A 64-year-old man presented with a 6-month history of lightheadedness, intermittent balance, and coordination difficulties. T wo months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild wordfinding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain (Figs 1–3). Of note, this patient’s presentation predated the COVID-19 pandemic. Cerebrospinal fluid analysis revealed predominant pleocytosis (23 × 106/L; normal range, [0–5] × 106/L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19–0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission (Fig 4).A T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI examination of the brain at admission showed hyperintensity in the left frontoparietal corona radiata and centrum semiovale (Fig 1A, 1B), with facilitated diffusion (Fig 1C, 1D). Susceptibility-weighted imaging showed bilateral deep medullary veins had a normal appearance (Fig 2A). A T1-weighted three-dimensional volumetric interpolated breath-hold gadolinium-enhanced examination showed a subtle punctate and linear enhancement pattern extending from the periventricular region toward the centrum semiovale in the left frontoparietal region (Fig 2B, 2C). Perfusion imaging of the brain revealed unremarkable findings (Fig 3A, 3B). MR spectroscopy (MRS) performed at the left centrum semiovale revealed an abnormal increase in the choline peak and a slightly decreased N-acetylaspartate peak (Fig 3C). Follow-up MRI of the brain 2 weeks after admission showed stable abnormal T2 signal intensity in the left corona radiata and centrum semiovale (Fig 4A). However, there was progression of the radial perivascular pattern of enhancement extending outward from the periventricular region (Fig 4B, 4C). In addition, new areas of T2 hyperintensity developed in the posterior fossa (Fig 4D) and were associated with an enhancement pattern like that in the supratentorial brain (Fig 4E, 4F). Further CSF analysis after this follow-up scan was positive for glial fibrillary acidic protein (GFAP) antibodies (anti-GFAP IgG). Surgical biopsy of white matter from the left centrum semiovale in the area with MRI changes showed nonneoplastic mononuclear perivascular infiltrates with frequent eosinophils, CD3-positive T lymphocytes, and CD138-positive plasma cells, but there were no vasculitic changes (Fig 5A, 5E, 5F). The surrounding white matter was predominated by diffuse gliosis and nonmonoclonal plasma cells (mixed λ and κ lineage) (Fig 5C, 5D). There were some clusters of macrophages surrounding mainly small blood vessels but without demyelination (Fig 5B). The presence of dense perivascular infiltrates of CD138 plasma cells in the white matter, suggesting locally produced antibodies, enabled us to confirm the clinical diagnosis of GFAP astrocytopathy. What is your diagnosis?