Case Presentation: A 27 y/o M presented after an episode of confusion and abnormal behavior. Patient reported 1 week of intermittent headaches, nausea, emesis, and dizziness. He had no sick contacts or recent travel. Family history was significant for SLE. On exam he had diffuse weakness but was otherwise neurologically intact without meningeal signs. Initial labs were largely unremarkable. On day 1, patient had an episode of seizure-like activity and subsequent Tmax of 105°F. He was then started on empiric coverage for meningitis and further workup including an MRI brain, lumbar puncture and EEG was performed. MRI showed leptomeningeal enhancement. Lumbar puncture showed increased lymphocytes, normal glucose and increased protein, but all infectious studies returned negative. EEG showed cerebral dysfunction without signs of epileptiform activity. Initial rheumatologic workup revealed a negative ANA but dsDNA and ribonuclear protein were elevated. At this point there was a broad differential, including severe neuropsychiatric lupus, CNS lymphoma, autoimmune encephalitis, or infectious etiology. Patient’s course was complicated by intubation for airway protection, development of obstructive hydrocephalous requiring extra ventricular drain placement and decompressive suboccipital craniectomy with biopsy. Dural biopsy was unremarkable and cerebellar biopsy showed edema with necrotic cells. Patient was started on high dose steroids initially, followed by IVIG empirically for autoimmune encephalitis or severe neuropsychiatric lupus. Eventually, patient was started on plasma exchange therapy given continued weakness and high suspicion for autoimmune encephalitis. On day 47 of admission, serum autoimmune encephalitis panel returned with positive glutamate decarboxylase (GAD65) IgG antibody titer confirming the diagnosis of autoimmune encephalitis. The patient then received rituximab with plan for repeat dose in 6 months. On day 69 patient was discharged to rehab.

Discussion: Autoimmune encephalitis (AIE) is a group of encephalitis syndromes associated with the presence of specific antibodies to neuronal proteins. Initial presenting symptoms of AIE are broad, but most common are psychiatric disturbances, and deficits of memory and cognition. As seen in this patient, headaches, hyperthermia, and CSF pleocytosis can lead to an infectious diagnosis. Psychiatric features can also lead to misdiagnosis and delay in treatment. Antibody tests are not an effective tool in early diagnosis as they take days to come back and may be negative in as many as half of cases. As a result, diagnosis of AIE relies largely on exclusion of other diagnoses.

Conclusions: This case highlights that hospitalist should entertain AIE as a diagnosis in a patient presenting with an unusual combination of symptoms, including behavioral disturbance, fever, and cognitive impairment. Autoimmune encephalitis is highly responsive to immunomodulatory therapy, hence early diagnosis and treatment can improve outcomes.