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

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.

Distinguishing neurocysticercosis epilepsy from epilepsy of unknown etiology using a minimal serum mass profiling platform

“…Patients aged 18 to 51 years were recruited at the Department of Neurological Sciences, Christian Medical College (CMC) and Hospital, Vellore, India, as described elsewhere (Prabhakaran et al, 2017). The study was approved by the Institutional Review Boards of CMC and the University of Oklahoma HSC, USA.…”

“…Patients were tested for HIV, HBV and HCV only as clinically indicated. All patients were tested for antigens and antibodies for cysticercosis (Prabhakaran et al, 2017).…”

Neuroimmune interaction in seizures and epilepsy: focusing on monocyte infiltration

“…It is also possible that differences in the pathological mechanisms governing the various models of epileptogenesis could result in the observed discrepancies in monocyte-related activity. When blood monocytes from patients suffering from neurocysticercosis (NCC), a disease related to Taenia solium (T. solium) infection and a leading cause of epilepsy in the developing world, were compared to those derived from patients with idiopathic epilepsy via microarray analysis, it was revealed that NCC-related monocytes had higher association with inflammatory/immune pathways than idiopathic epilepsy patients [145]. It has also been suggested that NCC will induce inflammatory monocyte-astrocyte crosstalk [146].…”

Distinguishing patients with idiopathic epilepsy from solitary cysticercus granuloma epilepsy and biochemical phenotype assessment using a serum biomolecule profiling platform

“…In this regard, IPA analysis of differentially expressed proteins/peptides highlighted the importance of inflammation, neurological damage, blood brain barrier effects, cognition, cell death, behavior, and seizure-related pathway changes taking place in patients with SCG compared to patients with IE. Inflammatory and neurological responses have been previously documented in both NCC and SCG-related epilepsy as well as IE [1,12,50]. Finding proteins/ peptides that are known to be related to seizure phenotypes in patients with SCG and IE lends credence to the ability of the mass profiling platform and methodology described here to help decipher these pathologies.…”

“…Randomization of serum samples resulted in loss of discrimination between the groups, suggesting there exists a physiological basis for the observed patient group discriminatory results. Notably, the sensitivity test metric (true positive rate) of this LOOCV analysis exceeded that of serum EITB for SCG [13,50]. It is likely the positive results of these studies are due to the large number of different identifiers (mass peaks) applied by this approach, as opposed to more specific tests such as EITB and antigen ELISA [19,20,51].…”