Different Phenotypes at Onset in Neuromyelitis Optica Spectrum Disorder Patients with Aquaporin-4 Autoimmunity

视神经脊髓炎谱系障碍患者伴水通道蛋白4自身免疫时的不同发病表型

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Abstract

BACKGROUND: Although rare, brain abnormalities without optic neuritis (ON) or transverse myelitis (TM) diagnosed with neuromyelitis optica spectrum disorder (NMOSD) have been reported in patients positive for the aquaporin-4 (AQP4) antibody. OBJECTIVE: To analyze demographic and clinical differences among NMOSD patients without ON or TM, those with either ON or TM, and patients with simultaneous ON and TM at disease onset. METHODS: In this retrospective study, patients who were positive for the AQP4 antibody, as detected using a cell-based assay, at the Second Affiliated Hospital of Guangzhou Medical University in China were recruited. Demographic and clinical data were obtained from each patient's medical record. RESULTS: A total of 292 patients were included in this study and were divided into four subgroups based on their initial manifestations: (i) NMOSD without ON or TM (NMOSD-ON(-)TM(-), n = 70); (ii) NMOSD with ON (NMOSD-ON(+), n = 95); (iii) NMOSD with TM (NMOSD-TM(+), n = 116); and (iv) simultaneous ON and TM [neuromyelitis optica (NMO), n = 11]. We found that age at onset was lower in the NMOSD-ON(-)TM(-) group than that in the other groups. The interval from the first episode to relapse was shorter in the NMOSD-ON(-)TM(-) group than that in NMOSD-TM(+) group. Cerebral spinal fluid white cell counts and protein levels were significantly higher in the NMOSD-ON(-)TM(-) group than those in the other groups. Lower Expanded Disability Status Scale scores were observed in the NMOSD-ON(-)TM(-) group. Brain abnormalities, including in area postrema and hemisphere lesions, were more frequent in the NMOSD-ON(-)TM(-) group. Kaplan-Meier analysis showed that patients in the NMOSD-ON(-)TM(-) group experienced earlier relapse than those in other groups. Conversion to NMO in the NMOSD-ON(+) group was greater than that in the other groups. Only 14 patients (4.8%, 14/292) had pure brain abnormalities, of which 12 had disease duration of several more years and 8 (57.1%) experienced relapses. CONCLUSION: NMOSD patients with different initial manifestations present with significant differences in clinical features during follow-up. Patients with long-term AQP4 autoimmunity in the brain in the absence of ON or TM are not common.

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