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Antagonism of peripheral inflammation reduces the severity of status epilepticus.

ABSTRACT: Status epilepticus (SE) is one of the most serious manifestations of epilepsy. Systemic inflammation and damage of blood-brain barrier (BBB) are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures. Whether an inflammatory-vascular-BBB mechanism could apply to the lithium-pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear cells. Serum IL-1beta levels increased and BBB damage occurred concurrently to increased theta EEG activity. These events occurred prior to SE induced by cholinergic exposure. SE was elicited by lithium and pilocarpine irrespective of their sequence of administration supporting a common pathogenetic mechanism. Since IL-1beta is an etiologic trigger for BBB breakdown and its serum elevation occurs before onset of SE early after LiCl and pilocarpine injections, we tested the hypothesis that intravenous administration of IL-1 receptor antagonists (IL-1ra) may prevent pilocarpine-induced seizures. Animals pre-treated with IL-1ra exhibited significant reduction of SE onset and of BBB damage. Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus.

SUBMITTER: Marchi N

PROVIDER: S-EPMC3045783 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Antagonism of peripheral inflammation reduces the severity of status epilepticus.

Marchi Nicola N Fan Qingyuan Q Ghosh Chaitali C Fazio Vincent V Bertolini Francesca F Betto Giulia G Batra Ayush A Carlton Erin E Najm Imad I Granata Tiziana T Janigro Damir D

Neurobiology of disease 20081028 2

Status epilepticus (SE) is one of the most serious manifestations of epilepsy. Systemic inflammation and damage of blood-brain barrier (BBB) are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures. Whether an inflammatory-vascular-BBB mechanism could apply to the lithium-pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear ...[more]

PMID: 19010416

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Project description:BackgroundCurrent prognostic scores for status epilepticus (SE) may not be adequate for patients in ICU who usually have more severe systemic conditions or more refractory episodes of SE. We aimed to compare the prognostic performance of two SE scores, Status Epilepticus Severity Score (STESS) and Epidemiology-Based Mortality Score in Status Epilepticus (EMSE) score, with four systemic severity scores, Acute Physiology and Chronic Health Evaluation 2 (APACHE-2), Simplified Acute Physiology Score 2 (SAPS-2), Sequential Organ Failure Assessment (SOFA) score, and Inflammation, Nutrition, Consciousness, Neurologic function and Systemic condition (INCNS) score in critically ill patients with SE.MethodsThis retrospective observational study of a prospectively identified SE cohort was conducted in the ICU at a tertiary-care center. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and associations with outcomes of STESS, EMSE, INCNS, APACHE-2, SAPS-2, and SOFA score for the prediction of in-hospital mortality and no return to baseline condition were assessed.ResultsBetween January 2015 and December 2020, 166 patients with SE in ICU were included in the study. In predicting in-hospital death, APACHE-2 (0.72), SAPS-2 (0.73), and SOFA score (0.71) had higher AUCs than STESS (0.58) and EMSE (0.69). In predicting no return to baseline condition, the AUC of APACHE-2 (0.75) was the highest, and the AUC of INCNS (0.55) was the lowest. When the specificity approached 90%, the sensitivity values of these scores were not quite acceptable (< 40%). Neither SE scores nor systemic severity scores had desirable prognostic power. In the multivariate logistic regression analyses, the best combinations of scores always included at least one or more systemic severity scores.ConclusionsSTESS and EMSE were insufficient in outcome prediction for SE patients in ICU, and EMSE was marginally better than STESS. Systemic illness matters in ICU patients with SE, and SE scores should be modified to achieve better accuracy in this severely ill population. This study mostly refers to severely ill patients in the ICU.

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Antagonism of peripheral inflammation reduces the severity of status epilepticus.

Publications

Antagonism of peripheral inflammation reduces the severity of status epilepticus.

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