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Sevoflurane as bridge therapy for plasma exchange and Anakinra in febrile infection-related epilepsy syndrome.

ABSTRACT: Febrile infection-related epilepsy syndrome (FIRES) is a devastating immune inflammatory-mediated epileptic encephalopathy. Herein, we discuss a previously healthy 8-year-old boy with FIRES in whom high dosages of conventional and nonconventional anesthetics were ineffective in treating SE, as were ketogenic diet, intravenous corticosteroids, and immunoglobulins. After 29 days of prolonged SRSE, the patient was successfully treated with sevoflurane paired with plasma exchange, for a total of five days, thus obtaining a stable EEG suppression burst pattern with no adverse events. Anakinra at the dosage of 100 mg b.i.d. was started seven days after sevoflurane and plasma exchange had been discontinued and was effective in ensuring non-recurrence of SE. Sevoflurane as bridge therapy for immunosuppressive treatment could be considered an early, safe, and effective option in treating convulsive SE in which an autoimmune-inflammatory etiology can reasonably be hypothesized.

SUBMITTER: L'Erario M

PROVIDER: S-EPMC8633474 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

Project description: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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Long-term neuropsychological outcomes in children with febrile infection-related epilepsy syndrome (FIRES) treated with anakinra.

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Whole-exome and HLA sequencing in Febrile infection-related epilepsy syndrome.

Project description:Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy characterized by new-onset refractory status epilepticus with a prior febrile infection. We performed exome sequencing in 50 individuals with FIRES, including 27 patient-parent trios and 23 single probands, none of whom had pathogenic variants in established genes for epilepsies or neurodevelopmental disorders. We also performed HLA sequencing in 29 individuals with FIRES and 529 controls, which failed to identify prominent HLA alleles. The genetic architecture of FIRES is substantially different from other developmental and epileptic encephalopathies, and the underlying etiology remains elusive, requiring novel approaches to identify the underlying causative factors.

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Functional deficiency in endogenous interleukin-1 receptor antagonist in patients with febrile infection-related epilepsy syndrome.

Project description:ObjectiveWe recently reported successful treatment of a child with febrile infection-related epilepsy syndrome (FIRES), a subtype of new onset refractory status epilepticus, with the recombinant interleukin-1 (IL1) receptor antagonist (IL1RA) anakinra. On this basis, we tested whether endogenous IL1RA production or function is deficient in FIRES patients.MethodsLevels of IL1β and IL1RA were measured in serum and cerebrospinal fluid (CSF). The inhibitory activity of endogenous IL1RA was assessed using a cell-based reporter assay. IL1RN gene variants were identified by sequencing. Expression levels for the secreted and intracellular isoforms of IL1RA were measured in patient and control cells by real-time polymerase chain reaction.ResultsLevels of endogenous IL1RA and IL1β were elevated in the serum and CSF of patients with FIRES (n = 7) relative to healthy controls (n = 10). Serum from FIRES patients drove IL1R signaling activity and potentiated IL1R signaling in response to exogenous IL1β in a cell-based reporter assay. Functional assessment of endogenous IL1RA activity in 3 FIRES patients revealed attenuated inhibition of IL1R signaling. Sequencing of IL1RN in our index patient revealed multiple variants. This was accompanied by reduced expression of intracellular but not secreted isoforms of IL1RA in the patient's peripheral blood mononuclear cells.InterpretationOur findings suggest that FIRES is associated with reduced expression of intracellular IL1RA isoforms and a functional deficiency in IL1RA inhibitory activity. These observations may provide insight into disease pathogenesis for FIRES and other inflammatory seizure disorders and may provide a valuable biomarker for therapeutic decision-making. Ann Neurol 2019;85:526-537.

| S-EPMC6450741 | biostudies-literature

Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES).

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Febrile infection-related Epilepsy Syndrome (FIRES): a severe encephalopathy with status epilepticus. Literature review and presentation of two new cases.

Project description:FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with "new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction.Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement.FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy.

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Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection.

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| S-EPMC7493773 | biostudies-literature

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