Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis is a common autoimmune encephalitis. It is commonly associated with underlying malignancy. We present a 24-year-old patient with sudden onset of behavioral changes and acute psychosis who was treated with antipsychotics followed by the development of generalized rigidity, facial twitching, and sympathetic overactivity. MRI and EEG were inconclusive. The neuroleptic malignant syndrome was presumed and bromocriptine was started. Multiple antiepileptics were started to control this twitching without success. NMDA receptor reactivity in the CSF established the diagnosis. Searching for underlying malignancy was unyielding except for an anterior mediastinal mass seen on the CT chest. The patient had only mild improvement in response to corticosteroids, plasmapheresis, and intravenous immunoglobulin (IVIG). Significant improvement was achieved after the thymectomy. This case serves to remind clinicians of key aspects of the disease including general rigidity and paroxysmal sympathetic hyperactivity, and the potential to confuse these with other diagnoses including neuroleptic malignant syndrome. This case is also unique in that the association with thymic hyperplasia is very rare and only a few cases were reported in English literature.
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