In most synaptic antibody-mediated autoimmune encephalitis, brain MRI is normal or shows non-specific medial temporal T2 hyperintensities. Anti-GABA-A receptor encephalitis, though clinically similar, presents with asynchronous multifocal cortical and subcortical FLAIR hyperintensities on head imaging. These findings evolve over the course and treatment of the disease.

Case 1: A 62-year-old man with history of autologous stem cell transplant for multiple myeloma developed anosmia followed by intractable vertigo. Brain MRI demonstrated multifocal non-enhancing cortical and subcortical FLAIR hyperintensities. He was treated with IV methylprednisolone with clinical and radiographic improvement but had seizures and recurrent lesions once steroids were tapered. Brain biopsy showed non-specific inflammatory changes. CSF and serum analysis revealed anti-GABA-A antibodies. Rituximab was administered. He had transient worsening followed by complete resolution 2 months later.

Case 2: A 17-year-old male presented with facial twitching, ataxia, and encephalopathy in the setting of several days of anosmia, hypogeusia, and headaches. Brain MRI demonstrated cortical and subcortical lesions, which progressed throughout his hospitalization. He was treated with antiepileptic medications, intravenous methylprednisolone, plasmapheresis, and IVIG. CSF analysis revealed anti-GABA-A antibodies. He received rituximab and monthly IVIG for 6 months with full clinical and radiologic recovery.

The combination of dynamic gray- and white-matter lesions on brain MRI and severe seizures is strongly suggestive of anti-GABA-A receptor encephalitis. The cause of MRI changes is unclear but could be related to prolonged seizure or antibody effect on brain fluid homeostasis. In children, anti-GABA-A receptor antibodies are thought to develop as a parainfectious phenomenon; in adults, antibodies are more commonly associated with malignancy. In patients with appropriate clinical and MRI findings, evaluation for autoantibodies in serum and CSF must be undertaken, and immune therapy may result in recovery.