Abstract Details

Title Neurofilament light chain levels in anti-NMDAR encephalitis and primary psychiatric psychosis

Topic Autoimmune Neurology

Presentation(s) S41 - Autoimmune Neurology 3: Autoimmune Encephalitis, Paraneoplastic Neurologic Disorders, Antibody-Mediated Diseases, Immunology (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background Differentiating NMDARe from a first episode of psychosis (FEP) caused by a psychiatric disease (pFEP) is challenging, as spinal taps are difficult to obtain in psychiatric facilities. A separate problem is the lack of biomarkers of NMDARe severity and outcome.

Objective To assess the performance of neurofilament light chain (NfL) testing in anti-NMDAR encephalitis (NMDARe) and its differential diagnosis.

Design/Methods NfL were determined with Single molecule array (SiMoA) in patients with NMDARe, pFEP, herpes simplex encephalitis (HSE), and healthy subjects (HC). Receiver operating characteristic (ROC) analyses were performed to assess the prediction accuracy of serum NfL (sNfL) levels for NMDARe and pFEP, and to obtain cutoffs of clinical utility.

Results 118 patients with NMDARe (33 with isolated psychosis), 45 pFEP, 36 HSE, and 36 HC were studied. NMDARe patients with seizures/status epilepticus, ICU admission, CSF pleocytosis (>20 WBC/µL), and without early immunotherapy were more likely to have higher sNfL than NMDARe without these features. NfL levels at diagnosis of NMDARe did not correlate with outcome at 1 year follow-up assessed with the modified Ranking Scale (mRS). NMDARe patients had significantly higher NfL than pFEP and HC, and lower than HSE patients. ROC analysis of sNfL levels between NMDARe with isolated psychosis and pFEP provided an AUC of 0.93 (95% CI 0.87-0.99) and a sNfL cutoff ≥15 pg/mL to distinguish these disorders (sensitivity 85%, specificity 96%, positive likelihood ratio 19.3). Forty-three/45 (96%) pFEP had sNfL<15pg/mL whereas 5/33 (15%) NMDARe with isolated psychosis were below this cutoff. None of the HSE and 35/36 (97%) HC had sNfL<15pg/mL.

Conclusions NfL measured at diagnosis of NMDARe associated with several features of disease severity but not with long-term outcome. sNfL cutoff ≥15pg/mL correctly classified 96% of pFEP and 85% of NMDARe with isolated psychosis. Patients with FEP of unclear etiology and sNfL≥15pg/mL should undergo CSF NMDAR-antibody testing.

Authors/Disclosures
Mar Guasp, MD (Hospital Clínic Barcelona - IDIBAPS) PRESENTER	Dr. Guasp has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Thais Armangue, MD (IDIBAPS-HClinic)	Dr. Armangue has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Armangue has received research support from ISCIII(Spanish institute of health) -PI21/00316, Marato TV3, La Caixa Research Foundadion, Pablove Foundation (689368), Torrons Vicens Foundation (PFNR0144), 2021 Invest AEP.
Eugenia Martinez-Hernandez, MD (Hospital Clinic Barcelona)	The institution of Dr. Martinez-Hernandez has received research support from Instituto de Salud Carlos III. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel and speaking honoraria with Biogen. Dr. Martinez-Hernandez has received personal compensation in the range of $0-$499 for serving as a travel honoraria with UCB.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Amaia Muñoz-Lopetegi (Hospital Clinic of Barcelona)	Ms. Muñoz-Lopetegi has nothing to disclose.
Albert Saiz (Hospital Clinico De Barcelona)	Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janseen. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for novartis. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.
	No disclosure on file
	No disclosure on file
Francesc R. Graus, MD (IDIBAPS)	Dr. Graus has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Graus has received intellectual property interests from a discovery or technology relating to health care.
Luis Querol, MD, PhD (Hospital de la Santa Creu i Sant Pau)	Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. The institution of Dr. Querol has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ArgenX. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Querol has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. The institution of Dr. Querol has received research support from GBS-CIDP Foundation International. The institution of Dr. Querol has received research support from Grifols. The institution of Dr. Querol has received research support from ISCIII. The institution of Dr. Querol has received research support from CIBERER. The institution of Dr. Querol has received research support from UCB.
Josep O. Dalmau, MD, PhD, FAAN	Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas Research Institute of America. Dr. Dalmau has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Research & Development . Dr. Dalmau has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. An immediate family member of Dr. Dalmau has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Dalmau has received research support from Sage Therapeutics. The institution of Dr. Dalmau has received research support from Edmond J.Safra Foundation . The institution of Dr. Dalmau has received research support from La Caixa Foundation. The institution of Dr. Dalmau has received research support from Spanish Ministry of Health (ISCIII). The institution of Dr. Dalmau has received research support from Euroimmun, Inc. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Dalmau has received intellectual property interests from a discovery or technology relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care. Dr. Dalmau has received publishing royalties from a publication relating to health care.