Recent Patents on Inflammation &Allergy Drug Discovery
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128
Recent Patents on Inflammation & Allergy Drug Discovery 2018, 12, 128-135
REVIEW ARTICLE
Febrile Infection-Related Epilepsy Syndrome (FIRES): An Overview of
Treatment and Recent Patents
Kam L. Hon
1,*
, Alexander K.C. Leung
2
and Alcy R. Torres
3
1
Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong;
2
Department of Pediatrics, the
University of Calgary, Alberta Children’s Hospital, Calgary, Alberta, Canada;
3
Department of Pediatrics, Division of
Child Neurology, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA.
A R T I C L E H I S T O R Y
Received: April 09, 2018
Revised: May 03, 2018
Accepted: May 06, 2018
DOI:
10.2174/1872213X12666180508122450
Abstract: Background: New-Onset Refractory Status Epilepticus (NORSE) refers to a clinical
presentation in a patient without active epilepsy or other existing relevant neurological disorder, with
new onset of refractory status epilepticus in the absence of a clear acute or active structural, metabolic,
or toxic cause. Febrile Infection-Related Epilepsy Syndrome (FIRES) is a subset of NORSE that
requires a febrile infection between 24 hours and 2 weeks prior to the onset of refractory status
epilepticus, with or without fever at the onset of status epilepticus, and with no restriction to the age of
the patient. The literature on FIRES is scarce.
Objective: This article reviews the pathophysiology, clinical features, and various treatment modalities
in the treatment of FIRES.
Methods: A Medline/Pubmed search was conducted using Clinical Queries with the key terms "Febrile
Infection-Related Epilepsy Syndrome", “FIRES”, "New-Onset Refractory Status Epilepticus" and
“NORSE”. The search strategy included meta-analyses, randomized controlled trials, clinical trials,
reviews and pertinent references. Patents were searched using the key term "FIRES", “NORSE” and
“Febrile Epilepsy Syndrome” from www.google.com/patents, www.uspto.gov, and
www.freepatentsonline.com.
Results: FIRES almost invariably begins with a mild nonspecific febrile illness in an otherwise healthy
individual. Twenty-four hours to two weeks later, seizures begin and quickly become very frequent and
worsen, becoming status epilepticus. Seizures can be simple motor, complex partial or secondary gen-
eralized. The exact etiology is not known. It is possible that the syndrome is caused by an inflammatory
or autoimmune mechanism.
Seizures in FIRES are notoriously very difficult to treat. Treatment modalities include, among others,
various antiepileptic drugs, ketogenic diet, intravenous corticosteroids, intravenous immunoglobulin,
and burst-suppression coma. The outcome is poor; most children are left with significant cognitive
disability and refractory epilepsy. Recent patents for the management of FIRES are discussed.
Conclusion: FIRES is a rare epilepsy syndrome of unclear etiology in which children, usually of school
age, suddenly develop very frequent seizures after a mild febrile illness. Seizures in FIRES are typically
difficult to treat. The prognosis is poor.
Keywords: Antiepileptic drugs, corticosteroids, fever, immunoglobulin, ketogenic diet, new-onset refractory status epilepticus,
FIRES, NORSE, seizures.
1. INTRODUCTION
Status epilepticus in a previously healthy child preceded
by a minor febrile infection is a diagnostic and therapeutic
challenge [1]. A number of acronyms or syndromes have
*Address correspondence to this author at the Department of Paediatrics,
The Chinese University of Hong Kong, 6/F, Clinical Sciences Building,
Prince of Wales Hospital, Shatin, Hong Kong; Tel: (852) 3505 2856;
Fax: (852) 2636 0020; E-mail: ehon@hotmail.com.
been proposed to describe the condition, including Febrile
Infection-Related Epilepsy Syndrome (FIRES), New-Onset
Refractory Status Epilepticus (NORSE), Acute Encephalitis
with Refractory Repetitive Partial Seizures (AERRPS), and
Devastating Epileptic Encephalopathy in School-Aged Chil-
dren (DESC) [2]. In particular, two syndromes, Idiopathic
Hemiconvulsion-Hemiplegia and Epilepsy (IHHE) in infants
and New-Onset Refractory Status Epilepticus (NORSE) in
adults, share many similarities with FIRES [3]. The syn-
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