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Jan J G M Verschuuren - One of the best experts on this subject based on the ideXlab platform.
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sox1 antibodies in lambert eaton Myasthenic Syndrome and screening for small cell lung carcinoma
Annals of the New York Academy of Sciences, 2012Co-Authors: Alexander F Lipka, Maarten J Titulaer, Jan J G M VerschuurenAbstract:Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder of the neuromuscular synapse. About half of LEMS patients have an associated small cell lung carcinoma (SCLC), which is usually detected after diagnosis of LEMS. This short review summarizes clinical and serological markers shown to predict the presence of SCLC in LEMS patients. SOX1 antibodies are a specific marker for SCLC-LEMS but they are also found in SCLC patients without paraneoplastic neurological Syndromes. No relation to any clinical characteristic or survival effect has been found for SOX1-positive patients. Several clinical markers also discriminate between SCLC-LEMS and nontumor LEMS. Detailed analysis of these clinical and demographic characteristics from two independent patient cohorts has led to development of the DELTA-P score. This prediction model has provided for a simple clinical tool to indicate the presence of SCLC early in the course of the disease. The DELTA-P score can be used to guide tumor screening in individual patients.
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lambert eaton Myasthenic Syndrome from clinical characteristics to therapeutic strategies
Lancet Neurology, 2011Co-Authors: Maarten J Titulaer, Bethan Lang, Jan J G M VerschuurenAbstract:Summary Lambert–Eaton Myasthenic Syndrome (LEMS) is a neuromuscular autoimmune disease that has served as a model for autoimmunity and tumour immunology. In LEMS, the characteristic muscle weakness is thought to be caused by pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal. Half of patients with LEMS have an associated tumour, small-cell lung carcinoma (SCLC), which also expresses functional VGCC. Knowledge of this association led to the discovery of a wide range of paraneoplastic and non-tumour-related neurological disorders of the peripheral and central nervous systems. Detailed clinical studies have improved our diagnostic skills and knowledge of the pathophysiological mechanisms and association of LEMS with SCLC, and have helped with the development of a protocol for early tumour detection.
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igg fc n glycosylation changes in lambert eaton Myasthenic Syndrome and myasthenia gravis
Journal of Proteome Research, 2011Co-Authors: Maurice H J Selman, Maarten J Titulaer, Jan J G M Verschuuren, Erik H Niks, Manfred Wuhrer, Andre M DeelderAbstract:N-glycosylation of the immunoglobulin Fc moiety influences its biological activity by, for example, modulating the interaction with Fc receptors. Changes in IgG glycosylation have been found to be associated with various inflammatory diseases. Here we evaluated for the first time IgG Fc N-glycosylation changes in well-defined antibody-mediated autoimmune diseases, that is, the neurological disorders Lambert-Eaton Myasthenic Syndrome and myasthenia gravis, with antibodies to muscle nicotinic acetylcholine receptors or muscle-specific kinase. IgGs were purified from serum or plasma by protein A affinity chromatography and digested with trypsin. Glycopeptides were purified and analyzed by MALDI-FTICR−MS. Glycoform distributions of both IgG1 and IgG2 were determined for 229 patients and 56 controls. We observed an overall age and sex dependency of IgG Fc N-glycosylation, which was in accordance with literature. All three disease groups showed lower levels of IgG2 galactosylation compared to controls. In addit...
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3 4 diaminopyridine for the treatment of lambert eaton Myasthenic Syndrome
Expert Review of Clinical Immunology, 2010Co-Authors: Paul W Wirtz, Maarten J Titulaer, Jma Van Gerven, Jan J G M VerschuurenAbstract:The Lambert–Eaton Myasthenic Syndrome (LEMS) is an autoimmune disease in which antibodies against voltage-gated calcium channels inhibit cholinergic neurotransmission. LEMS is clinically characterized by muscle weakness and autonomic dysfunction. 3,4-diaminopyridine (3,4-DAP) blocks potassium channels in nerve terminals, resulting in an increase in acetylcholine release. This article describes the four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS. All trials demonstrated a significant effect on muscle strength and compound muscle action potential amplitude. Furthermore, the safety and tolerability of 3,4-DAP are reviewed. The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. Given the efficacy and safety of 3,4-DAP in LEMS, this drug is the mainstay for symptomatic treatment of LEMS.
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efficacy of 3 4 diaminopyridine and pyridostigmine in the treatment of lambert eaton Myasthenic Syndrome a randomized double blind placebo controlled crossover study
Clinical Pharmacology & Therapeutics, 2009Co-Authors: Paul W Wirtz, Jgc Van Hasselt, Maarten J Titulaer, Den J Hartigh, Jan J G M Verschuuren, J G Van Dijk, Rik C. Schoemaker, Ubbo R. Tjaden, Jma Van GervenAbstract:3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert–Eaton Myasthenic Syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, doubledummy, double-blind, randomized, crossover study in nine patients with LEMS. The Lambert–Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder characterized by proximal muscle weakness and depressed tendon reflexes. In LEMS, antibodies against presynaptic voltage-gated calcium channels inhibit the influx of calcium in the nerve terminal and consequently the release of acetylcholine into the neuromuscular synapse. Both 3,4diaminopyridine and pyridostigmine are used in the treatment. These two drugs have different sites of action at the synapse, which could lead to a synergistic effect on neuromuscular transmission. No studies have investigated the therapeutic effect of an acetylcholinesterase inhibitor, alone or in combination with 3,4-diaminopyridine, in LEMS. Therefore, we compared the effects of 3,4-diamino pyridine, pyridostigmine, the combination of both drugs, and placebo on muscle strength and results of repetitive nerve stimulation in patients with LEMS. In addition, concentration–effect relationships for neuromuscular parameters and drugs were described using pharmacokinetic/ pharmacodynamic (PK/PD) modeling. Results
Maarten J Titulaer - One of the best experts on this subject based on the ideXlab platform.
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sox1 antibodies in lambert eaton Myasthenic Syndrome and screening for small cell lung carcinoma
Annals of the New York Academy of Sciences, 2012Co-Authors: Alexander F Lipka, Maarten J Titulaer, Jan J G M VerschuurenAbstract:Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder of the neuromuscular synapse. About half of LEMS patients have an associated small cell lung carcinoma (SCLC), which is usually detected after diagnosis of LEMS. This short review summarizes clinical and serological markers shown to predict the presence of SCLC in LEMS patients. SOX1 antibodies are a specific marker for SCLC-LEMS but they are also found in SCLC patients without paraneoplastic neurological Syndromes. No relation to any clinical characteristic or survival effect has been found for SOX1-positive patients. Several clinical markers also discriminate between SCLC-LEMS and nontumor LEMS. Detailed analysis of these clinical and demographic characteristics from two independent patient cohorts has led to development of the DELTA-P score. This prediction model has provided for a simple clinical tool to indicate the presence of SCLC early in the course of the disease. The DELTA-P score can be used to guide tumor screening in individual patients.
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lambert eaton Myasthenic Syndrome from clinical characteristics to therapeutic strategies
Lancet Neurology, 2011Co-Authors: Maarten J Titulaer, Bethan Lang, Jan J G M VerschuurenAbstract:Summary Lambert–Eaton Myasthenic Syndrome (LEMS) is a neuromuscular autoimmune disease that has served as a model for autoimmunity and tumour immunology. In LEMS, the characteristic muscle weakness is thought to be caused by pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal. Half of patients with LEMS have an associated tumour, small-cell lung carcinoma (SCLC), which also expresses functional VGCC. Knowledge of this association led to the discovery of a wide range of paraneoplastic and non-tumour-related neurological disorders of the peripheral and central nervous systems. Detailed clinical studies have improved our diagnostic skills and knowledge of the pathophysiological mechanisms and association of LEMS with SCLC, and have helped with the development of a protocol for early tumour detection.
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igg fc n glycosylation changes in lambert eaton Myasthenic Syndrome and myasthenia gravis
Journal of Proteome Research, 2011Co-Authors: Maurice H J Selman, Maarten J Titulaer, Jan J G M Verschuuren, Erik H Niks, Manfred Wuhrer, Andre M DeelderAbstract:N-glycosylation of the immunoglobulin Fc moiety influences its biological activity by, for example, modulating the interaction with Fc receptors. Changes in IgG glycosylation have been found to be associated with various inflammatory diseases. Here we evaluated for the first time IgG Fc N-glycosylation changes in well-defined antibody-mediated autoimmune diseases, that is, the neurological disorders Lambert-Eaton Myasthenic Syndrome and myasthenia gravis, with antibodies to muscle nicotinic acetylcholine receptors or muscle-specific kinase. IgGs were purified from serum or plasma by protein A affinity chromatography and digested with trypsin. Glycopeptides were purified and analyzed by MALDI-FTICR−MS. Glycoform distributions of both IgG1 and IgG2 were determined for 229 patients and 56 controls. We observed an overall age and sex dependency of IgG Fc N-glycosylation, which was in accordance with literature. All three disease groups showed lower levels of IgG2 galactosylation compared to controls. In addit...
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3 4 diaminopyridine for the treatment of lambert eaton Myasthenic Syndrome
Expert Review of Clinical Immunology, 2010Co-Authors: Paul W Wirtz, Maarten J Titulaer, Jma Van Gerven, Jan J G M VerschuurenAbstract:The Lambert–Eaton Myasthenic Syndrome (LEMS) is an autoimmune disease in which antibodies against voltage-gated calcium channels inhibit cholinergic neurotransmission. LEMS is clinically characterized by muscle weakness and autonomic dysfunction. 3,4-diaminopyridine (3,4-DAP) blocks potassium channels in nerve terminals, resulting in an increase in acetylcholine release. This article describes the four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS. All trials demonstrated a significant effect on muscle strength and compound muscle action potential amplitude. Furthermore, the safety and tolerability of 3,4-DAP are reviewed. The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. Given the efficacy and safety of 3,4-DAP in LEMS, this drug is the mainstay for symptomatic treatment of LEMS.
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efficacy of 3 4 diaminopyridine and pyridostigmine in the treatment of lambert eaton Myasthenic Syndrome a randomized double blind placebo controlled crossover study
Clinical Pharmacology & Therapeutics, 2009Co-Authors: Paul W Wirtz, Jgc Van Hasselt, Maarten J Titulaer, Den J Hartigh, Jan J G M Verschuuren, J G Van Dijk, Rik C. Schoemaker, Ubbo R. Tjaden, Jma Van GervenAbstract:3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert–Eaton Myasthenic Syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, doubledummy, double-blind, randomized, crossover study in nine patients with LEMS. The Lambert–Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder characterized by proximal muscle weakness and depressed tendon reflexes. In LEMS, antibodies against presynaptic voltage-gated calcium channels inhibit the influx of calcium in the nerve terminal and consequently the release of acetylcholine into the neuromuscular synapse. Both 3,4diaminopyridine and pyridostigmine are used in the treatment. These two drugs have different sites of action at the synapse, which could lead to a synergistic effect on neuromuscular transmission. No studies have investigated the therapeutic effect of an acetylcholinesterase inhibitor, alone or in combination with 3,4-diaminopyridine, in LEMS. Therefore, we compared the effects of 3,4-diamino pyridine, pyridostigmine, the combination of both drugs, and placebo on muscle strength and results of repetitive nerve stimulation in patients with LEMS. In addition, concentration–effect relationships for neuromuscular parameters and drugs were described using pharmacokinetic/ pharmacodynamic (PK/PD) modeling. Results
Bethan Lang - One of the best experts on this subject based on the ideXlab platform.
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neuronal antibody detection and improved lung cancer prediction in lambert eaton Myasthenic Syndrome
Journal of Neuroimmunology, 2020Co-Authors: Paul Maddison, Paul Gozzard, Girija Sadalage, Philip Alexander Ambrose, Caroline J Chapman, Andrea Murray, Selina Thomsen, Antonio Berretta, Bethan LangAbstract:Abstract Since approximately 50% of patients with Lambert-Eaton Myasthenic Syndrome (LEMS) subsequently develop small-cell lung cancer (SCLC), it is important to be able to predict cancer occurrence in these patients at neurological presentation. We aimed to determine whether circulating biomarkers were effective and objective predictors of cancer development in LEMS. We found that the presence of either SOX2, N-type voltage gated calcium channel or GABAb antibodies at LEMS diagnosis was highly sensitive (84%) and specific (87%) for the detection of SCLC. Screening for SOX2 and neuronal antibodies is a useful adjunct to clinical predictive scoring tools in predicting SCLC in LEMS.
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po206 lambert eaton Myasthenic Syndrome results from bnsu survey
Journal of Neurology Neurosurgery and Psychiatry, 2017Co-Authors: Paul Maddison, Paul Gozzard, Girija Sadalage, Selina Thomsen, Bethan LangAbstract:The aims of the Lambert-Eaton Myasthenic Syndrome (LEMS) British Neurological Surveillance Unit (BNSU) survey was four-fold: firstly, to allow data collection on LEMS patients to establish a cohort of cases prospectively in order to determine, without bias, whether SCLC-LEMS patients survive longer than patients with SCLC without LEMS; secondly, to collect large serum samples to store as part of a LEMS biobank; thirdly to use previously published DELTA-P predictive scores prospectively in a real-world setting to measure its effectiveness in predicting cancer in LEMS patients at first diagnosis; and fourthly to test LEMS patients for the presence of other neuronal antibodies that may also be predictive of cancer. Between March 2010 and January 2017, we were notified of 111 new LEMS cases via the BNSU of the Association of British Neurologists. Of these, 45 (41%) LEMS patients returned a signed consent to us, and enrolled in the study. Ongoing survival data using multivariate Cox regression analysis showed that the presence of LEMS with SCLC conferred a significant survival advantage independent of the other prognostic variables (Hazard ratio 0.569, 95% CI 0.368–0.880, p=0.011). DELTA-P score was confirmed to aid in determining SCLC probability, with area under the ROC curve of 83.4%.
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long term survival in paraneoplastic lambert eaton Myasthenic Syndrome
Neurology, 2017Co-Authors: Paul Maddison, Paul Gozzard, Matthew J Grainge, Bethan LangAbstract:Objective: To establish whether improved tumor survival in patients with Lambert-Eaton Myasthenic Syndrome (LEMS) and small-cell lung cancer (SCLC) was due to known prognostic risk factors or an effect of LEMS independently, perhaps as a result of circulating factors. Methods: We undertook a prospective observational cohort study of patients with LEMS attending Nottingham University Hospitals, UK, or via the British Neurological Surveillance Unit. In parallel, patients with a new diagnosis of biopsy-proven SCLC were enrolled, examined for neurologic illness, and followed up until death or study end. Results: Between May 2005 and November 2014, we recruited 31 patients with LEMS and SCLC and 279 patients with SCLC without neurologic illness. Allowing for known SCLC survival prognostic factors of disease extent, age, sex, performance status, and sodium values, multivariate Cox regression analysis showed that the presence of LEMS with SCLC conferred a significant survival advantage independently of the other prognostic variables (hazard ratio 1.756, 95% confidence interval 1.137–2.709, p = 0.011). Conclusions: Improved SCLC tumor survival seen in patients with LEMS and SCLC may not be due solely to lead time bias, given that survival advantage remains after allowing for other prognostic factors and that the same degree of survival advantage is not seen in patients with paraneoplastic neurologic Syndromes other than LEMS presenting before SCLC diagnosis.
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chapter 74 autoantibodies in the lambert eaton Myasthenic Syndrome lems and amyotrophic lateral sclerosis als
Autoantibodies (Third Edition), 2014Co-Authors: Bethan Lang, Paul MaddisonAbstract:Autoantibodies to different subtypes of the voltage-gated calcium channel (VGCC) have been described in two very different neurological Syndromes, the Lambert-Eaton Myasthenic Syndrome (LEMS) and amyotrophic lateral sclerosis (ALS). In this chapter we discuss the evidence supporting the role of anti-P/Q-type VGCC autoantibodies in the pathogenesis of LEMS but challenging the role of any VGCC autoantibodies in ALS.
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lambert eaton Myasthenic Syndrome from clinical characteristics to therapeutic strategies
Lancet Neurology, 2011Co-Authors: Maarten J Titulaer, Bethan Lang, Jan J G M VerschuurenAbstract:Summary Lambert–Eaton Myasthenic Syndrome (LEMS) is a neuromuscular autoimmune disease that has served as a model for autoimmunity and tumour immunology. In LEMS, the characteristic muscle weakness is thought to be caused by pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal. Half of patients with LEMS have an associated tumour, small-cell lung carcinoma (SCLC), which also expresses functional VGCC. Knowledge of this association led to the discovery of a wide range of paraneoplastic and non-tumour-related neurological disorders of the peripheral and central nervous systems. Detailed clinical studies have improved our diagnostic skills and knowledge of the pathophysiological mechanisms and association of LEMS with SCLC, and have helped with the development of a protocol for early tumour detection.
Paul W Wirtz - One of the best experts on this subject based on the ideXlab platform.
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3 4 diaminopyridine for the treatment of lambert eaton Myasthenic Syndrome
Expert Review of Clinical Immunology, 2010Co-Authors: Paul W Wirtz, Maarten J Titulaer, Jma Van Gerven, Jan J G M VerschuurenAbstract:The Lambert–Eaton Myasthenic Syndrome (LEMS) is an autoimmune disease in which antibodies against voltage-gated calcium channels inhibit cholinergic neurotransmission. LEMS is clinically characterized by muscle weakness and autonomic dysfunction. 3,4-diaminopyridine (3,4-DAP) blocks potassium channels in nerve terminals, resulting in an increase in acetylcholine release. This article describes the four randomized placebo-controlled trials of 3,4-DAP in patients with LEMS. All trials demonstrated a significant effect on muscle strength and compound muscle action potential amplitude. Furthermore, the safety and tolerability of 3,4-DAP are reviewed. The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. Given the efficacy and safety of 3,4-DAP in LEMS, this drug is the mainstay for symptomatic treatment of LEMS.
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efficacy of 3 4 diaminopyridine and pyridostigmine in the treatment of lambert eaton Myasthenic Syndrome a randomized double blind placebo controlled crossover study
Clinical Pharmacology & Therapeutics, 2009Co-Authors: Paul W Wirtz, Jgc Van Hasselt, Maarten J Titulaer, Den J Hartigh, Jan J G M Verschuuren, J G Van Dijk, Rik C. Schoemaker, Ubbo R. Tjaden, Jma Van GervenAbstract:3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert–Eaton Myasthenic Syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, doubledummy, double-blind, randomized, crossover study in nine patients with LEMS. The Lambert–Eaton Myasthenic Syndrome (LEMS) is an autoimmune disorder characterized by proximal muscle weakness and depressed tendon reflexes. In LEMS, antibodies against presynaptic voltage-gated calcium channels inhibit the influx of calcium in the nerve terminal and consequently the release of acetylcholine into the neuromuscular synapse. Both 3,4diaminopyridine and pyridostigmine are used in the treatment. These two drugs have different sites of action at the synapse, which could lead to a synergistic effect on neuromuscular transmission. No studies have investigated the therapeutic effect of an acetylcholinesterase inhibitor, alone or in combination with 3,4-diaminopyridine, in LEMS. Therefore, we compared the effects of 3,4-diamino pyridine, pyridostigmine, the combination of both drugs, and placebo on muscle strength and results of repetitive nerve stimulation in patients with LEMS. In addition, concentration–effect relationships for neuromuscular parameters and drugs were described using pharmacokinetic/ pharmacodynamic (PK/PD) modeling. Results
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available treatment options for the management of lambert eaton Myasthenic Syndrome
Expert Opinion on Pharmacotherapy, 2006Co-Authors: Jan J G M Verschuuren, Paul W Wirtz, Maarten J Titulaer, Luuk N A Willems, Jma Van GervenAbstract:Lambert-Eaton Myasthenic Syndrome is a rare, but reasonably well-understood, antibody-mediated autoimmune disease that is caused by serum auto-antibodies and results in muscle weakness and autonomic dysfunction. One half of the patients have an idiopathic form, the other half a tumour-associated form of the disease. Three randomised trials and a large number of smaller clinical studies have resulted in a number of drugs becoming available for the treatment of Lambert-Eaton Myasthenic Syndrome. Several drugs are available for the symptomatic treatment of the disease, including guanidine, aminopyridines or acetylcholinesterase inhibitors. Other therapies aim to deplete the serum autoantibodies or to suppress the immune system. For this purpose, immunomodulating strategies, such as intravenous immunoglobulins or plasmapheresis, or several immunosuppressive agents are available. Chemotherapy has successfully ameliorated the course of disease in Lambert-Eaton Myasthenic Syndrome patients with an underlying tumour.
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lambert eaton Myasthenic Syndrome has a more progressive course in patients with lung cancer
Muscle & Nerve, 2005Co-Authors: Paul W Wirtz, A R Wintzen, Jan J G M VerschuurenAbstract:We studied whether a difference exists in the development of symptoms of the Lambert–Eaton Myasthenic Syndrome (LEMS) between patients with or without small cell lung cancer (SCLC). We assessed symptoms in 38 LEMS patients, 13 with SCLC, by interviewing them using a structured checklist, backed up by a review of their clinical records, and compared the frequency and time scale of symptoms during the course of LEMS. Bulbar (87%) and autonomic (95%) symptoms for the whole group were more common than reported in the literature. Frequencies of symptoms did not differ significantly between patients with and without SCLC, but symptoms in patients with SCLC appeared within a shorter time-frame, indicating a more rapid clinical course. The presence of a particular symptom associated with LEMS did not predict the presence of SCLC, but in patients with rapidly progressive LEMS the possibility of underlying lung cancer should be of particular concern. Muscle Nerve, 2005
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p q type calcium channel antibodies lambert eaton Myasthenic Syndrome and survival in small cell lung cancer
Journal of Neuroimmunology, 2005Co-Authors: Paul W Wirtz, A. Twijnstra, Bethan Lang, Francesc Graus, Albert Saiz, Arn M J M Van Den Maagdenberg, Pia A M De Koning Gans, Jan J G M VerschuurenAbstract:Abstract To assess the survival impact of the presence of P/Q-type calcium channel antibodies in patients with small cell lung carcinoma (SCLC), we examined the frequency of the antibodies and Lambert–Eaton Myasthenic Syndrome (LEMS) in 148 consecutive patients with SCLC, and in 30 patients with paraneoplastic cerebellar degeneration and SCLC, and studied their relation with survival. In both series, only patients with LEMS had a remarkably long survival, whereas presence of the antibodies without LEMS did not result in a better prognosis.
Donald B Sanders - One of the best experts on this subject based on the ideXlab platform.
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lambert eaton Myasthenic Syndrome
Reference Module in Neuroscience and Biobehavioral Psychology#R##N#Encyclopedia of the Neurological Sciences (Second Edition), 2014Co-Authors: Donald B SandersAbstract:The Lambert–Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune condition, in which weakness is caused by blocked release of the neurotransmitter acetylcholine from the motor nerve terminal. This condition was first described in patients with lung cancer but we now know that it results from an immune-mediated process directed against the voltage-gated calcium channels (VGCC) on the nerve terminal. Half the patients with LEMS have lung cancer and in these patients, antibodies directed against cancer cell components cross-react with the VGCC on the nerve terminals. In patients without cancer, LEMS results when antibodies to the VGCC are produced as part of a more general autoimmune state. LEMS is probably the most well-understood autoimmune disease, and knowledge gained from studying how it begins has wide implications for other, more common, autoimmune diseases.
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lambert eaton Myasthenic Syndrome electrodiagnostic findings and response to treatment
Neurology, 2000Co-Authors: Janice M Massey, Donald B SandersAbstract:Article abstract The authors reviewed the incidence of cancer, repetitive nerve stimulation findings, and response to treatment in 73 patients with Lambert-Eaton Myasthenic Syndrome. Thirty-one patients (42%) had lung cancer, 29 small cell. Doubling of the compound motor action potential amplitude in three tested distal muscles was seen in only 41% of patients. Treatment with 3,4-diaminopyridine produced moderate to marked self-reported functional improvement in 79% of the 53 treated patients.
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lambert eaton Myasthenic Syndrome clinical diagnosis immune mediated mechanisms and update on therapies
Annals of Neurology, 1995Co-Authors: Donald B SandersAbstract: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. It was first described as a paraneoplastic Syndrome in patients with lung cancer but we now know about half of the patients with LEMS do not have cancer. The diagnosis is made on the basis of the clinical findings and characteristic electromyographic patterns. Recent evidence indicates that LEMS results from an autoimmune attack directed against the voltage-gated calcium channels on the presynaptic motor nerve terminal. In patients with LEMS who have cancer, effective treatment of the underlying tumor frequently produces marked improvement of weakness as well. Otherwise, treatment involves the use of agents that improve neuromuscular transmission by increasing the release of neurotransmitter, and immunosuppression.
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repetitive nerve stimulation studies in the lambert eaton Myasthenic Syndrome
Muscle & Nerve, 1994Co-Authors: Donald B SandersAbstract:We compared changes in amplitude and area of surface recorded compound motor action potentials (CMAPs) during 20-Hz repetitive nerve stimulation and after maximum voluntary contraction in patients with the Lambert–Eaton Myasthenic Syndrome (LEMS), myasthenia gravis (MG), and normal controls. There was greater potentiation of CMAP amplitude after voluntary contraction than during 20-Hz stimulation in 10 of 14 LEMS patients; CMAP area increased more after exercise than during 20-Hz stimulation in all LEMS patients. Although abnormal potentiation of CMAP area and amplitude was seen in equal numbers of LEMS patients, more LEMS patients demonstrated a greater than 100% potentiation of CMAP area than of CMAP amplitude. We conclude that maximum voluntary contraction is preferable to brief 20-Hz RNS to demonstrate potentiation in LEMS because it is at least as sensitive and is less painful. Measurement of CMAP area in LEMS patients is not better than measuring the change in CMAP amplitude in demonstrating abnormal potentiation. Testing of a single hand muscle for potentiation in LEMS does not demonstrate abnormal potentiation in all LEMS patients. © 1994 John Wiley & Sons, Inc.
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repetitive nerve stimulation studies in the lambert eaton Myasthenic Syndrome
Muscle & Nerve, 1994Co-Authors: Richard W Tim, Donald B SandersAbstract:We compared changes in amplitude and area of surface recorded compound motor action potentials (CMAPs) during 20-Hz repetitive nerve stimulation and after maximum voluntary contraction in patients with the Lambert-Eaton Myasthenic Syndrome (LEMS), myasthenia gravis (MG), and normal controls. There was greater potentiation of CMAP amplitude after voluntary contraction than during 20-Hz stimulation in 10 of 14 LEMS patients; CMAP area increased more after exercise than during 20-Hz stimulation in all LEMS patients. Although abnormal potentiation of CMAP area and amplitude was seen in equal numbers of LEMS patients, more LEMS patients demonstrated a greater than 100% potentiation of CMAP area than of CMAP amplitude. We conclude that maximum voluntary contraction is preferable to brief 20-Hz RNS to demonstrate potentiation in LEMS because it is at least as sensitive and is less painful. Measurement of CMAP area in LEMS patients is not better than measuring the change in CMAP amplitude in demonstrating abnormal potentiation. Testing of a single hand muscle for potentiation in LEMS does not demonstrate abnormal potentiation in all LEMS patients.
