原发性抗磷脂综合征合并烟雾综合征一例并文献复习

doi:10.16150/j.1671-2870.2022.04.013

摘要/Abstract

摘要：

目的：分析1例原发性抗磷脂综合征（primary antiphospholipid syndrome,PAPS）合并烟雾综合征（moyamoya syndrome,MMS）患者的临床资料,并结合文献探讨APS合并MMS的临床特点。方法：收治1例PAPS合并MMS患者的临床资料,并检索国内外相关文献对该病进行分析总结。结果：本例患者为23岁女性,既往有2次病理妊娠史。此次以脑梗死起病,脑血管影像学检查示双侧颈内动脉重度狭窄或闭塞并侧支血管形成,符合MMS表现;腹部CT示脾肿大。患者经抗凝及免疫抑制剂等治疗后症状改善。检索国内外文献,共发现7例有详细临床资料的APS合并烟雾状血管改变患者,均为女性,平均年龄为26.6岁,临床表现异质性大,其中肢体无力是常见症状,临床上以动静脉血栓形成、病理性妊娠及持续性抗磷脂抗体阳性为主要表现,共6例患者进行详细随访,5例患者经抗凝、免疫抑制剂等治疗后症状改善,余1例患者因脑出血死亡。结论：APS为一种累及多系统的自身免疫性疾病,其合并MMS的病例报道非常罕见。APS的抗凝或抗血小板治疗与MMS的侧支血管存在出血风险存在相矛盾,应谨慎选择双重抗血小板治疗。

关键词: 抗磷脂综合征, 烟雾综合征, 病理性妊娠, 缺血性卒中, 脾肿大

Abstract:

Objective: To analyze the clinical data of a case of primary antiphospholipid syndrome (PAPS) combined with moyamoya syndrome (MMS), and to explore the clinical characteristics of APS combined with MMS. Methods:The clinical data of a patient with PAPS and MMS were collected and analyzed by searching the relevant literatures. Results: The patient was a 23 year old female with 2 pathological pregnancies. The disease started with cerebral infarction. Cerebrovascular imaging showed severe stenosis or occlusion of bilateral internal carotid arteries with collateral vessels formation, which was consistent with MMS findings. Abdominal CT showed splenomegaly. The symptoms were improved after anticoagulation and immunosuppressive therapy. Through literature review at home and abroad, 7 patients with APS complicated with smoky vascular changes with detailed clinical data were found, all of them were female, with an average age of 26.6 years. Their clinical manifestations were heterogeneous, in which limb weakness was a common symptom, with arteriovenous thrombosis, pathological pregnancy and persistent positive antiphospholipid antibody as the main clinical manifestations. A total of 6 patients were followed up in detail, and the symptoms of the 5 patients were improved after anticoagulation and immunosuppressive therapy. One patient died of cerebral hemorrhage. Conclusions: APS is an autoimmune disease involving multiple systems. The case report of APS with MMS is very rare. The anticoagulant or antiplatelet therapy of APS is contradictory to the risk of bleeding in the collateral vessels of MMS, so dual antiplatelet therapy should be carefully selected.

Key words: Antiphospholipid syndrome, Moyamoya syndrome, Pathological pregnancy, Ischemic stroke, Splenomegaly

中图分类号:

R743.9

宋洛卿, 戴廷军. 原发性抗磷脂综合征合并烟雾综合征一例并文献复习[J]. 诊断学理论与实践, 2022, 21(04): 497-503.

SONG Luoqing, DAI Tingjun. Primary antiphospholipid syndrome complicated with moyamoya syndrome: a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 497-503.

图/表 3

表1

7例APS合并烟雾状血管改变患者的临床资料总结

文献	年龄（岁）	主要临床表现	实验室检查	影像学表现			结果
Booth F, et al^[6]	7.5	嗜睡;头痛;运动性失语;偏侧肢体无力	血沉↑;aCL（+）	MRA示左侧颈内动脉明显狭窄;左侧前后交通动脉侧支血管烟雾状改变;MRI示左侧基底节区及额顶叶高信号影	华法林×5个月（INR保持2.5~4.0）减至低剂量ASA	30	语言及运动功能改善;出现认知障碍;脑血流量较前改善
Yamashita Y, et al^[7]	12	构音障碍;面部及肢体不自主运动;努南综合征表型	PTL↓;PT↑;APTT↑; aCL（+）;LA（+）; β₂GP1（+）;ANA（+）; GH↓	MRA示双侧颈内动脉狭窄,右侧为著伴远端血管烟雾状改变;MRI示右侧基底节区低信号影	ASA（100 mg/d）+生长激素+匹莫齐特(1.5 mg/d）×24个月	24	不自主运动完全好转;脑血流量明显改善
Shuja Ud Din MA, et al^[8]	41	面部及偏侧肢体无力	aCL（+）;β₂GP1（+）	MRA示右侧颈内动脉狭窄;右侧大脑中、后动脉侧支血管烟雾状改变;MRI示右侧颞叶、基底节区及双侧半卵圆区高信号影	ASA×2周	12	症状完全改善
Wang等^[5]	43	偏侧肢体无力	aCL（+）;β₂GP1（+）	CTA示双侧大脑中动脉闭塞;CT示双侧半卵圆区及基底节区多处低密度灶;B超示子宫腺肌症	ASA(100 mg/d)+氯吡格雷(75 mg/d)×7 d;ASA(100 mg/d)+氯吡格雷(75 mg/d)+曲普瑞林(3.75 mg/4周)	2	死亡（脑室出血）
左瑜等^[9]	17	头晕头痛;视力下降	PT↓ ;aCL（+）; LA（+）;β₂GP1（+）;	DSA示双侧颈内动脉远端及大脑前、中动脉近端闭塞伴侧支血管烟雾状改变;CT示蛛网膜下腔出血	ASA（100 mg/d）;甲泼尼龙（40 mg/d）→激素序贯口服;氨肽素（3 000 mg/d）	3	头痛、头晕及视力减退明显改善,血小板恢复正常
岳月红等^[10]	22	运动性失语;面部及肢体无力	aCL（+）;TT3↑; TT4↑;FT4↑;TSH↓; TRAb（+）	MRA示双侧颈内动脉末端狭窄伴远端血管烟雾状改变;MRI示左侧额叶及左侧基底节区大片状高信号影	抗血小板;控制甲亢	-	-
王梓等^[11]	44	头痛	aCL（+）	DSA示左侧大脑中动脉起始部闭塞伴侧支血管烟雾状改变	不详	2	症状完全改善

表1

图1

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参考文献 33

[1]	Gris JC, Brenner B. Antiphospholipid antibodies: neuropsychiatric presentations[J]. Semin Thromb Hemost, 2013, 39(8):935-942. doi: 10.1055/s-0033-1357488 URL
[2]	Mayer M, Cerovec M, Rados M, et al. Antiphospholipid syndrome and central nervous system[J]. Clin Neurol Neurosurg, 2010, 112(7):602-608. doi: 10.1016/j.clineuro.2010.03.023 URL
[3]	Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives[J]. Lancet Neurol, 2008, 7(11):1056-1066. doi: 10.1016/S1474-4422(08)70240-0 pmid: 18940695
[4]	顾宇翔, 毛颖. 烟雾病诊疗的挑战和机遇[J]. 中华神经外科杂志, 2019, 35(7):649-652.
	Gu YX, Mao Y. Challenges and opportunities of moyamoya disease diagnosis and treatment[J]. Chin J Neurosurg, 2019, 35(7):649-652.
[5]	Wang Z, Fu Z, Wang J, et al. Moyamoya syndrome with antiphospholipid antibodies: a case report and literature review[J]. Lupus, 2014, 23(11):1204-1206. doi: 10.1177/0961203314540761 pmid: 24939972
[6]	Booth F, Yanofsky R, Ross IB, et al. Primary antiphospholipid syndrome with moyamoya-like vascular changes[J]. Pediatr Neurosurg, 1999, 31(1):45-48. pmid: 10545822
[7]	Yamashita Y, Kusaga A, Koga Y, et al. Noonan syndrome, moyamoya-like vascular changes, and antiphospholipid syndrome[J]. Pediatr Neurol, 2004, 31(5):364-366. pmid: 15519121
[8]	Shuja-Ud-Din MA, Ahamed SA, Baidas G, et al. Moyamoya syndrome with primary antiphospholipid syndrome[J]. Med Princ Pract, 2006, 15(3):238-241. pmid: 16651844
[9]	左瑜, 李春, 张淼, 等. 抗磷脂综合征合并烟雾病血管改变一例[J]. 中华风湿病学杂志, 2015, 19(2):125-126.
	Zuo Y, Li C, Zhang M, et al. A case of antiphospholipid syndrome with vascular changes in moyamoya disease[J]. Chin J Rheumatol, 2015, 19(2):125-126.
[10]	岳月红, 赵永波, 肖向建, 等. 烟雾病合并甲状腺功能亢进症和抗磷脂综合征:1例报告并文献复习[J]. 国际脑血管病杂志, 2016, 24(2):150-153.
	Yue YH, Zhao YB, Xiao XJ, et al. Moyamoya disease complicated with hyperthyroidism and antiphospholipid syndrome:a case report and literature review[J]. Int J Cerebrovasc Dis, 2016, 24(2):150-153.
[11]	王梓, 张磊, 陈吉相, 等. 与抗心磷脂抗体综合征相关的烟雾病1例报道[J]. 卒中与神经疾病, 2016, 23(2):136.
	Wang Z, Zhang L, Chen JX, et al. A case report of moyamoya disease associated with anticardiolipin antibody syndrome[J]. Stroke & Nerv Dis, 2016, 23(2):136.
[12]	Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome(APS)[J]. J Thromb Haemost, 2006, 4(2):295-306. pmid: 16420554
[13]	Petri M. Epidemiology of the antiphospholipid antibody syndrome[J]. J Autoimmun, 2000, 15(2):145-151. pmid: 10968901
[14]	石慧, 杨程德. 2019年欧洲抗风湿病联盟成人抗磷脂综合征治疗推荐解读:高风险抗体谱的定义和抗凝方案细化[J]. 中华风湿病学杂志, 2020, 24(2):73-78.
[15]	Carmi O, Berla M, Shoenfeld Y, et al. Diagnosis and management of catastrophic antiphospholipid syndrome[J]. xpert Rev Hematol, 2017, 10(4):365-374.
[16]	Cohen D, Berger SP, Steup-Beekman GM, et al. Diagnosis and management of the antiphospholipid syndrome[J]. BMJ, 2010, 340:c2541. doi: 10.1136/bmj.c2541 URL
[17]	Shi H, Teng JL, Sun Y, et al. Clinical characteristics and laboratory findings of 252 Chinese patients with anti-phospholipid syndrome: comparison with Euro-Phospholipid cohort[J]. Clin Rheumatol, 2017, 36(3):599-608. doi: 10.1007/s10067-017-3549-1 pmid: 28130684
[18]	Aringer M, Costenbader K, Daikh D, et al. 2019 European league against rheumatism/American college of rheumatology classification criteria for systemic lupus erythematosus[J]. Arthritis Rheumatol, 2019, 71(9):1400-1412. doi: 10.1002/art.40930
[19]	Shiboski CH, Shiboski SC, Seror R, et al. 2016 American college of rheumatology/european league against rheumatism classification criteria for primary Sjögren′s syndrome: a consensus and data-driven methodology involving three international patient cohorts[J]. Arthritis Rheu-matol, 2017, 69(1):35-45.
[20]	中华医学会风湿病学分会. 2018中国类风湿关节炎诊疗指南[J]. 中华内科杂志, 2018, 57(4):242-251.
	Rheumatology branch of Chinese Medical Association. 2018 Chinese guideline for the diagnosis and treatment of rheumatoid arthritis[J]. Chin J Int Med, 2018, 57(4):242-251.
[21]	slam MA, Alam F, Kamal MA, et al. ‘Non-Criteria’ Neu-rologic Manifestations of Antiphospholipid Syndrome: A Hidden Kingdom to be Discovered[J]. CNS Neurol Disord Drug Targets, 2016, 15(10):1253-1265. doi: 10.2174/1871527315666160920122750 URL
[22]	Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients[J]. Arthritis Rheum, 2002, 46(4):1019-1027. doi: 10.1002/art.10187 URL
[23]	Fujieda Y, Atsumi T, Amengual O, et al. Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid syndrom[J]. Lupus, 2012, 21(14):1506-1514. doi: 10.1177/0961203312458469 pmid: 22936124
[24]	Kaushik S, Federle MP, Schur PH, et al. Abdominal thrombotic and ischemic manifestations of the antiphospholipid antibody syndrome: CT findings in 42 patients[J]. Radiology, 2001, 218(3):768-771. pmid: 11230653
[25]	Cacciapaglia F, Vadacca M, Coppolino G, et al. Spontaneous splenorenal shunt in a patient with antiphospholipid syndrome: the first case reported[J]. Lupus, 2007, 16(1):56-58. pmid: 17283587
[26]	Manner H, Jung B, Tonassi L, et al. Successful treatment of catastrophic antiphospholipid antibody syndrome (CAPS) associated with splenic marginal-zone lymphoma with low-molecular weight heparin, rituximab and bendamustine[J]. Am J Med Sci, 2008, 335(5):394-397. doi: 10.1097/MAJ.0b013e31815203ad pmid: 18480659
[27]	Vassilakopoulos TP, Pangalis GA, Siakantaris MP, et al. Kikuchi's lymphadenopathy: a relatively rare but important cause of lymphadenopathy in Greece, potentially associated with the antiphospholipid syndrome[J]. Rheumatol Int, 2010, 30(7):925-932. doi: 10.1007/s00296-009-1077-2 pmid: 19693507
[28]	Cikrikcioglu MA, Hursitoglu M, Erkal H, et al. Splenomegaly in primary antiphospholipid syndrome without accompanying portal hypertension or comorbidity[J]. Pathophysiol Haemost Thromb, 2010, 37(2-4):104-109. doi: 10.1159/000327506 URL
[29]	Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome[J]. N Engl J Med, 2009, 360(12):1226-1237. doi: 10.1056/NEJMra0804622 URL
[30]	烟雾病和烟雾综合征诊断与治疗中国专家共识编写组, 国家卫生计生委脑卒中防治专家委员会缺血性卒中外科专业委员会. 烟雾病和烟雾综合征诊断与治疗中国专家共识(2017)[J]. 中华神经外科杂志, 2017, 33(6):541-547.
	Chinese expert consensus compilation group for the diagnosis and treatment of moyamoya disease and moyamoya syndrome, national health and family planning commission stroke prevention and treatment expert committee ischemic stroke surgery professional committee. consensus of Chinese experts on the diagnosis and treatment of moyamoya disease and moyamoya syndrome(2017)[J]. Chin J Neurosurg, 2017, 33(6):541-547.
[31]	Sciascia S, Amigo MC, Roccatello D, et al. Diagnosing antiphospholipid syndrome: ‘extra-criteria’ manifestations and technical advances[J]. Nat Rev Rheumatol, 2017, 13(9):548-560. doi: 10.1038/nrrheum.2017.124 pmid: 28769114
[32]	刘畅, 赵金霞. 抗磷脂综合征相关血管病变的诊治进展[J]. 中华风湿病学杂志, 2021, 25(4):277-282.
	Liu C, Zhao JX. Progress in diagnosis and treatment of antiphospholipid syndrome related vascular diseases[J]. Chin J Rheumatol, 2021, 25(4):277-282.
[33]	赵久良, 李梦涛, 田新平, 等. 血栓性抗磷脂综合征的十个常见问题[J]. 中华内科杂志, 2020, 59(10):820-823.
[14]	Shi H, Yang CD. Interpretation of 2019 European League Against Rheumatism recommendations for the manage-ment of antiphospholipid syndrome in adults: definition of high-risk antiphospholipid antibodies pro-file and refinement of anticoagulation regimen[J]. Chin J Rheumatol, 2020, 24(2):73-78.
[33]	Zhao JL, Li ML, Tian XP, et al. Top 10 questions that rheumatologists should know about thrombotic antiphospholipid syndrome[J]. Chin J Int Med, 2020, 59(10):820-823.