## 5 Symptoms of NMOSD
### Imaging and Diagnosis of NMOSD
Few patients suffer from respiratory failure due to cervical myelitis [71]. Up to 4% of patients with acute myelitis also suffer bilateral ON and brainstem manifestations with symptomatic brain lesions [72]. MRI analysis revealed that long cord lesions with central necrosis and cavitation in the 3 rd or 4 th vertebral segments over weeks or months are the most prominent clinical characteristic of NMOSD [73]. Thus, MRI diagnosis accurately understands specific clinical outcomes of the inflammatory myelopathies and would support required relapse preventive treatment methods for the disease [69]. Numerous studies help distinguish MOGAD from MS and AQP4+ NMOSD. The clinical manifestations of MOGAD are heterogenous, including ON, myelitis, and multifocal demyelination in the CNS, which can often resemble acute disseminated encephalomyelitis (ADEM). MRI results differentiate MOGAD from MS and AQP4+ NMOSD with perineural optical nerve enhancement. Other possible methods of differentiating MOGAD diagnosis from MS and AQP4+ NMOSD include the cell-based assay and antibody titer for MOG-IgG [74]. Differential diagnosis of ON was characterized in MOGAD and AQP4+ NMOSD. AQP4-ON shows long, unilateral lesions mostly affecting the posterior optic nerves through T1 gadolinium enhancement [63]. MOG-ON shows longer, bilateral lesions mostly affecting the anterior of the optic nerve with perineural T2 hypersensitivity and gadolinium enhancement [75]. MOG and AQP4 optic lesions extend into the intracranial and pre-chiasmicsegments of the optic nerve compared to MS [76; 77]. Bilateral ON and longitudinal optic nerve lesions are common in MOGAD and AQP4\({}^{+}\) NMOSD, respectively. MRI studies with different MOGAD cohorts revealed localized lesions in the deep white matter and area postrema [78]. In another study, lesions were observed in the supratentorial deep white matter [79]. These MRI studies help distinguish the MOG and AQP4 seropositive patients through the key indicator that the AQP4 cohort preferentially showed no deep white matter lesions compared to the MOG type. Another unique feature in MOGAD is the leptomeningeal enhancement and cortical/juxtacortical lesions, which are absent in AQP4\({}^{+}\) NMOSD patients [80]. AQP4\({}^{+}\) NMOSD displayed distinctive lesions in anatomical locations such as the peri ependymal. Periapaductal and hypothalamic areas showed no imaging abnormalities in the MOGAD cohort [81]. Brain lesions are more commonly reported in pediatric-onset NMOSD than adult-onset, making it difficult to differentiate ADAM and NMOSD. Pediatric ADAM presents with longitudinally extensive transverse myelitis such as NMOSD. Therefore, myelitis is not considered a reliable sign or predictor of NMOSD in pediatrics [82]. Pediatric NMOSD and ADAM can be differentiated through thalamic involvement. Thalamic involvement in NMOSD is infrequent, with a limited non-specific lesion, whereas thalamic involvement in ADAM is more frequent with a large, asymmetric lesion. Thus, the thalamic lesion location favors differentiating NMOSD and ADAM [82]. [PERSON] et al. reported that brain lesions in the putamen and hypothalamus favor the diagnosis of ADAM and NMOSD, respectively [83]. NMOSD is occasionally associated with primary SS and systemic lupus erythematosus (SLE). Non-infectious inflammatory myelitis was reported in parameoplastic myelitis and SS [84]. Most myelitis cases are related to SS, having longitudinally extensive spinal cord involvement that has been used as a diagnostic criterion for NMOSD. Critically, the clinical, radiological, and prognostic spectra have not differentiated SS from NMOSD, yet AQP4-ab is presented only in NMOSD patients [85]. SLE patients were also reported to have CNS lupus with headache, seizure, and memory impairment. Myelitis and optic neuritis were also found in a few SLE patients. Although the symptoms are the same, CNS lupus manifestation in SLE is distinct from that in NMOSD [86].