To the Editor: Zika virus (ZIKV) is

To the Editor:

Zika virus (ZIKV) is a mosquito-borne flavivirus that is transmitted primarily by Aedes aegypti mosquitoes.1 Starting in May 2015, an outbreak of ZIKV infection has been reported in Brazil in association with an increasing number of neonates with congenital microcephaly in ZIKV-affected regions.1 In these areas, the prevalence of congenital microcephaly increased by a factor of 20 over the prevalence before the outbreak.1 ZIKV RNA has been identified in the brain of a fetus with congenital microcephaly.2 In addition, ZIKV RNA was identified in the amniotic fluid of two women whose fetuses had congenital microcephaly detected on prenatal ultrasonography.1 These events and observations prompted concern about the possible association between congenital microcephaly and the recent outbreak of ZIKV infection in Brazil.3 Only limited imaging data about the brain anomalies that may be associated with intrauterine ZIKV infection are available.
We report findings obtained by means of head computed tomography (CT) in 23 infants (13 female) with congenital microcephaly in which the clinical and epidemiologic data are compatible with congenital ZIKV infection in the Pernambuco state of Brazil. Head CTs were obtained for clinical reasons between September and December 2015. Samples of cerebrospinal fluid were available for serologic testing in 7 of the 23 infants, and results on enzyme-linked immunosorbent assay for ZIKV IgM antibody were positive in all 7 samples. Findings on serologic analysis regarding TORCH infection (toxoplasmosis, other [syphilis, varicella, parvovirus, and human immunodeficiency virus], rubella, cytomegalovirus, and herpes simplex) were negative in all 23 infants.
Head CT images were obtained at a mean age of 36 days after birth (range, 3 days to 5 months). Intracranial calcifications were seen in all the infants and mainly involved the frontal lobe (in 69 to 78% of the infants) and the parietal lobe (in 83 to 87%) (Figure 1FIGURE 1
Computed Tomography in Eight Infants with Congenital Microcephaly.
). The calcifications were located mainly at the corticomedullary junction (in 53 to 86%). The configuration of the calcifications was mostly punctate (in 72 to 100%), with a predominately bandlike distribution (in 56 to 75%). The calcifications were seen in the basal ganglia (in 57 to 65%) and in the thalamus (in 39 to 43%). Ventriculomegaly was found in all the infants and was rated as severe in the majority (53%) and involving only the lateral ventricles in 43%. All the infants had global hypogyration of the cerebral cortex that was severe (only the Sylvian fissure was obviously present) in 78% of the infants. Cerebellar hypoplasia was present in 17 of the infants (74%) and involved only one cerebellar hemisphere in 3 infants. In 2 infants, the brain stem was globally hypoplastic. In all the infants, there was abnormal hypodensity of the white matter, and in 87% of the patients it diffusely involved all the cerebral lobes. In 1 infant, chronic encephalomalacic changes from ischemic stroke in the vascular territory of the left middle cerebral artery were seen.
Intrauterine ZIKV infection appears to be associated with severe brain anomalies, including calcifications, cortical hypogyration, ventriculomegaly, and white-matter abnormalities, although we cannot determine with certainty when ZIKV infection may have occurred during fetal development in these 23 infants. Our findings are nonspecific and may be seen in other congenital viral infections. The global presence of cortical hypogyration and white-matter hypomyelination or dysmyelination in all the infants and cerebellar hypoplasia in the majority of them suggest that ZIKV is associated with a disruption in brain development rather than destruction of brain. The neuronal and glial proliferation as well as neuronal migration appear to be affected. The mothers of the microcephalic infants in our study population had symptoms
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(e.g., low-grade fever and cutaneous rash) that were compatible with ZIKV infection during the first or second trimester of pregnancy, similar to the findings in other studies.4 Tang et al. found that ZIKV directly infects human cortical neural progenitor cells with high efficiency, resulting in stunted growth of this cell population and transcriptional dysregulation.5 This observation supports the type of disruptive, anomalous brain development that we found in these infants.

Results (English) 3:

给编辑：齐卡病毒（ZIKV）是一种由蚊子传播的黄病毒，主要由埃及伊蚊传播。1个月开始的2015，ZIKV感染暴发的报告已在巴西有越来越多的新生儿先天性畸形在ZIKV影响地区的协会。1在这些地区，先天性小头畸形的患病率增加20的一个因素在爆发流行。1 ZIKV RNA已经在一个先天性小头畸形胎儿的大脑识别。2此外，ZIKV RNA是在两个女性的胎儿产前超声检查发现先天性小头畸形，羊水鉴定。1这些事件和观察结果提示可能的协会之间的关系先天性小头畸形和巴西最近爆发ZIKV感染。3只有有限的影像资料，可能与宫内感染有关的大脑异常ZIKV可用。我们报告的结果获得通过头部计算机断层扫描（CT）23例（13女）先天性小头畸形的临床和流行病学数据与在巴西的伯南布哥州先天ZIKV感染兼容。九月和十二月之间获得了2015的临床原因是头CTS。脑脊液样本中7的23例可用于血清学检测和酶联免疫吸附试验ZIKV IgM抗体阳性7例。关于TORCH感染的血清学分析结果（弓形体病、其他[梅毒、水痘、细小病毒、人类免疫缺陷病毒]，风疹，巨细胞病毒，单纯疱疹）均阴性23例。在出生后的平均年龄为36天（范围3天5个月），获得了头部的影像。颅内钙化在所有婴儿和主要涉及额叶（在69到78%的婴儿）和顶叶（83到87%）（图1CT对八例先天性小头畸形。）。钙化主要位于皮髓质交界处（53至86%）。的配置主要是点状钙化（72至100%），与主要的带状分布（56到75%）。钙化在基底神经节（57到65%）出现在丘脑（39到43%）。脑室扩大在所有的婴儿中发现，在大多数评为严重（53%），仅涉及43%侧脑室。所有的婴儿有大脑皮层，是严重的全球hypogyration（只有外侧裂明显存在）在78%的婴儿。小脑发育不全为17的婴儿（74%），涉及3个婴儿只有一个小脑半球。2例，脑干是全局性。在所有的婴儿，有白质异常的低，而在这弥漫性累及所有脑叶87%例。1婴儿，慢性encephalomalacic变化在左大脑中动脉血管缺血性中风了。宫内ZIKV感染似乎是严重的脑异常，包括相关的钙化，皮质hypogyration，脑室扩大，白质异常，虽然我们不能确定当ZIKV感染可能在胎儿发育期间发生的这23个婴儿。我们的研究结果是非特异性的，可以看到在其他先天性病毒感染。皮质hypogyration和白质髓鞘或髓鞘形成障碍在所有的婴儿，他们中的大多数小脑发育不全的全球性的存在表明ZIKV与破坏大脑的发展而不是破坏大脑相关。神经元和神经胶质细胞的增殖以及神经元的迁移似乎受到影响。在我们的研究人群的小头儿母亲的症状11:50:22（例如，低热、皮疹），与ZIKV感染兼容的第一或第二妊娠期间，在其他的研究结果相似。4唐等人。发现ZIKV直接感染人类大脑皮质神经祖细胞具有很高的效率，导致发育不良这一细胞群和转录失调。5这个观察支持性的类型，异常的大脑发育，我们发现这些婴儿。