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Neuron Specific Enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus

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Abstract

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure. A rapid diagnosis is fundamental to initiate antiepileptic treatment and to prevent the development of neurological sequels. Several serum and cerebrospinal fluid biomarkers have been proposed to help in the diagnosis of SE. Nevertheless, previous studies were conducted on too small patient cohorts, precluding the utilization of interesting biomarkers for the SE diagnosis. Here, we aimed to assess the ability of Neuron Specific Enolase (NSE), S100-beta protein (S100B) and progranulin to help in the diagnosis of SE in a large cohort of patients (36 control patients, 56 patients with pharmacoresistant epilepsy and 82 SE patients). Blood NSE, S100B and progranulin levels were higher in SE patients when compared with control patients or patients with pharmacoresistant epilepsy. Both NSE and progranulin levels were higher in cerebrospinal fluid from SE patients when compared with control patients. The receiver-operating characteristics curves revealed good accuracy at detecting SE for serum S100B (AUC 0.748) and plasma progranulin (AUC 0.756). The performances were lower for serum NSE (AUC 0.624). Eighty-four percent of patients with serum S100B levels above 0.09 ng/mL presented with a SE, whereas 90% of patients without SE had serum S100B levels lower than 0.09 ng/mL. Serum S100B levels were not significantly different according to SE etiology, SE semiology or SE refractoriness. Our results confirm that NSE, S100B and progranulin levels are increased after SE. We suggest that serum S100B levels might be added to clinical evaluation and electroencephalogram to identify difficult-to-diagnose form of SE.

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Availability of data and materials

All data are available on request upon the corresponding author.

Code availability

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Abbreviations

CONT:

Control patients

CSF:

Cerebrospinal fluid

EEG:

Electroencephalogram

EPI:

Pharmacoresistant epileptic patients

ICU:

Intensive Care Unit

NPV:

Negative predictive value

NSE:

Neuron Specific Enolase

NRSE:

Non-refractory status epilepticus

PPV:

Positive predictive value

PSRSE:

Prolonged super-refractory status epilepticus

ROC:

Receiver-operating characteristics

RSE:

Refractory status epilepticus

S100B:

S100-beta protein

SE:

Status epilepticus

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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 Assistance 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, AP-HP, Pitié-Salpêtrière Hospital, Paris, France

    Aurélie Hanin, Valerio Frazzini, Louis Cousyn, Virginie Lambrecq & Vincent Navarro

  2. AP-HP, Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Pitié-Salpêtrière Hospital, Paris, France

    Aurélie Hanin, Valerio Frazzini, Louis Cousyn, Virginie Lambrecq & Vincent Navarro

  3. Sorbonne Université, Paris, France

    Jérôme Alexandre Denis, Virginie Lambrecq & Vincent Navarro

  4. AP-HP, Endocrine and Oncological Biochemistry Department, Pitié-Salpêtrière Hospital, Paris, France

    Jérôme Alexandre Denis

  5. AP-HP, Metabolic Biochemistry Department, Pitié-Salpêtrière Hospital, Paris, France

    Françoise Imbert-Bismut, Benoit Rucheton & Dominique Bonnefont-Rousselot

  6. UTCBS, CNRS, INSERM, Université de Paris, Paris, France

    Dominique Bonnefont-Rousselot

  7. AP-HP, Neuro-Intensive Care Unit, Pitié-Salpêtrière Hospital, Paris, France

    Clémence Marois & Sophie Demeret

  8. AP-HP, Center of Reference for Rare Epilepsies, Pitié-Salpêtrière Hospital, Paris, France

    Vincent Navarro

Authors
  1. Aurélie Hanin
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  2. Jérôme Alexandre Denis
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  3. Valerio Frazzini
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  4. Louis Cousyn
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  5. Françoise Imbert-Bismut
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  6. Benoit Rucheton
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  7. Dominique Bonnefont-Rousselot
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  8. Clémence Marois
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  9. Virginie Lambrecq
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  10. Sophie Demeret
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  11. Vincent Navarro
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Contributions

Drafting the manuscript for content: AH and VN. Major role in the acquisition of data: AH, JAD, VF, FI-B, BR, CM, and VL. Study concept and design: AH, DB-R, SD, and VN. Analysis or interpretation of data: AH, JAD, VF, SD, and VN. Statistical analysis: AH. Obtaining funding: AH and VN. Revising the manuscript for content: JAD, VF, FI-B, BR, DB-R, CM, VL, and SD.

Corresponding author

Correspondence to Vincent Navarro.

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Conflicts of interest

Vincent Navarro reports personal fees from UCB Pharma, EISAI, GW Pharma and LivaNova, outside the submitted work. Sophie Demeret reports individual payment from UCB Pharma, Regeneron and ARGENX. The other authors report no disclosures.

Ethical 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., Denis, J.A., Frazzini, V. et al. Neuron Specific Enolase, S100-beta protein and progranulin as diagnostic biomarkers of status epilepticus. J Neurol 269, 3752–3760 (2022). https://doi.org/10.1007/s00415-022-11004-2

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  • DOI: https://doi.org/10.1007/s00415-022-11004-2

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