Pediatric Nephrology and Dialysis Unit, Pediatric Hospital "Giovanni XXIII", Bari, Italy.
Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Pediatr Nephrol. 2019 Mar;34(3):517-527. doi: 10.1007/s00467-018-4112-2. Epub 2018 Oct 25.
Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC).
TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab.
The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI).
A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.
血栓性微血管病（TMA）是一种临床综合征，涵盖了一大组罕见但严重的疾病，包括血栓性血小板减少性紫癜（TTP）以及典型和非典型溶血尿毒综合征（HUS）。补体系统在 TTP 和非典型 HUS 中的关键作用是众所周知的，但最近的报告描述了它在由产志贺毒素大肠杆菌（STEC）引起的胃肠道感染继发的 HUS 发病机制中的作用。
TMA 主要影响肾脏，但经常描述其肾脏外并发症。中枢神经系统（CNS）的受累通常是一种危及生命的情况，它可能导致 HUS 患者在克服疾病急性期后出现严重的长期残疾。在本研究中，我们回顾性分析了意大利南部一家三级儿科医院的儿科队列，其中 12/54 名儿童（22%的病例）发生了这种并发症，其中 5 名严重神经受累的患者已成功接受依库珠单抗治疗。
我们队列中脑损伤的巨大临床变异性促使我们回顾性构建了一个“神经评分”，用于评估神经受累的临床严重程度。由于最严重的 CNS 受累而导致更高神经评分的患者，在早期接受依库珠单抗治疗的患者中，获得了良好的临床反应（5 名患者中有 4 名）。总之，在 STEC-HUS 中严重神经受累的儿童中早期使用依库珠单抗治疗与磁共振成像（MRI）观察到的急性肾损伤（AKI）和神经病变的完全消退相关。
“神经评分”可能是一种有用的工具，可用于指导早期使用依库珠单抗治疗 STEC-HUS 中的 CNS 并发症，尽管迫切需要未来的前瞻性对照研究来验证这种治疗方法。
