CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus

ABSTRACT Objective Cryptogenic new‐onset refractory status epilepticus (cNORSE) is a devastating condition characterized by the de novo onset of status epilepticus with unclear etiology. The identification of relevant early biomarkers in cNORSE is important to elucidate pathophysiology, aid clinical...

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Main Authors: Yihui Goh, Yoonhyuk Jang, Soo Jean Shin, Soo Hyun Ahn, Su Yee Mon, Yoon Hee Shin, Kon Chu, Sang Kun Lee, Soon‐Tae Lee
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Annals of Clinical and Translational Neurology
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Online Access:https://doi.org/10.1002/acn3.70043
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author Yihui Goh
Yoonhyuk Jang
Soo Jean Shin
Soo Hyun Ahn
Su Yee Mon
Yoon Hee Shin
Kon Chu
Sang Kun Lee
Soon‐Tae Lee
author_facet Yihui Goh
Yoonhyuk Jang
Soo Jean Shin
Soo Hyun Ahn
Su Yee Mon
Yoon Hee Shin
Kon Chu
Sang Kun Lee
Soon‐Tae Lee
author_sort Yihui Goh
collection DOAJ
description ABSTRACT Objective Cryptogenic new‐onset refractory status epilepticus (cNORSE) is a devastating condition characterized by the de novo onset of status epilepticus with unclear etiology. The identification of relevant early biomarkers in cNORSE is important to elucidate pathophysiology, aid clinical decision‐making, and prognosticate outcomes in cNORSE. Methods CSF samples were obtained within 7 days of NORSE onset from an adult cNORSE cohort in a national referral center in South Korea. Nineteen patients with cNORSE were studied: 9 were male (47.4%) and the median age was 35.0 [IQR: 27.0–54.3] years. CSF from 21 patients with other neurological diseases (atypical parkinsonism, postural orthostatic hypotension syndrome, epilepsy, and cerebellar ataxia) was used as controls. Proteomic analysis was conducted using the Olink platform, and potential biomarker candidates were correlated with clinical data and MRI findings. Results Based on correlation analyses between proteomic data and clinical outcomes, total tau (t‐tau) was selected as a potential biomarker. Patients with cNORSE had higher CSF t‐tau levels than controls (p < 0.001). Early detection of high CSF t‐tau was associated with the presence of hippocampal atrophy in the postacute phase of cNORSE (p = 0.044). The initial elevation of t‐tau levels also correlated with a higher number of anti‐seizure medications used (p = 0.031) and less improvement in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores 1 month after NORSE onset (p = 0.066). T‐tau levels were correlated with CSF pro‐inflammatory cytokines/chemokines and mediators of neuronal damage. Interpretation Elevated CSF t‐tau levels detected early after cNORSE onset may be a useful marker of initial brain injury and predict subsequent hippocampal atrophy.
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spelling doaj-art-3b565647d552431c845902ce2c2ab4cb2025-08-20T01:52:39ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-05-011251054106410.1002/acn3.70043CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status EpilepticusYihui Goh0Yoonhyuk Jang1Soo Jean Shin2Soo Hyun Ahn3Su Yee Mon4Yoon Hee Shin5Kon Chu6Sang Kun Lee7Soon‐Tae Lee8Department of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaDepartment of Neurology Seoul National University Hospital, Seoul National University College of Medicine Seoul South KoreaABSTRACT Objective Cryptogenic new‐onset refractory status epilepticus (cNORSE) is a devastating condition characterized by the de novo onset of status epilepticus with unclear etiology. The identification of relevant early biomarkers in cNORSE is important to elucidate pathophysiology, aid clinical decision‐making, and prognosticate outcomes in cNORSE. Methods CSF samples were obtained within 7 days of NORSE onset from an adult cNORSE cohort in a national referral center in South Korea. Nineteen patients with cNORSE were studied: 9 were male (47.4%) and the median age was 35.0 [IQR: 27.0–54.3] years. CSF from 21 patients with other neurological diseases (atypical parkinsonism, postural orthostatic hypotension syndrome, epilepsy, and cerebellar ataxia) was used as controls. Proteomic analysis was conducted using the Olink platform, and potential biomarker candidates were correlated with clinical data and MRI findings. Results Based on correlation analyses between proteomic data and clinical outcomes, total tau (t‐tau) was selected as a potential biomarker. Patients with cNORSE had higher CSF t‐tau levels than controls (p < 0.001). Early detection of high CSF t‐tau was associated with the presence of hippocampal atrophy in the postacute phase of cNORSE (p = 0.044). The initial elevation of t‐tau levels also correlated with a higher number of anti‐seizure medications used (p = 0.031) and less improvement in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores 1 month after NORSE onset (p = 0.066). T‐tau levels were correlated with CSF pro‐inflammatory cytokines/chemokines and mediators of neuronal damage. Interpretation Elevated CSF t‐tau levels detected early after cNORSE onset may be a useful marker of initial brain injury and predict subsequent hippocampal atrophy.https://doi.org/10.1002/acn3.70043hippocampal atrophynew onset refractory status epilepticustau
spellingShingle Yihui Goh
Yoonhyuk Jang
Soo Jean Shin
Soo Hyun Ahn
Su Yee Mon
Yoon Hee Shin
Kon Chu
Sang Kun Lee
Soon‐Tae Lee
CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus
Annals of Clinical and Translational Neurology
hippocampal atrophy
new onset refractory status epilepticus
tau
title CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus
title_full CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus
title_fullStr CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus
title_full_unstemmed CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus
title_short CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New‐Onset Refractory Status Epilepticus
title_sort csf tau is a biomarker of hippocampal injury in cryptogenic new onset refractory status epilepticus
topic hippocampal atrophy
new onset refractory status epilepticus
tau
url https://doi.org/10.1002/acn3.70043
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