A 36-year-old woman was admitted to our hospital with chief complaints of progressive dysuria with burning pain and pruritus of extremities for two months, and spasms of left upper and lower extremities for one month. The patient reported persistent fever (maximum body temperature: 40°C) and headache with frequent hiccups and vomiting starting three months ago. Her body temperature returned to normal about one month later, but she then developed urinary retention. Neurological examination on admission revealed weakness in the left upper and lower limbs (Medical Research Council graded as 5—) with episodic spasms, hypoesthesia below the level of both knees, and subjective burning pain and pruritus at the extremities. The Babinski’s sign was positive bilaterally. The expanded disability status scale (EDSS) score at nadir was 4.5. The CSF test revealed a slightly elevated protein level of 666 mg/l (normal range: 150-450 mg/l), and the IgG index was 0.73 (normal range: ≤ 0.7). Oligoclonal bands were positive in CSF but negative in serum. Serum and CSF were both negative for aquaporin-4 IgG (AQP4-IgG), myelin oligodendrocyte glycoprotein IgG (MOG-IgG), and myelin basic protein IgG (MBP-IgG). Brain MRI suggested the area postrema lesion and spinal cord MRI showed demyelinating lesions in the cervical and thoracic segments (). No abnormalities were detected on related tests for infection and immune indicators, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-cardiolipin antibodies, and tumor markers. She was initially diagnosed with AQP4-IgG-seronegative NMOSD and received methylprednisolone pulse therapy (MPPT) and five infusions of intravenous immunoglobulin (IVIG). Since then, she had a marked alleviation of symptoms and was able to urinate normally. She continued to take oral prednisone to prevent relapse without any other additional immunosuppressants. Five months later, she reported right optic neuritis (ON) when she was still taking 30 mg of prednisone daily. Her visual acuity in the right eye was 0.5 with painful eye rotation. High titers of GFAP-IgG detected in CSF (1:3.2, cell-based assay) led to the diagnosis of GFAP astrocytopathy. Other central demyelinating antibodies remained negative, including AQP4-IgG, MBP-IgG, and MOG-IgG. She received oral azathioprine and prednisone for sequential therapy after undergoing MPPT again. In April 2020, she experienced a relapse of ON in her right eye (OD=0.3 and eye pain) and then received a reduced-dose RTX (500 mg) to prevent relapse. Burning pain in the extremities was dramatically relieved after RTX treatment. Unfortunately, four months later, she developed pulmonary symptoms and was diagnosed with pulmonary aspergillosis requiring antifungal treatment. Femoral head necrosis was identified during the same period of her hospitalization. A month thereafter, ON in the left eye (OS=0.5) was noted when the CD19+ B-cell percentage was 3.8% of lymphocytes. She received plasma exchanges and then switched to mycophenolate mofetil (MMF) (1.0 g orally, twice daily). She maintained stable conditions for one year and then developed severe bilateral vision loss (OD: light perception and OS=0.3) with eye pain and increased numbness in the extremities (EDSS=4). Visual evoked potentials suggested no P100 waveform elicited in both eyes. Optic nerve MRI suggested bilateral optic nerve dilatation with gadolinium enhancement, and spinal cord MRI suggested C3-4 level enhanced lesions. She was treated with IVIG and received another reduced-dose RTX regimen (100 mg intravenously on Day 1 and then 500 mg intravenously on Day 2). Although there was an improvement in vision, she developed an anaphylactic-like reaction 7 days after the initial dosage and was hospitalized in the neurological intensive care unit due to anaphylaxis. After 2.5 months, the CD19+ B-cell percentage rose to 4.5% and was maintained at 4.1% for the retest of B-cells 5 days later. She strongly requested another RTX infusion due to fear of relapse. Unfortunately, she had an allergic reaction (laryngeal edema and dyspnea) a few minutes after RTX administration, even though we had given her premedication including antihistamines, antipyretics and corticosteroids before administration in consideration of infusion reactions. She switched back to MMF for relapse prevention. However, two months thereafter, she again experienced vision loss in her right eye (finger count/20 cm) and limited adduction of the right eye with diplopia. Brainstem lesions were suspected but not identified on brain MRI. Optic nerve MRI suggested right optic nerve enhancement, suggesting a relapse. After treatment with IVIG, subcutaneous OFA (20 mg on Days 1, 7, and 14, and 20 mg monthly thereafter) was introduced on 28 June 2022 due to persistent relapses and adverse events associated with RTX. One month after receiving OFA administration, her visual acuity returned to 0.2, numbness with burning pain and pruritus in the extremities was significantly relieved, and spasms in the left upper and lower extremities disappeared. The CD19+ B-cell count decreased significantly. As of 19 April 2023, she had received twelve subcutaneous injections of OFA with no relapse, a CD19+ B-cell percentage of 0, and a serum IgM level of 17.0 mg/dL ().