Hippocampal sclerosis: the missing link of cysticercosis epileptogenesis?

Abstract

A closed workshop was held in Atahualpa, Ecuador, with support from Universidad Espiritu Santo—Ecuador. Aims of the workshop were to gain more insights on the suggested association between neurocysticercosis (NCC), epilepsy, and hippocampal sclerosis (HS), and to design a study that will help to better characterize this association, namely, is there a causal relationship between NCC and HS, and, if so, is this association linked to chronic unprovoked seizures? Investigators have long been concerned with the lack of correlation between location of parenchymal brain cysticerci, seizure semiology, and electroencephalography (EEG) findings in a sizable proportion of patients with epilepsy and NCC. In addition, many patients with parenchymal brain cysts or calcifications have never had seizures. This led some authors to suggest that both epilepsy and NCC might merely occur by chance in areas where this parasitic disease is endemic. Although this is theoretically possible, there is some evidence suggesting a causal relationship between NCC and seizures, including the higher prevalence of epilepsy in cysticercotic-endemic areas when compared with nonendemic regions and the occurrence of inflammatory changes surrounding calcified cysticerci immediately after a seizure in about 50% cases.1 Information from surgical series of patients with medically refractory epilepsy and NCC suggest that chronic seizures often come from an associated ipsilateral HS and not from the calcified parasite. In many of such patients, seizure freedom was achieved by resection of the affected hippocampus alone,2, 3 although some authors have reported that resection of both the hippocampus and the calcified cysticercus was associated with a better outcome.4 In the presence of HS, however, it is unclear whether resection of the cyst alone is sufficient to eliminate seizures. It is plausible that recurrent reactive seizures (or status epilepticus) from repeated inflammation of the parasite induce HS, which then becomes responsible for the chronic epileptic disorder. Cysticerci are not necessarily located within limbic circuits, requiring a remote deleterious effect of reactive seizures on hippocampal neurons.5 Alternatively, calcified cysticerci could lead to inflammation-mediated hippocampal damage without causing seizures.6 In this case, periodic exposure of trapped parasitic antigens to the host's immune system might account for recurrent inflammatory events that trigger HS. Experimental evidence showing that repeated endotoxin exposure correlate with hippocampal damage, support this hypothesis.7 Figure 1 is a diagram depicting the complex circuit of events associating NCC, seizures, and HS. The panel agreed that a population-based cohort study would be the best way to confirm a causal relationship between NCC and HS, and to characterize this association with the occurrence of chronic epilepsy. For this, adults residing in cysticercotic-endemic villages should undergo neuroimaging studies to identify those with a single calcified parenchymal brain cysticercus (case patients). The selection of individuals with a single lesion would provide a better model for assessing the role of either the cysticercus or the HS in epileptogenesis. Case patients and similar numbers of age- and sex-matched individuals with no evidence of NCC (controls) have to be evaluated with repeated neuroimaging at the end of the study (5 years) to assess the numbers of persons who develop HS in the follow-up. In addition, epilepsy prevalence at enrollment and incidence during the follow-up must be assessed in all participants (irrespective of their case/control status), as well as characterization of clinical and neurophysiologic patterns, initially and at completion of the study. If isolated calcifications can cause HS and mesial temporal lobe epilepsy, it will be of great value to elucidate the epileptogenic mechanisms involved. This could not only lead to novel treatments to prevent epilepsy in people with NCC, but promote the development of antiepileptogenic interventions in other forms of acquired epilepsy. This study was partially supported by University Espiritu Santo—Ecuador, Guayaquil, Ecuador. H.H. Garcia is supported by a Wellcome Trust International Senior Fellowship in Public Health and Tropical Medicine. None of the authors has any conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.