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Case Reports
. 2018 Feb 9;15(1):38.
doi: 10.1186/s12974-018-1063-2.

Systemic autoinflammation with intractable epilepsy managed with interleukin-1 blockade

Allen D DeSena  1 , Thuy Do  2 , Grant S Schulert  3
Affiliations
Case Reports

Systemic autoinflammation with intractable epilepsy managed with interleukin-1 blockade

Allen D DeSena et al. J Neuroinflammation. .

Abstract

Background: Autoinflammatory disorders are distinguished by seemingly random episodes of systemic hyperinflammation, driven in particular by IL-1. Recent pre-clinical work has shown a key role for IL-1 in epilepsy in animal models, and therapies for autoinflammation including IL-1 blockade are proposed for refractory epilepsy.

Case presentation: Here, we report an adolescent female with signs of persistent systemic inflammation and epilepsy unresponsive to multiple anti-epileptic drugs (AED). She was diagnosed with generalized epilepsy with a normal brain MRI and an electroencephalogram (EEG) showing occasional generalized spike and slow wave discharges. Her diagnostic evaluation showed no signs of autoimmunity or genetic causes of epilepsy or periodic fever syndromes but persistently elevated serum inflammatory markers including S100 alarmin proteins. She experienced prompt clinical response to IL-1 blockade with first anakinra and then canakinumab, with near complete resolution of clinical seizures. Additionally, she displayed marked improvements in quality of life and social/academic functioning. Baseline gene expression studies on peripheral blood mononuclear cells (PBMC) from this patient showed significantly activated gene pathways suggesting systemic immune activation, including focal adhesion, platelet activation, and Rap1 signaling, which is an upstream regulator of IL-1β production by the NLRP3 inflammasome. It also showed activation of genes that characterize inflammasome-mediated autoinflammatory disorders and no signs of interferon activation. This gene expression signature was largely extinguished after anakinra treatment.

Conclusions: Together, these findings suggest that patients with epilepsy responsive to immune modulation may have distinct autoinflammatory features supporting IL-1 blockade. As such, IL-1 blockade may be highly efficacious adjunctive medication for certain refractory epilepsy syndromes.

Keywords: Anakinra; Canakinumab; IL-1beta; Seizures.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Cincinnati Children’s Hospital Institutional Review Board (IRB 2011-1517), and informed consent was obtained from all patients and/or their legal guardians.

Consent for publication

Consent for publication was obtained from all patients and/or their legal guardians.

Competing interests

Dr. Schulert has received consulting fees from Novartis. The other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
IL-1 blockade leading to resolution of systemic inflammation in patient with refractory epilepsy
Fig. 2
Fig. 2
PBMC gene expression signatures before and after anakinra treatment. Gene expression was quantified using the AmpliSeq Transcriptome kit and the Ion Torrent S5 system as described. Heatmaps show hierarchical clustering of normalized log-2 RPKM from patient PBMC as well as three pediatric control samples. a Heatmap showing genes with > 2-fold difference between pre-treatment sample and mean of control samples. b Heatmap showing genes associated with autoinflammatory interferonopathies, as determined in [6]. c Heatmap showing immune response genes associated with the IL-1-driven autoinflammatory disorder CAPS [18]
See this image and copyright information in PMC

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