Clinical characteristics of 27 children with febrile infection-related epilepsy syndrome in a single center

Abstract

To investigate the clinical characteristics of febrile infection-related epilepsy syndrome (FIRES). We used trajectory analysis and logistic regression analysis to investigate the clinical characteristics and prognostic risk factors respectively. Twenty-seven patients (16 males) were included. The median age of onset was 7 (IQR: 4–9) years. Routine cerebrospinal fluid (CSF) examination was normal. Electroencephalogram (EEG) showed frequent microseizures and electroseizures in all patients. Eight patients had claustrum signs in the acute phase. Anesthetics and anti-seizure medications (ASM) were used in all patients. All patients received immunotherapy, including plasma exchange (n = 4), immunoglobulin (n = 26), and corticosteroids (n = 19). Trajectory diagrams of seizure showed 6 patients had bimodal disease course. Besides, we found there may be a linear relationship between body temperature and convulsion frequency (R² = 0.25). The median Glasgow outcome scale (GOS) was 3 (IQR: 1–4). Nine deaths occurred, including abandonment of treatment (n = 3), hemodynamic instability (n = 3), brain hernia (n = 2), and brain hernia with hemodynamic instability (n = 1). Seizure onset combined with fever (p = 0.003), periodic discharge (p = 0.002), and non-ketogenic diet (non-KD) (p = 0.005) were independent risk factors for death. The KD group (n = 10) had lower mortality (p = 0.009), lower convulsion frequency at latest follow-up (p < 0.001), less ASM (p = 0.002), and higher GOS (p < 0.001) than non-KD group (n = 17). Therefore, some FIRES patients may have bimodal disease course. There may be a linear relationship between body temperature and convulsion frequency. Seizure onset combined with fever, periodic discharge and KD may affect the prognosis.

Keywords

children / FIRES / ketogenic diet / trajectory analysis

References

[1] Specchio N, Wirrell EC, Scheffer IE, et al. International League against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE task force on nosology and definitions. Epilepsia. 2022;63(6):1398-1442.

[2] Wickström R, Taraschenko O, Dilena R, et al. International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): summary and clinical tools. Epilepsia. 2022;63(11):2827-2839.

[3] Sculier C, Barcia Aguilar C, Gaspard N, et al. Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort). Epilepsia. 2021;62(7):1629-1642.

[4] Goh Y, Tay SH, Yeo LLL, Rathakrishnan R. Bridging the gap: tailoring an approach to treatment in febrile infection-related epilepsy syndrome. Neurology. 2023;100(24):1151-1155.

[5] Girardin ML, Flamand T, Roignot O, et al. Treatment of new onset refractory status epilepticus/febrile infection-related epilepsy syndrome with tocilizumab in a child and a young adult. Epilepsia. 2023;64(6):e87-e92.

[6] Howe CL, Johnson RK, Overlee BL, Sagen JA, Mehta N, Farias-Moeller R. Drug-resistant seizures associated with hyperinflammatory monocytes in FIRES. Ann Clin Transl Neurol. 2023;10(5):719-731.

[7] Fetta A, Crotti E, Campostrini E, et al. Cannabidiol in the acute phase of febrile infection-related epilepsy syndrome (FIRES). Epilepsia Open. 2023;8(2):685-691.

[8] Kramer U, Chi CS, Lin KL, et al. Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome: a multicenter study on 77 children. Epilepsia. 2011;52(11):1956-1965.

[9] Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018;3(2):175-192.

[10] Subspecialty Group of Neurology, The Society of Pediatrics, Chinese Medical Association, China Association Against Epilepsy, Editorial Board, Chinese Journal of Pediatrics. Consensus on ketogenic diet therapy for epilepsy and related nervous system diseases. Chin J Pediatr. 2019;57(11):820-825.

[11] Myers KA, McMahon JM, Mandelstam SA, et al. Fatal cerebral edema with status epilepticus in children with Dravet syndrome: report of 5 cases. Pediatrics. 2017;139(4):e20161933.

[12] Ammirati E, Moslehi JJ. Diagnosis and treatment of acute myocarditis: a review. JAMA. 2023;329(13):1098-1113.

[13] Liu Q, Tan B, Zhang J, et al. Premature mortality risk in individuals with convulsive epilepsy: results from a longitudinal, prospective, population-based study. Epilepsy Res. 2023;197:107243.

[14] Ferlini L, Maenhout C, Crippa IA, et al. The association between the presence and burden of periodic discharges and outcome in septic patients: an observational prospective study. Crit Care. 2023;27(1):179.

[15] Peluso L, Rechichi S, Franchi F, et al. Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation. Crit Care. 2020;24(1):629.

[16] Fukuma K, Tojima M, Tanaka T, et al. Periodic discharges plus fast activity on electroencephalogram predict worse outcomes in poststroke epilepsy. Epilepsia. 2023;64(12):3279-3293.

[17] Sansevere AJ, Dibacco ML, Zhang B, et al. Sporadic and periodic interictal discharges in critically ill children: seizure associations and time to seizure identification. J Clin Neurophysiol. 2023;40(2):130-135.

[18] Willems LM, Trienekens F, Knake S, et al. EEG patterns and their correlations with short-and long-term mortality in patients with hypoxic encephalopathy. Clin Neurophysiol. 2021;132(11):2851-2860.

[19] Jones KG, Lybbert C, Euler MJ, et al. Diversity of electroencephalographic patterns during propofol-induced burst suppression. Front Syst Neurosci. 2023;17:1172856.

[20] Madžar D, Reindl C, Giede-Jeppe A, et al. Impact of timing of continuous intravenous anesthetic drug treatment on outcome in refractory status epilepticus. Crit Care. 2018;22(1):317.

[21] Phabphal K, Chisurajinda S, Somboon T, Unwongse K, Geater A. Does burst-suppression achieve seizure control in refractory status epilepticus. BMC Neurol. 2018;18(1):46.

[22] Sculier C, Gaspard N. New-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. Curr Opin Neurol. 2023;36(2):110-116.

[23] Peng P, Peng J, Yin F, et al. Ketogenic diet as a treatment for super-refractory status epilepticus in febrile infection-related epilepsy syndrome. Front Neurol. 2019;10:423.

[24] Teng LY, Lee VW, Murugesu S, et al. Glycemic biomarkers in children with drug-resistant epilepsy on various types of ketogenic diet therapies: a cross-sectional study. Epilepsia. 2022;63(8):2011-2023.

[25] Schoeler NE, Simpson Z, Zhou R, Pujar S, Eltze C, Cross J. Dietary management of children with super-refractory status epilepticus: a systematic review and experience in a single UK tertiary centre. Front Neurol. 2021;12:643105.

[26] Chomtho S, Uaariyapanichkul J, Chomtho K. Outcomes of parenteral vs enteral ketogenic diet in pediatric super-refractory status epilepticus. Seizure. 2022;96:79-85.

[27] Worden LT, Abend NS, Bergqvist AGC. Ketogenic diet treatment of children in the intensive care unit: safety, tolerability, and effectiveness. Seizure. 2020;80:242-248.

[28] Norwitz NG, Sethi S, Palmer CM. Ketogenic diet as a metabolic treatment for mental illness. Curr Opin Endocrinol Diabetes Obes. 2020;27(5):269-274.

[29] Gerges M, Selim L, Girgis M, El Ghannam A, Abdelghaffar H, El-Ayadi A. Implementation of ketogenic diet in children with drug-resistant epilepsy in a medium resources setting: Egyptian experience. Epilepsy Behav Case Rep. 2018;11:35-38.

[30] Xia S, Lin R, Jin L, et al. Prevention of dietary-fat-fueled ketogenesis attenuates BRAF V600E tumor growth. Cell Metab. 2017;25(2):358-373.

[31] Thijs RD, Surges R, O'Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393(10172):689-701.

[32] Figlerowicz M, Mazur-Melewska K, Kemnitz PL, Mania A. Pediatric postviral autoimmune disorders of the CNS. Future Virol. 2020;15(5):307-315.

[33] Wickström R, Ygberg S, Lindefeldt M, Dahlin M. Altered cytokine levels in cerebrospinal fluid following ketogenic diet of children with refractory epilepsy. Epilepsy Res. 2021;177:106775.

[34] The Brain Trauma Foundation. The American association of neurological surgeons. The joint section on neurotrauma and critical care. Age. J Neurotrauma. 2000;17(6-7):573-581.

[35] Muccioli L, Pensato U, Di Vito L, Messia M, Nicodemo M, Tinuper P. Teaching NeuroImage: claustrum sign in febrile infection-related epilepsy syndrome. Neurology. 2022;98(10):e1090-e1091.

RIGHTS & PERMISSIONS

2024 2024 The Author(s). Pediatric Discovery published by John Wiley & Sons Australia, Ltd on behalf of Children's Hospital of Chongqing Medical University.