Paraneoplastic syndromes associated with breast cancer can present with neuromyelitis optica spectrum disorder (NMOSD) symptoms and elevated titers of aquaporin-4 (AQP4) immunoglobulin (IgG), suggesting that breast cancer screening should be considered in elderly patients with new-onset NMOSD.

Researchers reached these findings in a meta-analysis recently published in Neurological Sciences.

Although NMOSD is considered an idiopathic autoimmune disorder, new evidence suggests that AQP4 IgG expression leading to neurological symptoms can also be present in the context of paraneoplastic syndrome.

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According to the literature, breast carcinoma is the malignancy most commonly associated with breast cancer. However, it has also been reported in lung, ovarian, bladder, and cervical cancer. Currently, tumor screening is not part of the initial workup of patients with NMOSD.

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Therefore, the authors aimed to assess the temporal relationship between the onset of paraneoplastic NMOSD symptoms and breast cancer diagnosis.

“This would help to better characterize the unique clinical phenotypes of NMOSD and aid in prompt clinical diagnosis in the appropriate clinical setting,” the authors wrote.

Researchers searched clinical databases such as PubMed and ScienceDirect for cases of paraneoplastic NMOSD secondary to breast cancer using PRISMA guidelines, obtaining 19 cases from 12 different records.

All 19 patients were women, with a mean age of 51 years. The most common clinical manifestations were speech disturbances and myopathy symptoms. In 8 cases, the breast cancer diagnosis occurred at least 1 month after the NMOSD diagnosis; in 3 cases, the breast cancer diagnosis occurred at least a month before the NMOSD diagnosis; and in 5 cases, both diagnoses were made within the same month. Methylprednisolone was the most common treatment for NMOSD symptoms.

The authors recognized the low number of cases included as a limitation of the study and recommended a repeat analysis of the available literature when more cases are reported.

“Further consideration should be given to more frequent active cancer screening in older patients with new-onset NMOSD,” they concluded.


Srichawla BS, Doshi K, Cheraghi SN, Sivakumar S. The temporal relationship of paraneoplastic aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and breast cancer: a systematic review and meta-analysis. Neurol Sci. Published online July 7, 2023. doi:10.1007/s10072-023-06952-0