BACKGROUND AND OBJECTIVES 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. METHODS 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. RESULTS 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, p < 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, p = 0.017) per relapse, followed by brain plus other phenotypes (β = 0.782, 95% CI 0.029-1.03, p < 0.001) and isolated TM (β = 0.295, 95% CI 0.074-0.549, p < 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, p < 0.001) in the LogMAR score. Race, sex, and timing of acute treatment did not significantly affect these disability outcomes (EDSS and LogMAR scores). DISCUSSION 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.

中文翻译：

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临床攻击对 AQP4 抗体视神经脊髓炎谱系疾病患者残余残疾的定量贡献。


背景和目的 水通道蛋白 4 抗体阳性视神经脊髓炎谱系疾病 （AQP4-NMOSD） 的疾病相关残疾仅归因于临床发作。然而，很少有研究评估 NMOSD 发作与残余残疾之间的关系。因此，我们旨在量化临床发作对 AQP4-NMOSD 患者残余残疾的贡献。方法 这项回顾性观察性单中心研究招募了来自牛津国家 NMO 服务的患者，纳入标准为 （1） AQP4-NMOSD 诊断和 （2） 至少有 1 个残疾评分 （扩展残疾状况量表 [EDSS] 或最小分辨率角 [LogMAR] 评分的对数）记录在发作后 ≥6 个月记录（定义为残余残疾）。结局指标是 EDSS 和 LogMAR 评分。使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果的影响。结果 共有 165 例 AQP4-NMOSD 患者 （中位发病年龄 43 岁，范围 2-84 岁;女性 140 例 [84.8%];欧洲白人患者，92 [55.8%];非洲或非洲裔英国患者，40 [24.2%];亚裔或亚裔英国患者，20 [12.1%];包括多种族或未知种族患者，13 名 [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）。每次复发的 EDSS 评分平均增加 0.304 （95% CI 0.074-0.553，p < 0.001），个体复发表型表现出不同的影响：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% CI 0.233-2.207，p = 0.017），其次是大脑加其他表型 （β = 0.782,95% CI 0.029-1.03， p < 0.001） 和孤立的 TM （β = 0.295,95% CI 0.074-0.549，p < 0.001），而单独的脑和视神经复发均与 EDSS 评分的残余变化无关。年龄较大的发病年龄与更严重的运动障碍相关，其中主要发生在病程早期，而年轻患者表现出轻度的初始残疾，随着复发而恶化更明显。每次 ON 攻击导致 LogMAR 评分平均增加 0.464 （95% CI 0.199-0.741，p < 0.001）。种族、性别和急性治疗时间对这些残疾结局 （EDSS 和 LogMAR 评分） 没有显著影响。讨论 AQP4-NMOSD 患者复发对残余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，并在较新的干预措施的成本效益分析中为长期残疾提供建模工具。