Studies of neurocysticercosis and animal cestode infections

National Institute Of Allergy And Infectious Diseases

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Abstract

We reported on our long-term experience of patients with ventricular neurocysticercosis. The clinical symptoms, therapeutic approaches and treatments differ in neurocysticercosis depending on the type of brain involvement. Location in specific compartments tend to cause relatively unique syndromes requiring specific diagnostic and therapeutic approaches and treatments. Cysts that lodge in the ventricles of the brain mostly cause symptoms and signs related to cerebral spinal fluid blockage causing and inflammation in and around the ventricles. There was a range of clinical symptoms. However, patients commonly presented in extremis requiring acute neurosurgical interventions to relieve obstruction and lessen inflammation. Cysts were usually removed surgically and some patients who had only cysts did well without any further treatments. Other patients required cysticidal treatment and mechanical shunts to relieve brain pressure. Overall, despite a period of intensive medical care, all survived and did well over the long term with mild residual complaints. A minority were significantly disabled long term. This is the first paper that was able to follow patients in detail over a long period of time and demonstrate pitfalls in diagnosis and treatment and prognosis of patient with this particular involvement. Radiological and inflammatory changes induced by combined treatment with the cysticidal drugs albendazole and praziquantel was studied in naturally infected pigs with neurocysticercosis. Disease manifestations in neurocysticercosis (NCC) are frequently due to inflammation of degenerating Taenia solium brain cysts due either to the natural history of disease or as a result of cysticidal treatment. The pig is the natural intermediate host of T. solium and undergoes a similar pathophysiology response to treatment as human infection and treatment. Acute changes in MRI parameters and inflammation were determine at 0, 2 and 5 days after treatment with praziquantel and albendazole. An increase in inflammation and enhancement ( leakage of gadolinium dye) occurred at 2 days and 5 days after initiation of treatment accompanied by a decrease in cyst size. Cysts with lower cyst volume ratios showed increased post-treatment inflammation, loss of vesicular fluid and cyst wall wrinkling. A significant and drastic reduction of cyst size and increased pericystic enhancement occur in the initial days after antiparasitic treatment as an effect of acute perilesional immune response. These significant changes showed that early anthelmintic efficacy (day two) can be detected using magnetic resonance imaging. Failure to observe early changes could be a sign of treatment failure prompting change in dosing. One of the major problems in the treatment of neurocysticercosis in humans is the inflammation directed to degenerating cysts that develops early on after starting cysticidal drug treatment. This early immune response was previously studied in pigs naturally infected with neurocysticercosis after a single dose of praziquantel. These responses closely mimic those found in humans. Our studies demonstrated that the tumor necrosis factor alpha (TNF-alpha )and other pro inflammatory cytokines are acutely induced after a single dose of the cysticidal agent, praziquantel. High dose corticosteroids are usually used in human infection to suppress the harmful inflammation that occurs normally and after the initiation of drug treatment. However, corticosteroids can cause harmful side effects and alternative drugs to better and more safely control inflammation is needed. Using a similar but modified model of naturally infected pigs described above, we studied whether the preadministration of etanercept, an anti-TNF-alpha blocking agent, commonly used in human inflammatory conditions was able to control early treatment induced neuroinflammation compared to corticosteroids or non- treated pigs. A large number of proinflammatory, regulatory cytokines and other participating molecules were quantified at 5 days post treatment and compared to corticosteroids. Overall, TNF-alpha blockade using etanercept treatment modulated a surprisingly large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molecules. Taken together, these data suggest that TNF-a;lpha blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis. Corticosteroids showed similar less pronounced effects compared to etanercept. New guidelines for the diagnosis, evaluation and treatment of human neurocysticercosis were developed by a panel of experts in the field. Although too complicated to summarize here, this is an important publication because neurocysticercosis is not well studied, there are many disagreements among experts and the literature commonly differs on recommendations depending on the author. These guidelines are a consensus among experts and form the basis of how the diagnosis, approach and treat patients with this uncommon disorder in most economically advanced regions.