From Service de Médecine Interne 2, Centre National de Référence Maladies Systémiques Rares et Histiocytoses (F.C.A., Z.A., J.H.), Service de Neuroradiologie (D.G., B.L.-Y.), Service d'Anatomopathologie (F.C.), Service de Médecine Nucléaire (P.M.), Service de Neuropathologie (D.S.), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne Université; Service de Neurologie 2-Mazarin (A.I., K.H.-Z.), Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Sorbonne Université, Paris; Département de Pathologie (J.-F.E.), EA4340, Université Versailles-Saint Quentin, Assistance Publique Hôpitaux de Paris, Hôpital Ambroise Paré, Boulogne; and Service d'Hématologie Pédiatrique, Centre de Référence National Histiocytoses (J.D.), Hôpital Trousseau, Sorbonne Université, Paris, France.
Neurology. 2020 Nov 17;95(20):e2746-e2754. doi: 10.1212/WNL.0000000000010748. Epub 2020 Sep 4.
CNS involvement in Erdheim-Chester disease (ECD) leads to substantial morbidity and mortality. To assess CNS manifestations in a French cohort of 253 patients with ECD, we determined clinical characteristics and outcomes, including those under targeted therapies.
This was a retrospective longitudinal study. CNS manifestations were determined by clinical examination and brain or spine MRI. Targeted therapy efficacy was assessed using global assessment from a physician and a radiologist. The study was approved by the ethics committee Comité de Protection des Personnes Ile de France III.
Ninety-seven of 253 patients (38%) with ECD had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptom onset (mean 50.5 years), as well as with the presence of the mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than that of patients with ECD without CNS involvement (124 months vs 146 months, = 0.03). Seventy-four CNS MRIs were centrally reviewed, which showed 3 patterns: tumoral in 66%, pseudo-degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF or MEK inhibitors) was associated with improved symptoms in 43% of patients and MRI improvement in 45%.
CNS manifestations are typically associated with poor prognosis in patients with ECD. Three distinct patterns can be recognized: tumoral, pseudodegenerative, and vascular.
This study provides Class III evidence that targeted therapy leads to clinical or imaging improvement in almost 50% of patients.
中枢神经系统（CNS）受累是 Erdheim-Chester 病（ECD）患者发病和死亡的主要原因。为评估 253 例法国 ECD 患者的 CNS 表现，我们确定了其临床特征和结局，包括接受靶向治疗的患者。
这是一项回顾性纵向研究。通过临床检查和脑或脊柱 MRI 确定 CNS 表现。采用医生和放射科医生的整体评估来评估靶向治疗的疗效。本研究获得了法兰西岛 III 保护委员会的伦理批准。
253 例 ECD 患者中 97 例（38%）存在 CNS 受累。CNS 受累与诊断时年龄较轻（平均 55.5 岁）和症状发作时年龄较轻（平均 50.5 岁）显著相关，也与 突变（77%的病例）、黄斑瘤（34%）和尿崩症（36%）的存在相关。存在 CNS 受累的患者中位生存期明显短于无脑内受累的患者（124 个月 vs 146 个月， = 0.03）。对 74 份 CNS MRI 进行了中心审查，结果显示有 3 种类型：肿瘤型占 66%，假性退行性占 50%，血管型占 18%。靶向治疗（BRAF 或 MEK 抑制剂）可使 43%的患者症状改善，45%的患者 MRI 改善。
CNS 表现与 ECD 患者的不良预后相关。可识别出 3 种不同的表现类型：肿瘤型、假性退行性和血管型。
本研究提供了 III 级证据，表明靶向治疗可使近 50%的患者临床或影像学改善。
