Hippocampal sclerosis: The missing link of cysticercosis epileptogenesis?
2014; Wiley; Volume: 55; Issue: 12 Linguagem: Inglês
10.1111/epi.12899
ISSN1528-1167
AutoresÓscar H. Del Brutto, Jerome Engel, Dawn Eliashiv, Noriko Salamon, Héctor H. García,
Tópico(s)Parasite Biology and Host Interactions
ResumoEpilepsiaVolume 55, Issue 12 p. 2077-2078 Gray MattersFree Access Hippocampal sclerosis: The missing link of cysticercosis epileptogenesis? Oscar H. Del Brutto, Oscar H. Del Brutto [email protected] School of Medicine, University Espiritu Santo—Ecuador, Guayaquil, EcuadorSearch for more papers by this authorJerome Engel Jr., Jerome Engel Jr. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.ASearch for more papers by this authorDawn S. Eliashiv, Dawn S. Eliashiv Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.ASearch for more papers by this authorNoriko Salamon, Noriko Salamon Department of Neuroradiology, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.ASearch for more papers by this authorHector H. García, Hector H. García Center for Global Health, Tumbes, Peru Department of Microbiology, School of Sciences, Peruvian University Cayetano Heredia, Lima, Peru Cysticercosis Unit, National Institute of Neurological Sciences, Lima, PeruSearch for more papers by this author Oscar H. Del Brutto, Oscar H. Del Brutto [email protected] School of Medicine, University Espiritu Santo—Ecuador, Guayaquil, EcuadorSearch for more papers by this authorJerome Engel Jr., Jerome Engel Jr. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.ASearch for more papers by this authorDawn S. Eliashiv, Dawn S. Eliashiv Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.ASearch for more papers by this authorNoriko Salamon, Noriko Salamon Department of Neuroradiology, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.ASearch for more papers by this authorHector H. García, Hector H. García Center for Global Health, Tumbes, Peru Department of Microbiology, School of Sciences, Peruvian University Cayetano Heredia, Lima, Peru Cysticercosis Unit, National Institute of Neurological Sciences, Lima, PeruSearch for more papers by this author First published: 29 December 2014 https://doi.org/10.1111/epi.12899Citations: 11AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL 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. Figure 1Open in figure viewerPowerPoint Diagram showing the complex relationship between parenchymal brain cysticercosis, seizures, and hippocampal sclerosis. Seizures related to living cysts (vesicular stage) have been described but are assumed to be rare. In contrast, seizures are frequent during cysticerci degeneration (colloidal stage); in this case, inflammation surrounding dying parasites is the most commonly accepted mechanism causing acute seizures. When parasites die (calcified stage), reactive seizures may result from intermittent bouts of inflammation probably related to exposure of trapped cysticercal antigens to the host's immune system. Both acute and recurrent reactive seizures, if repetitive, may cause hippocampal sclerosis, which, in turn, could be the source of chronic epilepsy. On the other hand, colloidal as well as calcified cysticerci may directly induce hippocampal sclerosis by inflammation-mediated (local or remote) damage of hippocampal neurons causing permanent epileptogenesis and chronic hippocampal epilepsy. 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. Acknowledgments 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. Disclosure 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. References 1Nash TE, Del Brutto OH, Butman JA, et al. Calcific neurocysticercosis and epileptogenesis. Neurology 2004; 62: 1934– 1938. 2Leite JP, Terra-Bustamante VC, Fernandes RMF, et al. Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy. Neurology 2000; 55: 1485– 1491. 3Witchert-Ana L, Velasco TR, Terra-Bustamante VC, et al. Surgical treatment for mesial temporal lobe epilepsy in the presence of massive calcified neurocysticercosis. Arch Neurol 2004; 61: 1117– 1119. 4Rathore C, Thomas B, Kesavadas C, et al. Calcified neurocysticercosis lesions and antiepileptic drug-resistant epilepsy: a surgically remediable syndrome? Epilepsia 2013; 54: 1815– 1822. 5Singh G, Burneo JG, Sander W. From seizures to epilepsy and its substrates: neurocysticercosis. Epilepsia 2013; 54: 783– 792. 6Bianchin MM, Velasco TR, dos Santos AC, et al. On the relationship between neurocysticercosis and mesial temporal lobe epilepsy associated with hippocampal sclerosis: coincidence or a pathogenic relationship? Pathog Glob Health 2012; 106: 280– 285. 7Kahn MS, Kranjac D, Alonzo CA, et al. Prolonged elevation in hippocampal Aβ and cognitive deficit following repeated endotoxin exposure in the mouse. Behav Brain Res 2012; 229: 176– 184. Citing Literature Volume55, Issue12December 2014Pages 2077-2078 FiguresReferencesRelatedInformation
Referência(s)