In March 2021, a 54-year-old female with history significant for MS diagnosed in 2013, on interferon-1beta for 7 years, squamous cell carcinoma of the neck status post neck dissection and tonsillectomy 2 weeks prior, presented to the hospital with 1 day of left sided weakness and right gaze deviation lasting 6 h, suggestive of partial onset seizure. En route to the hospital, the patient had an ictal episode consisting of bilateral arm flexion and turning to the left lasting around 15 s during which she was unresponsive. On arrival to the emergency department, the patient demonstrated postictal confusion and lethargy. There was no prior history of stroke or seizures. Patient’s exam was notable for right gaze preference, though able to track across midline, and 4/5 strength in left upper extremity, and 3/5 strength in left lower extremity with National Institutes of Health (NIH) Stroke Scale of 4 on admission. The initial concern was for stroke and patient had computed tomography angiogram (CTA) Head and Neck were unremarkable. Patient’s laboratory values were notable for C-reactive protein (CRP) of 12.74 mg/L, erythrocyte sedimentation rate (ESR) of 42 mm/hr. LP showed CSF remarkable only for isolated elevated protein at 61.6. Patient’s vitals were only significant elevated blood pressure at 160/68 mmHg. Urgent MRI Brain revealed extensive patchy and confluent T2/FLAIR hyperintensity of the subcortical U-fibers, most concentrated in the occipital and parietal lobes, but also visualized in the frontal lobes, bilaterally. Also, innumerable punctate foci of post contrast enhancement, with subtle cortical gradient low signal at the apical pre-and post-central gyral region suggestive of petechial hemorrhage. Overall, these findings are most consistent with posterior reversible encephalopathy syndrome (PRES) Fig.. The patient was taking beta-interferon (Extavia) every other day (QOD) 0.3 mg for MS totaling 15 doses monthly. Her home interferon therapy was discontinued due to concern of PRES secondary to interferon vs carcinomatous/paraneoplastic process. No further seizure episodes were noted during inpatient stay, which was confirmed with continuous electroencephalography (EEG) that was negative for ictal activity. Upon repeat examination on April 5th, ESR was 37 and CRP was 7.14. The EEG recording showed no evidence of ictal activity. A repeat MRI was performed 3 days later, showing improvement of the imaging features most suggestive of PRES. She was not restarted on immunomodulatory therapy after PRES diagnosis. The previously noted multifocal patchy enhancement of mostly the cortex in both cerebral hemispheres, predominantly in the bilateral parieto-occipital locations are no longer enhancing. The superimposed T2 and T2 FLAIR hyperintensities involving mostly the white matter and some of the cortex in these regions were minimally improved. However, there was new T2 FLAIR signal in the sulci diffusely in the bilateral cerebral convexities predominantly adjacent to the areas of T2 FLAIR hyperintensity likely related to the vascular hemodynamics of PRES perhaps with protein leakage, Fig..