Apathy in autoimmune GFAP Astrocytopathy: A case series and literature review

Abstract

Background

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a newly recognized disease characterized by the presence of GFAPα antibodies in cerebrospinal fluid and linear perivascular radial enhancement on contrast-enhanced MRI. Apathy, although infrequently reported, has emerged as a potential core symptom of GFAP astrocytopathy, distinct from cognitive dysfunction, depression, and consciousness disturbances.

Objective

This study aimed to investigate the prevalence and characteristics of apathy in GFAP astrocytopathy cases treated at our institution.

Methods

We retrospectively analyzed six cases of GFAP astrocytopathy diagnosed at our hospital, focusing on the presence and course of apathy. Apathy was assessed based on Marin and Stuss's criteria, which define it as a marked decrease in spontaneity not attributable to general physical condition, consciousness disturbance, cognitive impairment, or mood disorder. Imaging studies, including MRI and brain perfusion SPECT, were conducted to explore the potential anatomical correlates of apathy.

Results

Of the six cases, four presented with apathy. All cases showed improvement following treatment. MRI and SPECT analyses revealed decreased blood flow in regions associated with apathy, such as the anterior cingulate cortex, orbitofrontal cortex, thalamus, and basal ganglia.

Conclusion

Apathy appears to be a relatively common and potentially core symptom in GFAP astrocytopathy, often associated with specific brain regions implicated in its pathophysiology. Recognizing and addressing apathy in these patients could facilitate earlier diagnosis and more targeted therapeutic strategies. Further research with larger cohorts and standardized diagnostic criteria is needed to deepen our understanding of apathy in GFAP astrocytopathy.