Studies of neurocysticercosis and animal cestode infections

National Institute Of Allergy And Infectious Diseases

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Abstract

Most of the morbidity and mortality due to neurocysticercosis is due to inflammation directed to degenerating cysts that that occurs as a consequence of the natural course of disease or as a result of anthelmintic treatment. Corticosteroids are commonly used at the start and during treatment to control on-going and/or treatment induced inflammation. Because long-term and high dose corticosteroids are commonly required to control inflammation, severe corticosteroid induced side effects are common. Tumor necrosis factor alpha (TNF-alpha ) is an essential component of the inflammatory response in neurocysticercosis. Previously we showed that preadministration of etanercept (ETN) was able to penetrate the brain of infected pigs and inhibit TNF-alpha and other proinflammatory cytokines. Since ETN is effective and safe in humans and was likely effective in an animal model of NCC, we used etanercept in humans with NCC as a corticosteroid sparing or replacement agent. We reported the effects of in 16 patients treated at the Clinical Center of NIH. Twelve patients with extraparenchymal NCC were administered ETN with corticosteroids (11/12,91.7%) and/or methotrexate (9/12, 75.0%). The median age of the subgroup with extraparenchymal NCC was 40 years(range 2657 years) and 66.7% were male. They were administered ETN for a median period of 311 days (range 31461 days) and then followed for a median of 3.4 years (range 0.36.6 years). Among nine assessable patients, all improved clinically after starting ETN and one deteriorated transiently. Of the remaining three, one was lost to follow-up and two patients have improved but had not completed their assigned course. Four additional persons with recurrent perilesional edema (PE) episodes were given ETN for a median of 400.5 days (range 366854 days) and followed post-ETN for a median of 1.7 years (range 0.22.4 years). All PE patients improved and two successfully tapered corticosteroids. Etanercept administration was associated with clinical improvement, stable disease, absence of recurrence, and lack of serious side effects. Etanercept appears to contribute to the control of inflammation and facilitate corticosteroid taper. An unusual case of spinal subarachnoid NCC was reported. Despite evaluations at major medical centers in the U.S. she was undiagnosed for 15 years but finally diagnosed after whole genome sequencing of her spinal CSF. The patient suffered from disabling spinal pain and was dependent on corticosteroids to control the pain. After years of dependency on corticosteroids, she was begun on anakinra which was partially effective as a corticosparing agent. Only after the addition of etanercept was she able to taper off of steroids and complete anthelminthic treatment. Since the addition of etanercept was the only change in treatment along with the start of anthelmintic therapy this strongly suggests its utility to control inflammation in NCC. A qPCR assay to diagnose extraparenchymal neurocysticercosis and follow efficacy of treatment was reported. The test was 100% sensitive and specific in CSF and was able to assess cure in about 94%. The test will likely replace the cestode antigen assay because it is as sensitive and specific, does not require specialized reagents, and its methodology commonly available.