Disease relevance of Lambert-Eaton Myasthenic Syndrome

• Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis and which is of possible neural crest origin, is present in approximately 70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by fatigable muscle weakness [1].
• Antagonism of voltage-gated calcium channels in small cell carcinomas of patients with and without Lambert-Eaton myasthenic syndrome by autoantibodies omega-conotoxin and adenosine [2].
• Nine had mixed subacute neurological presentations (5 brainstem or limbic encephalitis, 3 cerebellar ataxia, 2 Lambert-Eaton myasthenic syndrome, 1 autonomic neuropathy, and 1 motor neuropathy) [3].
• Four patients with Eaton-Lambert syndrome, four patients with congenital myasthenia, and one patient with myasthenia gravis were treated with oral 4-aminopyridine for periods of up to 10 months, doses varying from 40 to 200 mg per day [4].
• Similarly, there was no binding of sera from patients with Guillain-Barré, amyotrophic lateral sclerosis, multiple sclerosis, or Lambert-Eaton myasthenic syndrome [5].

High impact information on Lambert-Eaton Myasthenic Syndrome

• 3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome [6].
• The Lambert-Eaton myasthenic syndrome (LEMS) is a disorder of neuromuscular transmission, often associated with small cell lung carcinoma (SCLC), and characterized by reduced quantal release of acetylcholine from the motor nerve terminals [7].
• The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen [8].
• In the Lambert-Eaton myasthenic syndrome (LEMS), there is a decreased release of acetylcholine quanta from the nerve terminal by nerve impulse [9].
• Reduction of calcium currents by Lambert-Eaton syndrome sera: motoneurons are preferentially affected, and L-type currents are spared [10].

Chemical compound and disease context of Lambert-Eaton Myasthenic Syndrome

• Eaton-Lambert myasthenic syndrome: long-term treatment of three patients with prednisone [11].
• Findings are similar to those in human Lambert-Eaton myasthenic syndrome and passively transferred Lambert-Eaton myasthenic syndrome in mice, and thus suggest that antibody to a synaptotagmin-voltage-dependent Ca2+ channel complex may be involved in the pathogenesis of Lambert-Eaton myasthenic syndrome [12].
• Guanidine and germine in Eaton-Lambert syndrome [13].
• Treatment of Lambert-Eaton syndrome: 3,4-diaminopyridine and pyridostigmine [14].
• Edrophonium test in Eaton-Lambert syndrome: quantitative oculography [15].

Biological context of Lambert-Eaton Myasthenic Syndrome

• The authors studied sera from 36 patients with Lambert-Eaton myasthenic syndrome (LEMS) by immunoblots using the recombinant protein derived from the DNA sequence encoding for the domain III S5-S6 linker of the P/Q-type voltage-gated calcium channel al subunit [16].
• Humoral immunity against glutamic acid decarboxylase and tyrosine phosphatase IA-2 in Lambert-Eaton myasthenic syndrome [17].
• The ectopic expression of neuronal P/Q-type voltage-gated calcium channels in small cell lung carcinoma (SCLC) is thought to induce antisynaptic autoimmunity in the paraneoplastic Lambert-Eaton myasthenic syndrome [18].
• AUTHORS' CONCLUSIONS: Limited evidence from randomised controlled trials showed that either 3,4-diaminopyridine or intravenous immunoglobulin improved muscle strength scores and compound muscle action potential amplitudes in patients with Lambert-Eaton myasthenic syndrome [19].

Anatomical context of Lambert-Eaton Myasthenic Syndrome

• The Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition in which weakness results from a presynaptic abnormality of acetylcholine release at the neuromuscular junction [20].
• We established a SCLC cell line from a woman with Lambert-Eaton myasthenic syndrome (LEMS) who developed antibodies to both the P/Q-type voltage-gated calcium channels (VGCC) and the muscle acetycholine receptor (AChR) [21].
• Plasma and IgG obtained from 10 Lambert-Eaton myasthenic syndrome (LES) patients (5 with carcinoma, 5 without associated cancer), 6 healthy subjects, and 1 patient with small-cell lung cancer (SCLC) were examined in their ability to recognize chromaffin cell antigens on Western blots [22].
• Serum and plasma from patients with Lambert-Eaton Myasthenic Syndrome reduce depolarization-dependent uptake of 45Ca2+ into rat cortical synaptosomes [23].

Gene context of Lambert-Eaton Myasthenic Syndrome

• High innate production of interleukin-10 and tumor necrosis factor-alpha contributes to susceptibility for non-paraneoplastic Lambert-Eaton myasthenic syndrome [24].
• Non-paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated autoimmune disorder, in which genetically determined interleukin-10 (Il-10) and tumor necrosis factor-alpha (TNF-alpha) could play a role in the susceptibility for the disease [24].
• Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats [12].
• Approximately 43% (3 of 7) of Lambert-Eaton myasthenic syndrome sera specifically recognized MysB fusion protein, whereas none of 34 control sera did [25].
• Voltage-gated calcium channel-binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both alpha 1 and beta subunits of the calcium channel [26].

Analytical, diagnostic and therapeutic context of Lambert-Eaton Myasthenic Syndrome

• In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome [6].
• Patients with small cell lung cancer (SCLC) survive longer if they have the antibody-mediated Lambert-Eaton myasthenic syndrome (LEMS), making this autoimmune disorder a prototype disease for studying cancer immunosurveillance [27].
• Following chemotherapy these resolved, but 5 months later the patient developed Lambert Eaton syndrome which responded to 3,4-diaminopyridine [28].

References