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Febrile infection-related epilepsy syndrome with claustrum lesion: an underdiagnosed inflammatory encephalopathy

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Abstract

Objective

To summarize the clinical characteristics and prognosis of febrile infection-related epilepsy syndrome with claustrum lesions (FIRES-C).

Method

Clinical data of FIRES-C patients were collected retrospectively. The study reviewed and analyzed their clinical manifestations, treatment strategies, and prognosis.

Result

Twenty patients were enrolled, including 13 females and 7 males, with a median onset age of 20.5 years. All patients developed seizures after fever, with a median interval of 5 days. Brain MRI showed symmetric lesions in the claustrum in all patients. The median interval from seizure onset to abnormal MRI signals detection was 12.5 days. All patients had negative results for comprehensive tests of neurotropic viruses and antineuronal autoantibodies. Seventy percent of cases had been previously empirically diagnosed with autoimmune encephalitis or viral encephalitis before. All patients received anti-seizure medicine. Eleven patients (55%) received antiviral therapy. All patients received immunotherapy, including glucocorticoids (100%), intravenous immunoglobulin (IVIg) (65%), plasma exchange (PLEX) (10%), tocilizumab (10%), rituximab (5%), and cyclophosphamide (5%). Sixty percent of patients received long-term immunotherapy (≥ 3 months). The median follow-up was 11.5 months;60% of patients were diagnosed with refractory epilepsy.

Conclusion

Bilateral claustrum lesion on MRI is a distinctive neuroimage feature for FIRES, which may serve as an indication for the initial clinical assessments. FIRES-C should be classified as a type of inflammatory encephalopathy characterized by a monophasic nature. Some FIRES-C patients respond to immunotherapy and antiseizure treatments but most experience refractory epilepsy as a long-term outcome.

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Data availability

Data available on request from the authors.

References

  1. Hirsch LJ, Gaspard N, van Baalen A et al (2018) Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia 59(4):739–744. https://doi.org/10.1111/epi.14016

    Article  PubMed  Google Scholar 

  2. van Baalen A, Vezzani A, Häusler M, Kluger G (2017) Febrile infection-related epilepsy syndrome: clinical review and hypotheses of epileptogenesis. Neuropediatrics 48(1):5–18. https://doi.org/10.1055/s-0036-1597271

    Article  PubMed  Google Scholar 

  3. Nixon J, Bateman D, Moss T (2001) An MRI and neuropathological study of a case of fatal status epilepticus. Seizure 10(8):588–591. https://doi.org/10.1053/seiz.2001.0553

    Article  CAS  PubMed  Google Scholar 

  4. Meletti S, Slonkova J, Mareckova I et al (2015) Claustrum damage and refractory status epilepticus following febrile illness. Neurology 85(14):1224–1232. https://doi.org/10.1212/WNL.0000000000001996

    Article  PubMed  PubMed Central  Google Scholar 

  5. Meletti S, Giovannini G, d’Orsi G et al (2017) New-onset refractory status epilepticus with claustrum damage: definition of the clinical and neuroimaging features. Front Neurol 8:111. https://doi.org/10.3389/fneur.2017.00111

    Article  PubMed  PubMed Central  Google Scholar 

  6. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the commission on classification and terminology of the international league against epilepsy. Epilepsia. 1981;22(4):489–501. https://doi.org/10.1111/j.1528-1157.1981.tb06159.x

  7. Fisher RS (2017) The new classification of seizures by the International League Against Epilepsy 2017. Curr Neurol Neurosci Rep 17(6):48. https://doi.org/10.1007/s11910-017-0758-6

    Article  PubMed  Google Scholar 

  8. Kwan P, Arzimanoglou A, Berg AT et al (2010) Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51(6):1069–1077. https://doi.org/10.1111/j.1528-1167.2009.02397.x

    Article  CAS  PubMed  Google Scholar 

  9. Dalmau J, Graus F (2023) Diagnostic criteria for autoimmune encephalitis: utility and pitfalls for antibody-negative disease. The Lancet Neurology 22(6):529–540. https://doi.org/10.1016/S1474-4422(23)00083-2

    Article  CAS  PubMed  Google Scholar 

  10. Lyon G, Dodge PR, Adams RD (1961) The acute encephalopathies of obscure origin in infants and children. Brain 84(4):680–708. https://doi.org/10.1093/brain/84.4.680

    Article  CAS  PubMed  Google Scholar 

  11. van Baalen A, Stephani U, Kluger G, Häusler M, Dulac O (2009) FIRES: febrile infection responsive epileptic (FIRE) encephalopathies of school age. Brain Dev. 31(1):91. https://doi.org/10.1016/j.braindev.2008.05.004. (author reply 92-93)

    Article  PubMed  Google Scholar 

  12. Mikaeloff Y, Jambaqué I, Hertz-Pannier L et al (2006) Devastating epileptic encephalopathy in school-aged children (DESC): a pseudo encephalitis. Epilepsy Res 69(1):67–79. https://doi.org/10.1016/j.eplepsyres.2006.01.002

    Article  CAS  PubMed  Google Scholar 

  13. Sakuma H, Awaya Y, Shiomi M et al (2010) Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis. Acta Neurol Scand 121(4):251–256. https://doi.org/10.1111/j.1600-0404.2009.01198.x

    Article  CAS  PubMed  Google Scholar 

  14. Pavone P, Corsello G, Raucci U et al (2022) Febrile infection-related epilepsy syndrome (FIRES): a severe encephalopathy with status epilepticus. Literature review and presentation of two new cases. Ital J Pediatr. 48:199. https://doi.org/10.1186/s13052-022-01389-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Perulli M, Cicala G, Turrini I et al (2022) Fighting autoinflammation in FIRES: the role of interleukins and early immunomodulation. Epilepsy Behav Rep 18:100531. https://doi.org/10.1016/j.ebr.2022.100531

    Article  PubMed  PubMed Central  Google Scholar 

  16. Silva G, Jacob S, Melo C, Alves D, Costa D (2018) Claustrum sign in a child with refractory status epilepticus after febrile illness: why does it happen? Acta Neurol Belg 118(2):303–305. https://doi.org/10.1007/s13760-017-0820-9

    Article  PubMed  Google Scholar 

  17. Sakuma H, Tanuma N, Kuki I, Takahashi Y, Shiomi M, Hayashi M (2015) Intrathecal overproduction of proinflammatory cytokines and chemokines in febrile infection-related refractory status epilepticus. J Neurol Neurosurg Psychiatry 86(7):820–822. https://doi.org/10.1136/jnnp-2014-309388

    Article  PubMed  Google Scholar 

  18. Miskin C, Hasbani DM (2014) Status epilepticus: immunologic and inflammatory mechanisms. Semin Pediatr Neurol 21(3):221–225. https://doi.org/10.1016/j.spen.2014.09.001

    Article  PubMed  Google Scholar 

  19. Vezzani A, Dingledine R, Rossetti AO (2015) Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application. Expert Rev Neurother 15(9):1081–1092. https://doi.org/10.1586/14737175.2015.1079130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kurada L, Bayat A, Joshi S, Koubeissi MZ (2019) The claustrum in relation to seizures and electrical stimulation. Front Neuroanat 13:8. https://doi.org/10.3389/fnana.2019.00008

    Article  PubMed  PubMed Central  Google Scholar 

  21. Benarroch EE (2021) What is the role of the claustrum in cortical function and neurologic disease? Neurology 96(3):110–113. https://doi.org/10.1212/WNL.0000000000011280

    Article  PubMed  Google Scholar 

  22. Yanagida A, Kanazawa N, Kaneko J et al (2020) Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus. Neurol Neuroimmunol Neuroinflamm 7(5):e849. https://doi.org/10.1212/NXI.0000000000000849

    Article  PubMed  PubMed Central  Google Scholar 

  23. Iizuka T, Kanazawa N, Kaneko J et al (2017) Cryptogenic NORSE: its distinctive clinical features and response to immunotherapy. Neurol Neuroimmunol Neuroinflamm 4(6):e396. https://doi.org/10.1212/NXI.0000000000000396

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lai YC, Muscal E, Wells E et al (2020) Anakinra usage in febrile infection related epilepsy syndrome: an international cohort. Ann Clin Transl Neurol 7(12):2467–2474. https://doi.org/10.1002/acn3.51229

    Article  PubMed  PubMed Central  Google Scholar 

  25. Stredny CM, Case S, Sansevere AJ, Son M, Henderson L, Gorman MP (2020) Interleukin-6 blockade with tocilizumab in Anakinra-refractory febrile infection-related epilepsy syndrome (FIRES). Child Neurol Open. 7:2329048X20979253. https://doi.org/10.1177/2329048X20979253

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was funded by the National High-Level Hospital Clinical Research Funding (grant no. 2022-PUMCH-B-120) and the CAMS Innovation Fund for Medical Sciences (grant no. CIFMS: 2021-I2M-1–003).

Author information

Authors and Affiliations

  1. Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

    Lin Bai, Nan Lin, Siyuan Fan, Haitao Ren, Qiang Lu & Hongzhi Guan

  2. Department of Neurology, Affiliated Hospital of Hebei University, Baoding, Hebei, China

    Weiying Di

  3. Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China

    Zucai Xu

  4. Department of Neurology, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia, China

    Bin Liu

  5. Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

    Jiawei Wang

Authors
  1. Lin Bai
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  10. Hongzhi Guan
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Consortia

the Encephalitis Collaborative Group

Contributions

Lin Bai: drafting the paper, design of the work, contributions to the acquisition, and analysis of data for the work. Weiying Di, Zucai Xu, Bin Liu, Nan Lin, Siyuan Fan, Haitao Ren, Qiang Lu, and Jiawei Wang: collecting the data, design of the work, and reviewing. Hongzhi Guan: design of the work, contributions to the interpretation of data for the work, and reviewing.

Corresponding author

Correspondence to Hongzhi Guan.

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Ethical approval

This retrospective study included cases registered in the Encephalitis and Paraneoplastic Syndrome Project and received approval from the Ethics Committee of PUMCH (approval no. JS-891). Written informed consent was obtained from all patients.

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Bai, L., Di, W., Xu, Z. et al. Febrile infection-related epilepsy syndrome with claustrum lesion: an underdiagnosed inflammatory encephalopathy. Neurol Sci 45, 3411–3419 (2024). https://doi.org/10.1007/s10072-024-07363-5

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  • DOI: https://doi.org/10.1007/s10072-024-07363-5

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