2026 ECNP Congress

PS01-1213

Phenotyping of atypical psychiatric inpatients screened for autoimmune encephalitis

Serifegul Turkan — R.S. Ilhan, K.C. Can, B. Duman, B. Colak, E.T. Ozel Kızıl, M.C. Saka, S. Erdogan, C. Yucesan, R. Yilmaz, E. Tuzun, M. Araz, G. Cinar · Ankara University, Psychiatry, Ankara, Türkiye

2026 ECNP Congress

Introduction

Autoimmune encephalitis (AE) frequently presents with predominant psychiatric symptoms, and antibody-negative cases pose particular diagnostic challenges in psychiatric settings [1]. The Pollak 2020 international consensus introduced autoimmune psychosis criteria (yellow and red flags) to guide screening [2], while the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score has been proposed for triaging antibody testing. The relative diagnostic contribution of clinical flags, APE2 and individual paraclinical investigations—particularly FDG-PET—in distinguishing seropositive from antibody-negative AE among psychiatric inpatients remains poorly characterised.

Aims

We aimed to (1) describe the paraclinical profile of atypical psychiatric inpatients screened with autoimmune psychosis criteria; (2) compare clinical and paraclinical features of seropositive AE versus antibody-negative AE-suspected cases; and (3) assess the added diagnostic value of FDG-PET over MRI.

Methods

This single-centre prospective study consecutively enrolled 50 inpatients admitted with atypical psychiatric presentations meeting Pollak 2020 autoimmune psychosis criteria (≥1 yellow or red flag); 24 patients subsequently reclassified as non-AE were excluded, yielding 26 (24 women; median age 46 years, range 26–69). All underwent CSF analysis with a six-antibody panel (NMDAR, CASPR2, LGI1, GABA-B, AMPA, DPPX) by cell-based assay, with supplementary serum testing. Additional antibody testing (anti-Yo, anti-Ma, anti-GAD) was requested on clinical grounds in selected patients. Patients underwent EEG, FDG-PET (when available) and cranial MRI. Assessments included Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI) and Bush–Francis Catatonia Rating Scale (BFCRS). Seropositive cases were classified as definite AE following Graus 2016 criteria [1]; antibody-negative cases were classified as possible AE according to Endres et al.2022[3]. Comparisons used Mann–Whitney U and Fisher’s exact tests with Bonferroni correction (α=0.007).

Results

Five patients (19%, 95% CI 7–39%) had seropositive AE (two anti-NMDAR, one anti-Yo, one anti-Ma, one anti-GAD) and 21 (81%) met criteria for antibody-negative AE-suspected. APE2 was ≥4 in all 26. Onset was acute or subacute in 23/26 (88%); catatonia (BFCRS-positive) in 17/26 (65%); all 18 assessable patients scored MoCA <26. Seropositive cases had significantly higher red flag counts (median 3 vs 1; p=0.001), APE2 scores (8 vs 5; p=0.003) and yellow flag counts (6 vs 4; p=0.011). Seropositive cases more often demonstrated CSF pleocytosis (3/5 vs 2/21; p=0.034), bilateral mesiotemporal MRI involvement (3/4 vs 1/18; p=0.010) and abnormal EEG (4/5 vs 5/20; p=0.040). FDG-PET was abnormal in 16/18 (89%, 95% CI 65–99%) versus 15/22 (68%, 95% CI 45–86%) for MRI; six patients with normal MRI showed abnormal FDG-PET. Among antibody-negative cases with interpretable FDG-PET (n=16), cortical hypometabolism—predominantly frontotemporal or frontoparietal—was the most common pattern (9/16, 56%).

Conclusions

Among atypical psychiatric inpatients screened with autoimmune psychosis criteria, antibody-negative AE-suspected cases comprised the majority. Red flag count and APE2 score significantly distinguished seropositive cases after Bonferroni adjustment; CSF pleocytosis, mesiotemporal MRI involvement and abnormal EEG showed nominal associations. FDG-PET was more often abnormal than MRI, identifying abnormalities in six MRI-negative patients, predominantly cortical hypometabolism in antibody-negative cases. Broader implementation of lumbar puncture in psychiatric clinics is likely to further increase identification of these immune-mediated cases, warranting validation in larger multicentre cohorts.

References

  1. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.
  2. Pollak TA, Lennox BR, Müller S, et al. Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry 2020; 7:93–108.
  3. Endres, Dominique et al. Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany. Molecular psychiatry vol. 27,3 (2022): 1479-1489.