Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.
Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.
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DOI：
10.1186/s12936-022-04163-0
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发表时间：
2022-06-21
期刊：
影响因子：
3
通讯作者：
Taylor, Terrie E.
中科院分区：
文献类型：
--
作者：
O'Brien, Nicole F.;Fonseca, Yudy;Johnson, Hunter C.;Postels, Douglas;Birbeck, Gretchen L.;Chimalizeni, Yamikani;Seydel, Karl B.;Gushu, Montfort Bernard;Phiri, Tusekile;June, Sylvester;Chetcuti, Karen;Vidal, Lorenna;Goyal, Manu S.;Taylor, Terrie E.
在撒哈拉以南非洲，脑疟疾导致大量儿童死亡和神经残疾。CM中典型的经颅多普勒超声（TCD）血流速度和波形的几种不同改变已被描述，但这些异常的机制因素尚不清楚。如果确定，有针对性的，tcd指导的CM辅助治疗可以改善预后。这是一项前瞻性观察性研究，研究对象是2018年1月至2021年6月在马拉维布兰太尔招募的6个月至12岁CM儿童。就诊时进行病史、体格检查、实验室分析、脑电图和磁共振成像。入院TCD结果根据先验定义确定表型分组。对血流动力学、代谢或颅内扰动导致其他疾病中观察到的这些表型之间的关系进行了评估。出院时的神经预后采用儿科脑功能分类（PCPC）评分进行评估。174名患者入组。TCD检查正常的7例（4%），符合充血标准的57例（33%），低血流标准的50例（29%），微血管阻塞标准的14例（8%），血管痉挛标准的11例（6%），孤立后循环高血流标准的35例（20%）。低血流组的心脏指数（CI）较低，全身血管阻力指数（SVRI）较高（p < 0.003），但这些值在年龄上是正常的（CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dcm -5m2）。其他参数在表型间差异不显著。总体而言，118名儿童（68%）有良好的神经预后。23例（13%）死亡，33例（19%）有神经功能障碍。充血和孤立性后路高血流的参与者的结果最好（分别为77%和89%的pcpc1 - 2）。低流量的参与者获得良好结果的可能性最小（42%的pcpc1 - 2） （p < 0.001）。预后良好的儿童（短暂充血反应比（THRR） 1.12[1.04,1.2]）的大脑自动调节能力明显优于预后较差的儿童（THRR 1.05 [0.98,1.02], p = 0.05）。在非疟疾疾病中导致TCD表型的常见病理生理机制在CM儿童中不是致病的。其他的机制因素，包括脑血管系统的机械因素和血管张力的生物活性调节因子，应该被探索。
Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1–2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1–2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.
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