Department of Neurology, Haga Hospital, The Hague, the Netherlands.
Curr Treat Options Neurol. 2013 Apr;15(2):224-39. doi: 10.1007/s11940-012-0213-6.
Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia are neuromuscular transmission disorders occurring with or without associated malignancy. Due to the common antibody-mediated pathophysiology, immunosuppression has an important role in the treatment of each of these disorders. Symptomatic treatment is more variable. Pyridostigmine is first-line treatment in generalized MG. Response seems to be better in patients with acetylcholine receptor (AChR) antibodies than in patients with antibodies against muscle-specific tyrosine kinase (MuSK). Pyridostigmine can be sufficient in mild MG, although most patients need additional immunosuppressive therapy. If so, prednisolone is efficient in the majority of the patients, with a relatively early onset of clinical effect. High drug dosage and treatment duration should be limited as much as possible because of serious corticosteroid-related side effects. As long-term treatment is needed in most patients for sustainable remission, adding non-steroid immunosuppressive drugs should be considered. Their therapeutic response is usually delayed and often takes a period of several months. In the meantime, corticosteroids are continued and doses are tapered down over a period of several months. There are no trials comparing different immunosuppressive drugs. Choice is mainly based on the clinician's familiarity with certain drugs and their side effects, combined with patients' characteristics. Most commonly used is azathioprine. Alternatively, tacrolimus, cyclosporine A, mycophenolate mofetil or rituximab can be used. The use of cyclophosphamide is limited to refractory cases, due to serious side effects. Plasma exchange and intravenous immunoglobulin induce rapid but temporary improvement, and are reserved for severe disease exacerbations because of high costs of treatment. It is recommended that computed tomography (CT) of the thorax is performed in every AChR-positive MG patient, and that patients are referred for thymectomy in case of thymoma. In patients without thymoma, thymectomy can be considered as well, especially in younger, AChR-positive patients with severe disease. However, definite proof of benefit is lacking and an international randomized trial to clarify this topic is currently ongoing. When LEMS is suspected, always search for malignancy, especially small cell lung carcinoma with continued screening up to two years. In paraneoplastic LEMS, cancer treatment usually results in clinical improvement of the myasthenic symptoms. 3,4-Diaminopyridine is first-line symptomatic treatment in LEMS. It is usually well tolerated and effective. When immunosuppressive therapy is needed, the same considerations apply to LEMS as described for MG. Peripheral nerve hyperexcitability in neuromyotonia can be treated with anticonvulsant drugs such as phenytoin, valproic acid or carbamazepine. When response in insufficient, start prednisolone in mild disease and consider the addition of azathioprine. Plasma exchange or intravenous immunoglobulin is indicated in severe neuromyotonia and in patients with neuromyotonia combined with central nervous system symptoms, a clinical picture known as Morvan's syndrome.
重症肌无力(MG)、Lambert-Eaton 肌无力综合征(LEMS)和肌强直是伴或不伴相关恶性肿瘤的神经肌肉传递障碍。由于常见的抗体介导的病理生理学,免疫抑制在这些疾病的每种治疗中都起着重要作用。对症治疗则更为多变。在全身性 MG 中,吡啶斯的明是一线治疗药物。与抗肌肉特异性酪氨酸激酶(MuSK)抗体的患者相比,乙酰胆碱受体(AChR)抗体的患者似乎对其更有反应。吡啶斯的明在轻度 MG 中可能就足够了,尽管大多数患者需要额外的免疫抑制治疗。如果是这样,泼尼松龙在大多数患者中有效,其临床效果的出现相对较早。由于严重的皮质类固醇相关副作用,应尽可能限制高剂量和治疗时间。由于大多数患者需要长期治疗以维持缓解,因此应考虑添加非甾体类免疫抑制剂。它们的治疗反应通常较迟,通常需要几个月的时间。在此期间,继续使用皮质类固醇,并在几个月的时间内逐渐减少剂量。没有比较不同免疫抑制剂药物的试验。选择主要基于临床医生对某些药物及其副作用的熟悉程度,结合患者的特点。最常用的是硫唑嘌呤。另外,他克莫司、环孢素 A、霉酚酸酯或利妥昔单抗也可使用。由于严重的副作用,环磷酰胺的使用仅限于难治性病例。血浆置换和静脉注射免疫球蛋白可迅速但暂时改善病情,由于治疗费用高昂,因此仅用于严重疾病恶化的情况。建议对每个 AChR 阳性 MG 患者进行胸部 CT 检查,并在有胸腺瘤的情况下将患者转至胸腺切除术。在没有胸腺瘤的患者中,也可以考虑进行胸腺切除术,特别是对于年轻、AChR 阳性且病情严重的患者。然而,缺乏明确的获益证据,目前正在进行一项国际随机试验以阐明这一问题。当怀疑为 LEMS 时,始终要寻找恶性肿瘤,特别是小细胞肺癌,需持续筛查长达两年。在副肿瘤性 LEMS 中,癌症治疗通常会导致肌无力症状的临床改善。3,4-二氨基吡啶是 LEMS 的一线对症治疗药物。它通常耐受性良好且有效。当需要免疫抑制治疗时,LEMS 的治疗考虑与 MG 相同。神经肌强直中的周围神经兴奋性过高可用苯妥英、丙戊酸或卡马西平等抗惊厥药物治疗。如果反应不足,轻度疾病用泼尼松龙治疗,并考虑添加硫唑嘌呤。当病情严重或出现伴有中枢神经系统症状的神经肌强直(即莫尔万综合征)时,应进行血浆置换或静脉注射免疫球蛋白。