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. 2025 May 19.
doi: 10.1111/epi.18450. Online ahead of print.

Patients with status epilepticus and new-onset refractory status epilepticus display drastically altered fecal microbiomes compared to chronic epilepsy patients

Claude Steriade  1   2 , Scott C Thomas  3 , Fangxi Xu  3 , Amit Ahituv  1 , Aurélie Hanin  4   5 , Maria Pleshkevich  1 , Samantha Hwang  3 , Alexandra Ramirez  6 , Brandon Foreman  6 , Jiyeoun Yoo  7 , Onome Eka  7 , Marissa Kellogg  8 , Audrey Oliger  8 , Mark S Wainwright  9 , Mikaela Morales  9 , Nicolas Gaspard  4   10 , Lawrence J Hirsch  4 , Orrin Devinsky  1 , Deepak Saxena  3
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Patients with status epilepticus and new-onset refractory status epilepticus display drastically altered fecal microbiomes compared to chronic epilepsy patients

Claude Steriade et al. Epilepsia. .

Abstract

Objective: New-onset refractory status epilepticus (NORSE) occurs in people without pre-existing epilepsy or a rapidly identified structural, toxic, metabolic, or other cause. NORSE is a rare disorder with high morbidity and mortality rates and limited evidence for effective therapies. We aimed to assess whether the gut microbiome of NORSE and status epilepticus (SE) differs from that of chronic epilepsy, whether NORSE differs from SE at different disease time points, and to examine the correlations between specific gut microbiota and cytokines in NORSE and SE.

Methods: This longitudinal cohort study observed patients with NORSE (n = 15), SE (n = 17), and chronic epilepsy who were not in SE (n = 12). NORSE patients were recruited through the NORSE Consortium. Patients with NORSE and SE underwent longitudinal serial biospecimen collection. Fecal samples were subjected to whole-community shotgun metagenomics to characterize microbiome features. Cohorts were evaluated for prokaryotic, eukaryotic, and functional diversity. Correlations between blood inflammatory cytokine levels and microbiome features and covariate analysis with critical illness and clinical treatments were examined for NORSE and SE patients during and after SE resolution.

Results: During SE, NORSE and SE patients had significantly different prokaryotic, eukaryotic, and functional microbiome levels compared to chronic epilepsy patients without SE. Limited microbiome differences were observed within and between NORSE and SE, although these groups displayed differing correlation patterns between microbial species and cytokines. Patients who later died or were tube-fed harbored significantly different microbiomes than those who survived or were orally fed.

Significance: NORSE and SE patients present with a more variable and dramatically different fecal microbiome than chronic epilepsy patients, which may indicate gut dysbiosis that may be reciprocally linked to inflammatory responses. Although NORSE and SE patients had similar microbiome structures, fungal and bacterial correlates with inflammatory cytokines differed between NORSE and SE, with confounding factors influencing microbiome structure. Our data suggest a microbiome-specific response to NORSE and SE, with implications for future treatment strategies.

Keywords: NORSE; cytokines; gut microbiome; neuroinflammation; status epilepticus.

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References

REFERENCES

    1. Rossetti AO, Lowenstein DH. Management of refractory status epilepticus in adults: still more questions than answers. Lancet Neurol. 2011;10(10):922–930.
    1. Hirsch LJ, Gaspard N, van Baalen A, Nabbout R, Demeret S, Loddenkemper T, et al. Proposed consensus definitions for new‐onset refractory status epilepticus (NORSE), febrile infection‐related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59(4):739–744.
    1. Ritter LM, Nashef L. New‐onset refractory status epilepticus (NORSE). Pract Neurol. 2021;21(2):119–127.
    1. Sculier C, Gaspard N. New onset refractory status epilepticus (NORSE). Seizure. 2019;68:72–78.
    1. Sheikh Z, Hirsch LJ. A practical approach to in‐hospital management of new‐onset refractory status epilepticus/febrile infection related epilepsy syndrome. Front Neurol. 2023;14:1150496.

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