脑淀粉样血管病相关炎症与脑实质活检阳性的原发性中枢神经系统血管炎：一项对比研究。

Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

机构信息

From Neurology (L.G., O.O.-W., A.T.-B., D.W., P.V., G.Q.), CHU de Rouen; Radiology (G.B., F.B.), CHRU de Tours; Service des Urgences Neurovasculaires (J.C., S.A.), Hôpital Pitié-Salpêtrière, Sorbonne Université, AP-HP, Stare Team, iCRIN, Institut du Cerveau, Paris; Neurology (D. Renard, A.W., E. Thouvenot), CHU de Nîmes; Neurology (N.R., C.G., J.P.), CHU de Toulouse; Neurology (X.A., C.A., P.M.L.), CHU de Montpellier; Radiology (E.G.), CHU de Rouen; Neurology (P.K.), CHU de Luxembourg; Neurology (D.S., N.O., T.A.), CH de Perpignan; Neurology (M.F.), Hospices Civils de Lyon; Neurology (F.P.), CH de Versailles; Neurology (G.T., C.I.), GHU Paris; Geriatric Medicine (M. Verny), Hôpital Pitié-Salpêtrière, AP-HP, Paris; Neurology (L.H.), CHRU de Nancy; Neurology (M. Gaudron), CHRU de Tours; Neurology (S.V.), CHU de Rennes; Neurology (N.D., H.Z.), CHU de Lille; Neurology (B.G.), CHU de Nantes; Université Grenoble Alpes (O.D.), INSERM, U1216, Neurology, CHU de Grenoble Alpes, Grenoble Institute Neurosciences; Neurology (S.G.), CHU de Angers; UR2CA-URRIS (B.C.), Stroke Unit, CHU Pasteur 2, Nice Cote d'Azur University; Internal Medicine (M.L., S.B.), CHU de Nice; Internal Medicine (M.G.-V.), Hôpital Croix-Rousse, Lyon; Neurology (L.K.), CHRU de Strasbourg; Neurology (L.D.), CH de Lorient, France; Neurology (N.L.), CHU de Liège/CHR la Citadelle, Liège, Belgique; Neurology (S.L.), Hôpital du Sacré-cœur de Montréal; Neurology (A.P.), CH de l'Université de Montréal, Québec, Canada; Internal Medicine (A.R., B.T.), Université Paris-Cité, Hôpital Cochin, AP-HP; Neurology (D.W.-L.), Hôpital Foch, Suresnes; Internal Medicine (M. Vautier), Hôpital Pitié-Salpêtrière, Paris; Neurology (S.C.), CH de Gonesse; Internal Medicine (A. Neel), CHU de Nantes; Université Caen-Normandie (O.M., R.S., E. Touzé, A. Nehme), Neurology, CHU de Caen-Normandie; Internal Medicine (T.P.), Hôpital Bichat; Internal Medicine (C.C.-O.), Hôpital Lariboisière; Neurology (E.J.), Hôpital Lariboisière, Paris; Neurology (M.S.), HIA Sainte-Anne, Toulon; Neurology (L.P.-M.), CHU de Clermont-Ferrand; Neurology (M.A.K.), CH Troyes; Neurology (F.L.), CH d'Orsay; Neurology, CH de Saint-Denis; Université de Franche-Comté (E.M.), LINC Laboratoire de Recherches Intégratives en Neurosciences et Psychologie Cognitive et CMRR, Service de Neurologie, CHU de Besançon; Neurology (Q.T., M. Graber), CHU de Dijon; Neurology (Y.B.), CH de Béziers; Neurology (G.B.-F., D. Ratiu), CH de Narbonne, France; Vasculitis Clinic (C.P.), Mount Sinai Hospital, University of Toronto, Ontario, Canada; and Université Caen-Normandie (H.D.B.), Internal Medicine, CHU de Caen-Normandie, France.

出版信息

Neurology. 2024 Jul 23;103(2):e209548. doi: 10.1212/WNL.0000000000209548. Epub 2024 Jun 20.

DOI:10.1212/WNL.0000000000209548

PMID:38900992

Abstract

BACKGROUND AND OBJECTIVES

Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS.

METHODS

Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk.

RESULTS

This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, < 0.001), acute subarachnoid hemorrhage (15% vs 2%, = 0.02), cortical superficial siderosis (27% vs 4%, < 0.001), ≥1 lobar microbleed (94% vs 26%, < 0.001), past intracerebral hemorrhage (17% vs 4%, = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, < 0.01), and leptomeningeal enhancement (70% vs 27%, < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, < 0.01), motor deficits (56% vs 36%, = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS ( = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, = 0.04).

CONCLUSION

Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

摘要

背景与目的

脑淀粉样血管病相关性炎症（CAA-RI）和经活检证实的原发性中枢神经系统血管炎（BP-PACNS）具有重叠的临床影像学表现。目前尚不清楚临床和影像学特征是否可以区分 CAA-RI 和 BP-PACNS，以及这两种疾病是否具有不同的复发率。本研究的目的是比较 CAA-RI 与 BP-PACNS 患者的临床影像学表现和复发率。

方法

本研究纳入了来自 2 个回顾性多中心队列的 CAA-RI 和 BP-PACNS 患者。CAA-RI 患者经活检证实或符合可能的临床影像学标准。BP-PACNS 患者具有中枢神经系统血管炎的组织病理学证实，无继发性病因。神经放射科医生对脑 MRI 进行阅读，对 CAA-RI 或 BP-PACNS 的诊断不了解。使用单变量逻辑回归模型比较临床影像学特征。使用单变量 Fine-Gray 亚分布风险模型比较复发率，以死亡为竞争风险。

结果

本研究纳入了 104 例 CAA-RI 患者（平均年龄 73 岁，48%为女性）和 52 例 BP-PACNS 患者（平均年龄 45 岁，48%为女性）。与 BP-PACNS 患者相比，CAA-RI 患者更常出现符合可能的 CAA-RI 标准的脑白质高信号病变（93% vs 51%， < 0.001）、急性蛛网膜下腔出血（15% vs 2%， = 0.02）、皮质表浅铁沉积（27% vs 4%， < 0.001）、≥1 个脑叶微出血（94% vs 26%， < 0.001）、既往颅内出血（17% vs 4%， = 0.04）、≥21 个可见的侧脑室周围血管周围间隙（34% vs 4%， < 0.01）和软脑膜强化（70% vs 27%， < 0.001）。BP-PACNS 患者更常出现头痛（56% vs 31%， < 0.01）、运动障碍（56% vs 36%， = 0.02）和非缺血性实质钆增强（82% vs 16%， < 0.001）。CAA-RI 和 BP-PACNS 患者的急性缺血性病变患病率分别为 18%和 22%（ = 0.57）。对 CAA-RI 具有最高特异性的特征是急性蛛网膜下腔出血（98%）、皮质表浅铁沉积（96%）、既往颅内出血（96%）和≥21 个可见的侧脑室周围血管周围间隙（96%）。可能的 CAA-RI 标准在区分活检阳性的 CAA-RI 和 BP-PACNS 时具有 71%的敏感性（95%CI 44%-90%）和 91%的特异性（95%CI 79%-98%）。在缓解后的前 2 年内，CAA-RI 的复发率低于 BP-PACNS（风险比 0.46，95%CI 0.22-0.96， = 0.04）。

结论

CAA-RI 和 BP-PACNS 患者的临床影像学特征不同。CAA-RI 的特异性标志物包括蛛网膜下腔受累的出血征象、既往颅内出血、≥21 个可见的侧脑室周围血管周围间隙和可能的 CAA-RI 标准。在某些情况下，活检仍然是 CAA-RI 诊断的必要手段。在疾病缓解后的前 2 年内，CAA-RI 的复发率低于 BP-PACNS。