Objective:

Autoimmune encephalitis (AE) with anti-BR serine/threonine kinase 2 (BRSK2) antibodies has been reported only once, in a patient with small-cell lung cancer (SCLC). We describe another case, triggered by intracranial infection and without tumor.

Background:

Design/Methods:

A 45-year-old man was admitted in February 2023. Five months earlier he had been treated elsewhere for “viral encephalitis” complicated by fever and impaired consciousness, and had required  ventilatory support. Four months before admission he was discharged with residual mental slowness. Two months before admission he began to talk nonsense and experienced visual and auditory hallucinations.  Routine AE antibodies were negative. CSF showed IgG-specific oligoclonal bands and an increased intrathecal IgG synthesis rate. PET-CT showed bilateral fronto-parietal and basal-ganglia hypometabolism without malignancy.  Intravenous steroids followed by oral taper, combined with IVIG, together with sodium valproate and clonazepam for psychiatric symptoms, produced gradual clinical improvement. MMSE score rose from 14 to 27 and MoCA from 7 to 19 before discharge. Oral prednisone was continued and later switched to mycophenolate mofetil. At 2-year follow-up, only mild anxiety/depression persisted and no tumor emerged. Serum and CSF were tested with a tissue-based assay, which showed IgG mainly binding to the cytoplasm of dentate granule cells in the hippocampus with mild neuropil staining, suggesting anti-BRSK2 reactivity. An in-house cell-based assay was then established by transfecting HEK293 cells with human BRSK2 plasmid.

Results:

Both serum and CSF IgG from the patient co-localized with commercial rabbit anti-human BRSK2 antibody on the membrane of BRSK2-transfected HEK293 cells, indicating the presence of specific anti-BRSK2-IgG. Patient’s antibodies are IgG1 subclass, with titers higher in serum（1:100 ) than CSF ( 1:2).

Conclusions: