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Inflammation is a key risk factor for persistent seizures in neurocysticercosis.

ABSTRACT: Objective: We conducted a retrospective, case-control study of neurocysticercosis patients to ascertain early markers that identify subjects likely to develop treatment-resistant seizures.

Methods: Clinical histories and imaging studies from 38 neurocysticercosis patients who had been followed for 18 months after treatment were evaluated. Both pairwise and multifactorial analyses were conducted to identify factors associated with continued seizures.

Results: Eleven of 38 patients continued to have seizures during the follow-up period. On univariate analysis, the number of neurocysticercosis lesions, number of bands on the baseline neurocysticercosis western blot, edema volumes on follow-up MRI scans, edema volume changes between baseline and follow-up images, and proportion of calcified lesions with perilesional edema were all significantly increased in subjects who had persistent seizures during the 18-month follow-up period. On multivariate analyses using recursive partition and random forest algorithms, variables associated with persistent seizures included: the number of total and calcified lesions, presence of perilesional edema, the rate of change in the lesion and edema volumes from baseline to follow-up, and the number of bands on the neurocysticercosis western blot.

Interpretation: Measures of both inflammation and disease burden are key risk factors for persistent seizures despite anticonvulsant treatments in patients with neurocysticercosis. Inflammation is therefore a potentially modifiable risk factor for the frequently seen severe seizure disorders in patients with neurocysticercosis.

SUBMITTER: Herrick JA

PROVIDER: S-EPMC5945963 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Inflammation is a key risk factor for persistent seizures in neurocysticercosis.

Herrick Jesica A JA Maharathi Biswajit B Kim Jin Suh JS Abundis Gerardo G GG Garg Anjali A Gonzales Isidro I Saavedra Herbert H Bustos Javier A JA Garcia Hector H HH Loeb Jeffrey A JA

Annals of clinical and translational neurology 20180410 5

<h4>Objective</h4>We conducted a retrospective, case-control study of neurocysticercosis patients to ascertain early markers that identify subjects likely to develop treatment-resistant seizures.<h4>Methods</h4>Clinical histories and imaging studies from 38 neurocysticercosis patients who had been followed for 18 months after treatment were evaluated. Both pairwise and multifactorial analyses were conducted to identify factors associated with continued seizures.<h4>Results</h4>Eleven of 38 patie ...[more]

PMID: 29761125

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Project description:Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ).We followed the methods from a previously developed treatment model of NCC in naturally infected swine. The four study groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN, 25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed transcription of a wide range of proinflammatory, regulatory and matrix protease encoding genes at 120 hr post PZQ treatment in capsules of cysts that demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier dysfunction) compared to animals not receiving ETN. Transcription was significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)-?, and interferon (IFN)-?; the inflammation regulating genes cytotoxic T-lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming growth factor (TGF)-?; the tissue remodeling genes matrix metalloprotease (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes regulating endothelial function vascular endothelial growth factor (VEGF)1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-?, IL-6, IFN-?, TGF-? and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups.Overall, TNF-? blockade using ETN treatment modulated expression of a 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-? blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis.

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Inflammation is a key risk factor for persistent seizures in neurocysticercosis.

Publications

Inflammation is a key risk factor for persistent seizures in neurocysticercosis.

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