Objective Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a steroid-responsive meningoencephalomyelitis, sometimes presenting with atypical clinical signs such as movement disorders or psychiatric and autonomic features. Diagnosis relies on clinical presentation, detection of GFAP autoantibodies in CSF as well as ancillary MRI biomarkers. We aimed to characterize two patients seropositive for GFAP antibodies in CSF presenting with a highly atypical clinical picture of isolated neurocognitive and autonomic features resembling neurodegenerative dementia in absence of cranial MRI abnormalities.
Methods Semiquantitative, clinicoradiological, serologic and immunohistochemical analysis of two cases with longitudinal observation over a time course of 18–24 months.
Results Both patients had rapidly progressive amnestic syndromes in absence of other focal neurologic signs. Cranial MRI was grossly unremarkable while functional neuroimaging showed cortical and subcortical metabolic changes. Tissue-based assays (TBA) of CSF confirmed GFAP-specific astrocytic binding patterns in rat corpus callosum and hippocampus in both cases. Incomplete steroid response prompted therapy escalation to B-cell depletion, which improved or stabilized disease courses over the observation time.
Conclusions These cases suggest that rapidly progressive amnestic syndromes with psychiatric and autonomic features may be a novel phenotype of GFAP astrocytopathy as well as a potentially underrecognized mimic of neurodegenerative dementia amenable to immunomodulation. We recommend including GFAP-AB screening using TBA in the work-up of rapidly progressive dementias especially when autoimmune etiologies are suspected.