GABA-A Receptor Encephalitis After Autologous Hematopoietic Stem Cell Transplant forMultiple Myeloma: Three Cases and Literature Review.

Abstract

Background and objectives: The relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABA_A receptor (GABA_AR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABA_AR encephalitis in patients with a history of prior aHSCT for MM.

Methods: A case series of 3 patients. Anti-GABA_AR antibody was tested at the University of Pennsylvania Laboratory.

Results: The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABA_AR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABA_AR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABA_AR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement.

Discussion: We highlight the importance of considering anti-GABA_AR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.