S100B Protein: a Diagnostic Aid in Episodes of Transient Loss of Consciousness? (EPILEPSY)

Diagnostic Performance of S100B Protein Measurement in Episodes of Transient Loss of Consciousness: a Prospective Cohort Study

S100B protein is a biomarker produced mainly by astrocytes and released into the bloodstream in the event of brain injury, with levels rising rapidly and markedly in acute conditions such as traumatic brain injury, stroke, or epileptic seizures, before declining quickly. Increased S100B levels following a convulsive seizure have been reported, suggesting potential value in distinguishing epilepsy from other causes; however, its use in the etiological assessment of transient loss of consciousness has not yet been studied. Loss of consciousness represents a common reason for Emergency Department visits and involves a wide range of causes, making diagnosis challenging due to often limited clinical history and resulting in numerous investigations. A biomarker such as S100B could help guide diagnosis more rapidly, particularly in distinguishing epilepsy from other causes, thereby reducing the need for additional tests and shortening hospital stay. To date, no study has evaluated the performance of S100B measurement in the etiological workup of transient loss of consciousness. The hypothesis underlying this study is that measurement of S100B levels in the Emergency Department could help differentiate epileptic seizures from other etiologies, particularly cardiac causes, and thus reduce additional investigations and hospital stay. This prospective observational study primarily aims to assess the diagnostic performance of S100B measurement for identifying epilepsy compared with other causes of transient loss of consciousness in adult patients presenting to the Emergency Department for this reason. The study will begin on April 30 and will last 15 months. In practice, eligible patients who do not oppose participation will undergo an additional blood sample at the time of initial sampling required for clinical management, with this sample used to measure plasma S100B levels; patient management will otherwise remain identical to standard care. Three months after the Emergency Department visit, an adjudication committee composed of a neurologist, a cardiologist, and an emergency physician will determine the final diagnosis based on all available data, including any additional investigations performed after the initial visit. The primary endpoint is the area under the ROC curve (AUROC) of S100B measurement, evaluating its ability to discriminate epilepsy from other causes of transient loss of consciousness.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Cryptogenic Epilepsy

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Christian KASSASSEYA, Dr; Phone Number: 01.49.81.21.11; Email: christian.kassasseya@aphp.fr

Study Locations

• France
  • Île-de-France Region
    • Créteil, Île-de-France Region, France, 94000
      • Hopital Henri Mondor
      • Contact: Christian KASSASSEYA, Dr; Phone Number: 01.49.81.21.11; Email: christian.kassasseya@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of adult patients presenting to the Emergency Department of Henri Mondor University Hospital during the inclusion period for an episode of transient loss of consciousness. Eligible patients will be screened consecutively and included if they meet all predefined inclusion criteria and none of the exclusion criteria.

Description

Inclusion Criteria:

• • Adult ≥ 18 years old

  • Presentation to the Emergency Department of Henri Mondor University Hospital
  • History of loss of consciousness
  • Undergoing a blood test as part of Emergency Department care
  • Covered by social security
  • Has agreed to participate in the study

Exclusion Criteria:

• Symptoms occurring more than 12 hours ago

  • History of head trauma without brain imaging performed
  • History of head trauma with intracranial bleeding confirmed on brain imaging
  • Refusal to participate in the study
  • Pregnant and/or breastfeeding women
  • Individuals unable to provide consent, particularly due to cognitive impairment
  • Individuals under legal protection:
  • Placed under guardianship
  • Deprived of liberty (incarcerated or hospitalized without consent)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
S100B Evaluation Cohort for Transient Loss of Consciousness

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the ROC curve (AUROC) of S100B measurement, assessing its ability to discriminate epilepsy from other causes of transient loss of consciousness	The primary outcome measure is the area under the ROC curve (AUROC) of S100B measurement, assessing its ability to discriminate epilepsy from other causes of transient loss of consciousness. The reference standard is the final diagnosis established by an adjudication committee at 3 months, blinded to the S100B result. The AUROC will be estimated with its 95% confidence interval (95% CI). Statistical significance will be assessed using a test comparing the AUROC to 0.5. The test will be considered of diagnostic interest if the AUROC is ≥ 0.75 and/or if the lower bound of the 95% CI is > 0.65, and if the p-value of the test versus 0.50 is < 0.05.	15 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the optimal S100B threshold for the diagnosis of epilepsy using Youden's index		15 months
Assessment of the diagnostic performance associated with the optimal S100B threshold for epilepsy diagnosis (sensitivity, specificity, positive predictive value, and negative predictive value).		15 months
Subgroup analyses based on adjudicated etiological diagnoses	Diagnostic performance of S100B will be evaluated separately within each etiological subgroup defined by the adjudication committee (epilepsy, cardiac syncope, hypoglycemia, vasovagal syncope)	15 Months
Analysis of S100B levels according to patient comorbidities	Plasma S100B concentrations will be measured using standard immunoassay techniques.	15 months
Analysis of results based on the time between symptom onset and sample collection (in hours).		15 months
Analysis of results according to patient age (<65 years, 65-79 years, and ≥80 years).		15 months
Analysis of results based on the occurrence of head trauma during the episode and, if applicable, the time between the trauma and the measurement of S100B (in hours).		15 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Biomarker-guided diagnosis; Diagnostic differentiation between epilepsy and other causes of transient loss of consciousness; Early diagnostic orientation in the Emergency Department; Diagnostic performance of S100B measurement in transient loss of consciousness
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: APHP251504

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No