Abstract : Myelin-Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) is a novel autoimmune CNS disorder, previously categorized as a subtype of neuromyelitis optica. Although MOG-IgG antibodies are present in most cases, in some patients the disorder may develop without any detectable antibodies. Diagnosing such seronegative MOGAD is challenging and requires diagnostic vigilance. Accurate differentiation from other CNS autoimmune disorders is crucial for introducing effective treatment and improving patients’ long-term outcomes. A literature review was conducted using PubMed, Scopus, Web of Science, and ScienceDirect databases. Keywords included: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, Autoimmune Demyelinating Diseases, CNS Autoimmune Demyelinating Disorders, Neuromyelitis Optica, and Autoimmune Encephalitis. A total of 35 articles were selected based on relevance and quality of evidence regarding seronegative MOGAD. Patients with seronegative MOGAD often exhibit classical clinical phenotypes, such as optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis, but lack detectable MOG antibodies in serum. Diagnostic reliance on cerebrospinal fluid analysis and imaging is critical for these cases. Advanced diagnostic techniques, including live cell-based assays and biomarker studies, improve sensitivity and specificity. Seronegative cases frequently present with monophasic disease courses and demonstrate variable responses to immunotherapy. High-dose corticosteroids and plasma exchange remain the cornerstone of acute management, while maintenance therapies such as rituximab and mycophenolate mofetil are employed in recurrent cases. Seronegative MOGAD requires a multifaceted diagnostic approach incorporating serological, imaging, and cerebrospinal fluid analyses. Continued research into antibody-independent mechanisms and biomarkers is essential for optimizing diagnosis and treatment.