Seizures are the most common clinical manifestation of cerebral cysticercosis and occur in the presence of viable, dying, and calcified or non-calcified dead cysts. How calcified cysts provoke seizures is not known but recent observations demonstrated edema around some calcified lesions at the time of seizure activity and disappearance during periods when seizures were not occurring. Edema associated with foci in idiopathic epilepsy is highly unusual so that this observation suggests that the mechanism(s) associated with calcified cysts is unique. Documenting and understanding this phenomenon is important for a number of reasons. First, although by definition these lesions are inactive, e.g., not living larvae and do not require anti-parasitic treatment, they are frequently mistaken for active lesions and patients undergo unnecessary treatment. Second, a likely reason for perilesional edema is intermittent antigen release and subsequent host immune response resulting in inflammation and edema. If proven, then the treatment for this would not only involve suppression of seizure activity with anti- seizure medication, but also the use of anti-inflammatory medications such as corticosteroids. A study was initiated in Peru to determine 1) the frequency of perilesional edema around calcifications 2) the frequency of associated symptoms 3) what lesions and patients have a propensity to undergo this phenomenon 4) the natural history of perilesional edema and 5) whether treatment of patients with perilesional edema with corticosteroids results in enhanced regression of edema and clinical benefit. During accrual of patients to perform the above study, a baseline MRI was obtained in patients with or without current symptoms. A prospective study of patients with a history of seizures and only calcific neurocysticercosis is on going in Peru and accrual of patients is continuing. Preliminary analysis showed that approximately 23.4% of prospectively followed patients with only calcifications and a history of seizures have had a seizure after about 3 years of follow-up. 50.0% of those with seizure have had perilesional edema. This suggests that seizures are relatively common in this population and perilesional edema is caused or associated with about one-half of the episodes. The treatment arm of the study was stopped because there was no statistical way to show benefit of corticosteroids. Accural was stopped in this study but study patients are still being followed.? ? A new treatment protocol for neurocysticercosis began enrolling patients in Lima, Peru. The purpose of the protocol is to determine if enhanced dosing of corticosteroids for one month with a two week taper decreases seizure frequency compared to 10 days of corticosteroids in albendazole treated patients with intraparenchymal cysticercosis without an unacceptable increase in side effects or a decrease in treatment efficacy. Much of the pathology and subsequently symptoms caused by cysticercosis are due to the host's immune response to the parasite that causes inflammation, seizures or focal neurological deficits. This leads to cyst degeneration, granuloma formation and/or calcification. The cysticidal agents, albendazole and praziquantel, initiate a similar process and until recently it was unclear if clinical benefit occurred with treatment. A recent double blinded randomized treatment sudy showed a clear benefit of treatment compared to no treatment . Although an overall decrease in generalized seizures was found after treatment with a standard regimen of albendazole and 6 mg dexamethasone/day for 10 days, a relative increase in seizures in the first month compared to later time periods suggested that inflammation was inadequately suppressed. Exactly what is the best way to suppress treatment-induced inflammation has not been studied and therefore is not known. The current protocol is an open label controlled study comparingg the previous dexamethasone dosing of 10 days of 6 mg/day of dexamethasone with an enhanced dosing of 4 weeks of 8 mg/day with a 2 week taper. Albendazole dosing of both groups is identical. The primary end point is the number of seizures at specific time periods over the subsequent year, the number and severity of side effects and cure rates at 1 year.? ? Collaborative studies with Dr. Mahanty have been started to study the immune responses to cestodes that occur during the natural course of disease and also after treatment with the cysticidal agents albendazole and praziquantel. In cysticercosis the treatment of viable cysts many times initiates a vigorous immune response that appears similar if not identical to the type of inflammation found during the course of the natural infection. Seizures and other symptoms are common during treatment. Consequently, the problem in treatment is how to minimize symptoms and long-term damage due to treatment without preventing or inhibiting evolution to a relatively less destructive and less symptomatic granuloma. This question cannot be readily studied in humans. Therefore, studies using the cestode T. crassiceps infection in mice have been initiated to answer this and other questions.

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National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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Nash, T E; Singh, G; White, A C et al. (2006) Treatment of neurocysticercosis: current status and future research needs. Neurology 67:1120-7
Garcia, Hector H; Del Brutto, Oscar H; Nash, Theodore E et al. (2005) New concepts in the diagnosis and management of neurocysticercosis (Taenia solium). Am J Trop Med Hyg 72:3-9
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