicName=Neurol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Fri Jul 23 06:29:24 CST 2021, time=2021-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=975929, encodeId=3b459e59298d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=51705231149, createdName=1479ea96m27暂无昵称, createdTime=Tue Jun 22 21:19:58 CST 2021, time=2021-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=975731, encodeId=394f9e5731c2, content=👏🏻, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=91315530943, createdName=zhangyating_zoey, createdTime=Tue Jun 22 09:47:17 CST 2021, time=2021-06-22, status=1, ipAttribution=)]
    2021-06-22 1479ea96m27暂无昵称

    学习

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1765875, encodeId=17011e65875b4, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Tue Mar 01 05:29:24 CST 2022, time=2022-03-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1890265, encodeId=200a18902659c, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Mon Dec 06 21:29:24 CST 2021, time=2021-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1801682, encodeId=fec9180168237, content=<a href='/topic/show?id=91f1e4142bd' target=_blank style='color:#2F92EE;'>#神经丝#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74142, encryptionId=91f1e4142bd, topicName=神经丝)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1d01326, createdName=lizhou0204, createdTime=Wed Jul 07 20:29:24 CST 2021, time=2021-07-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2033258, encodeId=d053203325828, content=<a href='/topic/show?id=e4d4e414363' target=_blank style='color:#2F92EE;'>#神经丝蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74143, encryptionId=e4d4e414363, topicName=神经丝蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c39f145, createdName=smlt2008, createdTime=Tue Mar 15 00:29:24 CST 2022, time=2022-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2001373, encodeId=163f20013e3b1, content=<a href='/topic/show?id=d5df12695e6' target=_blank style='color:#2F92EE;'>#Neurol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12695, encryptionId=d5df12695e6, topicName=Neurol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Fri Jul 23 06:29:24 CST 2021, time=2021-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=975929, encodeId=3b459e59298d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=51705231149, createdName=1479ea96m27暂无昵称, createdTime=Tue Jun 22 21:19:58 CST 2021, time=2021-06-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=975731, encodeId=394f9e5731c2, content=👏🏻, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=91315530943, createdName=zhangyating_zoey, createdTime=Tue Jun 22 09:47:17 CST 2021, time=2021-06-22, status=1, ipAttribution=)]
    2021-06-22 zhangyating_zoey

    👏🏻

    0

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