Chen Bo, Francis Anna, Cooper Sarah A, Dobson Ruth, Hacohen Yael, Halfpenny Christopher, Hemingway Cheryl, Hobart Jeremy C, O'Sullivan Eoin, Rashid Waqar, Martin Roswell J, Williams Victoria, Ramdas Sithara, Geraldes Ruth, Leite Maria Isabel S, Palace Jacqueline
From the Nuffield Department of Clinical Neurosciences (B.C., A.F., R.G., M.I.S.L., J.P.), Oxford University Hospitals, United Kingdom; Department of Neurology (B.C.), Tongji Hospital of Tongji Medical College, Huazhong University of Science of Technology, Wuhan, China; University Hospitals Sussex National Health Service Foundation Trust (S.A.C.), Brighton; Centre for Preventive Neurology (R.D.), Wolfson Institute of Population Health, Queen Mary University of London; Queen Square Multiple Sclerosis Centre (Y.H.), UCL Institute of Neurology, Faculty of Brain Sciences, University College London; Department of Paediatric Neurology (Y.H.), Great Ormond Street Hospital for Children, London; Department of Neurology (C. Halfpenny), University Hospital Southampton NHS Foundation Trust; Department of Neurology (C. Hemingway), Great Ormond Street Hospital for Children, London and Institute of Neurology; Department of Neurology (J.C.H.), University of Plymouth Faculty of Health and University Hospitals; Department of Ophthalmology (E.O.S.), King's College Hospital NHS Foundation Trust, London; Department of Neurology (W.R.), St George's University Hospitals NHS Foundation Trust, London; Department of Neurology (R.J.M.), Gloucestershire Hospitals National Health Service Foundation Trust; Department of Neurology (V.W.), King's College Hospital NHS Foundation Trust, London; Department of Neurology (V.W.), Guy's and St Thomas' National Health Service Foundation Trust, London; Department of Paediatric Neurology (S.R.), John Radcliffe Hospital, Oxford; and Neurology Department (R.G.), Wexham Park Hospital, Frimley Foundation Health Trust, Slough, United Kingdom.
Neurology. 2025 Jan 14;104(1):e210137. doi: 10.1212/WNL.0000000000210137. Epub 2024 Dec 12.
Disease-related disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) is solely attributed to clinical attacks. However, few studies have assessed the relationship between attacks and residual disability in NMOSD. Thus, we aimed to quantify the contribution of clinical attacks to the residual disability in patients with AQP4-NMOSD.
This retrospective observational single-center study enrolled patients from the Oxford National NMO Service, with the inclusion criteria as (1) AQP4-NMOSD diagnosis and (2) availability of at least 1 disability score (Expanded Disability Status Scale [EDSS] or logarithm of the minimum angle of resolution [LogMAR] score) recorded ≥6 months after attack (defined as residual disability). The outcome measures were EDSS and LogMAR scores. Univariable and multivariable linear mixed-effect models were used to quantify the effect of clinical relapses on the outcomes.
A total of 165 patients with AQP4-NMOSD (median onset age, 43 years, range 2-84; women, 140 [84.8%]; White European patients, 92 [55.8%]; African or African British patients, 40 [24.2%]; Asian or Asian British patients, 20 [12.1%]; multiracial or unknown racial patients, 13 [7.9%]) were included, with the median time of disability measurement since the last attack being 32 months (range 6-197). The mean increase in the EDSS score per relapse was 0.304 (95% CI 0.074-0.553, < 0.001), with individual relapse phenotypes showing different effects: the transverse myelitis (TM) + optic neuritis (ON) phenotype contributed most, with an increase of 1.290 (95% CI 0.233-2.207, = 0.017) per relapse, followed by brain plus other phenotypes (β = 0.782, 95% CI 0.029-1.03, < 0.001) and isolated TM (β = 0.295, 95% CI 0.074-0.549, < 0.001), while neither brain nor optic nerve relapse alone was associated with a residual change in the EDSS score. Older onset age was correlated with more severe motor disability where this mainly occurred early in the disease course while younger patients exhibited mild initial disability that worsened more significantly with relapses. Each ON attack led to a mean increase of 0.464 (95% CI 0.199-0.741, < 0.001) in the LogMAR score. Race, sex, and timing of acute treatment did not significantly affect these disability outcomes (EDSS and LogMAR scores).
The quantitative contribution of relapse to the residual disability in patients with AQP4-NMOSD varies across phenotypes, and this relapse-related disability progression may also vary by the onset age. Although this retrospective single-center study may need validation in other data sets, these findings may help predict disability and provide a modeling tool for longer term disability in the cost-effective analysis of newer interventions.
水通道蛋白4抗体阳性视神经脊髓炎谱系障碍（AQP4-NMOSD）中与疾病相关的残疾完全归因于临床发作。然而，很少有研究评估发作与NMOSD残留残疾之间的关系。因此，我们旨在量化临床发作对AQP4-NMOSD患者残留残疾的影响。
这项回顾性观察性单中心研究纳入了牛津国家NMO服务中心的患者，纳入标准为：（1）AQP4-NMOSD诊断；（2）在发作后至少6个月记录到至少1个残疾评分（扩展残疾状态量表[EDSS]或最小分辨角对数[LogMAR]评分）（定义为残留残疾）。结局指标为EDSS和LogMAR评分。采用单变量和多变量线性混合效应模型来量化临床复发对结局的影响。
共纳入165例AQP4-NMOSD患者（发病年龄中位数为43岁，范围2-84岁；女性140例[84.8%]；白种欧洲患者92例[55.8%]；非洲或非裔英国患者40例[24.2%]；亚洲或亚裔英国患者20例[12.1%]；多种族或种族不明患者13例[7.9%]），自上次发作以来残疾测量的中位时间为32个月（范围6-197个月）。每次复发时EDSS评分的平均增加为0.304（95%可信区间0.074-0.553，P<0.001），不同复发表型显示出不同的影响：横贯性脊髓炎（TM）+视神经炎（ON）表型贡献最大，每次复发增加1.290（95%可信区间0.233-2.207，P=0.017），其次是脑部加其他表型（β=0.782，95%可信区间0.029-1.03，P<0.001）和孤立性TM（β=0.295，95%可信区间0.074-0.549，P<0.001），而单独的脑部或视神经复发均与EDSS评分的残留变化无关。发病年龄较大与更严重的运动残疾相关，这主要发生在疾病病程早期，而年轻患者表现出轻度的初始残疾，随着复发残疾恶化更为明显。每次ON发作导致LogMAR评分平均增加0.464（95%可信区间0.199-0.741，P<0.001）。种族、性别和急性治疗时机对这些残疾结局（EDSS和LogMAR评分）没有显著影响。
复发对AQP4-NMOSD患者残留残疾的定量贡献因表型而异，这种与复发相关的残疾进展也可能因发病年龄而异。尽管这项回顾性单中心研究可能需要在其他数据集中进行验证，但这些发现可能有助于预测残疾，并为新干预措施的成本效益分析中的长期残疾提供建模工具。
