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Autoantibodies are the cause of the chronic inflammatory diseases known as neuromyelitis optica spectrum disorders (NMOSD). Serum antibodies (Abs) that specifically target the aquaporin-4 (AQP-4) water channel are the cause of recurrent episodes of optic neuritis, myelitis, and/or brain stem disorders. In contrast to AQP-4 Abs, myelin oligodendrocyte glycoprotein (MOG) Abs are detected in some patients exhibiting nonmotor cognitive impairment. These days, the term "MOG-encephalomyelitis" (MOG-EM) is frequently used to describe these clinical syndromes. The diagnosis of these cases involves the use of magnetic resonance imaging, optical coherence tomography, antibody detection, and additional laboratory testing. By detecting the patient's Abs in their serum or cerebrospinal fluid (CSF), indirect immunofluorescence (IIF) aids in the proper diagnosis. We highlight five NMOSD cases where serum anti-MOG antibody positivity was found using IIF, but CSF was not. In none of the cases, anti-AQP Abs were found. Effective patient management strategies include the treatment of acute attacks and long-term immunosuppressive drugs such as rituximab, azathioprine, and immunoglobulins. IIF is a quick and easy tool to detect anti-MOG Abs in patients with NMOSD/myelin oligodendrocyte glycoprotein antibody-associated disorder. CSF testing for MOG or AQP-4 Abs is not usually advised. It does not offer additional benefits to help with MOG-EM or NMOSD diagnosis., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)