Tardieu Marc, Brunelle Francis, Raybaud Charles, Ball William, Barret Béatrice, Pautard Brigitte, Lachassine Eric, Mayaux Marie-Jeanne, Blanche Stéphane
Department of Pediatric Neurology, Hôpital Bicêtre AP-HP, Le Kremlin Bicêtre.
AJNR Am J Neuroradiol. 2005 Apr;26(4):695-701.
Mitochondrial dysfunction has been reported in HIV-negative children perinatally exposed to zidovudine, a drug often used in HIV-seropositive mothers during pregnancy. The purpose of this study was to determine the incidence of cerebral MR imaging findings in HIV-uninfected children exposed to zidovudine who present with unexplained neurologic symptoms.
Two expert groups conducted a systematic, retrospective review of all cerebral MR images available in a multicentric, nationwide French prospective cohort of children born to HIV-seropositive mothers to identify imaging abnormalities. Experts were blinded to each others' interpretations, to the children's neurologic symptoms, and to laboratory evidence of mitochondrial dysfunction. The incidence of abnormalities was determined and compared with the neurologic presentation and laboratory evidence of mitochondrial dysfunction.
MR images from 49 HIV-uninfected children (mean age, 26 months) were available for study. All children were perinatally exposed to zidovudine. Twenty-two had probable or established mitochondrial dysfunction according to their symptoms and laboratory data. Twenty-seven children without mitochondrial dysfunction presented with unexplained neurologic symptoms (n = 14) or nonneurologic symptoms (n = 7), and six were asymptomatic. Sixteen of 22 MR images in children with mitochondriopathy were considered abnormal in both independent analyses. Diffuse hyperintensity in the supratentorial white matter (n = 9) and in the tegmentum pons (n = 9) were the most frequent anomalies. Imaging abnormalities were often multifocal (n = 10) and sometimes associated with necrotic areas (n = 3) and volume loss (n = 8). Although 19 of 27 MR images of children without mitochondrial dysfunction were mainly normal, abnormal images were observed in five of 14 children with unexplained neurologic symptoms and in three of six asymptomatic children.
Images observed in children with antiretroviral-induced mitochondrial dysfunction are similar to those observed in congenital mitochondrial diseases. These images were also observed in symptomatic or asymptomatic children without evidence of systemic mitochondrial dysfunction.
据报道，在围产期暴露于齐多夫定的HIV阴性儿童中存在线粒体功能障碍，齐多夫定是一种常用于HIV血清阳性母亲孕期的药物。本研究的目的是确定在出现不明原因神经症状的、暴露于齐多夫定的HIV未感染儿童中，脑部磁共振成像（MR）检查结果的发生率。
两个专家小组对法国一个多中心、全国性的前瞻性队列中所有可获得的脑部MR图像进行了系统的回顾性分析，该队列中的儿童均为HIV血清阳性母亲所生，以确定成像异常情况。专家们对彼此的解读、儿童的神经症状以及线粒体功能障碍的实验室证据均不知情。确定异常情况的发生率，并与神经症状表现及线粒体功能障碍的实验室证据进行比较。
有49名HIV未感染儿童（平均年龄26个月）的MR图像可供研究。所有儿童均在围产期暴露于齐多夫定。根据症状和实验室数据，22名儿童可能存在或已确诊线粒体功能障碍。27名无线粒体功能障碍的儿童出现了不明原因的神经症状（n = 14）或非神经症状（n = 7），6名儿童无症状。在两项独立分析中，22名患有线粒体病的儿童的MR图像中有16名被认为异常。幕上白质（n = 9）和脑桥被盖部（n = 9）的弥漫性高信号是最常见的异常。成像异常通常为多灶性（n = 10），有时伴有坏死区域（n = 3）和体积缩小（n = 8）。虽然27名无线粒体功能障碍儿童的MR图像中有19名主要为正常，但在14名有不明原因神经症状的儿童中有5名以及6名无症状儿童中有3名观察到了异常图像。
抗逆转录病毒药物引起线粒体功能障碍的儿童中观察到的图像与先天性线粒体疾病中观察到的图像相似。在有症状或无症状且无全身线粒体功能障碍证据的儿童中也观察到了这些图像。
