Meisel Andreas, Sieb Jörn P, Le Masson Gwendal, Postila Ville, Sacconi Sabrina
Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
HELIOS Hanseklinikum Stralsund, Stralsund, Germany.
Neurol Ther. 2022 Sep;11(3):1071-1083. doi: 10.1007/s40120-022-00354-8. Epub 2022 May 5.
Lambert-Eaton myasthenic syndrome (LEMS) is characterized by autoantibodies against voltage-gated calcium channels (VGCC) at the neuromuscular junction causing proximal muscle weakness, decreased tendon reflexes, and autonomic changes. The European LEMS registry aimed to collate observational safety data for 3,4-diaminopyridine phosphate (3,4-DAPP) and examine long-term outcomes for patients with LEMS.
Thirty centers across four countries participated in the non-interventional European LEMS registry. Any patients diagnosed with LEMS by means of clinical assessment and abnormal neurophysiological testing, or clinical assessment and positive for VGCC antibodies were eligible to participate. Patients were monitored using standard assessments for LEMS-related clinical manifestations.
Among 96 evaluable participants, 50 (52.1%) were being treated with 3,4-DAPP, 21 (21.9%) with 3,4-diaminopyridine (3,4-DAP), and 25 (26.0%) with other treatments (e.g., pyridostigmine, corticosteroids, immunoglobulins, and azathioprine); 74 participants (77.1%) were exposed to 3,4-DAPP at any time. Quantitative myasthenia gravis scores were similar across treatment groups. Muscle strength was generally good and maintained during follow-up. Cerebellar ataxia, defined as a negative Romberg's test and at least one other positive ataxia test, was observed in 30 (56.6%) patients. Most participants had reduced reflex tone and limited functioning. Sustained or improved functioning was observed in participants administered 3,4-DAPP. Inconsistent and sporadic functional improvement and regression was observed with 3,4-DAP and other treatments. Fifty-five treatment-related adverse events (AEs) were reported by 32 (33.3%) participants. Eight (8.3%) participants reported nine treatment-related serious AEs. No new safety signals were identified.
No new safety signals were observed following long-term management of LEMS with 3,4-DAPP.
兰伯特-伊顿肌无力综合征（LEMS）的特征是神经肌肉接头处针对电压门控钙通道（VGCC）的自身抗体，导致近端肌无力、腱反射减弱和自主神经改变。欧洲LEMS注册研究旨在整理3,4-二氨基吡啶磷酸盐（3,4-DAPP）的观察性安全性数据，并研究LEMS患者的长期预后。
四个国家的30个中心参与了非干预性欧洲LEMS注册研究。任何通过临床评估和异常神经生理学测试确诊为LEMS的患者，或临床评估且VGCC抗体呈阳性的患者均有资格参与。使用针对LEMS相关临床表现的标准评估方法对患者进行监测。
在96名可评估的参与者中，50名（52.1%）正在接受3,4-DAPP治疗，21名（21.9%）接受3,4-二氨基吡啶（3,4-DAP）治疗，25名（26.0%）接受其他治疗（如吡啶斯的明、皮质类固醇、免疫球蛋白和硫唑嘌呤）；74名参与者（77.1%）在任何时候都接触过3,4-DAPP。各治疗组的重症肌无力定量评分相似。肌肉力量总体良好且在随访期间保持稳定。30名（56.6%）患者出现小脑共济失调，定义为罗姆伯格试验阴性且至少一项其他共济失调试验阳性。大多数参与者反射张力降低且功能受限。接受3,4-DAPP治疗的参与者出现功能持续或改善。3,4-DAP和其他治疗观察到功能改善和减退不一致且呈散发性。32名（33.3%）参与者报告了55例与治疗相关的不良事件（AE）。8名（8.3%）参与者报告了9例与治疗相关的严重AE。未发现新的安全信号。
3,4-DAPP长期治疗LEMS后未观察到新的安全信号。
