Antiphospholipid syndrome, migraine and stroke
Antiphospholipid syndrome, migraine and stroke
复制标题
抗磷脂综合征、偏头痛和中风
作者：
G. Hughes
自从抗磷脂（休斯）综合征（APS）被描述以来，已经有四分之一个多世纪了。这种促血栓形成疾病的特征是存在抗磷脂抗体（aPL），导致血栓形成的趋势增加，在怀孕期间，导致复发性流产和其他产科并发症。引人注目的是，APS可以影响静脉和动脉，后者导致例如心肌梗死和中风。大脑似乎特别容易受到该综合征的影响，伴随着血栓形成和缺血，神经系统表现从记忆丧失到运动障碍，从非典型多发性硬化到癫痫。此外，aPL的某些临床相关性可能直到最近才被认识到。例如，1985年首次认识到的与癫痫发作（包括颞叶癫痫）的相关性可能是实质性的--例如，最近的一份报告表明20%的特发性青少年癫痫病例与aPL有关。然而，休斯综合征的两个最重要的临床神经学表现是偏头痛和中风。偏头痛，在其所有形式，可以说是最常见的临床表现的综合征。许多休斯综合征患者在40岁时出现血栓形成、短暂性脑缺血发作（TIA）或中风，他们有严重头痛史，通常是偏头痛，可追溯到童年。有趣的是，偏头痛往往有家族史，现在有许多包括偏头痛，APS和中风的大型家族队列报道。量化休斯综合征（和狼疮）头痛和偏头痛患病率的尝试受到众所周知的分类困难的限制。这是双重重要的，因为在狼疮和抗磷脂抗体患者中与认知障碍的联系需要澄清。例如，在最近的一项关于狼疮认知障碍及其与头痛关系的研究中，怀特洛和斯潘根贝格得出结论，. .只有APS（Hughes）综合征被证明会导致狼疮患者认知功能受损。头痛的原因还不确定。然而，最引人注目的临床观察结果之一是，当开始用肝素或华法林抗凝治疗时，头痛通常完全消失，比如，外周血栓形成，或者在妊娠期用肝素预防。这一观察结果导致在某些APS病例中使用2-3周的低分子量肝素治疗试验，其中头痛越来越严重。中风是目前国际公认的休斯综合征的一个重要表现-严重程度从小TIA到灾难性的致命性脑梗死。休斯综合征对中风这个巨大的医学、社会和经济问题的相对贡献是什么？公布的数据各不相同，从所有中风的7%到美国一项主要的中风合作研究的41%不等。然而，后一项研究因一些缺点而受到批评，包括依赖单一的aPL评估。罗马的一项重要研究发现，在年轻人群（45岁以下）中，五分之一的中风与aPL有关。如果这样的估计是正确的（尽管aPL测试标准化存在缺陷，但临床经验表明它们是正确的），那么我们有一大群人，通过简单的血液测试，就可以确定他们有中风的风险，并且可以对他们进行预防性抗聚集剂或抗凝治疗。此外，更好地认识到即使接受华法林抗凝治疗，APS患者发生血栓形成的风险也高于出血，这将导致更适当的治疗。抗磷脂综合征的发现为医学和流行病学的研究开辟了新的途径。联系人：Graham Hughes，负责人，伦敦狼疮中心，伦敦桥医院，伦敦SE 1 2 PR，英国。电子邮件地址：hcaconsultant.co.uk @ graham.hughes
It is over a quarter of a century since the description of the antiphospholipid (Hughes) syndrome (APS). This pro-thrombotic condition, characterized by the presence of antiphospholipid antibodies (aPL), results in an increased tendency to thrombosis and, in pregnancy, to recurrent miscarriage and other obstetric complications. Strikingly, APS can affect both veins and arteries, the latter leading, for example, to myocardial infarction and stroke. The brain appears to be particularly susceptible to the syndrome, with its attendant thrombosis and ischaemia, the neurological presentations ranging frommemory loss to movement disorders, from atypical multiple sclerosis to epilepsy. Additionally, some of these clinical associates of aPL may well have been under-recognizeduntil recently.Forexample, theassociationwith seizures (including temporal lobe epilepsy) first recognized in 1985, may well be substantial – a recent report suggesting that20%ofcasesof idiopathic teenage epilepsy were linked to aPL, for example. However, the two most important clinical neurological manifestations of Hughes syndrome are migraine and stroke. Migraine, in all its forms, is arguably the commonest clinical manifestation of the syndrome. Many Hughes syndrome patients presenting with thrombosis, transient ischaemic attacks (TIAs) or stroke at, say, the age of 40, give a history of severe headaches, often migrainous, dating back to childhood. Interestingly, there is often a family history of migraine, and a number of large family cohorts embracing migraine, APS and stroke are now being reported. Attempts at quantifying the prevalence of headache and migraine in Hughes syndrome (and in lupus) are limited by the well known difficulties in classification. This is doubly important as the links with cognitive impairment, in both lupus and in patients with antiphospholipid antibodies need clarification. For example, in a recent study of cognitive impairment in lupus, and its relationship to headache, Whitelaw and Spangenberg concluded that . . . ‘it is only APS (Hughes) syndrome which has been documented to produce impaired cognitive function in lupus’. The cause of the headache is uncertain. However, one of the most striking clinical observations is the often complete disappearance of the headaches when anticoagulation with heparin or warfarin is started, say, for a peripheral thrombosis, or with heparin prophylaxis in pregnancy. This observation has led to the use of a 2–3-week therapeutic trial of low-molecular-weight heparin in some cases of APS in which increasingly severe headaches are a feature. Stroke is now internationally recognized as an important manifestation of Hughes syndrome – the severity ranging from small TIAs to catastrophic fatal cerebral infarction. What is the relative contribution of Hughes syndrome to the huge medical social and economic problem of stroke? Published figures vary, ranging from 7% of all strokes to 41% in a major collaborative American stroke study. The latter study has, however, been criticised for a number of shortcomings, including the reliance on single aPL assessments. An important study from Rome found that in a younger population (under 45) a striking one in five of all strokes were associated with aPL. If such estimates are correct (and despite flaws in the standardization of aPL testing, clinical experience suggests that they are), then here we have a large group of individuals who, with a simple blood test, could be identified as being at risk of stroke and in whom preventative anti-aggregant or anticoagulant treatment could be instituted. Furthermore, a greater awareness of the fact that even on warfarin anticoagulation, patients with APS are at greater risk of thrombosis than from bleeding, would lead to more appropriate treatment. The discovery of the antiphospholipid syndrome has opened up new avenues for research in medicine and in epidemiology. Correspondence to: Graham Hughes, Head, The London Lupus Centre, London Bridge Hospital, London SE1 2PR, UK. Email: graham.hughes@hcaconsultant.co.uk