This case report presents a unique case of a difficult differential diagnosis of autoimmune encephalitis (AE) in the setting of Mycoplasma pneumoniae. A 40-year-old female with a history of Hashimoto thyroiditis, polycystic ovarian syndrome, and a lower respiratory infection presented to the emergency department with new-onset progressive neurological symptoms. These included generalized tonic-clonic seizure and worsening respiratory status that required intubation and tracheostomy. Blood cultures returned positive for M. pneumoniae. We concluded this to be a mixed diagnosis case of anti-glutamic acid decarboxylase 65 (anti-GAD65), Bickerstaff's brainstem encephalitis (BBE), Hashimoto's encephalopathy (HE), and Miller Fisher Syndrome (MFS) concurrently in the setting of M. pneumoniae. Initial treatment with intravenous immunoglobulin showed minimal improvement; however, subsequent treatment with plasmapheresis proved to be beneficial for the patient. Over the course of the plasma exchange therapy (PLEX), the patient slowly became more alert, attentive, and verbal. She was able to answer simple questions and follow commands. Common trends of age, gender, presenting symptoms, associated antibodies, and sessions of PLEX in different AE diseases were identified through a literature review. Only 69.7% of the cases implemented PLEX or plasmapheresis. Currently, there is no standard protocol for the treatment of AE. Our case report aims to present a clinically complicated example of AE and to provide further evidence to support PLEX as an important therapeutic option.