A 30-year-old female patient presented to another center in September 2019 with primary manifestations of upper limb muscle spasms and was diagnosed as multiple sclerosis (MS). In November 2019, she was admitted in our center with complaints of headache and lower limbs paresis. The patient's headache was positional aggravated by lying down. Opthalmoscopy examination revealed bilateral papilledema. Paresis was progressive and within 4 days, had increased from force level 5 from 5, to 1 from 5, and also she had a sensory level belowT4, which all representing acute myelitis. Brain MRI revealed periventricular lesions, periependymal enhancement and linear enhancement of corpus callosum (Figure 1- A, B, C). Cervical MRI revealed longitudinal extensive transverse myelitis (LETM) with ring enhancement (Figure 2- A, B, C). 
Brain MR venography (MRV) was normal. Lumbar puncture (LP) was performed for her. Opening pressure (OP) was 42 cm H2O in the first LP, so we began tablet acetazolamide 250mg twice daily and tablet lasix 20mg daily for the patient. CSF profile was white blood cell (WBC) count 99 cells (85% lymphocytes, 15% neutrophil), glucose 45, protein 55, and red blood cell (RBC) count 10. The patient's CSF samples were sent for rule out of tuberculosis, brucellosis, and Cryptococcus, which all of them were negative and also all other vascular, autoimmune diseases, and malignancies were considered and ruled out. The second patient's LP also had OP 27 cm H2O. Due to severe presentation of disease, we also began the plasmapheresis and corticosteroid simultaneously. According to the clinical evidences and imaging, the patient's positive anti- aquaporin antibody (AQP4-IGg), the diagnosis of NMOSD was established in terms of the revised 2015 criteria, and rituximab was then ordered for her. After foregoing treatments, the patient's headache gradually improved, muscle force returned to 4/5, and the patient was discharged after 23 days. No other disease was found in the studies that explained the patient's headache.