Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.
Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.
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DOI：
10.1212/wnl.0000000000012778
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发表时间：
2021-11-02
期刊：
影响因子：
9.9
通讯作者：
Piazza F
中科院分区：
文献类型：
--
作者：
Antolini L;DiFrancesco JC;Zedde M;Basso G;Arighi A;Shima A;Cagnin A;Caulo M;Carare RO;Charidimou A;Cirillo M;Di Lazzaro V;Ferrarese C;Giossi A;Inzitari D;Marcon M;Marconi R;Ihara M;Nitrini R;Orlandi B;Padovani A;Pascarella R;Perini F;Perini G;Sessa M;Scarpini E;Tagliavini F;Valenti R;Vázquez-Costa JF;Villarejo-Galende A;Hagiwara Y;Ziliotto N;Piazza F
这项工作的目的是研究自发性淀粉样蛋白相关成像异常（ARIA）样脑淀粉样血管病相关炎症（CAA-ri）治疗后的自然历史和结果。这是一项多中心、以医院为基础的纵向、前瞻性观察研究，研究对象是2013年1月至2017年3月期间通过炎症性脑淀粉样血管病和阿尔茨海默病β标志物国际网络招募的符合CAA-ri诊断标准的住院患者。在3个月、6个月、12个月和24个月的随访中，采用系统的数据收集方案，包括T1加权、梯度回忆回声t2 *、流体抑制t2加权（流体衰减反转恢复）和1.5T MRI上获得的T1后钆增强图像。对临床、治疗和时间点信息不知情的研究者进行核磁共振成像的集中读取。主要结果为生存、临床和放射学恢复、脑出血（ICH）和CAA-ri的复发。该研究纳入113名参与者（确诊10.6%，可能71.7%，可能17.7%）。平均年龄72.9岁；女性占43.4%；37.1%为APOEε4携带者；36.3%有阿尔茨海默病病史；33.6%有ICH病史。基线时皮质浅表性铁沉着患者有脑出血史和随访时新发脑出血更常见（分别为52.6%对14.3%,p < 0.0001和19.3%对3.6%,p < 0.009）。首次出现CAA-ri后，70.3%（95%置信区间[CI] 61.6%-78.5%）和84.1%（95%置信区间[CI] 76.2%-90.6%）的患者在3个月和12个月内临床恢复，随后分别有45.1% （95% CI 36.4%-54.8%）和77.4% （95% CI 67.7%-85.9%）的患者放射学恢复。在首次发作的临床放射学消退后，38.3% （95% CI 22.9%-59.2%）在接下来的24个月内至少复发一次。突然停止静脉注射高剂量皮质类固醇脉冲治疗比口服逐渐减少治疗更容易复发（风险比4.68,95% CI 1.57-13.93; p = 0.006）。这些来自最大的CAA-ri患者纵向队列登记的结果支持该疾病的临床-放射急性表现的短暂性和潜在复发性炎症性质，以及静脉注射皮质类固醇脉冲治疗后缓慢口服逐渐减少预防复发的有效性。我们的研究结果强调了鉴别诊断β-淀粉样蛋白驱动疾病中自发性ARIA样事件的重要性，包括暴露于免疫治疗药物的阿尔茨海默病患者的治疗相关ARIA。
The goal of this work was to investigate the natural history and outcomes after treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy–related inflammation (CAA-ri). This was a multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic criteria recruited through the Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease βiomarkers International Network from January 2013 to March 2017. A protocol for systematic data collection at first-ever presentation and at subsequent in-person visits, including T1-weighted, gradient recalled echo–T2*, fluid-suppressed T2-weighted (fluid-attenuated inversion recovery), and T1 postgadolinium contrast-enhanced images acquired on 1.5T MRI, was used at the 3-, 6-, 12-, and 24-month follow-up. Centralized reads of MRIs were performed by investigators blinded to clinical, therapeutic, and time-point information. Main outcomes were survival, clinical and radiologic recovery, intracerebral hemorrhage (ICH), and recurrence of CAA-ri. The study enrolled 113 participants (10.6% definite, 71.7% probable, and 17.7% possible CAA-ri). Their mean age was 72.9 years; 43.4% were female; 37.1% were APOEε4 carriers; 36.3% had a history of Alzheimer disease; and 33.6% had a history of ICH. A history of ICH and the occurrence of new ICH at follow-up were more common in patients with cortical superficial siderosis at baseline (52.6% vs 14.3%, p < 0.0001 and 19.3% vs 3.6%, p < 0.009, respectively). After the first-ever presentation of CAA-ri, 70.3% (95% confidence interval [CI] 61.6%–78.5%) and 84.1% (95% CI 76.2%–90.6%) clinically recovered within 3 and 12 months, followed by radiologic recovery in 45.1% (95% CI 36.4%–54.8%) and 77.4% (95% CI 67.7%–85.9%), respectively. After clinicoradiologic resolution of the first-ever episode, 38.3% (95% CI 22.9%–59.2%) had at least 1 recurrence within the following 24 months. Recurrence was more likely if IV high-dose corticosteroid pulse therapy was suddenly stopped compared to slow oral tapering off (hazard ratio 4.68, 95% CI 1.57–13.93; p = 0.006). These results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiologic acute manifestations of the disease and the effectiveness of slow oral tapering off after IV corticosteroid pulse therapy in preventing recurrences. Our results highlight the importance of differential diagnosis for spontaneous ARIA-like events in β-amyloid–driven diseases, including treatment-related ARIA in patients with Alzheimer disease exposed to immunotherapy drugs.