Abstract Details

Title Immunotherapy Principles and Biomarkers in Cryptogenic New-Onset Refractory Status Epilepticus (cNORSE)

Topic Autoimmune Neurology

Presentation(s) C18 - Measuring and Changing Outcomes in Autoimmune Encephalitis (4:38 PM-4:45 PM)
P1 - Poster Session 1 (12:00 PM-1:00 PM)

Poster/Presentation
Number 012

Background Cryptogenic new-onset refractory status epilepticus (cNORSE) remains poorly understood, with limited knowledge regarding its clinical progression, prognostic factors, and treatment guidelines.

Objective

This study aims to present the longitudinal clinical profiles, predictive factors for outcomes, optimal regimen and duration of immunotherapy, and pathogenic biomarkers in cNORSE patients.

Design/Methods

Patients with cNORSE, as defined by consensus criteria, were screened from a prospective autoimmune encephalitis screening cohort at a national referral hospital in Korea. The primary outcomes assessed were longitudinal functional scales, seizure frequency, and the number of anti-seizure medications. Key parameters included NORSE-related clinical features such as the duration of unconsciousness, immunotherapy profiles, and serial MRI scans, alongside pathogenic biomarkers such as cytokine/proteomics analysis and whole genome sequencing (WGS).

Results

A total of 74 cNORSE patients were analyzed, with a mean age of 38.0 ± 18.2 years, including 36 males (48.6%). Poor one-year outcomes (mRS≥3) were predicted by the presence of mesial temporal lobe (mTL) and extra-mTL lesions at the 3-month MRI, as well as prolonged unconsciousness (≥ 60 days). Patients with mTL atrophy experienced a higher seizure burden post-NORSE. The SIRT protocol, consisting of steroid/IVIg, rituximab, and tocilizumab, was identified as the most effective treatment, with the optimal duration of immunotherapy appearing to be more than 18 weeks. Elevated levels of innate autoinflammatory cytokines were observed in serum and CSF, correlating with MRI lesion burden. Although no specific mutations were found in WGS, cNORSE patients had higher polygenic risk scores for other autoimmune-autoinflammatory diseases, correlating with immunotherapy response and showing a higher variant burden in brain tissue-enriched genes. An increased CSF tau level in cNORSE patients was a predictor for one-year outcomes.

Conclusions

This study provides insights into the clinical dynamics, prognostic factors, immunotherapy guidance, and genomic-proteomic biomarkers for cNORSE. These findings could help standardize the understanding of cNORSE pathogenesis and improve clinical decision-making.

Authors/Disclosures
Soo Hyun Ahn, MD (Seoul National University Hospital) PRESENTER	Dr. Ahn has nothing to disclose.
Yoonhyuk Jang, MD, PhD	Mr. Jang has nothing to disclose.
Sung Eun Hong	No disclosure on file
Su Yee Mon	No disclosure on file
Ji Hye You, NP (Seoul National University Hospital)	Ms. YOU has nothing to disclose.
Kyung-ll Park, MD (Seoul National University Hospital)	No disclosure on file
Han Sang Lee	No disclosure on file
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Murim Choi	No disclosure on file
Kon Chu (Seoul National University Hospital)	No disclosure on file
Sang Kun Lee, MD (Seoul national University Hospital)	Prof. Lee has nothing to disclose.
Soon-Tae Lee, MD, PhD (Department of Neurology, Seoul National University Hospital)	Prof. Lee has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Advanced Neural Technologies. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Prof. Lee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Celltrion. The institution of Prof. Lee has received research support from Roche. The institution of Prof. Lee has received research support from Celltrion. Prof. Lee has received intellectual property interests from a discovery or technology relating to health care.