Glial fibrillary acidic protein (GFAP) astrocytopathy is an immune-mediated disease of the central nervous system which can affect the entire central neuroaxis.. It is often associated with malignancy and affected patients present with a variety of symptoms, including meningitis, encephalitis, myelitis, and optic disc papillitis. 

A 26-year-old immunocompetent male presented to Ochsner Health  with a one-week history of headache, fever, and nuchal rigidity. Initial lumbar puncture revealed lymphocytic pleocytosis with elevated protein (150 cells/mm³) and normal glucose (46 mg/dL). Patient was started on antimicrobials for presumed meningitis. MRI brain showed diffuse meningeal enhancement with restricted diffusion in multiple areas of the brain. MRI of the cervical spinal cord showed T2 hyperintensity along the pial and ependymal margin of spinal cord. Despite empiric antimicrobials, his neurologic exam worsened with loss of brainstem reflexes. Repeat LP revealed lymphocytic pleocytosis with elevated protein (135 cells/mm³). In the CSF, MS profile, aquaporin-4 antibody, culture, and cytology were negative. In the serum, aquaporin 4 and MOG were negative. CSF autoimmune panel revealed antibodies to GFAP. There was no evidence of malignancy in the CT chest, abdomen, and pelvis. Patient was started on steroids and IVIG however, he remained in a persistent vegetative state. One time dose of rescue therapy with cyclophosphamide (1750 mg) was initiated, with continued steroid administration which showed improvement in patient’s neurologic examination.  Eight weeks after cyclophosphamide, he began visual tracking and following  verbal commands. 

Our case suggests  that cyclophosphamide, an alkylating agent that penetrates the blood brain barrier (BBB), should be considered for treatment of refractory GFAP astrocytopathy.