Saliba E, Debillon T, Auvin S, Baud O, Biran V, Chabernaud J-L, Chabrier S, Cneude F, Cordier A-G, Darmency-Stamboul V, Diependaele J-F, Debillon T, Dinomais M, Durand C, Ego A, Favrais G, Gruel Y, Hertz-Pannier L, Husson B, Marret S, N'Guyen The Tich S, Perez T, Saliba E, Valentin J-B, Vuillerot C
Service de réanimation néonatale et pédiatrique, hôpital Clocheville, CHU de Tours, 49, boulevard Béranger, 37000 Tours, France; Inserm U930, université François-Rabelais de Tours, bâtiment Vialle, 10, boulevard Tonnellé, 37032 Tours, France.
Clinique universitaire de médecine et réanimation néonatale, CHU de Grenoble, BP 217, 38043 Grenoble, France.
Arch Pediatr. 2017 Feb;24(2):180-188. doi: 10.1016/j.arcped.2016.11.005. Epub 2016 Dec 20.
Neonatal arterial ischemic stroke (NAIS) is a rare event that occurs in approximately one in 5000 term or close-to-term infants. Most affected infants will present with seizures. Although a well-recognized clinical entity, many questions remain regarding diagnosis, risk factors, treatment, and follow-up modalities. In the absence of a known pathophysiological mechanism and lack of evidence-based guidelines, only supportive care is currently provided. To address these issues, a French national committee set up by the French Neonatal Society (Société française de néonatologie) and the national referral center (Centre national de référence) for arterial ischemic stroke in children drew up guidelines based on an HAS (Haute Autorité de santé [HAS]; French national authority for health) methodology. The main findings and recommendations established by the study group are: (1) among the risk factors, male sex, primiparity, caesarean section, perinatal hypoxia, and fetal/neonatal infection (mainly bacterial meningitis) seem to be the most frequent. As for guidelines, the study group recommends the following: (1) the transfer of neonates with suspected NAIS to a neonatal intensive care unit with available equipment to establish a reliable diagnosis with MRI imaging and neurophysiological monitoring, preferably by continuous video EEG; (2) acute treatment of suspected infection or other life-threatening processes should be addressed immediately by the primary medical team. Persistent seizures should be treated with a loading dose of phenobarbital 20mg/kg i.v.; (3) MRI of the brain is considered optimal for the diagnosis of NAIS. Diffusion-weighted imaging with apparent diffusion coefficient is considered the most sensitive measure for identifying infarct in the neonatal brain. The location and extent of the lesions are best assessed between 2 and 4 days after the onset of stroke; (4) routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocysteinemia, the Lp(a) test, the MTHFR thermolabile variant should not be considered in neonates with NAIS. Testing for FV Leiden can be performed only in case of a documented family history of venous thromboembolic disease. Testing neonates for the presence of antiphospholipid antibodies should be considered only in case of clinical events arguing in favor of antiphospholipid syndrome in the mother; (5) unlike childhood arterial ischemic stroke, NAIS has a low 5-year recurrence rate (approximately 1 %), except in those children with congenital heart disease or multiple genetic thrombophilia. Therefore, initiation of anticoagulation or antithrombotic agents, including heparin products, is not recommended in the newborn without identifiable risk factors; (6) the study group recommends that in case of delayed motor milestones or early handedness, multidisciplinary rehabilitation is recommended as early as possible. Newborns should have physical therapy evaluation and ongoing outpatient follow-up. Given the risk of later-onset cognitive, language, and behavioral disabilities, neuropsychological testing in preschool and at school age is highly recommended.
新生儿动脉缺血性卒中(NAIS)是一种罕见事件,约每5000名足月儿或近足月儿中会有1例发生。大多数受影响的婴儿会出现癫痫发作。尽管这是一个已被充分认识的临床病症,但在诊断、危险因素、治疗及随访方式方面仍存在许多问题。由于缺乏已知的病理生理机制且没有循证指南,目前仅提供支持性治疗。为解决这些问题,由法国新生儿学会(Société française de néonatologie)和法国儿童动脉缺血性卒中国家转诊中心(Centre national de référence)设立的一个法国全国委员会,依据法国国家卫生管理局(Haute Autorité de santé [HAS])的方法制定了指南。研究组确定的主要发现和建议如下:(1)在危险因素中,男性、初产、剖宫产、围产期缺氧以及胎儿/新生儿感染(主要是细菌性脑膜炎)似乎最为常见。至于指南,研究组建议如下:(1)将疑似NAIS的新生儿转运至配备有可用设备的新生儿重症监护病房,以便通过MRI成像和神经生理监测(最好是连续视频脑电图)来确立可靠的诊断;(2)疑似感染或其他危及生命的病症应由初级医疗团队立即进行急性治疗。持续性癫痫发作应静脉注射20mg/kg负荷剂量的苯巴比妥进行治疗;(3)脑部MRI被认为是诊断NAIS的最佳方法。具有表观扩散系数的弥散加权成像被认为是识别新生儿脑梗死最敏感的方法。病变的位置和范围最好在卒中发作后2至4天进行评估;(4)对于患有NAIS的新生儿,不应常规检测血栓形成倾向(抗凝血酶、蛋白C、蛋白S缺乏、凝血因子V莱顿突变或凝血因子II 20210A)或检测其他生物学危险因素,如抗磷脂抗体、高凝血因子VIII、高同型半胱氨酸血症、脂蛋白(a)检测、亚甲基四氢叶酸还原酶不耐热变异体。仅在有静脉血栓栓塞性疾病家族史记录的情况下,才可进行凝血因子V莱顿突变检测。仅在有临床事件支持母亲患有抗磷脂综合征的情况下,才应考虑检测新生儿是否存在抗磷脂抗体;(5)与儿童动脉缺血性卒中不同,NAIS的5年复发率较低(约1%),患有先天性心脏病或多种遗传性血栓形成倾向的儿童除外。因此,对于无明确危险因素的新生儿,不建议启动抗凝或抗血栓药物治疗,包括肝素类产品;(6)研究组建议,若出现运动发育迟缓或早期用手偏好,建议尽早进行多学科康复治疗。新生儿应接受物理治疗评估并进行持续的门诊随访。鉴于后期出现认知、语言和行为障碍的风险,强烈建议在学龄前和学龄期进行神经心理测试。