Research Article: Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India

Date Published: June 16, 2017

Publisher: Public Library of Science

Author(s): Vasudevan Prabhakaran, Douglas A. Drevets, Govindan Ramajayam, Josephine J. Manoj, Michael P. Anderson, Jay S. Hanas, Vedantam Rajshekhar, Anna Oommen, Hélène Carabin, Fela Mendlovic.

Abstract: BackgroundNeurocysticercosis (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 findingsPatients 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/SignificanceExpression 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.

Partial Text: Neurocysticercosis (NCC) is a brain infection by Taenia solium larvae which is a common cause of acquired epilepsy. NCC may consist of single or multiple larvae (cysts) that progress from viable vesicular to colloidal and granuloma states and finally calcify. The time required for cysts to evolve and degenerate varies from a few months to several years. NCC is responsible for nearly half of all acquired epilepsies and about one third of active epilepsies in endemic areas [1–3]. This is particularly important since epilepsy affects from 5.8 to 15.4 people per 1,000 population worldwide with a preponderance in developing countries [4]. NCC causes the largest number of disability adjusted life years among foodborne diseases [5].

Analysis of host responses in peripheral blood is one possible avenue for developing new diagnostic tools [31]. Results presented here suggest that gene expression in peripheral blood monocytes can distinguish patients with NCC-related epilepsy from patients with Idiopathic Epilepsy and from subjects negative to standard antigen and antibody assays, with normal brain imaging, no seizures and presenting with headaches. Moreover, we found that expression of 15 selected target genes in carefully selected patients with different NCC-related brain lesions including SCG, SCC, and MNCC showed differences in the magnitude of gene expression between active and recovered infections. Such differences were also observed according to the type of lesion (granuloma, calcification, edema). In general, patients with NCC showed higher magnitude of expression than did patients with recovered NCC. In addition, gene expression among these target genes was reduced as lesions resolved, i.e. as seen by the granuloma to calcification progression. Our data add to the evidence that responses in blood monocytes may be used to investigate peripheral markers that differentiate patients with and without NCC-associated epilepsy [12].