No anti-IgLON5 antibody in carefully diagnosed PSP patients with "atypical" or variant clinical features.

BACKGROUND: "Atypical" features including REM sleep behaviour disorder (RBD) symptoms and visual hallucinations, and non-Richardson's syndrome (non-RS) variants, are increasingly recognized in progressive supranuclear palsy (PSP). A concern in clinical practice is missing PSP mimics, like anti-IgLON5 disease, an autoimmune encephalitis which can reportedly present with "PSP-like" features and is amenable to immunotherapy. We aimed to determine if anti-IgLON5 antibody is detectable in Movement Disorder Society criteria-diagnosed PSP patients exhibiting "atypical" features and variant phenotypes. METHODS: This was a cross-sectional study of 64 multi-ethnic Asian PSP patients who were recruited via convenience sampling from June 2023-April 2025. Patients were extensively phenotyped by movement disorder neurologists, and their sera tested for immunoglobulin G against IgLON5, using cell-based assays at a neuroimmunology reference laboratory. RESULTS: 37.5 % of the cohort had a non-RS phenotype, and 39.1 % had RBD symptoms and/or non-predominant visual hallucinations. Additionally, when the presence of other features that could be associated with a higher likelihood of anti-IgLON5 disease were also accounted for (i.e., comorbid autoimmune disease, orofacial dyskinesia, protracted disease duration, and/or lack of downgaze-predominant oculomotor abnormalities), these patients comprised 95.3 % of the cohort. Despite this, none tested positive for anti-IgLON5 antibody. CONCLUSION: Our results suggest that routine testing for anti-IgLON5 antibody in patients carefully diagnosed with PSP in movement disorder clinics is likely to be of very low yield. However, testing in research settings of larger cohorts of atypical and variant PSP presentations, applying consensus diagnostic criteria and detailed phenotypic characterization, may currently still be of value.