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遇到不典型“脑梗死”,这个疾病需警惕

2018-08-11 吴积宝(湖南郴州市第一人民医院神经内科) “林邑中枢”公众号

临床中有很多不典型的脑血管病患者。最近笔者遇到了一例以神经精神症状起病,头颅影像学提示颅内多发急性梗死的患者,但梗死灶不符合血管分布。现整理出来与大家分享。

临床中有很多不典型的脑血管病患者。最近笔者遇到了一例以神经精神症状起病,头颅影像学提示颅内多发急性梗死的患者,但梗死灶不符合血管分布。现整理出来与大家分享。

病例概述

66岁老年男性患者,因头昏1周,意识障碍4天入院。患者儿子代诉患者于1周前开始无明显诱因出现头昏、乏力,无发热、咳嗽、腹泻、腹痛、尿频、血尿等不适,未正规诊治,4天前出现言语障碍,不能按指令正确完成动作(如患者妻子要求其取衣架,患者不能正确完成,取衣服给妻子)。

当地医院检查颈椎腰椎CT提示颈椎、腰椎多发椎间盘突出;头颅MRI示多发脑梗塞,言语障碍加重,不能正确对答,夜间起床后不能正确走回病床,今日开始昏睡状态,不能进食,为求继续治疗,今转我院,门诊拟“脑梗死”收治我科。起病以来患者精神、食纳欠佳,大小便正常,近2个月体重无明显减轻。

入院查体:神志嗜睡,皮肤轻度黄染,查体欠配合,反应迟钝,缄默不语,双侧瞳孔等大等圆,直径3mm,对光反射灵敏,鼻唇沟基本对称,伸舌不配合,咽反射存在;颈软,四肢肌张力正常,肌力粗侧IV级,双侧腱反射正常,感觉查体不配合,双侧巴氏征可疑阳性。

双肺呼吸音稍粗,未闻及湿性啰音;心率为87次/分,心音正常,律齐,各瓣膜区未闻及明显病理性杂音。腹部平坦,腹肌软,无压痛及反跳痛,双下肢无水肿。

外院头颅磁共振提示急性多发脑梗死,遂以“脑血管病”收入治疗。入院后复查头颅磁共振弥散加权像(diffusion-weighted imaging,DWI)示右侧小脑半球、双侧顶叶、放射冠区及左侧额叶、右侧胼胝体压部可见多发、散在小片状高信号,考虑多发急性梗死灶(下图)。

入院头颅磁共振如下:



实验室检验结果:血红蛋白:89g/L;血小板计数:18×109 /L;乳酸脱氢酶(LDH):451U/L(正常参考值为0-240U/L);总胆红素(TBil)为45umol/L(正常参考值为3.0-25.8U/L);直接胆红素(DBil)为9.8umol/L(正常参考值为0-6.8U/L);间接胆红素为40umol/L(IBil)(正常参考值为0-18.1U/L);尿素氮(BUN)为10.58(正常参考值范围为1.8-8.0mmol/L)。

鉴于患者头颅磁共振多发梗死灶不符合血管分布;加之患者血小板计数明显下降及提示血管内溶血。请IBD%E8%AF%8A%E6%B2%BB%E8%BF%87%E7%A8%8B%E4%B8%AD%E7%9A%84%E8%AF%84%E4%BC%B0-Part%202" target="_blank">血液内科会诊初步考虑血栓性血小板减少性紫癜(TTP),进一步完善骨穿及外送标本行血浆ADAMTS13活性测定及流式细胞仪检测CD55与CD59的表达量,结果回报示血浆ADAMTS13活性<2.5%,且CD55和CD59检测结果排除了阵发性睡眠性血红蛋白尿症。

最终该患者诊断为血栓性血小板减少性紫癜(TTP)。随即予以血浆置换联合类固醇激素治疗。治疗1周监测血小板计数及乳酸脱氢酶无明显下降,并且患者临床症状逐渐加重至昏迷,考虑难治性TTP,随之予以加用利妥昔单抗(美罗华)免疫抑制治疗,1周后上述指标开始好转,临床症状也随之好转。

讨论

血栓性血小板减少性紫癜(TTP) 是临床少见的急危重症之一,病情凶险,病死率高。其本质上属于一种弥漫性微血管病变。自从1924年Moschcowitz首次报道以来,国内外陆续有相关报道。总结其临床表现主要为血小板减少、微血管病性溶血性贫血(MAHA)、神经精神症状、肾功能损害及发热等典型的五联征。

但是,在临床实际中患者往往无上述典型的五种临床表现,常表现为血小板减少和微血管病性溶血性贫血(MAHA)。而以神经系统症状为首发表现的则比较少见,容易误诊和漏诊。

目前,有关TTP的病因和发病机制仍未完全阐明。比较认可的机制是由于血浆中血管性血友病因子(vWF)裂解酶(ADAMTS13)缺乏或受抑制所导致。在正常情况下,血管内的多聚体vWF能被ADAMTS13裂解成小片段,而如果缺乏,则会导致高分子的vWF多聚体形成,引起血小板过度粘附,形成血小板性血栓,最终引起血小板减少、MAHA等一系列的病理生理过程。

在实验室检查方面除了血小板显着减低外,具特异性的指标是外周血中检出破碎红细胞和血浆ADAMTS13活性减低。另外,监测血清中乳酸脱氢酶(LDH)和血小板计数的动态变化可作为TTP疗效判断和复发的检测参考指标。临床中TTP 可分为遗传性和获得性,其中获得性疾病当中以特发性TTP 为主要的临床类型。常见于合并有自身免疫性疾病的患者。而继发性TTP则相对少见。

TTP发病机制复杂,病因众多。常见的诱发因素有药物、严重感染、自身免疫性疾病、肿瘤等。本例患者发病前1月因新房子装修,每天接触各种装修材料,并且每天在装修房子里留宿,不排除与装修材料中有害气体长期持续刺激诱发有关。

治疗上,目前血浆置换联合常规剂量糖皮质激素是治疗TTP的一线治疗选择。但在难治性及复发患者中,上述的方法效果往往不理想。这时则需要强化免疫抑制治疗,包括传统的和新型的免疫抑制药物。本例患者使用的利妥昔单抗则属于新型免疫抑制剂的代表。在难治性TTP患者中有比较好的效果。

该药属于抗CD20单克隆抗体,主要作用机制是封闭B淋巴细胞上的CD20抗原分子,从而抑制B淋巴细胞参与的所有免疫反应。因此从最初用于恶性B淋巴细胞瘤的治疗到目前多种自身免疫性疾病当中均有其适应症。对于该患者,我们分析应用利妥昔单抗后病情的缓解可能与其减少了抗ADAMST13自身抗体的生成有关。

回到本例患者我们分析其临床特点:首先,以神经精神症状起病,头颅影像学提示颅内多发急性梗死灶,但梗死灶不符合血管分布,无法解释患者的临床症状,且按脑血管病治疗无效;其次,实验室检验结果示血小板显着减少和存在微血管内溶血的表现。最后,确诊为TTP后采用常规的血浆置换联合糖皮质激素效果不佳,加用利妥昔单抗免疫抑制治疗后病情缓解。

总结该病例对我们的启示,第一,对于临床中不典型脑血管病患者,特别是临床症状不能用颅内病灶解释,同时合并有血小板减少时,需警惕TTP的可能,应尽早确诊和治疗,避免病情延误;第二,采用常规方法血浆置换联合糖皮质激素治疗效果不佳时加用利妥昔单抗可能对难治性TTP有效,有望成为新的一线治疗方案。

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    2018-08-13 asuraxia

    学习了

    0

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    2018-08-13 karmond
  4. [GetPortalCommentsPageByObjectIdResponse(id=1898641, encodeId=de80189864111, content=<a href='/topic/show?id=e5062028978' target=_blank style='color:#2F92EE;'>#不典型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20289, encryptionId=e5062028978, topicName=不典型)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Fri Apr 26 16:06:00 CST 2019, time=2019-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338391, encodeId=2a8833839106, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=127, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2018/07/31/88b7a0fe36b7bac9361f6feb3f050afa.jpg, createdBy=674d2404499, createdName=asuraxia, createdTime=Mon Aug 13 21:27:51 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1465118, encodeId=491c146511818, content=<a href='/topic/show?id=2dea8489010' target=_blank style='color:#2F92EE;'>#脑梗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84890, encryptionId=2dea8489010, topicName=脑梗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ccf56689148, createdName=karmond, createdTime=Mon Aug 13 14:06:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338094, encodeId=1eb9338094ee, content=认真学习,不断进步,把经验分享给同好。点赞了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30251637888, createdName=lietome15, createdTime=Sun Aug 12 09:06:24 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338076, encodeId=20383380e698, content=学习了!!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=187, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Sun Aug 12 07:20:09 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338068, encodeId=3c3233806868, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Sun Aug 12 06:51:46 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338021, encodeId=a24033802135, content=涨知识,学习了,值得借鉴的临床经验,获益匪浅,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/02/27/c53a212859edcad4f60a54feffff50bb.jpg, createdBy=67cf1525321, createdName=13718711b3m, createdTime=Sun Aug 12 01:43:31 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338016, encodeId=f9d133801683, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1bb241978, createdName=phoebeyan520, createdTime=Sun Aug 12 00:31:31 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338009, encodeId=bb2333800973, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM6DGOvNrRdcib3UmzMgpEQplCaQGBmjHytXQqvsuocO2uV2lOAaJibzDafJudKToVfU12LzwArHDb4TSrmU2hk5Qxzc6icoicBK3Dg/0, createdBy=a7901968505, createdName=明心见性, createdTime=Sun Aug 12 00:27:11 CST 2018, time=2018-08-12, status=1, ipAttribution=)]
    2018-08-12 lietome15

    认真学习,不断进步,把经验分享给同好。点赞了!

    0

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    2018-08-12 zb1235672

    学习了!!!!!

    0

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    2018-08-12 神功盖世

    0

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    2018-08-12 13718711b3m

    涨知识,学习了,值得借鉴的临床经验,获益匪浅,谢谢分享

    0

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    2018-08-12 phoebeyan520

    学习了,谢谢分享

    0

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    2018-08-12 明心见性

    学习了,谢谢分享

    0

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