Exploring the complex associations over time among albendazole treatment, cyst evolution, and seizure outcomes in neurocysticercosis

Abstract

Objective To develop a causal model for the occurrence of neurocysticercosis (NC)‐related seizures and test hypotheses generated from the model. Methods We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow‐up using generalized linear mixed effect models. Results We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time‐treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. Significance Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3‐6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.

Taenia solium Metacestode Factor as Probable Cause of Temporal Lobe Epilepsy

“…During the first few months after the treatment, the patients in the albendazole group had fewer seizures in comparison to the patients in the placebo group; however, in the long run, those in the placebo group had fewer seizures than the treated group. 13 The results of these works suggest that, as long as some parasites are alive (i.e., viable cysts), patients may experience seizures, which supports the hypothesis that the parasite produces and secretes some toxic substance that inhibits inflammation around cysts (Dixon/ Ridaura) and triggers mechanisms that lead to neuropathology (HS/epilepsy/seizures).…”

Zoonotic and vector-borne parasites and epilepsy in low-income and middle-income countries

“…Regardless of whether antihelminthic treatment is administered, many of the cysticerci evolve to calcified residue, which provides a substrate for ongoing seizures (or active epilepsy) in the setting of cerebral parenchymal neurocysticercosis83,84,91 . Hence, many individuals continue to have seizures in the long term despite the administration of antihelminthic treatment, as confirmed in a causal model of seizures associated with neurocysticercosis92 .Several trials and meta-analyses have demonstrated beneficial effects of corticosteroid administration, especially in solitary cerebral parenchymal cysticercosis93,94 , but the longterm effects of this treatment on seizure outcomes have not been defined. Primary prevention of T. solium cysticercosis entails a shift of focus from the clinic to the community.…”

A prospective cohort study to assess the frequency and risk factors for calcification in single lesion parenchymal neurocysticercosis

“…In one study, the association of cyst evolution, seizure recurrence and albendazole therapy was explored. The association was nonlinear and changed over time; most cysts either calcified or resolved completely, regardless of whether they were treated with albendazole [34].…”