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• W1520644557 abstract "To the Editors: Nash et al.1 have renewed the theory to consider neurocysticercosis (NC) as a human model of epileptogenesis. This theory, which was proposed 25 years ago,2 has not prospered so far, despite the advances of medicine, because, among other reasons, NC is still a neglected disease.3 At the moment, the updated approach proposed by Nash et al. seems appropriate; however, there are some additional issues that should be considered. NC could not only be a human model of epileptogenesis, but also a model to identify biomarkers for the propensity to generate seizures (i.e., ictogenesis), which might predict the development of an epilepsy condition. In this context, it is critical to differentiate between acute symptomatic seizures and recurrent unprovoked seizures (i.e., epilepsy). It is well known that acute seizures are the most common symptom in NC patients, but most do not develop into epilepsy.4 Nash et al. describe a “mechanism of chronic epilepsy from acute seizures occurs as degenerating cyst develops into a calcification…” which is consistent with previous proposals.5, 6 However, it is also important to remember that there are many clinical inconsistencies in the relationship between epilepsy and NC lesions. Parasite location may be remote from the potential epileptogenic region, and there is no correlation between the burden of lesions and the severity of the epilepsy.6 Patients with severe refractory seizures may have only one calcified lesion, and patients with multiple cysts or calcifications may have no seizures.6 Furthermore, calcified lesions are frequently encountered on computed tomography (CT) scans of asymptomatic individuals,7 which questions their epileptogenicity. The empirical observation of experienced neurologists from endemic countries is that NC and refractory epilepsy rarely coexist. This is consistent with a study of 512 patients in Brazil,8 which concluded that NC is an uncommon cause of intractable epilepsy and may represent only a coexistent pathology. The multifactorial concept proposed by Engel et al.9 based on the triad of epileptogenic abnormality, seizure threshold, and precipitating factors, could be applied for the development of seizures/epilepsy in patients with NC. In the context of NC, the epileptogenic abnormality relates to the number and localization of parasites, as well as their evolutionary phases over time5, 6 (Fig. 1A). Seizures occur when these three factors interact. NC epileptogenic mechanisms result in a reduction of seizures threshold until seizures occur (i.e., ictogenesis) hastened by the host immunologic response with a cascade of events or precipitating factors, such as blood–brain barrier breakdown, brain inflammation, and reactive astrogliosis (Fig. 1B). Some patients may also have a genetic predisposition to maintain a low seizure threshold leading to the chronic epileptic process (i.e., epileptogenesis). Considering the large amount of asymptomatic cases of NC in the population (probably >50% of infected patients6) and that few people with NC develop epilepsy,7, 10 it is possible that most patients do not have a genetic predisposition to maintain a low seizure threshold and acute seizures do not evolve to epilepsy (Fig. 1C). Measures of potential biomarkers of NC (e.g., quantitative magnetic resonance imaging, qualitative electroencephalography [EEG], serial magnetization transfer imaging, substance P, Toll-like receptor polymorphism), taken at different points of the evolution of the cyst phases, might have a predictive value for development of seizures or epilepsy. Current information about epileptogenicity of NC is scarce and based on anecdotal cases, providing weak evidence for causal inference. Prospective cohort studies are needed11 to assess the association of different evolutionary phases of the parasite, potential genetic predisposition, and the role of precipitating factors in the development of seizures and epilepsy, along with the development of relevant animal models.12 We have no conflicts of interest. 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." @default.
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• W1520644557 date "2015-06-01" @default.
• W1520644557 modified "2023-09-25" @default.
• W1520644557 title "Multifactorial basis of epilepsy in patients with neurocysticercosis" @default.
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• W1520644557 doi "https://doi.org/10.1111/epi.12978" @default.
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