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Acute Brain Injury in New-Onset Refractory Status Epilepticus and Etiology-Defined Status Epilepticus
Stefano Meletti1,2, Aurelie Hanin3,4, Giada Giovannini1
1Epilepsy Center and Neurophysiology Unit, Modena Academic Hospital, Modena, Italy.
JAMA Neurology
|April 27, 2026
Summary
New-onset refractory status epilepticus (NORSE) causes significant brain injury. Elevated neurofilament light chain (NfL) levels indicate this damage and correlate with poor outcomes, suggesting a critical window for intervention.
Area of Science:
- Neurology
- Neuroscience
- Biomarker Research
Background:
- Seizure-induced brain injury is a critical concern in new-onset refractory status epilepticus (NORSE).
- Identifying biomarkers for neuronal damage is crucial for timely therapeutic interventions and improved patient outcomes in NORSE.
- Quantifying acute brain injury is essential for understanding the pathophysiology of NORSE and related conditions.
Purpose of the Study:
- To quantify acute brain injury by measuring neurofilament light chain (NfL) and S100-beta (S100B) protein levels.
- To compare NfL and S100B levels in patients with cryptogenic NORSE (cNORSE) and etiology-defined status epilepticus (eSE) against control groups.
- To assess the association between NfL/S100B levels and short-term functional outcomes in patients with status epilepticus.
Main Methods:
- International cross-sectional study involving 36 hospitals in the US, 2 in Canada, and 1 each in Italy, France, and Belgium.
- Enrollment of patients with cNORSE and eSE during ongoing seizure activity, with comparison groups of chronic epilepsy patients and healthy individuals.
- Measurement of serum and cerebrospinal fluid (CSF) concentrations of neurofilament light chain (NfL) and S100-beta (S100B).
Main Results:
- NfL concentrations were significantly elevated in cNORSE (approx. 10-fold in CSF, 4-fold in serum) compared to eSE cohorts.
- Serum NfL levels in cNORSE were nearly 20-fold higher than in epilepsy and healthy control groups.
- NfL levels showed a rapid increase in the weeks following seizure onset and correlated strongly between serum and CSF.
- Elevated serum NfL was independently associated with poor functional outcomes at discharge.
- S100B concentrations did not differ significantly between groups or show a consistent temporal pattern.
Conclusions:
- Acute neuroaxonal injury is substantially greater in cNORSE compared to eSE and non-seizure control groups, as indicated by elevated NfL levels.
- The rapid early rise in NfL suggests a narrow therapeutic window for interventions in cNORSE.
- Prompt and effective neuroprotective strategies are essential for improving outcomes in patients with cNORSE.
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