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

Youming Long; Junyan Liang; Linzhan Wu; Shaopeng Lin; Cong Gao; Xiaohui Chen; Wei Qiu; Yu Yang; Xueping Zheng; Ning Yang; Min Gao; Yaotang Chen; Zhanhang Wang; Quanxi Su

doi:10.3389/fneur.2017.00062

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

Front Neurol. 2017 Feb 28:8:62. doi: 10.3389/fneur.2017.00062. eCollection 2017.

Authors

Youming Long¹, Junyan Liang¹, Linzhan Wu¹, Shaopeng Lin², Cong Gao¹, Xiaohui Chen², Wei Qiu³, Yu Yang³, Xueping Zheng⁴, Ning Yang⁵, Min Gao⁶, Yaotang Chen¹, Zhanhang Wang⁷, Quanxi Su⁸

Affiliations

¹ Department of Neurology, the Second Affiliated Hospital of GuangZhou Medical University, Guangzhou, Guangdong Province, China; Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Collaborative Innovation Center for Neurogenetics and Channelopathies, Guangzhou, China.
² Department of Emergency, The Second Affiliated Hospital of GuangZhou Medical University , Guangzhou, Guangdong Province , China.
³ Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, Guangdong Province , China.
⁴ Department of Neurology, The Affiliated Hospital of Qingdao University , Qingdao, Shandong Province , China.
⁵ Department of Neurology, The Fifth Affiliated Hospital of GuangZhou Medical University , Guangzhou, Guangdong Province , China.
⁶ Department of Neurology, The Second Chinese Medicine Hospital of Guangdong Province , Guangzhou, Guangdong Province , China.
⁷ Department of Neurology, Guangdong 999 Brain Hospital , Guangzhou, Guangdong Province , China.
⁸ Department of Neurology, Yunfu City People's Hospital , Yunfu, Guangdong Province , China.

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.

Keywords: aquaporin-4; brain; myelitis; neuromyelitis optica; optic neuritis.