Lambert-Eaton myasthenic syndrome (LEMS): a presynaptic autoimmune disorder affecting neuromuscular transmission

1987 ◽  
Vol 66 (5) ◽  
pp. S124
Keyword(s):  
Neuromuscular Transmission ◽  
Autoimmune Disorder ◽  
Myasthenic Syndrome

3,4-diaminopyridine Phosphate in the Treatment of Lambert-Eaton Myasthenic Syndrome

2012 ◽  
Vol 7 (1) ◽  
pp. 56
Author(s):  
Jörn Peter Sieb ◽  
Keyword(s):  
Neuromuscular Transmission ◽  
Autoimmune Disorder ◽  
Special Treatment ◽  
Orphan Medicinal Product ◽  
Local Hospital ◽  
Correct Dose ◽  
The Us ◽  
Myasthenic Syndrome ◽  
Drug Doses ◽  
Variable Quality

3,4-diaminopyridine (3,4-DAP, amifampridine) is the leading treatment for Lambert–Eaton myasthenic syndrome (LEMS), an autoimmune disorder with impaired neuromuscular transmission, for which few effective medications are currently available. 3,4-DAP has been available as a therapy for LEMS in special treatment programmes for approximately 25 years. As an unlicensed drug, doses for oral administration are required to be compounded by local, hospital or other compounding pharmacies from the base chemical. Administering the correct dose of 3,4-DAP is critical; overdosing can increase the risk of seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies, have shown a wide variation in the 3,4-DAP content of compounded preparations (22.2–125.2 %, n=9) and (53.5–128.5 %, n=21), thereby reflecting the possibility of patients receiving dosages that might be above safety limits or even markedly below efficacy limits. This inconsistency results from the variable quality and instability of the base chemical and compounding errors. A formulation of 3,4-DAP phosphate salt has now been licensed in Europe and the US with orphan medicinal product status and appears to be as efficacious as the base in relieving the symptoms of LEMS.

scholarly journals COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome

2021 ◽  
pp. 1-3
Author(s):  
Setareh Alabaf ◽  
Karen O'Connell ◽  
Sithara Ramdas ◽  
David Beeson ◽  
Jacqueline Palace
Keyword(s):  
High Risk ◽  
Neuromuscular Transmission ◽  
Genetic Disorders ◽  
Severe Disease ◽  
Congenital Myasthenic Syndrome ◽  
Referral Centre ◽  
History Of ◽  
Myasthenic Syndrome ◽  
The Uk ◽  
Rare Group

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

scholarly journals 3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome ◽  
Randomised Controlled

Abstract Background Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. Methods We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. Conclusions The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

UNUSUAL DECREMENTAL RESPONSE IN LAMBERT EATON MYASTHENIC SYNDROME

2015 ◽  
Vol 86 (11) ◽  
pp. e4.50-e4
Author(s):  
Girija Sadalage ◽  
Sajjad Ali ◽  
Paul Mocroft ◽  
Adrian Williams ◽  
Saiju Jacob
Keyword(s):  
High Frequency ◽  
Autoimmune Disorder ◽  
Clinical Suspicion ◽  
High Frequency Stimulation ◽  
Repetitive Nerve Stimulation ◽  
Standing Up ◽  
Neurology Clinic ◽  
History Of ◽  
Myasthenic Syndrome ◽  
Walking Difficulty

Lambert Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction caused by antibodies against voltage gated calcium channel antibodies. The neurophysiological hallmark of LEMS is incremental response to repetitive nerve stimulation, especially at high frequency stimulation.A 54-year-old gentleman presented to the Neurology clinic with a 9-month history of progressive walking difficulty. He had difficulty standing up from a sitting down position and the symptoms were worse towards the end of the day. He had a transient history of dry mouth when the symptoms started, but denied any postural dizziness, sweating or bowel/bladder symptoms. He denied having any double vision, droopy eyelids, speech or swallowing symptoms. He had lost 1.5 stones in weight over the preceding 7–8 months. Examination showed proximal muscle weakness with reduced reflexes, which could not be potentiated. A clinical suspicion of LEMS was made, but the neurophysiological examination (repeated on three occasions) showed consistently decremental response at low and high frequency stimulations.The VGCC antibody was positive (293, normal 0–45), confirming the clinical suspicion of LEMS. The AChR and MuSK antibodies were negative.This is an unusual neurophysiological finding of a decremental response in a patient with clinical and immunological evidence of LEMS.

scholarly journals 3,4-diaminopyridine Treatment for Lambert-Eaton Myasthenic Syndrome in Adults: A Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safetyof 3,4-diaminopyridine (3,4-DAP) in LEMS. Methods: We searched several databases to identify relevant studies, including PubMed, EMBASE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Controlled Trials Register.The primary outcome Quantitative Myasthenia Gravis (QMG) muscle score and secondary outcome compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results: Six randomised controlled trials (RCT) involving 115 patients with LEMS were included. A meta-analysis of the primary outcome showed a significant improvement of 2.33 (95% CI, -2.81 to -1.85, p<0.001) in QMG muscle score after treatment with 3,4-DAP. Moreover, a meta-analysis of the secondary outcome showed that the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment(mean difference 1.63 mV, 95% CI, 0.85 to 2.41, p<0.001). The overall assessment of all included trials showed low risk of bias and low heterogeneity. Conclusioins: The pooled results demonsrated that 3,4-DAP had a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude, which are moderate to high evidence from randomized controlled trials.

scholarly journals 3,4-diaminopyridine Treatment for Lambert-Eaton Myasthenic Syndrome in Adults: A Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome ◽  
Randomised Controlled

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. Methods: We searched several databases to identify relevant studies, including PubMed, EMBASE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Controlled Trials Register.The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results: Six randomised controlled trials (RCT) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.33 points (95% CI, -2.81 to -1.85, p<0.001) after treatment with 3,4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.63 mV, 95% CI, 0.85 to 2.41, p<0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. Conclusions: The pooled results of randomized controlled trials demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

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