An 83 year old male with history of hypertension, presented with sudden-onset of progressive multifocal neurological deficits including blurry vision, upper extremity weakness, numbness and clumsiness with imbalance resulting in multiple falls. A few days later, he reported dysphagia, intermittent expressive aphasia and confusion. Thirteen days prior, he received his second dose of Moderna vaccine. Examination showed mild bilateral upper motor neuron and cerebellar signs. Laboratory tests were unremarkable except for elevated ESR (72), low Vitamins-B12 (311 pg/mL), and D (14.9 ng/mL) levels, and iron deficiency anemia. MRI brain with gadolinium revealed non-enhancing multifocal and confluent supra/infratentorial T2/FLAIR hyperintensity lesions. Cerebrospinal fluid (CSF) analysis showed pleocytosis (white-cell count 13 with 60% lymphocytes), elevated protein (54), and glucose (80), suggestive of underlying inflammation. CSF cytology, meningoencephalitis panel, VDRL, JC-virus PCR, India-ink, acid-fast, bacterial and fungus cultures were negative. HIV antibody was negative. Intravenous Ceftriaxone was initiated until CSF cultures returned negative. Serum anti-MOG and anti-NMO were negative. Repeat imaging within a week showed decreased confluent T2 hyperintensities, but also demonstrated new areas of patchy involvement. The patient received intravenous methylprednisolone 1000 mg daily for 5 days. In the following weeks, his symptoms improved remarkably.