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

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

doi:10.3389/fneur.2017.00062

Abstract

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. 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. 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. 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. 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.

Highlights

Neuromyelitis optica (NMO) is generally a severe, idiopathic, immune-mediated inflammatory, demyelinating, and necrotizing disease that mainly involves the optic nerve and spinal cord, but rarely the brain
The present study found that initial manifestations without transverse myelitis (TM) or optic neuritis (ON) were not uncommon in NMO spectrum disorder (NMOSD) patients
In all the patients examined, the onset of brain/brainstem lesions was more frequent than that previously shown in a large study [12]

Summary

Introduction

Neuromyelitis optica (NMO) is generally a severe, idiopathic, immune-mediated inflammatory, demyelinating, and necrotizing disease that mainly involves the optic nerve and spinal cord, but rarely the brain. Limited forms of NMO, optic neuritis (ON) or transverse myelitis (TM), positive for the anti-AQP4 antibody are diagnosed as NMO spectrum disorder (NMOSD) [4, 5]. Increasing numbers of positive cases without optic nerve and spinal cord involvement have been reported, indicating that the requirement for the presence of either ON or TM may confound the definition of NMOSD [6]. The international panel for NMO diagnosis has updated the definition of NMOSD to include the presence or absence of anti-AQP4 antibody [2]. 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

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Conclusion