Co-Occurring NMDA-Receptor and Anti-GAD65 Antibodies in the CSF of a Patient With Encephalitis: Case Report

Abstract

Objective We describe a 58-year-old woman who presented with rapid cognitive changes and was found to have concurrent CSF NMDA and GAD65 receptor antibodies. Background Antibodies against NMDA and GAD65 receptors are associated with highly morbid autoimmune encephalitides. One case of co-occurring NMDA-R and anti-GAD65 antibodies in a patient with progressive cognitive changes and type I diabetes has previously been described. Herein, we describe a case of a previously high-functioning woman who experienced rapidly progressive cognitive changes secondary to autoimmune encephalitis (AE) with co-existent NMDAR and GAD65 antibodies. Design/Methods NA. Results A 58-year-old woman with adult-onset insulin-dependent diabetes mellitus, hypertension, and prior left-sided Bell's palsy presented to medical care for subacute cognitive decline characterized initially by inattention and difficulty with activities of daily living, progressing to profound global aphasia and seizures. Diagnostic testing revealed GAD65 antibody positivity in serum (33 nmol/L) and CSF (17.3 nmol/L) and negative serum but positive CSF NMDAR antibody. CSF showed pleocytosis (37 nucleated cells, 97% lymphocytes), elevated glucose (109 mg/dL), and normal protein (41 mg/dL). EEG showed right temporal epileptiform discharges. MRI was unrevealing. She was treated with IV steroids, IVIg, and rituximab, and has slowly improved on follow-up. Conclusions Co-existent CSF anti-NMDAR and anti-GAD65 AE is not well-described in the literature. While this patient's serum GAD65 titer was in a range that correlates with neurologic autoimmunity, it was not as high as is typically reported in AE, and could simply be a marker of her insulin-dependent diabetes. However, it was also definitively positive from the CSF, which usually correlates well with GAD65-associated AE. Clinically, the patient had AE features that can be seen associated with either NMDAR and/or GAD65 antibodies. It is interesting to consider whether the GAD65 positivity is most likely to correlate with the patient's adult-onset diabetes, her AE, or both.