Screening 1021 Swedish memory clinic visitors for autoantibody-mediated encephalitis.

INTRODUCTION

A treatable differential diagnosis to neurodegenerative dementia is autoimmune encephalitis (AE). In Sweden, the prevalence of AE varies considerably between regions, suggesting underdiagnosis. We hypothesized that some undetected AE patients would attend Swedish memory clinics.

METHODS

We retrospectively screened 1021 individuals attending the Karolinska University Hospital memory clinics for AE autoantibodies. Serum screening was performed with live cell-based assays (CBAs) for antibodies to contactin-associated protein-like 2 (CASPR2), gamma-aminobutyric acid receptor B (GABABR), immunoglobulin superfamily containing LAMP, OBCAM, and neurotrimin family member 5 (IgLON5), leucine-rich glioma-inactivated 1 (LGI1), and n-methyl-d-aspartate receptor (NMDA-R). Positive serum and CSF samples were further tested with fixed CBAs and tissue-based assays.

RESULTS

Eleven patients were antibody-positive in two or more independent tests. When investigating clinical information, three patients had phenotypes suggesting paraneoplastic (PE) or autoimmune encephalitis. These patients had antibodies to either CASPR2 or NMDA-R in serum and CSF and either had CSF-specific electrophoresis IgG-bands or increased Kappa free light-chain-intrathecal fraction. In four patients, available clinical information was insufficient to clarify if the antibodies were related to an ongoing or past encephalitis or lacked relevance, with a further three considered false positive. The final individual had previously been diagnosed with LGI1-AE. When the STAM3mP score, a tool for identifying treatment-responsive rapidly progressive dementia, was used on the seven previously undiagnosed patients with antibodies of possible relevance, six got one point, indicating potential treatment response.

CONCLUSION

AE is a rare differential diagnosis in our study of memory clinic visitors. Given the low prevalence, we conclude that AE autoantibody testing is not suitable for unselective screening in this setting. Instead, a rigorous clinical evaluation, potentially supported by tools like the STAM3mP score, might acceptably limit the number of missed AE cases among patients suffering from memory impairment, but further studies on pre-screening biomarkers are warranted.