We present the case of a 23-year-old female with a subacute history of complex additive neurology which consisted of progressive unilateral visual impairment and subsequent blindness of the right eye, in conjunction with distal lower motor neuron symptoms of weakness and sensory loss from T4 level down. Special investigations performed, included serology and an urgent magnetic resonance imaging (MRI) of the brain and spinal cord, which exhibited a diffuse demyelinating disease of the brain and spinal cord without the typical features of multiple sclerosis (MS) and laboratory findings, which were positive for the AQP-4 antibody, confirming the diagnosis of neuromyelitis optica (NMO). Pulsed methylprednisolone was initiated urgently with good effect and immunosuppression with cyclophosphamide was added after the exclusion of additional pathology. She experienced a complete resolution of her weakness and sensory impairment upon discharge; however, her unilateral visual loss remained. The recent advances in the identification of autoimmune biomarkers and the widening spectrum of imaging findings in NMO necessitate that the clinician and radiologist keep abreast of the current diagnostic tools and criteria that distinguish NMO from other demyelinating conditions.