Bert-Marcaz Charlotte, Fortanier Étienne, Briantais Antoine, Faucher Benoit, Bourguiba Rim, Swiader Laure, Schleinitz Nicolas, Corazza Giovanni, Jean Rodolphe, Bigot Adrien, Marianetti-Guingel Paola, Kostine Marie, Outh Roderau, Dieudonné Yannick, Lazaro Estibaliz, Vial Guillaume, Palat Sylvain, Frachet Simon, De Almeida Chaves Sébastien, Vinzio Stéphane, Sacré Karim, Robert Marie, Comont Thilbault, Dion Jérémie, Girardie Pierre, Lacombe Valentin, Langlois Vincent, Jachiet Vincent, Decker Paul, Moulinet Thomas, Grosleron Sylvie, Broner Jonathan, Guilpain Philippe, Samson Maxime, Terrier Benjamin, Georgin-Lavialle Sophie, Attarian Sharham, Mekinian Arsène, Delmont Emilien, Ebbo Mikael
Internal Medicine Department, Aix Marseille Univ, APHM, hôpital de la Timone, 264 Rue Saint-Pierre, 13385, Marseille, France.
Neurology Department, Reference Center for Neuromuscular Diseases and ALS, Aix-Marseille University, AP-HM, La Timone Hospital, Marseille, France.
J Neurol. 2025 Feb 1;272(2):181. doi: 10.1007/s00415-025-12902-x.
VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a recently described syndrome linked to somatic mutations in the UBA1 gene, causing systemic autoinflammatory manifestations. To date, few data are available concerning neurological manifestations. The aim of this study was to describe their prevalence, clinical spectrum and outcome under treatment.
Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry between November 2020 and March 2023. Additional cases were included after a national call for observations. Each patient with confirmed UBA1 somatic mutation and neurological manifestation was reviewed during multidisciplinary meetings. Clinical, radiological, biological characteristics, treatments, and outcome were described.
Of the 291 patients included in the French VEXAS Registry, 17 (6%) had central (CNS) or peripheral (PNS) neurological involvement, with 13 additional cases identified by the national call. Of the 30 patients included, 21 (70%) had PNS involvement and 9 (30%) CNS involvement. PNS involvements included polyneuropathy (n = 9), cranial nerve involvement (n = 7), non-length-dependent polyneuropathy (n = 5) and multiple mononeuropathy (n = 3). CNS involvements included encephalopathy (n = 6), lacunar cerebral infarcts (n = 4), posterior reversible encephalopathy syndrome (n = 3) and optic perineuritis (n = 2). Most neurological manifestations were improved by steroids (68%), steroid-sparing agents were used in 90% [most frequently ruxolitinib (n = 11), azacitidine (n = 8), tocilizumab (n = 4)], and mortality was 30% after a median follow-up of 4 years.
Neurological manifestations may occur in a small but possibly underestimated proportion of patients with VEXAS syndrome, are heterogeneous and can involve both PNS and CNS.
VEXAS综合征（空泡、E1酶、X连锁、自身炎症性、体细胞性）是一种最近描述的与UBA1基因体细胞突变相关的综合征，可引起全身性自身炎症表现。迄今为止，关于神经学表现的数据很少。本研究的目的是描述其患病率、临床谱以及治疗后的结局。
一项回顾性多中心研究，纳入2020年11月至2023年3月法国VEXAS注册中心的VEXAS综合征患者。在全国征集观察病例后纳入了更多病例。在多学科会议期间对每例确诊为UBA1体细胞突变且有神经学表现的患者进行了评估。描述了临床、影像学、生物学特征、治疗方法及结局。
在法国VEXAS注册中心纳入的291例患者中，17例（6%）有中枢神经系统（CNS）或周围神经系统（PNS）受累，通过全国征集又确定了13例。在纳入的30例患者中，21例（70%）有PNS受累，9例（30%）有CNS受累。PNS受累包括多发性神经病（n = 9）、脑神经受累（n = 7）、非长度依赖性多发性神经病（n = 5）和多发性单神经病（n = 3）。CNS受累包括脑病（n = 6）、腔隙性脑梗死（n = 4）、后部可逆性脑病综合征（n = 3）和视神经周围炎（n = 2）。大多数神经学表现通过类固醇治疗得到改善（68%），90%的患者使用了类固醇节省剂[最常用的是芦可替尼（n = 11）、阿扎胞苷（n = 8）、托珠单抗（n = 4）]，中位随访4年后死亡率为30%。
神经学表现在一小部分VEXAS综合征患者中可能会出现，但比例可能被低估，表现具有异质性，可累及PNS和CNS。
