Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated With Ascending Colon Cancer Expressing Aquaporin-4 and Glucose-Regulated Protein 78

与表达水通道蛋白4和葡萄糖调节蛋白78的升结肠癌相关的副肿瘤性视神经脊髓炎谱系障碍

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Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease, typically defined by the presence of optic neuritis and longitudinally extensive transverse myelitis. A 69-year-old woman presented with acute longitudinally extensive transverse myelitis and motor and sensory deficits. Laboratory testing confirmed the presence of aquaporin-4 (AQP4) antibodies, leading to a diagnosis of NMOSD. Her symptoms improved following methylprednisolone pulse therapy. Further evaluation revealed concurrent ascending colon cancer. Surgical resection of the tumor was performed while the patient was maintained on 10 mg of prednisolone. Immunohistochemistry revealed high expression of AQP4 and glucose-regulated protein 78 (GRP78) in tumor cells. GRP78 antibodies were also detected in the serum. Postoperatively, both AQP4 and GRP78 antibodies became undetectable, and no recurrence of NMOSD was observed during a six-month follow-up while continuing prednisolone therapy. NMOSD results from astrocytic injury caused by AQP4 antibodies, which require disruption of the blood-brain barrier (BBB) to penetrate the nervous system. Recent studies have shown that GRP78 antibodies may contribute to BBB disruption. We hypothesize that an immune response against tumor-expressed AQP4 and GRP78 triggered the production of corresponding antibodies, with GRP78 antibodies contributing to BBB breakdown and the onset of paraneoplastic NMOSD.

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