Case Presentation: The patient is a 58-year-old female who was initially treated at an outside facility for severe COVID-19 infection that presented as a nonverbal encephalopathy. During this, she developed seizures and required intubation for airway protection. Labs were notable for hemoglobin: 7.7g/dL, calcium: 8.1 mg/dL, and arterial ammonia: 107 mcg/dL. Encephalopathy at that time was thought to be a form of acute disseminated encephalomyelitis (ADEM). She was treated with pulse dose steroids with neurologic recovery. MRI during this time revealed DWI bilateral thalamic intensities. She continued to recover until 6 months later when she presented to our facility with encephalopathy. She had normocytic anemia without renal failure or hypercalcemia. CSF showed hyperproteinemia with IgG predominance and the presence of a monoclonal band . Additionally, an autoimmune encephalitis Mayo panel showed no known causes of autoimmune encephalitis (AIE). SPEP revealed a total protein of 10.3 g/dL and an M-spike of 4.3 g/dL. Serum-free light chain K/L was 0.27, kappa 4.9mg/L, and lambda 18.2mg/L. The workup for hyperviscosity was negative. There were no peripheral blood myeloid cells, no lytic lesions on PET/CT. Brain and spinal MRIs were negative for CNS leptomeningeal enhancements. She was treated with five days of pulse dose steroids, followed by five days of IVIG. She made a complete recovery and was discharged home. Bone marrow biopsy obtained during admission revealed plasma cell neoplasm with mildly atypical plasma cells accounting for 90% of core biopsy cellularity. FISH demonstrated t(11;14), monosomy for chromosome 13, a gain of 1q21 and 16q/MAF. She was diagnosed with IgG lambda MM R-ISS stage II with a high-risk genotype and was started on daratumumab plus lenalidomide/bortezomib/dexamethasone before ASCT without relapse of encephalopathy.

Discussion: When evaluating encephalopathy, common differentials include metabolic, infection, structural, and toxins. This is often presented as a mnemonic, MIST. Our case addresses encephalopathy not explained well with this mnemonic. Active differentials (ddx) were AIE, hyperammonemia-induced encephalopathy (HIE), hyperviscosity, and ADEM.Given the association of COVID and autoimmunity and MM with anti-NMDA encephalitis, AIE was high on the ddx and is not necessarily ruled out with a negative AIE panel. HIE is a rare complication of MM with few previously described cases in patients with advanced, chemotherapy-resistant MM. Given the known disruption of the blood-brain barrier (BBB) by SARS-CoV-2 and the unusually elevated CSF IgG, ADEM was considered. While no definitive answer was obtained, this case highlights an interesting case of encephalopathy that required investigation outside of normal schema.

Conclusions: Multiple myeloma (MM) typically presents with MM defining symptoms: Sixty-percent bone marrow plasmacytosis, Light kappa: lambda light chain ratio > 100, Magnetic resonance imaging with at least one focal lesion, hyperCalcemia, Renal failure, Anemia, or lytic Bone lesions, or more commonly referred to as “SLiM CRAB” criteria. We present a case of recurrent encephalopathy with unclear source in a patient subsequently diagnosed with MM.

IMAGE 1: DWI bilateral thalamic intensities