JNNP:与SARS-CoV-2相关的颅内血管炎的免疫抑制:对COVID-19患者脑血管病的治疗意义

2020-09-09 MedSci原创 MedSci原创

急性脑血管疾病,特别是缺血性中风,已成为COVID-19的严重并发症。但是,其机制和最佳治疗方法尚不完全清楚。在肺和心脏循环中,有证据表明血栓形成并发症可能与内皮炎症和损伤有关,但在脑血管系统中这种证

急性脑血管疾病,特别是缺血性中风,已成为COVID-19的严重并发症。但是,其机制和最佳治疗方法尚不完全清楚。在肺和心脏循环中,有证据表明血栓形成并发症可能与内皮炎症和损伤有关,但在脑血管系统中这种证据有限。我们证明了在COVID-19并发多处的患者中血管炎的直接影像学证据响应类固醇和靶向白介素-1(IL-1)和白介素-6(IL-6)抑制的缺血性中风。

一名患有2型糖尿病,高血压,高胆固醇血症和缺血性心脏病的64岁男子入院,有5天的干咳和发烧史。患者诊断患有COVID-19肺炎,需要早期插管,机械通气,正性肌力支持和血液滤过以治疗急性肾损伤。血液测试显示淋巴细胞减少症(0.6×109 / L),C反应蛋白升高(196 mg / L),肾功能不全(肌酐156μmol/ L)和D-二聚体升高(> 20 000μg/ L)。鉴于此,以及他需要持续进行肾脏替代治疗,该患者被全身性肝素化。鼻咽拭子逆转录酶PCR检测证实了SARS-CoV-2感染。入院第24天,在镇静后,近端上肢的阵挛性阵挛性运动没有适当的反应。 患者此时正在服用阿司匹林和静脉肝素。MRI脑显示左枕和右顶叶,枕和颞叶异常信号,可变的受限扩散和外周增强(图1)。 外观与右中脑动脉(MCA)和两个后脑动脉(PCA)区域的多个亚急性梗死相符。 磁共振血管造影显示右PCA和左PCA闭塞。 对比后体积T1 SPACE MRI序列显示长节段,同心异常,MCA,前脑动脉(ACA),椎动脉和基底动脉的血管壁增强(图1)。 外观提示弥漫性颅内血管炎并发多区域梗塞。

病毒学筛查显示患者先前有丙型肝炎病毒(血液中未检测到病毒RNA)和水痘带状疱疹病毒感染的证据,但没有活动性感染的迹象。肠病毒,乙型肝炎和艾滋病毒血清学均为阴性。抗核(ANA),抗中性粒细胞胞浆(ANCA)和抗磷脂抗体均为阴性。该患者先后静脉注射甲泼尼龙(每天1μg,持续3d天),然后口服泼尼松龙(每天60μmg)。给予左乙拉西坦治疗癫痫发作。根据经验处方了阿昔洛韦和头孢曲松。 6天后的临床评估显示,患者自发睁眼,没有固定,完整的脑干反射,并撤回了痛苦的刺激。经过多学科讨论,其中包括初步的阳性丙型肝炎血清学的潜在影响,每天两次以200μmg的剂量进行IL-1受体拮抗剂anakinra的脱标签试验。入院第42天(anakinra治疗的第5天)的后续MRI检查未发现新的梗塞,脑肿胀减轻和持续的异常血管壁增强。观察到神经学改善,患者现在定位于疼痛刺激。鉴于丙型肝炎病毒RNA试验阴性,将生物疗法改为静脉注射IL-6拮抗剂tocilizumab8μmg/ kg,每4周重复一次。 3天后(第47天)的神经系统评估显示,患者能够服从命令,说出一句话并坐下起床,进一步改善了病情。从那以后,随着AKI的解决和通气的成功断奶,患者的病情持续改善。第57天的影像学检查显示出治疗反应的证据,包括异常MCA和ACA血管壁增强的消失(图1)和椎基底动脉血管壁增强的减少。

尚不确定与COVID-19相关的脑血管疾病的最佳治疗干预措施。这些早期发现除了可以解决内皮感染和病毒复制的疗法外,还可以通过合理的试验来减少内皮炎症。在作者的病例中,重组IL-1拮抗剂anakinra的试验因其潜在的神经保护作用和早期在其他COVID-19相关血管炎性综合征中具有治疗益处的证据而被认为是合理的。COVID-19相关的颅内血管炎的案例中,对类固醇疗法以及IL-1和IL-6途径拮抗作用的治疗反应的临床和放射学证据进一步增加了免疫抑制的潜在益处,迫切需要探索抗细胞因子药物和抗病毒疗法的可能益处。这。

Dixon LCoughlan CKarunaratne K, et al Immunosuppression for intracranial vasculitis associated with SARS-CoV-2: therapeutic implications for COVID-19 cerebrovascular pathology

 

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    2021-03-02 hukaixun
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    2020-09-10 小刀医生
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    2020-09-10 刘煜

    阅读谢谢分享

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1937955, encodeId=bac0193e9553f, content=<a href='/topic/show?id=02de15902d3' target=_blank style='color:#2F92EE;'>#SARS-CoV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15902, encryptionId=02de15902d3, topicName=SARS-CoV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ab940, createdName=hukaixun, createdTime=Tue Mar 02 15:08:20 CST 2021, time=2021-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1953600, encodeId=8648195360064, content=<a href='/topic/show?id=5ba26462383' target=_blank style='color:#2F92EE;'>#治疗意义#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64623, encryptionId=5ba26462383, topicName=治疗意义)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=af68384, createdName=hanhaisha2008, createdTime=Sat Feb 27 01:08:20 CST 2021, time=2021-02-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1644859, encodeId=dc27164485965, content=<a href='/topic/show?id=e3eb89e17fb' target=_blank style='color:#2F92EE;'>#血管病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89717, encryptionId=e3eb89e17fb, topicName=血管病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=64bb23195917, createdName=Luyuxie_17, createdTime=Fri Dec 25 23:08:20 CST 2020, time=2020-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263253, encodeId=7682126325323, content=<a href='/topic/show?id=581e8968859' target=_blank style='color:#2F92EE;'>#血管炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89688, encryptionId=581e8968859, topicName=血管炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=909c71, createdName=shijzhiewnjhch, createdTime=Thu Sep 10 15:08:20 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1297477, encodeId=54a6129e47795, content=<a href='/topic/show?id=c0385134ab' target=_blank style='color:#2F92EE;'>#COVID-19患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5134, encryptionId=c0385134ab, topicName=COVID-19患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6976269, createdName=zhangph, createdTime=Thu Sep 10 15:08:20 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1321221, encodeId=7a021321221a9, content=<a href='/topic/show?id=ac0d159007f' target=_blank style='color:#2F92EE;'>#SARS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15900, encryptionId=ac0d159007f, topicName=SARS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8306486, createdName=小刀医生, createdTime=Thu Sep 10 15:08:20 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=884076, encodeId=5caf8840e65a, content=阅读谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 10 06:32:49 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=883756, encodeId=833c883e56dc, content=!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=db6a5416782, createdName=ms6000000002835907, createdTime=Wed Sep 09 00:27:05 CST 2020, time=2020-09-09, status=1, ipAttribution=)]
    2020-09-09 ms6000000002835907

    0

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