Portaro Simona, Brizzi Teresa, Sinicropi Stefano, Cacciola Alberto, De Cola Maria Cristina, Bramanti Alessia, Milardi Demetrio, Lupica Antonino, Bramanti Placido, Toscano Antonio, Rodolico Carmelo
IRCSS Centro Neurolesi "Bonino-Pulejo", Neuromuscular Disease Laboratory Department of Clinical and Experimental Medicine, University of Messina, Messina DIBIMIS, University of Palermo, Palermo, Italy.
Medicine (Baltimore). 2017 Sep;96(38):e7839. doi: 10.1097/MD.0000000000007839.
To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids.
Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation.
Five out of 7 patients presented a clinical improvement persisting at last 5-year follow-up; 2 out of them improved taking only 3,4-DAPP at the maximal dosage, whereas the remaining received concomitant medications, such as prednisone and azathioprine. However, the clinical amelioration was not statistically significant. No one of the patients reported severe adverse events, except one, complaining of transient chin and perioral paresthesias. A significant association between QMG and the type of pharmacological drugs therapy (P = .028) emerged. Indeed, we observed an improvement of the clinical condition in all 3 subjects treated with 3,4-DAPP and prednisone.
In this study, we confirm 3,4-DAPP treatment efficacy on muscle strength, but minor evidence of drug effectiveness have been demonstrated on the autonomic nervous system involvement and on the deep tendon reflexes reappearance, a part from patients who received 3,4-DAPP associated to prednisone.
报告我们对7例患者（4例男性和3例女性）的治疗经验，这些患者患有非副肿瘤性兰伯特-伊顿肌无力综合征，接受了磷酸3,4-二氨基吡啶（3,4-DAPP）单药治疗或与其他免疫抑制剂或类固醇联合治疗。
在特定时间点（即基线和最后5年随访）对患者进行评估，包括神经系统检查、针对突触前电压门控Cav2.1（P/Q型）钙离子通道（VGCC）的自身抗体检测、以最大自主收缩后复合肌肉动作电位（cMAP）幅度增加为重点的神经生理学评估、重症肌无力定量（QMG）和日常生活活动量表，以及自主神经系统受累评估。
7例患者中有5例在最后5年随访时临床症状持续改善；其中2例仅服用最大剂量的3,4-DAPP后症状改善，其余患者同时接受了如泼尼松和硫唑嘌呤等伴随药物治疗。然而，临床改善无统计学意义。除1例抱怨短暂的下巴和口周感觉异常外，没有患者报告严重不良事件。QMG与药物治疗类型之间存在显著关联（P = 0.028）。事实上，我们观察到所有3例接受3,4-DAPP和泼尼松治疗的患者临床状况均有改善。
在本研究中，我们证实了3,4-DAPP对肌肉力量的治疗效果，但在自主神经系统受累和深腱反射恢复方面，除接受3,4-DAPP联合泼尼松治疗的患者外，药物有效性的证据较少。
