Case Report: Semantic Variant of Primary Progressive Aphasia Associated With Anti-Glial Fibrillary Acid Protein Autoantibodies

Abstract

Background: Frontotemporal lobar degeneration is a heterogeneous disorder entailing a semantic variant of primary progressive aphasia (svPPA). A subtype of frontotemporal dementia associated with glutamate receptor subunit 3 (GluA3) antibody of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was recently identified. Here, we describe the novelty of a svPPA associated with anti-glial fibrillary acid protein (GFAP) antibodies.

Methods: To diagnose this 68-year-old woman we conducted a clinical examination, neuropsychological testing, CSF analysis, MRI and 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET)/computed tomography (CT) imaging.

Results: The clinical phenotype corresponds to a svPPA based on impaired confrontation naming and single-word comprehension. In addition, we observed spared speech production, impaired object knowledge, and surface dyslexia - further supporting the diagnosis of svPPA. Additional characteristic imaging features such as anterior temporal hypometabolism in 18F-FDG PET/CT confirmed patient's svPPA diagnosis. CSF analysis revealed signs of axonal degeneration, as both tau and phosphorylated tau proteins exceeded normal levels. Her serum showed anti-GFAP autoantibodies.

Conclusion: We diagnosed a svPPA in this patient and report an association between serum anti-GFAP antibodies and svPPA never reported in the literature so far, thereby expanding the clinical spectrum of svPPA and anti-GFAP-antibody related disease. Further research is needed to elucidate the underlying immunopathology of this disease entity to ultimately improve treatment.

Keywords: anti-GFAP antibody; autoimmunity; frontotemporal lobar degeneration (FTLD); immunotherapy; semantic variant of primary progressive aphasia (svPPA).