Blood and CSF anti-neuronal antibodies testing in psychotic syndromes: a retrospective analysis from a tertiary psychiatric hospital

Abstract

A Consensus of Psychoimmunology Experts (Pollak et al., 2019) established a set of red flags and proposed diagnostic criteria for psychosis of autoimmune origin (AIP). Previous studies on AIP are limited by the scarcity of CSF analysis, preventing the valorization of blood anti-neuronal antibodies (Ab). The aims of this study are to determine the relative frequency and characterize AIP in a cohort of psychotic patients that underwent CSF workup. This work is a retrospective study in a tertiary psychiatric hospital. Clinical and paraclinical data were collected from medical records, and patients were classified according to Pollak et al. (2019) criteria. From 68 patients, ten (14.7%) had positive anti-neuronal antibodies (Ab): n = 5 in CSF and blood (n = 4 anti-NMDAr, n = 1 -GAD65), and n = 5 in blood only (n = 1 anti-GABAb, n = 1 -GAD65, n = 1 -SOX1, n = 1 -NMDAr, n = 1 -zic4). After 5- (2-10)-year follow-up, n = 6/68 (8.8%) had AIP diagnosis in context of autoimmune encephalitis (AE), and the remaining (n = 4/10, blood-only Ab) alternative diagnoses (n = 2 dementia, n = 1 schizophrenia, n = 1 intellectual disability). Ten of the 13 patients that fulfilled criteria for possible AIP were mimics, and only three AE had criteria for probable AIP. All AIP developed neurological manifestations (mostly cognitive dysfunction); EEG was usually abnormal (66.7%), and all had normal MRI. We found statistically significant associations between AIP/AE and systemic autoimmune disease, presentation with seizures and EEG abnormalities. All AE developed neurological symptoms alongside psychosis. Ab positivity occurred predominantly in AE but also in other neuropsychiatric disorders. Clinical suspicion based on the knowledge of the described presentations of established Ab is crucial in the psychotic patient approach.

Keywords: Autoantibodies; Autoimmune diseases; Encephalitis; Psychotic disorders.