Creutzfeldt‐Jakob‐Like Presentation in Anti‐ AMPAR Encephalitis

A 68-year-old woman with no prior neurologic history presented with rapidly progressive right hemiparesis, homonymous hemianopia, and severe aphasia over 1 week. Brain magnetic resonance imaging (MRI) showed left temporo-parieto-insulo-occipital cortical diffusion restriction with low apparent diffusion coefficient and mild fluid-attenuated inversion recovery hyperintensity, and fluorodeoxyglucose positron emission tomography/computed tomography showed marked concordant hypometabolism (Fig A–F). She had no clinical seizures, and repeated prolonged electroencephalograms showed no epileptiform activity. Cerebrospinal fluid showed markedly elevated total tau (3,290pg/mL; reference, 150–450), but no pleocytosis, no intrathecal immunoglobulin G synthesis, and normal interleukin-6. Protein 14-3-3 and real-time quaking-induced conversion were negative. AMPA receptor antibodies were detected in both serum and cerebrospinal fluid, and breast carcinoma with nodal involvement was identified. Immunotherapy with rituximab and cyclophosphamide, together with oncologic treatment, led to slow partial recovery. Follow-up MRI showed cortical laminar necrosis after 2 weeks (Fig G) and progressive left hemispheric atrophy at 6 and 12 months (Fig H,I). Anti-AMPA receptor encephalitis is rare, but its clinicoradiologic spectrum extends beyond classic limbic encephalitis and can include extralimbic cortical involvement.1-3 Our case broadens this phenotype by showing a striking radiological Creutzfeldt-Jakob-like presentation at onset, associated with marked total tau elevation,4 despite negative prion biomarkers, absence of seizures, and subsequent evolution toward cortical laminar necrosis and unilateral hemispheric atrophy. Anti-AMPA receptor encephalitis should be considered in rapidly progressive focal cortical syndromes with cortical ribboning, especially when prion testing is negative and an underlying tumor is identified. Open access publication funding provided by COUPERIN CY26. K.D., M.B., D.L., and L.C. have contributed to conception and design of the study, acquisition and analysis of the data, drafting the text and preparing the figure. Nothing to report. The data that support the findings of this study are available from the corresponding author on reasonable request.