{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:59:27Z","timestamp":1785427167659,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"Medical University of Gda\u0144sk, Poland","doi-asserted-by":"publisher","award":["SG\/01\/2024"],"award-info":[{"award-number":["SG\/01\/2024"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SG\/01\/2024"],"award-info":[{"award-number":["SG\/01\/2024"]}],"id":[{"id":"https:\/\/ror.org\/019sbgd69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Distinguishing seizures from other causes of transient loss of consciousness in the emergency department (ED) is challenging. This PRISMA-guided systematic review evaluated serum brain injury biomarkers for the acute diagnosis of seizures in adults. We searched PubMed and Web of Science for studies published between 2015 and 2025 and included 14 studies in which blood sampling occurred shortly after the event, reflecting the ED diagnostic window. Given the heterogeneity across studies, the overall certainty of the evidence was low. Neuron-specific enolase (NSE) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) were consistently elevated after epileptic seizures compared to healthy controls. NSE effectively differentiated seizures from syncope, while UCH-L1 and glial fibrillary acidic protein (GFAP) distinguished epileptic from psychogenic non-epileptic seizures (PNESs). Neurofilament light chain (NfL) remained stable after a single seizure but increased markedly in status epilepticus (SE). S100B and BDNF results were inconsistent. Although no single biomarker serves as a standalone test, NSE and UCH-L1 are promising complementary diagnostic tools for identifying epileptic seizures in adults. Furthermore, NfL is a strong candidate marker for SE, reflecting neuroaxonal injury. Larger prospective, standardized studies are needed before routine ED implementation.<\/jats:p>","DOI":"10.3390\/ijms27146432","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:44:02Z","timestamp":1784544242000},"page":"6432","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Biomarkers of Brain Injury in Diagnosis of Patients After Seizure in Emergency Department: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-9116","authenticated-orcid":false,"given":"Mateusz","family":"Antonow","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"},{"name":"Emergency Department, University Clinical Centre, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-2912","authenticated-orcid":false,"given":"Mariusz","family":"Siemi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"},{"name":"Emergency Department, University Clinical Centre, 80-214 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/eurheartj\/ehy037","article-title":"2018 ESC Guidelines for the diagnosis and management of syncope","volume":"39","author":"Brignole","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1161\/01.CIR.0000149236.92822.07","article-title":"Syncope Evaluation in the Emergency Department Study (SEEDS): A Multidisciplinary Approach to Syncope Management","volume":"110","author":"Shen","year":"2004","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Furlan, L., Esposito, G.J., Gianni, F., Solbiati, M., Mancusi, C., and Costantino, G. (2024). Syncope in the Emergency Department: A Practical Approach. J. Clin. Med., 13.","DOI":"10.3390\/jcm13113231"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chen, Z., Brodie, M.J., Ding, D., and Kwan, P. (2023). Editorial: Epidemiology of epilepsy and seizures. Front. Epidemiol., 3, Correction in Neurology\u00a02017, 86, 642. https:\/\/doi.org\/10.1212\/WNL.0000000000004317.","DOI":"10.3389\/fepid.2023.1273163"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1212\/WNL.0000000000003509","article-title":"Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies","volume":"88","author":"Fiest","year":"2017","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.nbd.2018.05.007","article-title":"Epilepsy biomarkers\u2014Toward etiology and pathology specificity","volume":"123","author":"Lapinlampi","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s42494-020-00016-y","article-title":"The first-line management of psychogenic non-epileptic seizures (PNES) in adults in the emergency: A practical approach","volume":"2","author":"Toffa","year":"2020","journal-title":"Acta Epileptol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.seizure.2016.11.001","article-title":"25 years of advances in the definition, classification and treatment of status epilepticus","volume":"44","author":"Trinka","year":"2017","journal-title":"Seizure"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/ane.13616","article-title":"Blood biomarkers in epilepsy","volume":"146","author":"Banote","year":"2022","journal-title":"Acta Neurol. Scand."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kobylarek, D., Iwanowski, P., Lewandowska, Z., Limphaibool, N., Szafranek, S., Labrzycka, A., and Kozubski, W. (2019). Advances in the Potential Biomarkers of Epilepsy. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00685"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S1474-4422(16)00112-5","article-title":"Advances in the development of biomarkers for epilepsy","volume":"15","author":"Vezzani","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Huebschmann, N.A., Luoto, T.M., Karr, J.E., Berghem, K., Blennow, K., Zetterberg, H., Ashton, N.J., Simr\u00e9n, J., Posti, J.P., and Gill, J.M. (2020). Comparing Glial Fibrillary Acidic Protein (GFAP) in Serum and Plasma Following Mild Traumatic Brain Injury in Older Adults. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.01054"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/jnc.14574","article-title":"The S100B story: From biomarker to active factor in neural injury","volume":"148","author":"Michetti","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/14737159.2018.1428089","article-title":"An update on diagnostic and prognostic biomarkers for traumatic brain injury","volume":"18","author":"Wang","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1111\/epi.17132","article-title":"Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus","volume":"63","author":"Giovannini","year":"2022","journal-title":"Epilepsia"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Scatena, R. (2015). Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Advances in Cancer Biomarkers, Springer.","DOI":"10.1007\/978-94-017-7215-0"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1535-7511.2005.05312.x","article-title":"Brain-derived Neurotrophic Factor and Epilepsy\u2014A Missing Link?","volume":"5","author":"Scharfman","year":"2005","journal-title":"Epilepsy Curr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S1474-4422(25)00154-1","article-title":"A new characterisation of acute traumatic brain injury: The NIH-NINDS TBI Classification and Nomenclature Initiative","volume":"24","author":"Manley","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1007\/s00415-018-9026-1","article-title":"Effect of anti-seizure drugs on serum S100B in patients with focal seizure: A randomized controlled trial","volume":"265","author":"Maiti","year":"2018","journal-title":"J. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2018.09.028","article-title":"The diagnostic value of serum UCHL-1 and S100-B levels in differentiate epileptic seizures from psychogenic attacks","volume":"1704","author":"Asadollahi","year":"2019","journal-title":"Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.21037\/apm-20-1494","article-title":"Relationship of serum ATPase activity and the levels of neuron-specific enolase, S100B and B-cell lymphoma\/leukemia-2 with cognitive function after epileptic seizure","volume":"9","author":"Zhang","year":"2020","journal-title":"Ann. Palliat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1166\/mex.2021.2097","article-title":"The clinical value of EEG monitoring and silver nanoparticles to detect the levels of serum Nesfatin-1, S100\u03b2 and neuron-specific enolase in evaluating the severity and prognosis of epilepsy","volume":"11","author":"Yu","year":"2021","journal-title":"Mater. Express"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109131","DOI":"10.1016\/j.yebeh.2023.109131","article-title":"Neuro-glial degeneration in Status Epilepticus: Exploring the role of serum levels of Neurofilament light chains and S100B as prognostic biomarkers for short-term functional outcome","volume":"140","author":"Giovannini","year":"2023","journal-title":"Epilepsy Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.seizure.2023.02.012","article-title":"Changes in serum blood-brain barrier markers after bilateral tonic-clonic seizures","volume":"106","author":"Cudna","year":"2023","journal-title":"Seizure"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/epi4.13130","article-title":"The role of ubiquitin C-terminal hydrolase (UCH-L1) and protein S100B in differentiating patients with epileptic and psychogenic non-epileptic seizures\u2014Pilot study","volume":"10","author":"Ivancic","year":"2025","journal-title":"Epilepsia Open"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1111\/epi.17023","article-title":"Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology","volume":"62","author":"Alvim","year":"2021","journal-title":"Epilepsia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106612","DOI":"10.1016\/j.eplepsyres.2021.106612","article-title":"Kinetics of serum brain-derived neurotrophic factor (BDNF) concentration levels in epileptic patients after generalized tonic-clonic seizures","volume":"173","author":"Poniatowski","year":"2021","journal-title":"Epilepsy Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.seizure.2018.07.010","article-title":"Serum GFAP level: A novel adjunctive diagnostic test in differentiate epileptic seizures from psychogenic attacks","volume":"61","author":"Simani","year":"2018","journal-title":"Seizure"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.eplepsyres.2017.10.003","article-title":"Effect of carbamazepine and oxcarbazepine on serum neuron-specific enolase in focal seizures: A randomized controlled trial","volume":"138","author":"Maiti","year":"2017","journal-title":"Epilepsy Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tan, Z., Jiang, J., Tian, F., Peng, J., Yang, Z., Li, S., and Long, X. (2020). Serum Visinin-Like Protein 1 Is a Better Biomarker Than Neuron-Specific Enolase for Seizure-Induced Neuronal Injury: A Prospective and Observational Study. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.567587"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/ijpvm.IJPVM_129_20","article-title":"Differential Diagnosis of Seizure and Syncope by the Means of Biochemical Markers in Emergency Department Patients","volume":"13","author":"Masoumi","year":"2022","journal-title":"Int. J. Prev. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7326\/0003-4819-155-8-201110180-00009","article-title":"QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies","volume":"155","author":"Whiting","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"ref_33","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2024). Cochrane Handbook for Systematic Reviews of Interventions, Cochrane. Version 6.5 (Updated August 2024)."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6432\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:44:40Z","timestamp":1784544280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":33,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146432"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146432","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}