Febrile Infection-Related Epilepsy Syndrome

Abstract

Febrile infection-related epilepsy syndrome (FIRES) is a subset or variant of new-onset refractory status epilepticus in children. FIRES is characterized by the occurrence of a febrile episode between 24 hours and 2 weeks before the onset of refractory status epilepticus. A infectious cause is rarely identified in FIRES and an inflammatory or autoimmune etiology is implied. Seizures in FIRES are very difficult to control, and treatments include antiepileptic drugs, ketogenic diet, intravenous immunoglobulin, plasmapheresis, and corticosteroid therapy. The prognosis for patients with FIRES is poor, and most children are left with refractory epilepsy and cognitive impairment. The new consensus guidelines on the terminology of FIRES and recent interest in new treatment approaches have been welcome developments for clinicians who face the challenge of diagnosing and managing status epilepticus in a previously healthy child that occurs following a minor febrile episode. This review aims to provide clinicians with an update on the current hypotheses for the etiology, pathogenesis, clinical evaluation, management, and future directions in the diagnosis and treatment of FIRES.

Keywords

FIRES - epilepticus - refractory - epilepsy

• References

• 1 Bleck TP. Refractory status epilepticus. Curr Opin Crit Care 2005; 11 (02) 117-120
• 2 Brophy GM, Bell R, Claassen J. , et al; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17 (01) 3-23
• 3 Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011; 134 (Pt 10): 2802-2818
• 4 Hirsch LJ, Gaspard N, van Baalen A. , et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia 2018; 59 (04) 739-744
• 5 Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super-refractory status epilepticus. Seizure 2019; 68: 62-71
• 6 Lyon G, Dodge PR, Adams RD. The acute encephalopathies of obscure origin in infants and children. Brain 1961; 84: 680-708
• 7 Mikaeloff Y, Jambaqué I, Hertz-Pannier L. , et al. Devastating epileptic encephalopathy in school-aged children (DESC): a pseudo encephalitis. Epilepsy Res 2006; 69 (01) 67-79
• 8 Sakuma H. Acute encephalitis with refractory, repetitive partial seizures. Brain Dev 2009; 31 (07) 510-514
• 9 van Baalen A, Häusler M, Boor R. , et al. Febrile infection-related epilepsy syndrome (FIRES): a nonencephalitic encephalopathy in childhood. Epilepsia 2010; 51 (07) 1323-1328
• 10 Kramer U, Chi C-S, Lin K-L. , et al. Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children. Epilepsia 2011; 52 (11) 1956-1965
• 11 van Baalen A, Vezzani A, Häusler M, Kluger G. Febrile infection-related epilepsy syndrome: clinical review and hypotheses of epileptogenesis. Neuropediatrics 2017; 48 (01) 5-18
• 12 Howell KB, Katanyuwong K, Mackay MT. , et al. Long-term follow-up of febrile infection-related epilepsy syndrome. Epilepsia 2012; 53 (01) 101-110
• 13 Gaspard N, Hirsch LJ, Sculier C. , et al. New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES): State of the art and perspectives. Epilepsia 2018; 59 (04) 745-752
• 14 Hon KL, Leung AKC, Torres AR. Febrile infection-related epilepsy syndrome (FIRES): an overview of treatment and recent patents. Recent Pat Inflamm Allergy Drug Discov 2018; 12 (02) 128-135
• 15 van Baalen A, Häusler M, Plecko-Startinig B. , et al. Febrile infection-related epilepsy syndrome without detectable autoantibodies and response to immunotherapy: a case series and discussion of epileptogenesis in FIRES. Neuropediatrics 2012; 43 (04) 209-216
• 16 Sakuma H, Awaya Y, Shiomi M. , et al. Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis. Acta Neurol Scand 2010; 121 (04) 251-256
• 17 Sakuma H, Tanuma N, Kuki I, Takahashi Y, Shiomi M, Hayashi M. Intrathecal overproduction of proinflammatory cytokines and chemokines in febrile infection-related refractory status epilepticus. J Neurol Neurosurg Psychiatry 2015; 86 (07) 820-822
• 18 Meletti S, Giovannini G, d'Orsi G. , et al. New-onset refractory status epilepticus with claustrum damage: definition of the clinical and neuroimaging features. Front Neurol 2017; 8: 111
• 19 Illingworth MA, Hanrahan D, Anderson CE. , et al. Elevated VGKC-complex antibodies in a boy with fever-induced refractory epileptic encephalopathy in school-age children (FIRES). Dev Med Child Neurol 2011; 53 (11) 1053-1057
• 20 Caputo D, Iorio R, Vigevano F, Fusco L. Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABA_AR antibodies. Eur J Paediatr Neurol 2018; 22 (01) 182-185
• 21 Appenzeller S, Helbig I, Stephani U. , et al. Febrile infection-related epilepsy syndrome (FIRES) is not caused by SCN1A, POLG, PCDH19 mutations or rare copy number variations. Dev Med Child Neurol 2012; 54 (12) 1144-1148
• 22 Saitoh M, Kobayashi K, Ohmori I. , et al. Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS. J Neurol Sci 2016; 368: 272-276
• 23 Lee H-F, Chi C-S. Febrile infection-related epilepsy syndrome (FIRES): therapeutic complications, long-term neurological and neuroimaging follow-up. Seizure 2018; 56: 53-59
• 24 Jafarpour S, Stredny CM, Piantino J, Chapman KE. Baseline and outcome assessment in pediatric status epilepticus. Seizure 2019; 68: 52-61
• 25 Farias-Moeller R, Bartolini L, Pasupuleti A, Brittany Cines RD, Kao A, Carpenter JL. A practical approach to ketogenic diet in the pediatric intensive care unit for super-refractory status epilepticus. Neurocrit Care 2017; 26 (02) 267-272
• 26 Rivas-Coppola MS, Shah N, Choudhri AF, Morgan R, Wheless JW. Chronological evolution of magnetic resonance imaging findings in children with febrile infection-related epilepsy syndrome. Pediatr Neurol 2016; 55: 22-29
• 27 Tan AP. Febrile infection-related epilepsy syndrome (fires) with multifocal subcortical infarcts, a new imaging phenotype. Neuropediatrics 2018; 49 (05) 347-352
• 28 Farias-Moeller R, Bartolini L, Staso K, Schreiber JM, Carpenter JL. Early ictal and interictal patterns in FIRES: the sparks before the blaze. Epilepsia 2017; 58 (08) 1340-1348
• 29 Rantala H, Saukkonen AL, Remes M, Uhari M. Efficacy of five days' barbiturate anesthesia in the treatment of intractable epilepsies in children. Epilepsia 1999; 40 (12) 1775-1779
• 30 Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005; 62 (11) 1698-1702
• 31 Abend NS, Bearden D, Helbig I. , et al. Status epilepticus and refractory status epilepticus management. Semin Pediatr Neurol 2014; 21 (04) 263-274
• 32 Lowenstein DH, Aminoff MJ, Simon RP. Barbiturate anesthesia in the treatment of status epilepticus: clinical experience with 14 patients. Neurology 1988; 38 (03) 395-400
• 33 Nabbout R, Vezzani A, Dulac O, Chiron C. Acute encephalopathy with inflammation-mediated status epilepticus. Lancet Neurol 2011; 10 (01) 99-108
• 34 Singhi S, Murthy A, Singhi P, Jayashree M. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol 2002; 17 (02) 106-110
• 35 Morrison G, Gibbons E, Whitehouse WP. High-dose midazolam therapy for refractory status epilepticus in children. Intensive Care Med 2006; 32 (12) 2070-2076
• 36 Bellante F, Legros B, Depondt C, Créteur J, Taccone FS, Gaspard N. Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety. J Neurol 2016; 263 (04) 799-806
• 37 Krajčová A, Waldauf P, Anděl M, Duška F. Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care 2015; 19: 398
• 38 Baumeister FA, Oberhoffer R, Liebhaber GM. , et al. Fatal propofol infusion syndrome in association with ketogenic diet. Neuropediatrics 2004; 35 (04) 250-252
• 39 Ilvento L, Rosati A, Marini C, L'Erario M, Mirabile L, Guerrini R. Ketamine in refractory convulsive status epilepticus in children avoids endotracheal intubation. Epilepsy Behav 2015; 49: 343-346
• 40 Mirás Veiga A, Moreno DC, Menéndez AIG. , et al. Effectiveness of electroconvulsive therapy for refractory status epilepticus in febrile infection-related epilepsy syndrome. Neuropediatrics 2017; 48 (01) 45-48
• 41 Vezzani A, Rüegg S. The pivotal role of immunity and inflammatory processes in epilepsy is increasingly recognized: introduction. Epilepsia 2011; 52 (Suppl. 03) 1-4
• 42 Kenney-Jung DL, Vezzani A, Kahoud RJ. , et al. Febrile infection-related epilepsy syndrome treated with anakinra. Ann Neurol 2016; 80 (06) 939-945
• 43 Caraballo RH, Reyes G, Avaria MFL. , et al. Febrile infection-related epilepsy syndrome: a study of 12 patients. Seizure 2013; 22 (07) 553-559
• 44 Jun J-S, Lee S-T, Kim R, Chu K, Lee SK. Tocilizumab treatment for new onset refractory status epilepticus. Ann Neurol 2018; 84 (06) 940-945
• 45 Gaspard N. A new hose to extinguish the FIRES?. Epilepsy Curr 2019; 19 (02) 86-87
• 46 Millichap JJ, Millichap JG. Ketogenic diet as preferred treatment of FIRES. Pediatr Neurol Briefs 2015; 29 (01) 3
• 47 François LL, Manel V, Rousselle C, David M. [Ketogenic regime as anti-epileptic treatment: its use in 29 epileptic children]. Arch Pediatr 2003; 10 (04) 300-306
• 48 Nabbout R, Mazzuca M, Hubert P. , et al. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia 2010; 51 (10) 2033-2037
• 49 Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R. Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure 2016; 41: 62-65
• 50 Singh RK, Joshi SM, Potter DM, Leber SM, Carlson MD, Shellhaas RA. Cognitive outcomes in febrile infection-related epilepsy syndrome treated with the ketogenic diet. Pediatrics 2014; 134 (05) e1431-e1435
• 51 Rosemergy I, Adler J, Psirides A. Cannabidiol oil in the treatment of super refractory status epilepticus. A case report. Seizure 2016; 35: 56-58
• 52 Gofshteyn JS, Wilfong A, Devinsky O. , et al. Cannabidiol as a potential treatment for febrile infection-related epilepsy syndrome (FIRES) in the acute and chronic phases. J Child Neurol 2017; 32 (01) 35-40
• 53 Tan WW, Chan DWS, Lee JH, Thomas T, Menon AP, Chan YH. Use of magnesium sulfate infusion for the management of febrile illness-related epilepsy syndrome: a case series. Child Neurol Open 2015; 2 (01) X14550067
• 54 Zeiler FA, Zeiler KJ, Teitelbaum J, Gillman LM, West M. VNS for refractory status epilepticus. Epilepsy Res 2015; 112: 100-113
• 55 Gedela S, Sitwat B, Welch WP, Krafty RT, Sogawa Y. The effect of vagus nerve stimulator in controlling status epilepticus in children. Seizure 2018; 55: 66-69
• 56 Kamel H, Cornes SB, Hegde M, Hall SE, Josephson SA. Electroconvulsive therapy for refractory status epilepticus: a case series. Neurocrit Care 2010; 12 (02) 204-210
• 57 Lin J-J, Lin K-L, Hsia S-H, Wang H-S. ; CHEESE Study Group. Therapeutic hypothermia for febrile infection-related epilepsy syndrome in two patients. Pediatr Neurol 2012; 47 (06) 448-450
• 58 Zeiler FA, Zeiler KJ, Teitelbaum J, Gillman LM, West M, Kazina CJ. Lidocaine for Status Epilepticus in Pediatrics. Can J Neurol Sci 2015; 42 (06) 414-426
• 59 Vendrame M, Loddenkemper T. Surgical treatment of refractory status epilepticus in children: candidate selection and outcome. Semin Pediatr Neurol 2010; 17 (03) 182-189
• 60 Tang-Wai R, Mailo J, Rosenblatt B. Breaking the cycle: A comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children. Seizure 2017; 47: 34-41
• 61 Caraballo RH, Reyes G, Avaria MF. , et al. Febrile infection-related epilepsy syndrome: a study of 12 patients. Seizure 2013; 22 (07) 553-559