Neurology, Neuropsychiatry, Psychosomatics

Advanced search

The specific features and pattern of febrile infection-related epilepsy syndrome (FIRES) in children

Full Text:


The paper considers the etiology, pathogenesis, clinical presentations, diagnosis and treatment in children with febrile infection-related epilepsy syndrome (FIRES) and the aspects of identifying this disease as an individual nosological entity. It details a study of the possible etiological factors of FIRES, such as metabolic, genetic, and immunological disorders, aseptic inflammatory processes, as well as a search for a certain infectious agent by inoculations of different biological environments of the body and by polymerase chain reaction; the diagnostic characteristics of FIRES at the present stage, including the use of electroencephalography, positron emission tomography, and magnetic resonance imaging; different approaches to drug therapy for FIRES at the onset stages of its clinical manifestations, protracted status epilepticus, and drugresistant epilepsy. The issues of the predictable outcome of this disease, including survival and the probability of further development of epilepsy and maintenance of cognitive functions, are also viewed. Diagnostic criteria for the syndrome, such as age at its onset 3 to 15 years in previously healthy children; acute onset as fever to develop high-frequency focal seizures several days later; the absence of the identified disease pathogen detected by the examinations of cerebrospinal fluid, serum, and other environments of the body; the development of drug-resistant epilepsy and severe permanent cognitive and motor deficits after the completion of an acute period in most cases are presented. The paper is clinically exemplified by the authors’ observation of an 11-year-old boy who meets the above criteria for the syndrome, but has a relatively favorable course, without developing severe drug-resistant epilepsy.

About the Authors

L. V. Shalkevich
Belorussian Medical Academy of Postgraduate Education, Minsk, Belarus 3, P. Brovka, Build. 3, Minsk 220013, Republic of Belarus
Russian Federation

O. A. Lvova
Ural State Medical University, Ministry of Health of Russia, Yekaterinburg, Russia 3, Pepin St., Yekaterinburg 620028, Russia
Russian Federation

A. I. Kudlach
Belorussian Medical Academy of Postgraduate Education, Minsk, Belarus 3, P. Brovka, Build. 3, Minsk 220013, Republic of Belarus
Russian Federation

V. V. Komir
City Children’s Clinical Hospital for Infectious Diseases, Minsk, Belarus 53, Yakubovsky St., Minsk 220018, Republic of Belarus
Russian Federation


1. Van Baalen A, Hä usler 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(4):209–16. DOI:

2. Sakuma H, Fukumizu M, Kohyama J. Efficacy of anticonvulsants on acute encephalitis with refractory, repetitive partial seizures (AERRPS). No To Hattatsu. 2001;33(5):385–90.

3. Sahin M, Menache C, Holmes G, Riviello J. Outcome of severe refractory status epilepticus in children. Epilepsia. 2001;42:1461–7. DOI: 1157.2001.21301.x.

4. Baxter P, Clarke A, Cross H, et al. Idiopathic catastrophic epileptic encephalopathy presenting with acute onset intractable status. Seizure. 2003;12:379–87. DOI: 10.1016/S1059-311(02)00340-0.

5. Wilder-Smith E, Lim E, Teoh H, et al. The NORSE (New-onset Refractory Status Epilepticus) Syndrome: Defining a Disease Entity. Ann Acad Med Singapore. 2005;34:417–20.

6. Mikaeloff Y, Jambaque I, Hertz-Pannier L, et al. Devastating epileptic encephalopathy in school-aged children (DESC): a pseudo encephalitis. Epilepsy Res. 2006;69:67–9. DOI:

7. Мухин КЮ, Петрухин АС, Холин АА. Разрушительная эпилептическая энцефалопатия у детей школьного возраста. В кн.: Эпилептические энцефалопатии и схожие синдромы у детей. Москва: АртСервис Лтд; 2011. С. 243–51. [Mukhin KYu, Petrukhin AS, Kholin AA. Destructive epileptic encephalopathy at children of school age. In: Epilepticheskie entsefalopatii i skhozhie sindromy u detei [Epileptic encephalopathies and similar syndromes at children]. Moscow: ArtServis Ltd; 2011. Р. 243–51.

8. Van Baalen A, Hä usler M, Boor R, et al. Febrile infection-related epilepsy syndrome (FIRES): a nonencephalitic encephalopathy in childhood. Epilepsia. 2010;51(7):1323–8. DOI:

9. Kramer U, Chi C, Lin K, et al. Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and outcome. Epilepsia. 2011;52(11):1956–65. DOI:

10. Kramer U, Shorer Z, Ben-Zeev B, et al. evere refractory status epilepticus owing to presumed encephalitis. J Child Neurol. 2005;20:184–7.

11. Lin J, Lin K, Wang H, et al. Analysis of status epilepticus related presumed encephalitis in children. Eur J Paediatr Neurol. 2008;12:32–7. DOI: 2007.05.007.

12. Specchio N, Fusco L, Claps D, Vigevano F. Epileptic encephalopathy in children possibly related to immune-mediated pathogenesis. Brain Dev. 2010;32:51–6. DOI:

13. Caraballo RH, Reyes G, Lopez Avaria MF, et al. Febrile infection-related epilepsy syndrome: a study of 12 patients. Seizure. 2013;22(7):553–9. DOI:

14. Nabbout R, Vezzani A, Dulac O, Chiron C. Acute encephalopathy with inflammationmediated status epilepticus. Lancet Neurology. 2011;10(1):99–108. DOI:

15. Specchio N, Fusco L, Vigevano F. Acuteonset epilepsy triggered by fever mimicking FIRES (febrile infection-related epilepsy syndrome): the role of protocadherin 19 (PCDH19) gene mutation. Epilepsia. 2011;52:172–217.DOI:

16. Kramer U, Chi CS, Lin KL, et al. Febrile infection-related epilepsy syndrome (FIRES): does duration of anesthesia affect outcome? Epilepsia. 2011;52:28–30. DOI:

17. Евтушенко СК. Разрушительные и труднокурабельные формы эпилепсии и эпилептические энцефалопатии у детей. Международный неврологический журнал. 2012;6(52):15–26. [Evtushenko SK. Destructive and difficult-to-treat epileptic forms and epileptic encephalopathies in children. Mezhdunarodnyi nevrologicheskii zhurnal. 2012;6(52):15–26. (In Russ.)]

18. Харитонов ВИ. Новое в эпилептологии. Нейро News: психоневрология и нейропсихиатрия. 2013;7(52):10–1. [Kharitonov VI. New in an epileptologiya. Neiro News: psikhonevrologiya i neiropsikhiatriya. 2013;7(52):10–1. (In Russ.)]

19. 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;51:2033–7. DOI: 1167.2010.02703.x.

20. Кулагин АЕ, Шалькевич ЛВ. Неотложная терапия эпилептического статуса у детей. Новости хирургии. 2009;17(2):136–44. [Kulagin AE, Shal'kevich LV. Urgent therapy of the epileptic status at children. Novosti khirurgii. 2009;17(2):136–44. (In Russ.)]

For citation:

Shalkevich L.V., Lvova O.A., Kudlach A.I., Komir V.V. The specific features and pattern of febrile infection-related epilepsy syndrome (FIRES) in children. Neurology, Neuropsychiatry, Psychosomatics. 2014;6(4):65-71. (In Russ.)

Views: 1606

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)