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Clinico-biological markers for the prognosis of status epilepticus in adults

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Abstract

Prediction of mortality, functional outcome and recovery after status epilepticus (SE) is a challenge. Biological and clinical markers have been proposed to reflect the brain injury or to monitor critical ill patients’ severity. The aim of this study was to characterize short-term and long-term prognostic factors for SE patients hospitalized in intensive care unit. Patient’s outcome was assessed using the modified Rankin Scale at discharge and after 6–12 months. We first assessed the univariate prognosis significance of 51 clinical, demographic or biochemical markers. Next, we built multivariate clinico-biological models by combining most important factors. Statistical models’ performances were compared to those of two previous published scales STESS and mSTESS. Eighty-one patients were enrolled. Thirty-five patients showed a steady state while 46 patients clinically worsened at discharge: 14 died, 14 had persistent disability at 6–12 months and 18 recovered. Logistic regression analysis revealed that clinical markers (SE refractoriness, SE duration, de novo SE) were significant independent predictors of worsening while lipids markers and progranulin better predicted mortality. The association of clinico-biological variables allowed to accurately predict worsening at discharge (AUC > 0.72), mortality at discharge (AUC 0.83) and recovery at long-term (AUC 0.89). Previous scales provided lower prediction for worsening (AUC 0.63, STESS; 0.53, mSTESS) and mortality (AUC 0.56, STESS; 0.62, mSTESS) (p < 0.001). We proposed new clinico-biological models with a strong discrimination power for prediction of short- and long-term outcome of hospitalized status epilepticus patients. Their implementation in electronic devices may enhance their clinical liability.

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All data are available on request upon the corresponding author.

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The codes are available on request upon the corresponding author.

Abbreviations

AUC:

Area under the receiver operating characteristic curve

CSF:

Cerebrospinal fluid

FC:

Free cholesterol

ICU:

Intensive care unit

ML:

Machine learning

mRS:

Modified Rankin score

NORSE:

New-onset refractory status epilepticus

NPV:

Negative predictive value

PPV:

Positive predictive value

RSE:

Refractory status epilepticus

S100B:

S100-beta protein

SE:

Status epilepticus

SVM:

Support vector machine

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Acknowledgements

We thank Marion Houot (Sorbonne Université, Institut du Cerveau – Paris Brain Institute – ICM, Pitié-Salpêtrière Hospital) for her advices for statistical analysis.

Funding

This work received support from the “Investissements d’avenir” program ANR-10-IAIHU-06, from the “Fondation pour la Recherche Médicale” (FDM20170839111) and from the Fondation Assitance Publique-Hôpitaux de Paris (EPIRES- Marie Laure PLV Merchandising).

Author information

Authors and Affiliations

  1. Sorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, Inserm, CNRS, APHP, Hôpital de la Pitié-Salpêtrière, DMU Neurosciences 6, Paris, France

    Aurélie Hanin, Virginie Lambrecq, Benjamin Rohaut, Meriem Bouguerra, Mario Chavez & Vincent Navarro

  2. AP-HP, Hôpital de la Pitié-Salpêtrière, DMU Neurosciences 6, Epilepsy Unit and Clinical Neurophysiology Department, Paris, France

    Aurélie Hanin, Virginie Lambrecq & Vincent Navarro

  3. AP-HP, Hôpital de la Pitié-Salpêtrière, Neuro-Intensive Care Unit, Paris, France

    Sophie Demeret, Benjamin Rohaut, Clémence Marois & Meriem Bouguerra

  4. Groupe de Recherche Clinique en REanimation et Soins Intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE), Sorbonne Université, Paris, France

    Clémence Marois

  5. AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, Site Pitié-Salpêtrière, Service de Médecine Intensive ET Réanimation (Département R3S), Paris, France

    Alexandre Demoule

  6. Sorbonne Université, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France

    Alexandre Demoule

  7. Department of Clinical Chemistry, AP-HP, Hôpital Necker-Enfants Malades, Paris, France

    Jean-Louis Beaudeux

  8. Faculté de Pharmacie, Université de Paris, Paris, France

    Jean-Louis Beaudeux & Dominique Bonnefont-Rousselot

  9. Department of Metabolic Biochemistry, AP-HP, Hôpital de La Pitié-Salpêtrière, Paris, France

    Randa Bittar, Françoise Imbert-Bismut, Foudil Lamari, Benoit Rucheton & Dominique Bonnefont-Rousselot

  10. Sorbonne Université, UMR_S 1166 ICAN, 75013, Paris, France

    Randa Bittar

  11. Department of Endocrine and Oncological Biochemistry, AP-HP, Hôpital de la Pitié-Salpêtrière, Sorbonne Université, Paris, France

    Jérôme Alexandre Denis

  12. Unité des Technologies Chimiques et Biologiques Pour la Santé (UTCBS), INSERM U 1267, UMR 8258 CNRS, Université de Paris, Paris, France

    Dominique Bonnefont-Rousselot

  13. Center of Reference for Rare Epilepsies, Pitié-Salpêtrière Hospital, Paris, France

    Vincent Navarro

Authors
  1. Aurélie Hanin
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  2. Sophie Demeret
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  3. Virginie Lambrecq
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  4. Benjamin Rohaut
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  5. Clémence Marois
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  6. Meriem Bouguerra
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  7. Alexandre Demoule
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  8. Jean-Louis Beaudeux
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  9. Randa Bittar
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  10. Jérôme Alexandre Denis
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  11. Françoise Imbert-Bismut
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  12. Foudil Lamari
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  13. Benoit Rucheton
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  14. Dominique Bonnefont-Rousselot
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  15. Mario Chavez
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  16. Vincent Navarro
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Contributions

Conception and design of the study: AH, MC, VN. Acquisition and analysis of data: AH, SD, VL, BR, CM, MB, AD, RB, JAD, FIB, FL, BR, DBR, MC, VN. Drafting a significant portion of the manuscript or figures: AH, SD, VL, BR, CM, MB, AD, JLB, RB, JAD, FIB, FL, BR, DBR, MC, VN. Statistical analysis: AH, MC. Study supervision: SD, DBR, MC, VN.

Corresponding author

Correspondence to Vincent Navarro.

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Conflicts of interest

AH, SD, MC and VN have a patent pending related to the current research. VN reports personal fees from UCB Pharma, EISAI, GW Pharma and LivaNova, outside the submitted work. AD reports grants, personal fees and non-financial support from Philips and Lungpacer, personal fees from Baxter, Getinge, Lowenstein and Gilead, personal fees and non-financial support from Fisher & Paykel and Respinor and grants from French Ministry of Health, outside the submitted work. SD reports individual payment from UCB Pharma, Regeneron and ARGENX. The other authors report no disclosures related to the current research.

Ethics approval

The protocol was approved by our local (2012, CPP Paris-VI) and by the INSERM ethic committees (C16-16, 20152482). The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Hanin, A., Demeret, S., Lambrecq, V. et al. Clinico-biological markers for the prognosis of status epilepticus in adults. J Neurol 269, 5868–5882 (2022). https://doi.org/10.1007/s00415-022-11199-4

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