OBJECTIVE: We describe a young woman with recurrent encephalitis, with anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibodies in cerebrospinal fluid (CSF), who underwent monitoring with depth electrode and surface electroencephalography (EEG) and serial positron emission tomography (PET) scans. We provide a paradigm for the evaluation of patients with limbic encephalitis (LE). BACKGROUND: Anti-NMDAR autoimmunity is an increasingly recognized etiology of encephalitis. A 34 year-old woman with two prior episodes over nine years of behavioral changes, receptive and expressive aphasia, orofacial dyskinesias and complex partial and generalized tonic-clonic seizures presented now with memory problems, auditory hallucinations and right hemiparesis, concerning for recurrent encephalitis. DESIGN/METHODS: Case report. RESULTS: Initial studies revealed no CSF evidence of infectious causes, and there were no initial cerebral imaging or specific EEG abnormalities. With subsequent EEG evidence of rhythmic delta activity concerning for LE versus limbic status epilepticus (LSE), the patient was given a course of antiepileptic drugs and immunosuppression before implanted depth electrodes revealed no further seizures thus distinguishing encephalitic changes from LSE. PET scans demonstrated asymmetric hypermetabolism within limbic structures, as well as frontal, parietal, and occipital cortices. Anti-NMDAR encephalitis was diagnosed based on subsequent CSF antibody titers. With chronic immunomodulatory therapy, the resolution of PET abnormalities paralleled clinical improvement. CONCLUSIONS: This case of recurrent encephalitis with anti-NMDAR antibodies illustrates the challenges of diagnosing LE and distinguishing it from LSE. We discuss the parallels between these two conditions and propose a management paradigm to optimize evaluation and treatment. Study Supported by: Not applicable.