Stimulated single-fiber electromyography in Lambert-Eaton myasthenic syndrome.

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Electrodiagnosis is confirmed by an increase in compound muscle action potential amplitude during high-frequency repetitive nerve stimulation or following brief exercise. We describe the results of stimulated single-fiber electromyography in 4 patients with disorders of neuromuscular transmission: LEMS (2), LEMS/myasthenia gravis (MG) overlap (1), and MG (1). Stimulated SFEMG was performed in the extensor digitorum communis muscle with axonal intramuscular suprathreshold stimulation at low and high rates. In all 4 patients, a rate dependence of jitter was found. In LEMS and LEMS/MG, jitter and blocking improved with high stimulation rates, as compared with the opposite effect in MG. We conclude that stimulated SFEMG is a valuable technique in the diagnosis of LEMS.     

A Patient with Coexisting Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome

Background

The coexistence of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) is very rare and remains controversial.

Case Report

A 48-year-old woman initially presented with noticeable right ptosis and intermittent diplopia. She then developed fluctuating proximal limb weakness and difficulty in swallowing. The serum titer of anti-acetylcholine-receptor antibody was elevated and the edrophonium (Tensilon) test was positive. However, repetitive nerve stimulation revealed abnormalities typical of LEMS. The patient exhibited a good response to treatment with anticholinesterase inhibitors and steroids, and long-term evaluation disclosed that she presented with the clinical, electrophysiological, and immunological characteristics of both diseases.

Conclusions

The reported clinical and electrophysiological features suggest that this patient was a very rare case of combined MG and LEMS.     

Rats immunized with cholinergic synaptosomes: a model for Lambert-Eaton syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder characterized by reduced acetylcholine release at the neuromuscular junction. We report a model of the disease developed by active immunization of rats with purely cholinergic nerve terminals (synaptosomes) isolated from the Torpedo electric organ. Electromyographic studies of neuromuscular transmission in these rats showed a weak initial response followed by a pronounced incremental response to paired supramaximal stimuli (8 msec apart). There was no such response in control rats. There was no evidence of a postsynaptic transmission deficit in the synaptosomes immunized rats. We conclude that immunizing rats with Torpedo cholinergic nerve terminals causes a specific presynaptic dysfunction and may serve as a model for the study of LEMS.     

Lambert-Eaton肌无力综合征6例临床与电生理特点分析

目的探讨Lambert-Eaton肌无力综合征(LEMS)的临床及电生理特点。方法分析2002-2011年作者医院诊断的6例LEMS患者的临床资料及神经电生理检查结果。结果 6例患者起病年龄34～65岁(中位数53岁),病程0.5～35个月(中位数4个月)。4例患者最初诊断为重症肌无力。5例患者伴恶性肿瘤。6例患者均以肢体近端无力起病。5例患者腱反射减低或消失。3例患者伴口干、眼干等自主神经症状。5例患者行新斯的明试验,其中4例阳性。6例患者均行神经电生理检查,共9次。5例行针极肌电图检查共6次,其中结果显示肌源性改变3次,神经源性改变2次,正常1次。5例行7次神经传导速度检查,全部提示复合肌肉动作电位明显减低。6例共行9次重复神经电刺激(RNS)检查,全部提示高频刺激波幅递增。结论掌握LEMS的临床及电生理特征有助于及时正确诊断。     

Long-term follow-up of Lambert-Eaton syndrome treated with intravenous immunoglobulin

Recent reports have shown that patients with Lambert-Eaton myasthenic syndrome (LEMS) improve transiently after high-dose intravenous immunoglobulin (IVIG) administration. Information about the usefulness of IVIG for long-term treatment is rather scanty. Our findings demonstrate the efficacy of monthly IVIG courses at a dose of 0.4 g/kg/day for 5 days, in a 41-year-old patient with LEMS without detectable malignancy. Improvement in limb strength, peak expiratory flow rate, and electrophysiological parameters, as well as clinical signs following IVIG, was evident as early as 7 days after the first course and is still maintained at 24-months follow-up. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 674–678, 1997.     

Clinical aspects of neuromuscular transmission disorders

Autoimmune disorders of neuromuscular transmission are caused by antibodies (abs) directed against membrane proteins at the motor end-plate. Myasthenia gravis (MG) is due, in most cases, to abs against the nicotinic acetylcholine receptor (AChR). Anti-AChR-positive MG actually includes different disease entities: weakness can be confined to extrinsic ocular muscles or can be generalized; patients with generalized MG (G-MG) can be subdivided on the basis of age of onset, HLA association and thymic pathology. About 15% of G-MG patients are anti-AChR-negative; in a proportion of these cases serum abs against the muscle- specific kinase (MuSK) are found. Anti-MuSK-positive MG is characterized by predominant involvement of bulbar muscles and very low frequency of thymic pathology. The Lambert-Eaton myasthenic syndrome (LEMS) is caused by abs against voltage-gated calcium channels at nerve terminal. LEMS is characterized by muscle weakness and autonomic disturbances and it is paraneoplastic in over 50% of the cases. In neuromyotonia and cramp-fasciculation syndrome, that are thought to be due to anti-voltage-gated potassium channel abs, signs of peripheral nerve hyperexcitability can be associated with CNS features.     

Low-dose guanidine and pyridostigmine: relatively safe and effective long-term symptomatic therapy in Lambert-Eaton myasthenic syndrome

Guanidine hydrochloride is known to be highly effective in the symptomatic treatment of the Lambert-Eaton myasthenic syndrome (LEMS). However, because of its potentially dangerous side reactions of hematologic abnormalities and renal insufficiency, 3,4-diaminopyridine, which is not readily available in the United States, is recommended as the preferred drug for LEMS. We used low-dose guanidine and pyridostigmine combination therapy in 9 patients with LEMS and analyzed its long-term safety and effectiveness. In all patients, a liberal amount of pyridostigmine was used, while daily guanidine dose was kept below 1000 mg a day, and guanidine was given between pyridostigmine dosings. This combination therapy was used for 3–102 months (mean: 34.1 months) and improved clinical status in all patients. Although guanidine had to be discontinued due to severe gastrointestinal symptoms in 3 cases, no serious side reactions such as bone marrow suppressions or signs of renal insufficiency developed in any case. Thus, we conclude that low-dose guanidine therapy is relatively safe and effective for long-term symptomatic treatment of LEMS when it is combined with pyridostigmine. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20:1146–1152, 1997     

Lambert-Eaton myasthenic syndrome presenting with severe respiratory failure

Two cases of Lambert-Eaton myasthenic syndrome (LEMS) who presented with primary respiratory failure are reported. In each case, although not initially suspected clinically, the electrophysiological findings, which included reduced compound muscle action potential amplitudes, decrement to 3-Hz stimulation, and potentiation after 40-Hz stimulation, led to the diagnosis in the critical care unit. Electrophysiological studies of the respiratory system, including repetitive nerve stimulation of the phrenic nerve, were extremely valuable in management. As shown by these cases, the severe respiratory failure in LEMS is reversible with treatment. Thus, LEMS should be considered in cases of unexplained respiratory failure, other clinical features of the disorder sought, and the electrophysiological hallmarks looked for, including studies of the respiratory system. © 1996 John Wiley & Sons, Inc.     

Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases

To compare the clinical features of patients with the Lambert-Eaton myasthenic syndrome (LEMS) associated with carcinoma, with patients having LEMS but no cancer, reports on LEMS patients were analyzed systematically. Cancer was detected (CD group) in 62% of the 227 included cases. This CD group showed a male predominance (70%). No sex difference was found in patients in whom no cancer was detected (NCD group). Median age at onset of LEMS in the CD group was higher than in the NCD group (58 and 49.5 years, P<0.01). Median interval between onset of symptoms and diagnosis of LEMS was longest in NCD cases (P<0.001). CD patients had additional immunological disorders less frequently than NCD cases (6 and 27%, P<0.001). Symptoms distinguishing the CD group from the NCD group were weight loss (P<0.001) and need for prolonged artificial ventilation after anaesthesia (P<0.05). This analysis shows significant differences between CD and NCD cases of LEMS. The male predominance and higher age at onset in patients with a tumor probably reflects the characteristics of patients with small cell lung cancer. The high frequency of additional immunological disorders in patients without malignancy, together with the younger age at onset suggests a similar etiology as other non-paraneoplastic autoimmune diseases.     

Lambert-Eaton肌无力综合征45例临床及电生理回顾性分析

目的 通过对我院Lambert-Eaton肌无力综合征(Lambert-Eaton myasthenia syndrome,LEMS)患者的回顾性分析,分析此病的临床表现和伴发的神经电生理异常.方法 总结1993-2008年我院诊断的45例LEMS患者的一般情况、神经系统临床表现和体征、伴发的内科和全身疾病的情况.所有患者均进行神经电生理检测,包括神经传导速度(NCV)和重复神经电刺激(RNS).部分患者行针极肌电图和皮肤交感反射(SSR)检查.结果 (1)患者出现神经系统症状的平均年龄为(51.2±6.8)岁.最常见临床表现为双下肢无力(35例),其后依次为双上肢无力(10例)、构音障碍(3例)和颈肌无力(2例).神经系统体征中最常见为双下肢或上肢轻度力弱(40例),双下肢腱反射或跟反射减低或消失(38例)以及口干或便秘等自主神经症状(30例).(2)神经电生理检查:所有患者尺神经高频刺激递增达156% ～636%,其中29例同时出现低频递减.所有患者行NCV检查,感觉神经传导速度(SCV)异常或SCV合并运动神经传导速度异常者19例(42%).30例患者行针极肌电图检查,有异常发现者20例.25例行SSR的患者中发现13例异常.结论 LEMS最常见的临床症状为双下肢无力,其次为自主神经症状.患者除了有重复神经电刺激的异常,还伴有周围神经和肌肉的电生理异常以及自主神经系统的异常,提示临床表现可能混杂有神经或肌肉病变的原因.     

Stimulated single-fiber electromyography in Lambert-Eaton myasthenic syndrome before and after 3,4-diaminopyridine

A patient with LEMS unrelated to cancer was studied by stimulated single-fiber electromyography (SFEMG) before and 3 months after the onset of therapy with 3,4-diaminopyridine. All end-plates showed a progressive reduction in blockings and jitter with the increase in stimulation rate. Treatment significantly corrected this feature, but the overall pattern of frequency-improved jitter remained. Such widespread finding is rare but diagnostic for Lambert-Eaton myasthenic syndrome. Stimulated SFEMG can be used to monitor therapy in such patients. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 735–739, 1997.     

Electrophysiological diagnostic criteria of Lambert-Eaton myasthenic syndrome

Various parameters of the repetitive nerve stimulation (RNS) test of the abductor digiti quinti muscle were analyzed statistically in 34 patients with Lambert-Eaton myasthenic syndrome (LEMS). The sensitivity and specificity of the increments after exercise and after 50-HZ stimulation for the diagnosis of LEMS were compared with reference values in 40 normal subjects and data from 538 tests in patients with myasthenia gravis (MG). When we used a 100% increment (the "gold standard") as the normal limit for the postexercise facilitation (PEF) or the high-rate stimulation (HRS) test, the diagnosis of LEMS was confirmed in 29 (85%) cases. When a 60% increment was used as the normal limit, the diagnosis of LEMS was made in 97% of cases. In MG, a 60% increment was observed in only 4 of 538 cases by HRS and in none by the exercise test. Thus, the use of a 60% increment showed a sensitivity of 97% for the diagnosis of LEMS and a specificity of 99% in excluding MG. A 60% increment in either the PEF or HRS test for the diagnosis of LEMS is a desirable alternative to the 100% increment previously considered to be the gold standard for this diagnosis.     

Myasthenia gravis and Lambert-Eaton myasthenic syndrome in the same patient

An 18-year-old-woman developed symptoms of generalized myasthenia gravis (MG). Antibodies to the acetylcholine receptor were found in her serum, but electrodiagnostic testing showed abnormalities typical of the Lambert-Eaton myasthenic syndrome (LEMS). Following thymectomy, the thymus gland showed thymic hyperplasia typical of MG, and the patient responded to treatment with 3,4-diaminopyridine and pyridostigmine. There have been few reports in the literature of MG and LEMS coexisting in the same patient. In this case, electrodiagnostic tests, antibody studies, thymus pathology, and response to treatment suggest that both disorders contributed to the patient's symptoms. Thymic hyperplasia, so far only known to be associated with MG, provides strong evidence that both diseases were symptomatic.     

Lambert-Eaton Syndrome,an Unrecognized Treatable Pediatric Neuromuscular Disorder: Three Patients and Literature Review

BackgroundLambert-Eaton myasthenic syndrome, a presynaptic neuromuscular junction autoimmune disorder, rarely occurs in children. Patients typically present with proximal lower extremity weakness with areflexia.MethodsWe report three children presenting between ages 9 and 10 years diagnosed with Lambert-Eaton myasthenic syndrome 2 years, 1 year, and 5 months later, respectively. Their clinical attributes are correlated with nine other pediatric Lambert-Eaton myasthenic syndrome patients found in our literature review.ResultsThese patients were identified as having Lambert-Eaton myasthenic syndrome during their evaluation for proximal weakness. Low-amplitude compound muscle action potentials classically facilitating >100% with voluntary exercise and/or 50 Hz stimulation were essential to diagnosis. Three of the 12 children had associated malignancies, two of them had lymphoproliferative disorders with onset of symptoms more rapid than the rest, and the third had neuroblastoma. The nine nonparaneoplastic Lambert-Eaton myasthenic syndrome patients responded to immunomodulatory therapy with close return to their baseline function. Complete remission no longer necessitating medication was reported in two patients. Follow-up up to 17 years was available on two patients previously reported.ConclusionLambert-Eaton myasthenic syndrome is a diagnosis that must be considered in children presenting with unidentified proximal muscle weakness. In most children, Lambert-Eaton myasthenic syndrome is a primary autoimmune disorder that is treatable. Nevertheless, a search for malignancy is recommended.     

Lambert-Eaton肌无力综合征的自主神经系统表现

目的 对Lambert-Eaton肌无力综合征(LEMS)的临床表现和自主神经系统表现进行回顾性分析,总结自主神经系统损害和皮肤交感反射(skin sympathic response,SSR)的异常.方法 对53例临床确诊的LEMS进行回顾性研究,包括患者主诉、体征(尤其是自主神经系统症状和体征)、SSR的异常发现.结果 (1)最早出现的临床表现为双下肢力弱(n=41),最常见的自主神经系统表现为便秘(n=25)和口干(n=23),并可以在出现肢体力弱前出现(n=7).(2)自主神经系统表现:心血管系统异常4例:1例心动过缓,1例体位性低血压,2例心动过速.分泌腺体异常34例:23例口干,6例眼干,8例泌汗异常.28例患者有程度不同的胃肠道症状包括便秘或腹泻.2例患者主诉膀胱尿激惹症状.7例男性患者有性功能障碍.17例患者有皮肤划痕征异常.(3)33例行SSR检查,18例异常.结论 LEMS的自主神经系统表现广泛而常见.SSR可以在部分患者中发现异常.     

Practical aspects of 3,4-diaminopyridine treatment of the Lambert-Eaton myasthenic syndrome

3,4-Diaminopyridine (3,4-DAP) given alone or combined with pyridostigmine is the recommended basic therapy in the Lambert-Eaton myasthenic syndrome (LEMS). We present and exemplify our routine test protocol for monitoring drug introduction and treatment regimen of cholinergic drugs in LEMS. The individual drug responses vary and no recommended standard doses exist. Routine electrophysiological repetitive nerve stimulation studies recording amplitude of initial compound muscle action potential (CMAP) in thenar muscles correlate excellently with clinical myasthenic muscle power tests in clinically affected muscle groups. Therefore repetitive clinical muscle power tests, that often are complicated by painful myalgia and activation potentiation, can be replaced by recordings of CMAP in the introduction and clinical follow up of cholinergic drug treatment in LEMS. Also, adverse effects and other treatment problems from the experience of continuous treatment of 19 LEMS patients with 3,4-DAP for up to 10 years are presented.     

Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic syndrome and their families

Abstract. In view of the clustering of autoimmune diseases (AIDs), we studied the frequency and nature of additional AIDs in patients with the Lambert-Eaton myasthenic syndrome (LEMS) and their family members, in both small cell lung carcinoma (SCLC) related and non-tumour (NT) related cases. Additional AIDs in patients with LEMS were assessed by interviewing the patient and studying the medical record. Family histories up to second-degree family members were established by interviewing patients, controls and family members. Forty-four patients with LEMS were assessed, of whom eighteen (41%) had SCLC. In the NT group seven patients (27%) had an additional AID, in the SCLC group two (11 %) (p=0.20). Thyroid disorder (five patients) and insulin dependent diabetes mellitus (two patients) were the most common AIDs. AIDs were significantly more frequent in families of patients with NT-LEMS (64%) than in control families (27%) (p=0.002), which was not found in SCLC-LEMS (36%, p=0.53). Affected family members were linked to the NT-LEMS patient through the maternal line in all cases. In conclusion, AIDs were more frequently found in LEMS patients without a tumour and their families, which could not be shown for SCLC-LEMS. This suggests that NT-LEMS shares immunogenetic factors with other AIDs. In families of NT-LEMS, a remarkable preponderance of maternal inheritance was seen, as has been reported previously in myasthenia gravis.     

Myasthenia gravis Lambert‐Eaton overlap syndrome

Introduction: To assess whether a myasthenia gravis (MG) Lambert‐Eaton overlap syndrome (MLOS) exists. Methods: Case reports that met the universally accepted diagnostic criteria for MG and Lambert‐Eaton myasthenic syndrome (LEMS) were sought through a PubMed search. Fifty‐five possible cases of MLOS were identified. Results: Thirty‐nine cases met the diagnostic criteria for MG and LEMS. Analysis of clinical features showed that these patients have common MG and LEMS symptoms: oculo‐bulbar paresis and good response to anti‐cholinesterase for MG and limb weakness and decreased or absent reflexes for LEMS. All had the classical LEMS pattern in the repetitive nerve stimulation test: low compound muscle action potential amplitude and incremental response > 60% with brief exercise or at high rate of stimulation. Eight patients had combined positive acetylcholine receptor antibody (AChR‐ab) or muscle‐specific kinase‐ab and voltage‐gated calcium channel‐ ab tests. Conclusions: A myasthenia gravis Lambert‐Eaton overlap syndrome (MLOS) does exist. Muscle Nerve 53 : 20–26, 2016