V. Prabhakaran

Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India.

Objective: To determine the contribution of neurocysticercosis (NCC) to the causation of active epilepsy (AE) in a south Indian community. Methods: We conducted a door-to-door survey of 50,617 people between the ages of 2 and 60 years in a rural (38,105 people) and urban setting (12,512 people) in the Vellore district of the south Indian state of Tamil Nadu to identify patients with AE. Patients with AE were investigated with a contrast-enhanced CT scan and serologic study using enzyme-linked immunotransfer blot (EITB) for cysticercal antibodies. Results: We identified 194 patients with AE. The prevalence of AE was 3.83 per 1,000 people, with the prevalence in the urban clusters more than twice that in the rural clusters (6.23 vs 3.04 per 1,000) (p < 0.0001). A diagnosis of NCC was made in 46 (28.4%) of the 162 patients undergoing a CT scan, and EITB was positive in 21 (13%) patients. Overall, 55 (34%) patients were diagnosed with NCC (11 definitive NCC and 44 probable NCC). There was no significant difference in the prevalence of NCC causing AE in the urban (1.28 per 1,000) and rural (1.02 per 1,000) communities. Conclusions: NCC is the cause of nearly one-third of all cases of AE in both the urban and rural regions. Extrapolating our results to the country as a whole leads to an estimated disease burden of 1 million patients in India with AE attributable to NCC.

Long-term clinical evaluation of asymptomatic subjects positive for circulating Taenia solium antigens

Although presence of cysticercal antigens in serum is presumed to indicate active cysticercosis not all positive persons are symptomatic. The significance of a positive antigen test in asymptomatic individuals, in predicting development of symptomatic cysticercosis on long-term follow up, is unknown. Forty two of 48 persons from Vellore district, India who were positive for circulating serum cysticercal antigens were followed up for four to five years. None of them developed clinical evidence of neurocysticercosis or subcutaneous cysts. We conclude that asymptomatic individuals with circulating cysticercal antigens have a low risk of developing symptomatic cysticercosis within four to five years.

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

Background 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.

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

Neurocysticercosis is associated with epilepsy in pig-raising communities with poor sanitation. Current internationally recognized diagnostic guidelines for neurocysticercosis rely on brain imaging, a technology that is frequently not available or not accessible in areas endemic for neurocysticercosis. Minimally invasive and low-cost aids for diagnosing neurocysticercosis epilepsy could improve treatment of neurocysticercosis. The goal of this study was to test the extent to which patients with neurocysticercosis epilepsy, epilepsy of unknown etiology, idiopathic headaches and among different types of neurocysticercosis lesions could be distinguished from each other based on serum mass profiling. For this, we collected sera from patients with neurocysticercosis-associated epilepsy, epilepsy of unknown etiology, recovered neurocysticercosis, and idiopathic headaches then performed binary group comparisons among them using electrospray ionization mass spectrometry. A leave one [serum sample] out cross validation procedure was employed to analyze spectral data. Sera from neurocysticercosis patients was distinguished from epilepsy of unknown etiology patients with a p-value of 10-28. This distinction was lost when samples were randomized to either group (p-value = 0.22). Similarly, binary comparisons of patients with neurocysticercosis who has different types of lesions showed that different forms of this disease were also distinguishable from one another. These results suggest neurocysticercosis epilepsy can be distinguished from epilepsy of unknown etiology based on biomolecular differences in sera detected by mass profiling.

N-glycans govern the innate immune response in neurocysticercosis

In the terrestrial slug Limax, NO is necessary for the synchronous oscillation of the local field potential in the procerebrum, which is thought to be involved in the odor discrimination and/or odor aversion learning. But there is no description about the genomic structure of the molluscan NO synthase, nor has the evolutionary origin of neuronal NO synthase (NOS) of mammals been clarified. Here we identified two types of NOS mRNAs of the slug, which show differential expression patterns within the brain. One is expressed broadly in the brain but in the low level (limNOS1), whereas, interestingly, the other is almost exclusively in the procerebrum (limNOS2). We also determined the whole genomic structure for limNOS1. It is composed of as many as 32 exons comparable to human nNOS gene, and has very similar exon–intron structure to that of human nNOS. Our results indicated that Limax NOS and human nNOS share the prototypical gene structure of NOS, and that their organization is highly conserved during the evolutionary history.