妊娠合并视神经脊髓炎1例

2020-05-08 魏婧 熊智慧 黄佼 中国实用妇科与产科杂志

视神经脊髓炎(neuromyelitis optica,NMO)是一种免疫介导的中枢神经系统炎性脱髓鞘疾病,主要表现为视神经和脊髓受累[1]。因该疾病以神经元细胞的坏死为特点,临床表现多严重、预后常较

视神经脊髓炎(neuromyelitis optica,NMO)是一种免疫介导的中枢神经系统炎性脱髓鞘疾病,主要表现为视神经和脊髓受累[1]。因该疾病以神经元细胞的坏死为特点,临床表现多严重、预后常较差。妊娠合并视神经脊髓炎在临床并不多见。浙江大学医学院附属杭州市第一人民医院近期收治了1例相关病例,现结合文献复习将该病例报道如下。

1  病历摘要

患者23岁,因“孕31+3周,右侧肢体麻木3 d,颈后疼痛2d”于2018年5月9日急诊就诊于浙江大学医学院附属杭州市第一人民医院。患者末次月经为2017年10月1日,早孕期核对孕周无误。孕期在当地医院定期产检无特殊情况。入院前3 d患者睡眠后出现右侧手指末端明显麻木感,后逐渐出现右侧肢体麻木。入院前2 d出现颈后疼痛不适,颈部活动受限,无头晕头痛,无肢体偏瘫,无恶心呕吐,无大小便失禁等。既往史:孕2产0,既往人工流产1次。否认其他疾病史。


入院体格检查:体温37℃,脉搏86次/min,呼吸20次/min,血压134/79mmHg,身高160cm,体重57kg,皮肤无黄染,无瘀点瘀斑,存在颈抵抗,肌张力正常,心肺未闻及异常,四肢肌力正常,锁骨下平面右侧肢体感觉减弱,右侧巴氏征阳性,左侧巴氏征阴性。产科检查:宫高29cm,腹围90cm,宫缩未及,胎心率140次/min。


 入院后急诊颈椎MRI示:颈2~6水平椎管内脊髓增粗伴异常信号(见图1),头颅MRI示:两侧额顶叶皮层下、两侧脑室旁及两侧半卵圆中心区多异常信号灶,结合颈部MRI,考虑视神经脊髓炎可能。入院后予甲强龙静滴及丙种球蛋白冲击治疗4 d,患者右侧肢体麻木未缓解,颈部疼痛加剧,并出现左侧肢体麻木。入院后相关检查回报示:抗核抗体(ANA)1∶320,抗SS-A抗体:阳性,抗SS-B抗体:阴性,抗Ro-52抗体:阳性,抗线粒体抗体(AMA-2):弱阳性。腰椎穿刺检查示:脑脊液常规和生化检查正常,抗酸染色、细菌、真菌等培养均(-)。血清及脑脊液水通道蛋白(AQP4)-IgG均阳性。眼底检查及视神经MRI检查无特殊。经多学科会诊,妊娠合并视神经脊髓炎诊断基本明确。考虑疾病进展,完成1疗程促胎肺成熟后,入院第5天孕32周在全麻下行子宫下段剖宫产术,娩出1女婴,体重1750g,Apgar评分:1min 7分,5min 6分,10min7分,新生儿转NICU、产妇转ICU进一步治疗。产妇入ICU后,予行5次血浆置换,四肢麻木等症状逐渐缓解后转风湿免疫科,继续予甲强龙、吗替麦考酚酯片、硫酸羟氯喹片等治疗,病情稳定后于6月8日出院。新生儿入NICU后查:ANA 1∶100,抗SS-A抗体阳性,抗Ro-52抗体阳性,余阴性。未行水通道蛋白4抗体(AQP4-IgG)检查,住院期间未出现神经系统症状,住院13 d后恢复正常,出院。

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2  讨论

NMO于1894年由Devic提出,又称Devic病。NMO的发病主要与AQP4-IgG相关。NMO患者中AQP4-IgG的阳性率为68%~91%。AQP4是一种中枢神经系统的水通道蛋白,主要表达于星形胶质细胞的足突。当AQP4-IgG与星形胶质细胞足突上的AQP4结合后,通过激活补体,最终导致神经元细胞坏死[2-3]。  

目前国际上采用2015年NMO诊断小组制定的诊断标准[4]。既往的标准指病变仅限于视神经和脊髓。新的诊断标准也纳入了一些非视神经和脊髓的病变,统一命名为视神经脊髓炎谱系疾病(NMO spectrum disorders,NMOSD)。2016年我国也根据此标准制定了中国视神经脊髓炎谱系疾病的诊断与治疗指南[1]。按照血清学AQP4-IgG结果分层:(1)血清学AQP4-IgG阳性:具有至少1项临床核心特征:视神经炎、脊髓炎、最后区综合征(发作性呃逆、恶心、呕吐),排除其他原因,以及其他脑干综合征等。(2)血清学AQP4-IgG阴性或未知状态:需至少两项核心临床特征,至少1项核心特征为视神经炎,急性脊髓炎或最后区综合征,且需严格的MRI附加条件:视神经长T2信号或T1增强信号>1/2视神经长度;或长脊髓病变>3个连续椎体节段或其他综合征相应的改变[1]。

对于早期或临床特征、MRI表现不典型的病例,需进行相关的鉴别诊断,主要包括:其他的炎性脱髓鞘疾病,其他自身免疫性疾病:如系统性红斑狼疮,干燥综合征等出现神经系统受累,感染性及代谢性疾病:如结核、缺血缺氧性脑病、Wernick脑病等[1]。  

NMOSD好发于女性,女性患者约为男性患者的8~9倍,中位发病年龄在35~37岁之间,很多NMOSD患者尚处于生育年龄[5]。研究发现,NMOSD患者妊娠期间自然流产、子痫前期的发生风险显著增加。AQP4除了在中枢神经系统表达以外,在人和鼠的胎盘合体滋养细胞也有表达。在小鼠腹腔内灌注AQP4-IgG及补体,可导致胎盘组织的炎性浸润、坏死,引起胚胎的流产[6]。Nour等[7]对40例血清学AQP4-IgG阳性的NMOSD患者的54次妊娠进行回顾性研究,发现子痫前期的发生率达11.5%,特别是在合并其他多系统自身免疫性疾病或近期有自然流产史的患者中其发生风险明显增加。NMOSD患者发病之后妊娠的自然流产率较其发病之前也明显上升(43% vs. 7%),特别是在NMOSD疾病尚处于活动期的情况下妊娠其流产风险显著增加。Delgado-García等[8]研究则发现NMOSD发病前妊娠有近一半(42%)至少发生过1次妊娠丢失,可能与患者在NMOSD出现临床症状之前,其体内就存在亚临床水平的AQP4-IgG有关。

多位学者均发现产后1~3个月是NMOSD复发的高峰期[9-11],提示分娩可能是NMOSD复发的一个诱发因素。Kim等[9]研究发现,分娩后1~3个月和4~6个月NMOSD复发率明显增加(分别是妊娠前的5.3倍和3.7倍),产后复发率高达77%。Klawiter等[10]也同样指出产后3个月的复发率最高,特别指出AQP4-IgG阳性的NMOSD产妇产后复发的风险增加。Huang等[11]对中国南方地区的4个医院进行了多中心研究,发现产后半年NMOSD的复发率明显高于妊娠前。以上研究均提示我们NMOSD产妇产后的继续治疗十分重要。

妊娠期间母体AQP4-IgG可通过胎盘屏障到达胎儿体内,新生儿在出生后1~3个月血清中AQP4-IgG水平也升高,但是新生儿并没有表现出NMOSD相关的症状,可能与血脑屏障的完整性限制了血清中AQP4-IgG进入中枢神经系统有关[12]。Chang等[13]报道了1例NMOSD孕妇在24周超声发现胎儿缺指(趾)畸形行引产的病例,可能是目前唯一1例关于NMOSD与胎儿畸形的报道。该病例中胎儿双手及右足出现明显的缺指(趾)畸形。该孕妇既往无不良妊娠史,孕期无放射性、毒物等接触史,孕期停服硫唑嘌呤,仅服用小剂量甲强龙,胎儿引产后行染色体检查未见异常,胎盘病检提示中度炎症改变。目前已知AQP4-IgG能够通过胎盘到达胎儿血液循环,它是否会影响胎儿的生长发育,导致胎儿畸形目前病例较少,但仍值得我们关注。

NMOSD常与一些自身免疫性疾病如系统性红斑狼疮(SLE)[14]、抗磷脂综合征(APS)[15]、干燥综合征(pSS)[16]等共存。约近一半的NMOSD患者同时合并其他自身免疫标志物如抗核抗体、抗SS-A抗体、抗SS-B抗体、抗双链DNA抗体阳性的情况[1]。本例患者入院时血清抗核抗体、抗SSA抗体均阳性。因抗SS-A和(或)抗SS-B抗体能通过胎盘到达胎儿体内,引起胎儿或新生儿先天性心脏传导阻滞的风险增加,甚至引发胎儿心脏骤停[17],故临床也需要加强对胎儿心脏超声及心电图的检测。

NMOSD的临床处理急性期主要包括糖皮质激素、血浆置换、免疫球蛋白的治疗,缓解期治疗包括免疫抑制剂、单克隆抗体的治疗。NMOSD孕期用药的选择及安全性,也有多位学者进行了研究[18-20]。

本病例中患者急性起病,结合临床症状、颈部MRI、头部MRI及AQP4-IgG的检测,迅速明确了诊断。经糖皮质激素及大量丙种球蛋白冲击治疗后,患者症状未缓解且进一步加重,结合孕周的考虑,完成促胎肺成熟后,果断行剖宫产终止妊娠。术后给予血浆置换治疗,患者病情逐步稳定。患者产后定期风湿免疫科随诊,产后半年内疾病未复发。但产后第7个月患者疾病复发表现为视神经炎,双眼视力下降,并进行性加重,后多次风湿免疫科住院,经利妥昔单抗治疗后,目前视力逐渐恢复稳定。新生儿出院后定期复诊,生长发育正常,视力检查正常,未出现神经系统受损症状。

综上,对有NMOSD病史的患者,特别是血清学AQP4-IgG阳性者,避免在病情活动、血清AQP4-IgG水平较高时妊娠,孕期需风湿免疫科、神经内科及产科医生共同管理,产后仍需要在风湿免疫科进行规范的治疗,这对于预防疾病的复发、再生育时预防自然流产、子痫前期等并发症都有十分重要的意义。对于临床中一旦孕妇出现神经系统症状,如嗜睡、肢体麻木、呕吐、大小便失禁、视力下降等,除了考虑较多见的妊娠合并SLE、pSS所导致的神经系统受累以外,也要注意AQP4-IgG的检测,尽早明确诊断,尽早治疗。产科医生需提高对妊娠合并内科疾病的识别,促进多学科合作,加强高危孕产妇的管理,从而保障母婴安全[21]。

参考文献 略

原始出处:

魏婧,熊智慧,黄佼,王海滨等,妊娠合并视神经脊髓炎1例报告并文献复习[J],中国实用妇科与产科杂志,2020,36(2).

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    2022-12-08 逍遥游6828 来自湖北省

    AQP4阝阳性

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    2022-03-24 247593158

    学习

    0

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    2021-01-08 gj0740
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    2020-07-09 xlysu
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