From the Department of Neurology (L.D.K., S.D., D.C.H., T.K., B.-L.T., W.W.), University Hospital Heidelberg, Heidelberg University; Clinical Cooperation Unit (CCU) Neuro-Oncology (L.D.K., D.C.H., T.K., W.W.), German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research, Heidelberg; Department of Biostatistics (T.H.), German Cancer Research Center (DKFZ), Heidelberg, Germany; and Departments of Neurology and Neurosurgery (J.M.B.), Yale School of Medicine, New Haven, CT.
Neurology. 2024 Aug 27;103(4):e209698. doi: 10.1212/WNL.0000000000209698. Epub 2024 Aug 5.
Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts, and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL.
A systematic review of the literature (2004-2023) was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Studies reporting individual patient data on cases with definitive NL diagnosis were included. Clinical, radiologic, pathologic, and outcome information were extracted. Univariable and multivariable survival analyses were performed using log-rank tests and Cox proportional hazard models.
A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Infiltrated structures included peripheral nerves (56%), nerve roots (52%), plexus (33%), and cranial nerves (32%). Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (>90%). diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. The median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% CI 0.25-0.78; = 0.005), performance status (ECOG <2, HR: 0.30; 95% CI 0.18-0.52; < 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI 0.28-0.73; = 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters.
Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Yet, diagnostic delays in primary NL remain common. Rituximab-based therapy improves NL outcome. Findings may assist clinicians in early recognition, prognostic stratification, and treatment of NL.
神经淋巴病（NL）是指淋巴瘤对周围神经系统（PNS）的浸润。由于周围神经病的广泛鉴别诊断、缺乏更大的队列以及随后缺乏预后因素或共识治疗方法，NL 的诊断和治疗具有挑战性。本研究旨在定义 NL 的特征和预后因素。
使用 PubMed 和 Scopus 数据库对 2004 年至 2023 年的文献进行系统回顾，并按照 PRISMA 指南进行报告。纳入了报告明确 NL 诊断的病例的个体患者数据的研究。提取临床、放射学、病理学和结局信息。使用对数秩检验和 Cox 比例风险模型进行单变量和多变量生存分析。
共从 264 项研究中积累了 459 例 NL 病例。197 例患者为恶性肿瘤（原发性 NL）的首发表现。262 例患者在已知非霍奇金淋巴瘤（继发性 NL）后中位 12 个月时出现 PNS 复发。NL 主要表现为迅速恶化、不对称性疼痛性多发性神经病。受累结构包括周围神经（56%）、神经根（52%）、神经丛（33%）和颅神经（32%）。中位症状出现后 3 个月诊断成立，但在原发性 NL 中存在明显延迟。它主要依赖于 PNS 活检或 FDG-PET，其诊断率很高（>90%）。3%的病例诊断为罕见（3%）。大多数病例为 B 细胞（90%）淋巴瘤。96%的患者接受了肿瘤靶向治疗，通常包括甲氨蝶呤或利妥昔单抗为基础的化疗。中位总生存期为 18 个月。无神经系统外合并系统疾病的原发性 NL（危险比 [HR]：0.44；95%置信区间 0.25-0.78； = 0.005）、表现状态（ECOG <2，HR：0.30；95%置信区间 0.18-0.52； < 0.0001）和利妥昔单抗为基础的治疗（HR：0.46；95%置信区间 0.28-0.73； = 0.001）是在调整临床和社会人口统计学参数后，多变量分析中确定的有利预后标志物。
神经影像学模态的进步，特别是 FDG-PET，有助于 NL 的诊断，并提供了较高的诊断率。然而，原发性 NL 的诊断延迟仍然很常见。利妥昔单抗为基础的治疗改善了 NL 的预后。这些发现可能有助于临床医生早期识别、预后分层和治疗 NL。
