Prabhakaran Vasudevan, Drevets Douglas A, Ramajayam Govindan, Manoj Josephine J, Anderson Michael P, Hanas Jay S, Rajshekhar Vedantam, Oommen Anna, Carabin Hélène
Department of Neurological Sciences, Christian Medical College, Vellore, India.
Dept. of Internal Medicine, University of Oklahoma HSC, and the VA Medical Center, Oklahoma City, United States of America.
PLoS Negl Trop Dis. 2017 Jun 16;11(6):e0005664. doi: 10.1371/journal.pntd.0005664. eCollection 2017 Jun.
Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches.
METHODS/PRINCIPAL FINDINGS: Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications.
CONCLUSIONS/SIGNIFICANCE: Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to screen for and monitor NCC patients without brain imaging.
神经囊尾蚴病（NCC）是一种被忽视的热带病，给生活在印度等流行地区的人们带来了巨大的健康和经济负担。然而，在流行国家，利用脑部成像进行准确诊断的机会仍然很少，而且成本过高。本研究的目的是测试血液单核细胞基因表达是否能够区分患有NCC相关癫痫的患者与表现为特发性癫痫或特发性头痛且NCC阴性且无影像学病变的患者。
方法/主要发现：2013年1月至2014年10月期间，从印度韦洛尔基督教医学院医院神经科学系招募了年龄在18至51岁之间的患者。从76例NCC患者、10例康复的NCC（RNCC）患者、29例特发性癫痫患者和17例特发性头痛患者中分离出CD14 +血液单核细胞的mRNA。对6例NCC患者、6例特发性癫痫患者和4例特发性头痛患者进行了初步微阵列分析，以确定与其他组相比在NCC相关癫痫中差异表达的基因。该分析确定，与特发性癫痫患者相比，NCC患者中有1411个基因上调，733个基因下调。根据与NCC的可能相关性，选择了15个在NCC患者中相对于其他组上调的基因，并在所有患者样本中通过qPCR进行分析。使用线性回归模型评估患者之间的差异基因表达。对15个选定基因的qPCR分析显示，NCC患者中的基因表达通常较高，其次是RNCC、特发性头痛和特发性癫痫患者。在具有单个囊肿肉芽肿的NCC患者中，基因表达也通常较高，其次是混合病变和单个钙化患者。
结论/意义：血液单核细胞中某些基因的表达可以区分患有NCC相关癫痫的患者与患有活动性特发性癫痫和特发性头痛的患者。这些发现具有重要意义，因为它们可能会导致开发无需脑部成像即可筛查和监测NCC患者的新工具。
