Department of Neurovirology, National Institute of Mental Health & Neurosciences, Bangalore, India.
Department of Clinical Infection, Microbiology & Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
J Med Virol. 2024 May;96(5):e29666. doi: 10.1002/jmv.29666.
Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.
儿童急性脑炎综合征 (AES) 在印度构成重大公共卫生挑战。本研究旨在探索宿主炎症介质和神经丝 (NfL) 水平在鉴别病因、评估疾病严重程度和预测 AES 结局方面的作用。我们评估了来自印度南部 62 名患有恙虫病、病毒性病因和 COVID 相关多系统炎症综合征 (MIS-C) 的 AES 儿童的血清 (n=58) 中的 12 种介质和脑脊液 (CSF) (n=42) 中的 11 种介质。此外，还检测了血清 (n=20) 和 CSF (n=18) 中的 NfL 水平。记录了临床数据，包括格拉斯哥昏迷量表 (GCS) 和利物浦结局评分。在三组 AES 病因组中检查血清和 CSF 标志物发现了显著差异，恙虫病与病毒性和 MIS-C 病因有明显不同。与恙虫病相比，病毒性病因血清 CCL11 和 CCL2 升高，而 MIS-C 病例 HGF 水平高于恙虫病。然而，CSF 分析显示出不同的模式，恙虫病组的 IL-1RA、IL-1β 和 TNF 水平高于 MIS-C，而 CCL2 水平低于病毒性组。通过对特征进行建模，我们发现年龄≥3 岁且血清 CCL11<180pg/mL 可有效区分恙虫病与其他 AES 病因。血清 CCL11、HGF 和 IL-6:IL-10 比值升高与不良结局相关(p=0.038、0.005、0.02)。观察到 CSF 和血清 NfL 的正相关，以及 GCS 和血清 NfL 的负相关。入院时 GCS 异常和结局不良的儿童 NfL 中位数水平较高。在 AES 中测量免疫介质和脑损伤标志物提供了有价值的诊断见解，具有促进快速诊断和预后的潜力。CSF 和血清 NfL 之间的相关性以及不同病因之间独特的血清细胞因子谱表明，仅使用血液样本进行评估和监测是足够的。CCL11、HGF 水平升高和 IL-6:IL-10 比值升高与不良结局相关表明有希望的治疗探索途径，值得进一步研究。
