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A neglected population in the study of children with HIV infection and stroke
Developmental Medicine & Child Neurology ( IF 3.8 ) Pub Date : 2020-01-23 , DOI: 10.1111/dmcn.14474
Laura A Benjamin 1, 2
Affiliation  

Over the last two decades, human immunodeficiency virus (HIV) infection has been transformed from a short-lived fatal disease to a well-treated disorder, associated with a longer life expectancy. The burden of cardiovascular disease among people living with HIV infection has tripled over this period of time. The underlying aetiology of stroke among people living with HIV infection is heterogeneous and varies by the stage of HIV infection. Antiretroviral therapy to some degree, HIV-driven immune dysregulation, endothelial dysfunction, and metabolic derangement are all implicated in the mechanism but the major drivers still elude us. The prohibitive costs of using advanced imaging in regions where HIV is endemic has limited our understanding and progress in this field. Dlamini et al. used a low-cost, non-invasive imaging technique (transcranial Doppler [TCD]) to investigate evidence of intracranial vasculopathy in children who had HIV infection with or without a stroke. They compared this to a historical global control group who were similar in age. This study was conducted in Cape Town, South Africa where the HIV prevalence is approximately 13%. They excluded those with HIV encephalopathy, tuberculosis meningitis, and other neurological disorders. Stroke was defined using the World Health Organization clinical definition, and brain imaging was used as confirmation in most cases. The cohort included five and 37 HIV-positive children with and without a stroke respectively. Their corresponding mean age was 7 years 3 months and 7 years 10 months. The sex distribution in the none-stroke group was well balanced but males were higher (4:1) in the stroke group. The authors used the Adam’s criteria to diagnose an abnormal TCD velocity with time-averaged maximum mean velocities (TAMMVs), a proxy for intracranial stenosis. How abnormal and non-normal were defined was less clear. The key findings were that: (1) TAMMV was higher in the stroke group than in the non-stroke group. (2) TAMMV in HIV were commonly outside the range for typically developing children. Notably, 6 out of 37 asymptomatic children with HIV had evidence of vasculopathy. (3) CD4 cell count was non-significantly lower in children with HIV and non-normal TCD, and a trend for non-normal TCD was more common in children with untreated HIV. This supports the consensus that HIV treatment and the accompanying immune restoration reduces overall stroke risk. However, the risk may not be completely aborted. Unfortunately, the numbers are too small to investigate this important issue. (4) Exposure to stroke risk factors such as hypertension, cardiac disease, and varicella zoster was described. All of which can be interlinked with HIV infection or occur independently, and could contribute to an additive or synergistic stroke risk. Limitations to the study include: (1) a small sample size, which limits definitive conclusions. (2) The absence of screening for varicella zoster virus reactivation which is common in HIV infection and could offer an alternative explanation for the reported intracranial vasculopathy. (3) The possibility of a high insonation failure rate in this population. Despite these limitations, the authors have excelled in bringing together a technically challenging study and have demonstrated the utility of TCD in this setting. The results are consistent with observations found in adults. HIV-positive children (who are mostly infected through vertical transmission) offer a unique opportunity to understand the natural history of HIV infection and stroke, without the distraction of confounders which accompanies the ageing process found in adults. A more concerted effort is warranted so that better treatment interventions can be offered.

中文翻译:

艾滋病毒感染和中风儿童研究中被忽视的人群

在过去的二十年里,人类免疫缺陷病毒 (HIV) 感染已经从一种短暂的致命疾病转变为一种治疗良好的疾病,与更长的预期寿命相关。在这段时间内,艾滋病毒感染者的心血管疾病负担增加了两倍。HIV 感染者中风的潜在病因是异质的,并且因 HIV 感染的阶段而异。在某种程度上,抗逆转录病毒疗法、HIV 驱动的免疫失调、内皮功能障碍和代谢紊乱都与该机制有关,但主要的驱动因素仍然不为人知。在 HIV 流行地区使用先进成像的高昂成本限制了我们在该领域的理解和进展。德拉米尼等人。使用低成本,非侵入性成像技术(经颅多普勒 [TCD])来调查患有或不患有中风的 HIV 感染儿童颅内血管病变的证据。他们将其与历史上年龄相似的全球对照组进行了比较。这项研究是在南非开普敦进行的,那里的艾滋病毒流行率约为 13%。他们排除了 HIV 脑病、结核性脑膜炎和其他神经系统疾病的患者。中风是使用世界卫生组织的临床定义来定义的,并且在大多数情况下使用脑成像作为确认。该队列分别包括 5 名和 37 名患有中风和未中风的 HIV 阳性儿童。他们对应的平均年龄分别为7岁3个月和7岁10个月。非卒中组的性别分布均衡,但男性更高(4:1)中风组。作者使用 Adam 标准来诊断异常 TCD 速度和时间平均最大平均速度 (TAMMV),这是颅内狭窄的代表。异常和非正常的定义不太清楚。主要发现是:(1)卒中组的TAMMV高于非卒中组。(2) HIV 中的 TAMMV 通常超出正常发育儿童的范围。值得注意的是,37 名无症状感染 HIV 的儿童中有 6 名有血管病变的证据。(3) HIV 感染者和非正常 TCD 儿童的 CD4 细胞计数不显着降低,非正常 TCD 的趋势在未经治疗的 HIV 儿童中更为常见。这支持了 HIV 治疗和伴随的免疫恢复降低整体中风风险的共识。然而,风险可能不会完全中止。很遗憾,数量太少,无法调查这个重要问题。(4) 描述了暴露于高血压、心脏病和水痘带状疱疹等卒中危险因素。所有这些都可能与 HIV 感染相关或独立发生,并可能导致附加或协同的中风风险。该研究的局限性包括:(1)样本量小,这限制了明确的结论。(2) 没有对 HIV 感染中常见的水痘带状疱疹病毒再激活进行筛查,这可以为报告的颅内血管病变提供另一种解释。(3) 该人群中声波失败率高的可能性。尽管有这些限制,作者还是擅长将一项技术上具有挑战性的研究结合起来,并证明了 TCD 在这种情况下的效用。结果与在成人中发现的观察结果一致。HIV 阳性儿童(主要通过垂直传播感染)提供了一个独特的机会来了解 HIV 感染和中风的自然史,而不会分散伴随成年人衰老过程的混杂因素。需要更加协调一致的努力,以便提供更好的治疗干预措施。
更新日期:2020-01-23
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