de Boysson Hubert, Nehme Ahmad, Briant Anais R, Alamowitch Sonia, Aouba Achille, Arquizan Caroline, Boulouis Grégoire, Capron Jean, Casolla Barbara, Denier Christian, Dequatre Nelly, Detante Olivier, Derex Laurent, Godard Sophie, Gollion Cédric, Guillon Benoit, Humbertjean Lisa, Isabel Clothilde, Kerschen Philippe, Kremer Laurent, Lambert Nicolas, Lanthier Sylvain, Maarouf Adil, Néel Antoine, Papo Thomas, Poppe Alexandre Y, Régent Alexis, Sellimi Amina, Sibon Igor, Terrier Benjamin, Touzé Emmanuel, Vannier Stéphane, Weisenburger-Lile David, Zuber Mathieu, Parienti Jean-Jacques, Pagnoux Christian
Service de Médecine Interne, CHU de Caen, Caen, France.
Université Caen-Normandie, Caen, France.
Eur J Neurol. 2025 May;32(5):e70174. doi: 10.1111/ene.70174.
To determine whether hierarchical unsupervised cluster analysis identifies a phenotypic distinction in adult patients with primary CNS vasculitis (PCNSV).
An agglomerative hierarchical cluster analysis based on the Ward method was conducted, including 153 patients with complete baseline phenotypic characterization in the COVAC' registry.
The hierarchical analysis identified two main clusters. In Cluster 1 (n = 109 patients, 71%), patients more frequently had a motor deficit (p = 0.039), ≥ 1 acute brain infarct (p < 0.001), and ≥ 1 intracranial stenosis on CT or MR angiogram (p < 0.001) than patients in Cluster 2 (n = 44 patients, 29%). Conversely, patients in Cluster 2 more frequently had seizures (p < 0.001), cognitive impairment (p = 0.002), gadolinium-enhanced parenchymal lesions (p < 0.001), leptomeningeal enhancement (p < 0.001), ≥ 1 cerebral microbleed (p < 0.001), and intracranial hemorrhage(s) (p < 0.001). In multivariable logistic regression, gadolinium-enhanced parenchymal lesions were significantly associated with Cluster 2 lesions (OR = 35.53 [95% CI: 3.91-322.81], p = 0.002). Conversely, ≥ 1 acute brain infarct was significantly associated with Cluster 1 (OR = 0.003 [95% CI: 0.01-0.03], p < 0.001). A CNS biopsy was positive in 11/40 (28%) patients from Cluster 1 and 35/37 (95%) patients from Cluster 2 (p < 0.001). At 12 months, functional independence (modified Rankin scale score ≤ 2) did not differ between the two groups (p = 0.17). Relapse and mortality rates did not differ between the clusters (p = 0.17 and p = 0.23, respectively).
This unsupervised analysis of a large PCNSV cohort identified two different clinical and radiological phenotypes with different diagnostic work-ups, which confirms the relevance of distinguishing PCNSV phenotypes according to the sizes of affected vessels.
确定分层无监督聚类分析是否能识别出成人原发性中枢神经系统血管炎（PCNSV）患者的表型差异。
基于沃德法进行凝聚层次聚类分析，纳入了COVAC登记处中153例具有完整基线表型特征的患者。
层次分析确定了两个主要聚类。在聚类1（n = 109例患者，71%）中，与聚类2（n = 44例患者，29%）中的患者相比，患者更常出现运动功能缺损（p = 0.039）、≥1处急性脑梗死（p < 0.001）以及CT或磁共振血管造影显示≥1处颅内狭窄（p < 0.001）。相反，聚类2中的患者更常出现癫痫发作（p < 0.001）、认知障碍（p = 0.002）、钆增强实质病变（p < 0.001）、软脑膜强化（p < 0.001）、≥1处脑微出血（p < 0.001）以及颅内出血（p < 0.001）。在多变量逻辑回归分析中，钆增强实质病变与聚类2显著相关（比值比[OR] = 35.53 [95%置信区间：3.91 - 322.81]，p = 0.002）。相反，≥1处急性脑梗死与聚类1显著相关（OR = 0.003 [95%置信区间：0.01 - 0.03]，p < 0.001）。聚类1中40例患者中有11例（28%）中枢神经系统活检呈阳性，聚类2中37例患者中有35例（95%）呈阳性（p < 0.001）。在12个月时，两组之间功能独立性（改良Rankin量表评分≤2）无差异（p = 0.17）。聚类之间的复发率和死亡率无差异（分别为p = 0.17和p = 0.23）。
对一大群PCNSV患者进行的这项无监督分析识别出了两种不同的临床和放射学表型，其诊断检查方法不同，这证实了根据受累血管大小区分PCNSV表型的相关性。
