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

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.