A previously healthy, 74-year-old male, developed acute encephalopathy, diffuse rigidity, and hyperthermia. He had no prior exposure to antipsychotic or dopaminergic agents. Pertinent history included Covid infection six weeks prior and vaccinations for influenza and RSV seven days prior to symptom onset. Initially, he developed fever, chills, myalgias, and urinary retention followed by diplopia, gait instability, and confusion twenty-four hours later. Upon admission, he was febrile up to 101F and exam revealed a comatose patient with diffuse lead pipe rigidity and diffuse areflexia. Pertinent workup included: contrasted MRI of the neuraxis with non-contrast enhancing, patchy-amorphous supratentorial and infratentorial white matter and brainstem FLAIR hyperintensities; lumbar puncture with elevated protein (116 mg/dL) and pleocytosis (65 cells/UL, 47% lymphocytes, 41% neutrophils, and 12% monocytes); negative CSF infectious and inflammatory workup; and negative serum NMO, MOG antibodies. With high dose IV methylprednisolone and IVIG, patient had rapid and significant improvement of function with near complete resolution of symptoms. 

Diffuse demyelination and inflammation involving the bilateral basal ganglia and dopaminergic pathways can result in a clinical picture identical to NMS and is an important diagnostic consideration when no inciting medications for NMS are identified. Despite limited evidence presently, prognosis seems promising with immunomodulating treatments, given success of treatment with IV methylprednisolone with IVIG in our case and IV methylprednisolone with IV cyclophosphamide by Delgado et. al.