A 61-year-old woman presented with numbness and weakness in all of her extremities for over 2 months. She then went to the community clinic and received treatment of oral vitamin B12 (1 mg per day) with the guidance of community doctors. She felt slight improvement of the numbness when first got oral vitamin B12 treatment for about a week. However, after the orally treatment of vitamin B12 for one month, her symptoms worsened over time and interfered with her daily life. And then she was admitted to department of neurology in our hospital. The patient had Hashimoto’s thyroiditis and hypertension, as well as good compliance with the hypotensor. In addition, she had a good dietary intake with a negative history of alcohol, cigarettes, illicit drugs, or gastrointestinal surgery. She was conscious and fluent in speech when she arrived at our clinic. A neurological examination showed no abnormalities in cranial nerves. A marked increase in the deep tendon reflexes, mild weakness in the limbs (grade 4), and impaired vibration sensation and joint position were detected on the neurological examination. Neither Babinski’s sign nor Romberg’s sign were detected at that time. The scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were both 21 out of 30. Moreover, macrocytic anaemia was demonstrated by the laboratory tests. There was a decrease in red blood cells (RBCs) (2.47 × 10^12/L, reference range: 4.30–5.80 × 10^12/L) and haemoglobin (Hb) (106 g/L, reference range: 130–175 g/L), which were accompanied by an increase in MHC (42 pg, reference range: 27–34 pg), MCHC (360 g/L, reference range: 320–360 g/L), and MCV (116.7 fL, reference range: 82–100 fL). Furthermore, a lower vitamin B12 (147 pmol/L, reference range: 211–911 pmol/L) level was detected even after supplementary treatment with vitamin B12. The level of serum homocysteine (Hcy) (31.6 μmol/L, reference range: 4–15.4 μmol/L), an indicator of the function of vitamin B12 deficiency at the cellular level, was out of the normal range. The cerebrospinal fluid (CSF) showed normal leukocyte, chloride, glucose, and protein results. Anti-intrinsic factor antibody and tumour markers (CEA, AFP, CA125, CA724, CA19–9, and CA15–3) were all unremarkable. Nerve conduction studies and electromyogram (EMG) were normal. In spinal cord T2-weighted MRI, long segmental hyperintensities involving the posterior columns of the spinal cord were observed in sagittal images (C2 to C6), whereas a typical inverted “V-sign” was observed in axial images. No abnormality was found in the brain MRI scan. She was initially diagnosed with SCD for unknown reasons. As she was benefits from oral vitamin B12 supplementation at the very beginning, a high dose of supplementary intramuscular vitamin B12 injections (1.5 mg per day) was given immediately after she came to our department. And at the same time, a neuromyelitis optica (NMO) antibody test was then performed, as there was a longitudinally extended lesion on the sagittal MRI as well as the poor curative effect of vitamin B12 supplementation alone. The results showed that antibody targeting aquaporin 4 (AQP4) was positive in both the serum (12.86 u/ml) and in the CSF (7.98 u/ml), and a myelin-oligodendrocyte glycoprotein (MOG) antibody test was negative. She was then diagnosed with NMOSD coexisting with SCD. Subsequently, she received intravenous methylprednisolone treatment (500 mg/day for 3 days, 250 mg/day for 3 days, 120 mg/day for 3 days). Symptoms of weakness were improved via the intravenous methylprednisolone treatment. After intravenous methylprednisolone, she continued the oral prednisolone treatment for 6 months. The course of intramuscular vitamin B12 injections for 1 month with a following daily oral vitamin B12 supplementation treatment (1 mg per day) for 6 months. 3 months after discharged, except for slight numbness in the fingers, symptoms of paraesthesia and limb weakness had resolved. Additionally, her anaemia improved (RBC 3.48 × 10^12/L and Hb 127.0 g/L), and the vitamin B12 level in serum increased to more than the maximum measurable value. Signal abnormalities observed on the MRI also improved, both horizontally and longitudinally. During her next 6-month follow-up, her symptoms were completely relieved. In addition, no tumour signs were discovered during the follow-up period.