Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS

Saitoh, Makiko; Kobayashi, Kyozo; Ohmori, Iori; Tanaka, Y; Tanaka, Keiko; Inoue, Takeshi; Horino, Asako; Ohmura, Kayo; Kumakura, Akira; Takei, Yoshinori; Hirabayashi, Shinichi; Kajimoto, Madoka; Uchida, Takashi; Yamazaki, Shun; Shiihara, Takashi; Kumagai, Tadayuki; Kasai, Masahiro; Terashima, Hiroshi; Kubota, Masaya; Mizuguchi, Masashi

doi:10.1016/j.jns.2016.07.040

Cited by 48 publications

(60 citation statements)

References 35 publications

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“…Sakuma et al compared levels of both plasma and cerebrospinal fluid (CSF) cytokines in 27 cases of FIRES, 14 children with other inflammatory neurological disorders, and 18 children with noninflammatory neurological disorders and found markedly increased proinflammatory cytokines and chemokines in the FIRES cohort, particularly in the CSF. A candidate gene analysis comparing polymorphisms of cytokine‐related and sodium channel genes in 19 children with FIRES to healthy controls found a significant association in the RN2 allele of ILIRN and FIRES . This allele results in higher levels of IL‐1β and lower levels of IL‐1RA, suggesting that those with FIRES may have an underlying genetic predisposition to excessive neurogenic inflammation.…”

Section: Anakinramentioning

confidence: 99%

“…A candidate gene analysis comparing polymorphisms of cytokine-related and sodium channel genes in 19 children with FIRES to healthy controls found a significant association in the RN2 allele of ILIRN and FIRES. 9 This allele results in higher levels of IL-1β and lower levels of IL-1RA, suggesting that those with FIRES may have an underlying genetic predisposition to excessive neurogenic inflammation.…”

Section: Key Pointsmentioning

confidence: 99%

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Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

et al. 2018

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Summary The Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV) took place in Madrid, Spain, on May 13‐16, 2018 and was attended by 168 delegates from 28 countries. The conference provided a forum for professionals involved in basic science, clinical research, regulatory affairs, and clinical care to meet and discuss the latest advances related to discovery and development of drugs and devices aimed at improving the management of people with epilepsy. This progress report provides a summary of findings on investigational compounds for which data from both preclinical studies and studies in patients were presented. The compounds reviewed include anakinra, cannabidiol, cannabidivarin, fenfluramine, ganaxolone, medium‐chain fatty acids, padsevonil, and the valproic derivatives valnoctamide and sec‐butylpropylacetamide. On June 25, 2018, the US Food and Drug Administration approved a standardized formulation of cannabidiol oral solution for the treatment of seizures associated with Lennox‐Gastaut syndrome and Dravet syndrome in patients 2 years and older. The report shows that there continues to be a steady flow of potential antiepileptic drugs progressing to clinical development. Many of these compounds show innovative mechanisms of action, and some have already been tested in placebo‐controlled randomized controlled trials, with promising efficacy and safety results.

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Section: Anakinramentioning

confidence: 99%

Section: Key Pointsmentioning

confidence: 99%

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

et al. 2018

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“…Individual predisposition may be determined by allelic variations in HLA subtypes or cytokine pathways, as in other postinfectious neurological disorders. 27,28 Further studies to confirm these hypotheses are ongoing.…”

Section: Hypothesis: a Genetically Determined Postinfectious Cytokimentioning

confidence: 86%

“…Furthermore, whether this cytokine storm is sufficient to explain a long‐lasting severe episode of SE is also unclear, and additional mechanisms such as mitochondrial dysfunction or synaptic plasticity may occur. Individual predisposition may be determined by allelic variations in HLA subtypes or cytokine pathways, as in other postinfectious neurological disorders . Further studies to confirm these hypotheses are ongoing.…”

Section: Pathophysiological Hypothesis: a Genetically Determined Posmentioning

confidence: 99%

New‐onset refractory status epilepticus (NORSE) and febrile infection–related epilepsy syndrome (FIRES): State of the art and perspectives

et al. 2018

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We report the proceedings of the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. To promote awareness of this condition and foster research efforts, we conveyed the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. The conference was supported by The NORSE Institute (http://www.norseinstitute.org). This article summarizes the discussions that were held during the Symposium and presents our strategy to unravel the cause of these disorders and to improve patient care. The standardized definitions for these disorders that have been developed, are required to improve communication and facilitate the development of multicenter registries and biobanks. A distinction between childhood- and adult-onset forms of the syndrome is not supported by strong scientific evidence and it is argued that both should be studied together. Although the pathophysiology remains elusive, nascent evidence suggests a role for a postinfectious cytokine-mediated mechanism, which should be further investigated. It also appears important to develop tools for their early recognition and prompt treatment. Recent evidence suggests that specific electroencephalography (EEG) features might be helpful. The optimal treatment options remain to be determined; immune therapies are usually disappointing, but the ketogenic diet has proved effective in uncontrolled trials. NORSE and FIRES represent a very delicate clinical situation with specific communication issues between physicians and with patients and families. Standardized consensus definitions and a multidisciplinary multicenter strategy will help research efforts and improve clinical care for patients with NORSE and FIRES.

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“…Next‐generation sequencing panel for genetic epilepsy did not show significant variants. Based on evidence of IL1RN haplotype containing RN2 in a group of Japanese patients with FIRES and an association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, we tested for but we did not find these polymorphisms in the two genes in our patient.…”

Section: Case Reportmentioning

confidence: 95%

Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome

et al. 2019

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Summary Febrile infection–related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1β and inflammation‐related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.

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Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS

Cited by 48 publications

References 35 publications

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

New‐onset refractory status epilepticus (NORSE) and febrile infection–related epilepsy syndrome (FIRES): State of the art and perspectives

Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection–related epilepsy syndrome

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