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This article focuses on clinically relevant teaching points in spinal anatomy and localizing the lesion in myelopathy. The principles underlying spinal cord lesion localization are well established, but improvements in MRI and the discovery of pathologic antibodies associated with causes of transverse myelitis distinct from multiple sclerosis, such as aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG, have assisted in diagnosis. The spinal cord has a highly organized neuroanatomy of ascending and desce