Case 346: γ-Aminobutyric Acid A Receptor Encephalitis

A 66-year-old man with a history of hypertension presented with left-sided jaw jerking, repetitive movements, aphasia, and dysarthria. He was afebrile and in no acute distress, with mild hypertension (153/81 mm Hg). Routine laboratory studies were unremarkable. Brain MRI showed multiple nonenhancing supratentorial cortical and subcortical hyperintensities on T2-weighted fluid-attenuated inversion recovery (FLAIR) images, which were nonspecific for infectious, inflammatory, vascular, or neoplastic etiologies. CT of the chest, abdomen, and pelvis and MRI of the cervical and thoracic spine were unremarkable. CT angiography of the head and neck showed no areas of stenosis or occlusion. Extensive infectious, autoimmune, and paraneoplastic serologic tests were negative, including serum acetylcholinesterase, antinuclear antibody, erythrocyte sedimentation rate, C-reactive protein, aquaporin 4 and myelin oligodendrocyte glycoprotein (MOG) antibodies, treponemal testing, Tropheryma whipplei, human immunodeficiency virus, tick-borne disease panel, and COVID-19. Lumbar puncture showed 2% neutrophils (reference range, <6%), with normal protein and glucose levels. Cerebrospinal fluid (CSF) studies, including protein electrophoresis, JC virus, herpes simplex virus polymerase chain reaction, MOG antibodies, cytologic examination, and a paraneoplastic panel (Table), were negative. The patient was treated with nicardipine and levetiracetam, with clinical improvement. A presumptive clinical diagnosis of posterior reversible encephalopathy syndrome was made, with plans for short-interval surveillance imaging and possibly brain biopsy, which the patient initially declined. He was subsequently lost to follow-up. Three years later, he experienced several months of progressive mood alterations followed by the development of psychosis and two generalized tonic-clonic seizures. At readmittance, he was again afebrile and in no acute distress, with mild hypertension (150/70 mm Hg). His neurologic examination was remarkable only for symmetric hyperreflexia. Repeat laboratory testing, including human immunodeficiency virus and hepatitis serologic tests, remained negative. Lumbar puncture showed 1% neutrophils, with normal protein and glucose levels and absent oligoclonal bands. MOG antibodies and an autoimmune encephalitis panel (Table) were negative. Repeat brain MRI was performed.