Case of the Week

Background:

• Glial fibrillary acidic protein (GFAP) astrocytopathy is a rare but probably underdiagnosed autoimmune-related disease that affects the CNS, first described in 2016.¹ Antibodies target the glial fibrillary acidic protein, which is an intermediate filament expressed by astrocytes. Although the origin of this disease is unknown, up to 20% of cases occur as a paraneoplastic syndrome (benign or malignant neoplasm).

Clinical Presentation:

• Most patients present with an acute or subacute onset of meningo-encephalo-myelitis, with the main symptoms being headache, encephalopathy, involuntary movements, ataxia, optic papillitis, and myelitis. Early flu-like symptoms are often identified.

Key Diagnostic Features:

• Diagnosis mainly relies on the detection of GFAP-IgG in CSF, along with imaging. The most striking imaging findings include:
  • Brain: perivascular enhancement pattern (linear radial periventricular enhancement), T2- and FLAIR-hyperintensities in the supratentorial white matter, basal ganglia, and thalami
  • Spinal cord: longitudinally extensive “hazy” T2-hyperintensities, “speckle” intramedullary enhancement, periependymal and leptomeningeal enhancement

Differential Diagnoses:

• NMOSD and MOGAD: both entities can show similar spinal cord imaging findings as in GFAP astrocytopathy. However, supratentorial linear radial periventricular enhancement is uncommon in these diseases. Anti-aquaporin 4 and anti-MOG IgG are helpful when positive.
• CLIPPERS: perivascular enhancement predominantly involves brainstem and cerebellum; supratentorial structures are usually spared.
• CNS endovascular lymphoma: perivascular enhancement is accompanied by areas of restricted diffusion (cerebral infarcts) and hemorrhagic lesions.
• Infectious meningo-encephalo-myeliti: CSF analysis is the key.

Treatment:

• Most patients respond well to corticosteroids (if necessary, IV immunoglobulin therapy and/or plasma exchange). In relapsing and chronic forms, treatment may include immunosuppressors. In paraneoplastic forms, treatment may require removal of the tumor.