Materiały źródłowe

• #1 Lambert-Eaton Myasthenic Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507891/

  Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder affecting communication between nerves and muscles. This intricate disorder can manifest due to a paraneoplastic syndrome or a primary autoimmune disorder. The majority of cases are associated with small-cell lung cancer. […] The underlying pathophysiology involves the development of antibodies that target voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals, resulting in reduced acetylcholine (ACh) neurotransmitter release. This activity reviews the pathogenesis, diagnostic procedures, and treatment strategies for LEMS. […] LEMS is characterized by a reduction in Ach release from presynaptic nerve terminals, which arises from antibodies targeting VGCCs within the presynaptic neuronal cell membrane.

• #2 Lambert-Eaton Myasthenic Syndrome (LEMS): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1170810-overview

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, including proximal muscle weakness, depressed tendon reflexes, posttetanic potentiation, and autonomic changes. […] LEMS disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca2+ channels involved with neurotransmitter release. […] Physiologic studies of neuromuscular transmission demonstrate that ACh release from the motor nerve terminal is impaired in the Lambert-Eaton myasthenic syndrome (LEMS) muscle. An autoimmune attack directed against the voltage-gated calcium channels (VGCCs) on the presynaptic motor nerve terminal results in a loss of functional VGCCs at the motor nerve terminals.

• #3 Lambert–Eaton myasthenic syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Lambert%E2%80%93Eaton_myasthenic_syndrome

  LambertEaton myasthenic syndrome is caused by autoantibodies to the presynaptic membrane. […] It is the result of antibodies against presynaptic voltage-gated calcium channels, and likely other nerve terminal proteins, in the neuromuscular junction. […] In LEMS, antibodies against VGCC, particularly the P/Q-type VGCC and possibly the N-type VGCC antibody, decrease the amount of calcium that can enter the nerve ending, hence less acetylcholine can be released from the neuromuscular junction. […] Apart from the decreased calcium influx, a disruption of active zone vesicle release sites also occurs, which may also be antibody-dependent, since people with LEMS have antibodies to components of these active zones (including voltage-dependent calcium channels). […] The antibodies found in LEMS associated with lung cancer also bind to calcium channels in the cancer cells, and it is presumed that the antibodies originally develop as a reaction to these cells.

• #4 Lambert-Eaton Myasthenic Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507891/

  VGCC is a large transmembrane protein facilitating calcium ion influx into nerve terminals via multiple subunits. In LEMS, the functionality of VGCC is compromised due to the cross-linking of these channels mediated by IgG antibodies. More specifically, these antibodies specifically target the P/Q subtype of VGCC. Notably, 85% of patients with LEMS exhibit antibodies against the P/Q-type VGCC. […] Autoimmunity within the context of LEMS associated with SCLC follows a distinct mechanism. In these instances, the tumor tissue expresses VGCC. This antigenic expression within the tumor cells triggers autoantibody production. These autoantibodies exhibit cross-reactivity with presynaptic VGCC antigens. […] LEMS is a B-cell-mediated autoimmune neurological disorder specifically targeting the cell surface antigen (VGCC). The VGCC-IgG antibody is central to this disorder and directly contributes to its pathogenesis, leading to compromised neuromuscular transmission and manifesting as observable muscle weakness. […] In addition to muscle-related symptoms, the effects extend to the release of ACh neurotransmitter also relevant to autonomic ganglia. Consequently, this disruption results in clinical manifestations of autonomic involvement, including constipation and atypical pupillary responses to light stimuli.

• #5 Causes/Inheritance – Lambert-Eaton Myasthenic Syndrome (LEMS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/lambert-eaton-myasthenic-syndrome/causes-inheritance

  LEMS occurs when the immune system makes antibodies that selectively attack calcium channels. This leads to their internalization and destruction. As a result, in LEMS there are fewer calcium channels at nerve endings, leading to a reduction in ACh release and resulting muscle weakness. […] Some 85 to 90 percent of people with LEMS test positive for antibodies against the P/Q subtype of voltage-gated calcium channel, a specific subtype of calcium channel enriched at the nerve endings of motor neurons that control muscle contraction. These autoantibodies made by the persons own immune system bind to the calcium channels on nerve endings, leading to their internalization and destruction. As a result, people with LEMS have fewer calcium channels on their nerve endings. This results in less calcium entry during nerve activity, and since calcium is the trigger for ACh release, patients have less ACh release. When this ACh release drops to levels low enough that there is not enough to cause a muscle contraction, weakness occurs.

• #6 Lambert-Eaton Myasthenic Syndrome (LEMS): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1170810-overview

  The number of quanta released by a nerve impulse is diminished. However, because presynaptic stores of ACh and the postsynaptic response to ACh remain intact, rapid repetitive stimulation or voluntary activation that aids in the release of quanta will raise the endplate potential above threshold and permit generation of muscle action potential. […] More direct evidence has been accumulated supporting the autoimmune etiology of LEMS. Active zone particles (AZPs), which represent the voltage-gated calcium channels (VGCCs), are normally arranged in regular parallel arrays on the presynaptic muscle membrane. In patients with LEMS and in mice injected with LEMS immunoglobulin G (IgG), divalent antibodies against the VGCC cross-link the calcium channels, disrupting the parallel arrays. Ultimately, the AZPs cluster and decrease in number.

• #7 Lambert-Eaton Myasthenic Syndrome (LEMS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/lambert-eaton-myasthenic-syndrome

  Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease a disease in which the immune system attacks the body’s own tissues. The attack occurs at the connection between nerve and muscle (the neuromuscular junction) and interferes with the ability of nerve cells to send signals to muscle cells. […] Specifically, the immune system attacks the calcium channels on nerve endings that are required to trigger the release of chemicals (acetylcholine). With fewer calcium channels, the nerve ending releases less acetylcholine. Acetylcholine is a chemical messenger that triggers muscle contraction. In people with LEMS, the lowered levels of acetylcholine are not sufficient to cause normal muscle contractions, causing muscle weakness. […] In both forms of LEMS, the disease is caused by the immune system making antibodies against calcium channels on nerve endings, leading to a loss of some of these channels, which results in muscle weakness.

• #8 Lambert-Eaton-Myasthenic-Syndrome-Pathogenesis-and-Clinical-Findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/lambert-eaton-myasthenic-syndrome-pathogenesis-and-clinical-findings/lambert-eaton-myasthenic-syndrome-pathogenesis-and-clinical-findings/

  Lambert-Eaton Myasthenic Syndrome: Pathogenesis and Clinical Findings […] Acquired autoimmunity: mechanism unknown, possibly associated with other autoimmune diseases […] A paraneoplastic syndrome of small cell lung cancer (SCLC) in 50% of patients […] Tumour membrane expresses voltage-gated calcium channels (VGCCs), which normally exist on neurons and function in neurotransmission […] Immune response to foreign cancer cells triggers production of antibodies against VGCCs on the cell surfaces of presynaptic neurons […] Antibodies bind VGCCs, blocking Ca2+ […] Antibodies bind, cross-link, and from entering presynaptic neurons […] Ca2+ influx into the presynaptic neuron during its depolarization internalize VGCCs […] Since intracellular Ca2+ mediates neurotransmitter vesicle fusion with the presynaptic membrane, Ca2+ influx release of neurotransmitters like acetylcholine into the synaptic cleft

• #9 Lambert-Eaton myasthenic syndrome | MedLink Neurology

  https://www.medlink.com/articles/lambert-eaton-myasthenic-syndrome

  The primary pathophysiologic abnormality in Lambert-Eaton syndrome is a reduction of the calcium-dependent quantal release of acetylcholine triggered by a nerve impulse. […] Ultrastructural studies of muscle from Lambert-Eaton syndrome patients show a marked depletion of presynaptic active zones (the sites of synaptic vesicle exocytosis), paucity and disorganization of active zone intramembrane particles, and aggregation of the active zone particles into clusters. […] Expression of a heterogeneous array of voltage-gated calcium channels is a common if not universal feature of small cell lung carcinomas, from patients with and without Lambert-Eaton syndrome. […] Voltage-gated calcium channels may not be the sole targets of autoimmunity in Lambert-Eaton syndrome. […] The synaptic vesicle protein synaptotagmin associates with calcium channels, and plays a role in the docking of synaptic vesicles at the presynaptic membrane prior to acetylcholine release. […] Anti-synaptotagmin antibodies are present in a minority of patients with Lambert-Eaton syndrome.

• #10 Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States

  https://www.mdpi.com/2218-273X/12/6/740

  The presence of antibodies targeting AZ P/Q-type VGCCs is thought to support a LEMS diagnosis, but is not a complete explanation of the immune nature of LEMS. Although anti-P/Q-type VGCCs are the most common antibody reported, they are not present in 5–20% of LEMS patients. This suggests that the immune nature of LEMS is more complicated than simply the presence or absence of P/Q-type VGCC antibodies. In fact, LEMS patients have been shown to produce auto-antibodies to a variety of presynaptic proteins, including synaptotagmin and M1-type presynaptic muscarinic acetylcholine receptors. […] Early freeze fracture electron microscopy studies of biopsied muscle tissue from human LEMS patients showed a decrease in the number of presynaptic AZs and a disorganization of particles in the remaining AZs. Similar results were found using freeze fracture electron microscopy in presynaptic terminals of LEMS-model mouse NMJs. This disruption of the AZ structure was interpreted to be due to the antibody-mediated loss of P/Q-type VGCCs, which could explain the muscle weakness seen in LEMS patients.

• #11 Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States

  https://www.mdpi.com/2218-273X/12/6/740

  However, the lateral displacement of the remaining P/Q-type calcium channels may cause a further reduction in transmitter release, as the movement of VGCCs away from the calcium-sensing protein reduces their effectiveness. Therefore, disruptions in AZ organization may also play an important role in LEMS pathophysiology.

• #12 Diagnosis and Treatment of Lambert-Eaton Myasthenic Syndrome

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/diagnosis-and-treatment-of-lambert-eaton-myasthenic-syndrome/32113/

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune presynaptic disorder of the neuromuscular junction (NMJ) associated with weakness, reduced or absent muscle stretch reflexes, and autonomic dysfunction. […] LEMS is a presynaptic NMJ disorder in which ACh release is impaired. This most often is caused by autoantibodies against the P/Q-type VGCC, with impaired release of ACh from the presynaptic membrane resulting in transmission failure and the clinical symptoms of weakness and autonomic dysfunction. […] LEMS is a rare autoimmune disease that is considered to be idiopathic or part of a paraneoplastic syndrome associated with a malignancy. Up to 60% of LEMS diagnoses are paraneoplastic in the context of an either known or undiagnosed malignancy. […] The diagnosis of LEMS is based on the presence of the typical clinical triad, with support from serology and electrodiagnostic testing.

• #13 Lambert-Eaton myasthenic syndrome | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/lambert-eaton-myasthenic-syndrome?lang=us

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder of paraneoplastic or primary autoimmune etiology. […] Up to two-thirds of LEMS present as a paraneoplastic syndrome secondary to malignancy, which is nearly always small-cell lung cancer. […] Antibodies against the P/Q-type voltage-gated calcium channel (anti-VGCC) are relatively specific for the diagnosis. […] A diagnosis of LEMS should prompt a search for an underlying malignancy, at least including chest CT, with additional consideration of FDG-PET. […] Management includes treatment of the underlying malignancy (if present) and pharmacotherapy.

• #14 Causes/Inheritance – Lambert-Eaton Myasthenic Syndrome (LEMS) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/lambert-eaton-myasthenic-syndrome/causes-inheritance

  In cases where LEMS is associated with small cell lung cancer, it is thought that these cancer cells make the same types of calcium channels as motor neurons. This is because small cell lung cancer cells are derived from neuroendocrine cells in the lung that also use calcium to trigger the release of chemical messengers. Therefore, when the bodys immune system recognizes these cancer cells as a threat, antibodies are generated against the cancer cell proteins in an attempt to fight the cancer. These antibodies accidentally also recognize the same types of calcium channels on nerve endings, resulting in an attack on the motor nerve terminal. […] The trigger for LEMS without cancer is unknown, but may have a genetic component linked to autoimmunity. In any case, these patients also make antibodies that target calcium channels, and the neuromuscular disease is the same as in those with cancer.

• #15 The Role of Mutations on HLA Genes in Lambert-Eaton Myasthenic Syndrome

  https://www.gavinpublishers.com/article/view/the-role-of-mutations-on-hla-genes-in-lambert-eaton-myasthenic-syndrome

  In patients with LEMS associated with cancer, an immune-mediated response is initiated because VGCC is present on the surface of cancer cells and the immune system stimulates the production of antibodies to fight cancer cells. Antibodies made against VGCC on small cell lung cancer are believed to mistakenly attack VGCC in nerve membranes instead. […] In people without LEMS without cancer, there is a genetic link to human leukocyte antigen (HLA) genotypes. HLAs are proteins that are also present on the cell surface and their function is to regulate the human immune system. However, it is still unknown what causes these proteins to break down and produce antibodies.

• #16

  https://link.springer.com/article/10.1007/BF00194096

  LEMS is an antibody-mediated autoimmune disease that can occur in isolation, or as a paraneoplastic disorder in association with SCLC (60% of patients). The underlying defect is a reduction in the quantal release of the neurotransmitter ACh from the presynaptic nerve terminal at the neuromuscular junction. Experimental evidence indicates the autoantibodies are directed against nerve terminal VGCCs causing downregulation in the number of functional channels by cross-linkage. […] In cancer-associated LEMS it appears likely that antibodies initially provoked by tumour VGCCs cross-react with VGCCs at the nerve terminal, causing the clinical disorder. Antibodies against L-, N- and P-/Q- subtypes of the calcium channels have been identified and radioimmunoassays have been developed to help diagnose the disease. […] However, autoantibodies in LEMS are heterogenous; the antigenic targets include different VGCC subtypes, the intracellular beta subunit and the synaptic vesicle protein synaptotagmin. The disease phenotype may reflect the diversity and titre of these different antibodies.

• #17 Lambert-Eaton Myasthenic Syndrome – Samir P. Macwan, MD

  https://socalmusclenerve.com/lambert-eaton-myasthenic-syndrome/

  In patients who have LEMS associated with cancer, the immune mediated response is initiated because VGCC are present on the surface of cancer cells and the immune system triggers the production of antibodies to fight off cancer cells. The idea is that autoantibodies created against the VGCC on the small cell lung cancer mistakenly attack the VGCC on the nerve membrane instead. […] In people who have LEMS not associated with cancer, genetic associations have been made with human leukocyte antigen (HLA) genotypes. HLA are proteins also present on the cell surface, and their function is to regulate the human immune system. However, it is unknown what causes these proteins to go awry array and trigger autoantibody production.

• #18 Lambert-Eaton Myasthenic Syndrome (LEMS): Symptoms & Causes

  https://my.clevelandclinic.org/health/diseases/23202-lambert-eaton-myasthenic-syndrome-lems

  LEMS happens in people who have small-cell lung cancer. In this case, your bodys antibodies recognize their call to action when theres cancer in your body. However, instead of attacking the cancer cells (specifically, the calcium channel on cancer cells), it attacks the calcium channel at the end of nerve cells. And the sequence listed above happens. When this happens, your muscle cells cant pick up the message to contract to make your muscle move. […] Scientists think the cause of LEMS in people who dont have lung cancer is an immune response that simply goes awry. It remains unclear why this happens.

• #19 :: JCN :: Journal of Clinical Neurology

  https://thejcn.com/DOIx.php?id=10.3988/jcn.2024.0018

  LEMS is a rare presynaptic neuromuscular junctional disorder induced by antibodies to the voltage-gated calcium channel (VGCC) producing fatigue and muscle weakness. […] In LEMS, by blocking VGCC by VGCC antibody, Ca++ uptake in the pre-synapses is decreased. This decreases the release of acetylcholine (ACh) from the synaptic vesicles, inducing muscle weakness. […] The discovery of LEMS usually precedes that of cancer by several months to 2 years. […] The triad of findings in LEMS comprises proximal muscle weakness, weak or absent reflexes, and dysautonomia. […] The repetitive nerve stimulation (RNS) test is the key diagnostic test in LEMS. […] The VGCC antibody test was found to be positive in 91% of LEMS patients. […] Treatments for LEMS consist of immunotherapy, cancer therapy, and symptomatic treatment.

• #20 Lambert-Eaton Myasthenic Syndrome (LEMS): Treatment and more

  https://www.verywellhealth.com/lambert-eaton-myasthenic-syndrome-lems-5100988

  It’s thought that antibodies to these calcium channels are also present, as they are for people with T-LEMS. These individuals are said to have idiopathic LEMS. […] Although it’s not clear what is going on with idiopathic LEMS, dysregulation of the immune system seems to play a role. People with idiopathic LEMS commonly have variations of certain immune system genes (HLA genes) that increase one’s risk of different autoimmune diseases. […] When caused by an underlying cancer, LEMS belongs to a larger group of conditions known as paraneoplastic syndromes. These are syndromes that cause symptoms from the substances a tumor makes or the way the body responds to the tumor—not from the direct impact of the cancer itself.

• #21 Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/lambert-eaton-myasthenic-syndrome-clinical-features-and-diagnosis

  Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular junction transmission with the primary clinical manifestation of muscle weakness. Knowledge of subtle clinical features and laboratory abnormalities that accompany LEMS permits the early identification of the disorder. Early recognition is particularly important because of its strong association with small cell lung cancer (SCLC). […] LEMS is a disorder of reduced acetylcholine (ACh) release from the presynaptic nerve terminals, despite normal ACh vesicle number, normal ACh presynaptic concentration, and normal postsynaptic ACh receptors. Lambert and Elmqvist, through a series of elegant intracellular muscle recordings, found that patients with what is now called LEMS had the following unique features: Normal miniature endplate potential amplitude, demonstrating normal postsynaptic sensitivity to ACh; Markedly reduced evoked endplate potential amplitude, suggesting a significant reduction in ACh release.

• #22 Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/lambert-eaton-myasthenic-syndrome-clinical-features-and-diagnosis/print

  Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular junction transmission with the primary clinical manifestation of muscle weakness. […] LEMS is a disorder of reduced acetylcholine (ACh) release from the presynaptic nerve terminals, despite normal ACh vesicle number, normal ACh presynaptic concentration, and normal postsynaptic ACh receptors. […] Lambert and Elmqvist, through a series of elegant intracellular muscle recordings, found that patients with what is now called LEMS had the following unique features: Normal miniature endplate potential amplitude, demonstrating normal postsynaptic sensitivity to ACh; Markedly reduced evoked endplate potential amplitude, suggesting a significant reduction in ACh release.

• #23 Diagnosis and Treatment of Lambert-Eaton Myasthenic Syndrome

  https://practicalneurology.com/diseases-diagnoses/neuromuscular/diagnosis-and-treatment-of-lambert-eaton-myasthenic-syndrome/32113/

  The electrophysiologic triad of LEMS consists of low CMAP amplitude at rest, decrement on slow RNS, and incremental response at 50-Hz stimulation for 1 second or after brief 10-second exercise. […] Not all muscles show the characteristic electrophysiologic triad, particularly when brief exercise is the method used, likely because of the severity of associated muscle weakness impairing the quality of exercise. […] Single-fiber EMG may also be utilized to support a diagnosis of LEMS and is typically reserved for when there is strong suspicion for LEMS despite negative serology and nerve conduction studies.

• #24 Lambert-Eaton-Myasthenic-Syndrome-Pathogenesis-and-Clinical-Findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/lambert-eaton-myasthenic-syndrome-pathogenesis-and-clinical-findings/lambert-eaton-myasthenic-syndrome-pathogenesis-and-clinical-findings/

  However, with repeated stimulation of the presynaptic neuron (e.g. exercise), there is Ca2+ accumulation within the axon terminal, allowing for more neurotransmitter vesicle fusion with the presynaptic membrane […] Acetylcholine available to mediate muscle reflexes […] With high frequency repetitive nerve stimulation, number of compound CMAPS can be generated […] Autonomic dysfunction […] Post-activation facilitation: Repeated stimulation improves symptoms […] Can affect any muscle group, but muscles involved in speech, swallowing, and periocular muscles are often afflicted.

• #25 Myasthenia Gravis vs. Lambert Eaton Syndrome

  https://www.healthline.com/health/myasthenia-gravis/myasthenia-gravis-vs-lambert-eaton

  LEMS is a rare autoimmune disorder that affects communication between your nerves and muscles. […] In LEMS, your immune system mistakenly attacks the calcium channels in nerve endings, disrupting the release of specialized messenger molecules called neurotransmitters that trigger muscle contraction. As a result, your muscles cant tighten (contract) properly. […] Exercise can temporarily improve muscle strength in LEMS by increasing the release of neurotransmitters that stimulate muscle contraction. However, this effect is short-lived and doesnt provide long-term relief from symptoms. […] In LEMS, muscle response measured with electrical testing may improve with exercise.

• #26 Autonomic dysfunction detected by skin sympathetic response in Lambert-Eaton myasthenic syndrome: a case report | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02625-1

  Lambert-Eaton myasthenic syndrome (LEMS) is a type of paraneoplastic syndrome that may initially manifest itself with proximal weakness and gait abnormalities. Approximately up to 50% of LEMS patients have a primary autonomic dysfunction. […] In this case, we present the detailed results of SSR test on a patient suffering LEMS with autonomic disorder. Since autonomic dysfunction has a significant impact on clinical management and SSR test is an effective detection method, we recommend that SSR test be performed on patients with LEMS regularly. […] The Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal weakness and autonomic dysfunction. […] Approximately up to 50% of LEMS patients have a primary autonomic dysfunction including dry mouth, constipation, loss of sweating, orthostatic hypotension, pupillary abnormalities etc.

• #27 Review of the Diagnostic Challenges of Lambert–Eaton Syndrome Revealed Through Three Case Reports | Canadian Journal of Neurological Sciences | Cambridge Core

  https://www.cambridge.org/core/journals/canadian-journal-of-neurological-sciences/article/review-of-the-diagnostic-challenges-of-lamberteaton-syndrome-revealed-through-three-case-reports/199C1272374AFEEE24643F5C0F86913B

  Symptoms or signs of autonomic dysfunction have been found in up to 80% of LES patients and may be the presenting symptom in 6% of patients, preceding muscle weakness onset by years. […] Early recognition of a concurrent autonomic neuropathy in LES is important, because paraneoplastic syndrome with autonomic neuropathy is associated with a worse prognosis. […] In clinical practice, P/Q-type VGCCAb have the highest sensitivity and specificity in LES, rather than the rarer N- or L-type VGCCAb. […] A positive P/Q-type VGCCAb result is useful for distinguishing LES from MG, but results must be interpreted in the context of the clinical and electrophysiological findings in each individual patient.

• #28 Clinical, Pathophysiological and Electrodiagnostic Aspects of Lambert-Eaton Myasthenic Syndrome | IntechOpen

  https://www.intechopen.com/online-first/87108

  Given this, by altering the release of Ach, the entire cascade of neurotransmission and channel opening mentioned above end up reducing as well. A decreased amount of Ach translates into an underactivation of sodium and potassium channels in the postsynaptic membrane and reduces the action potential in the endplate. […] Therefore, the action potential ends up not occurring and, consequently, affects muscle contraction, which explains one of the main symptoms of the disease, muscle weakness. […] Association with tumor is reported in about 60% of patients with LEMS, in which the majority is due to smoking-related SCLC with neuroendocrine characteristics, but other malignant neoplasms are described in the literature, such as small cell lung carcinomas. […] Descriptions in the literature show assumptions about the initial human autoimmune response in patients with LEMS being generated against the antigens of the VGCC subunit in lung carcinoma, and the paraneoplastic form expresses VGCC of the N, L or P type, in addition to the P/Q subtypes and possibly N are targets of IgG-mediated autoimmunity in LEMS.

• #28 Clinical, Pathophysiological and Electrodiagnostic Aspects of Lambert-Eaton Myasthenic Syndrome | IntechOpen

  https://www.intechopen.com/online-first/87108

  Lambert-Eaton myasthenic syndrome (LEMS) is characterized by an autoimmune disorder of the neuromuscular junction, which, through a reduction in nerve terminal acetylcholine release mediated by antibodies against functional voltage-gated calcium channels (VGCCs) of the P/Q in presynaptic nerve terminals, leads to proximal muscle weakness, in addition to autonomic dysfunction and areflexia, constituting the classic triad of symptoms. […] LEMS is characterized by the presence of antibodies against presynaptic voltage-gated calcium channels (VGCCs) of the P/Q type, which provide a decrease in the levels of acetylcholine (ACh) that are released in the nerve terminal, providing one of the main symptoms encountered, such as weakness and fatigue. […] In Lambert-Eaton syndrome, the body produces autoantibodies to the presynaptic VGCC, which therefore results in a reduction of Ach released in the presynaptic nerve terminal.

• #29 Synaptic Compensatory Mechanism and its Impairment in Autoimmune Myasthenic Diseases

  https://www.immunologyresearchjournal.com/articles/synaptic-compensatory-mechanism-and-its-impairment-in-autoimmune-myasthenic-diseases.html

  The present data and discussions are concerned in an adaptive change of ACh release from the nerve terminal and its immunological impairment in the post-synaptic disease (myasthenia gravis, MG) and the presynaptic disease (Lambert-Eaton myasthenic syndrome, LEMS). […] In LEMS which is often associated with small-cell lung carcinoma (SCLC) expressing antigens immunologically cross-reactive with the nerve terminal proteins, we showed that M1-type mAChR antibodies are implicated in this presynaptic disorder, the pathogenicity of which has mainly referred to the antibodies directing to presynaptic components, P/Q-type VGCC and synaptotagmin 1. […] The compensatory mechanism that activates presynaptic M1-type mAChR and modulates the fast-mode of synaptic vesicle recycling may be restricted by coincident M1-type mAChR antibodies in LEMS.

• #30 Autonomic dysfunction detected by skin sympathetic response in Lambert-Eaton myasthenic syndrome: a case report | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-022-02625-1

  SSR test electrophysiologically confirms the involvement of autonomic nervous system. […] Until recently, little has been known about the mechanisms underlying autonomic dysfunction in immune-related neuromuscular junction diseases. […] Taking the high positivity rate of P/Q VGCC antibodies as well as the high incidence of autonomic dysfunction in patients with LEMS into consideration, the relationship between them needs to be investigated. […] Therefore, this case provide a rationale for investigating the effect of IVIg for autonomic dysfunction in LEMS patients with VGCC antibodies. […] Since SSR test is an effective way to detect autonomic dysfunction, we recommend that SSR test be performed on patients with LEMS regularly.

• #31

  https://www.alliedacademies.org/articles/understanding-lamberteaton-myasthenic-syndrome-pathophysiology-diagnosis-and-treatment-29408.html

  Research into LEMS is ongoing, with the aim of improving understanding, treatment, and ultimately finding a cure. Promising areas of research include: Understanding Autoimmune Mechanisms: Investigating the specific mechanisms by which autoantibodies target VGCCs and other components of the neuromuscular junction. Development of New Therapies: Exploring new immunosuppressive drugs, monoclonal antibodies, and other targeted therapies to modulate the immune response more effectively. […] Lambert-Eaton Myasthenic Syndrome is a rare autoimmune disorder that affects the neuromuscular junction, leading to muscle weakness, fatigue, and autonomic dysfunction.

• #32 Lambert-Eaton Myasthenic Syndrome | Concise Medical Knowledge

  https://www.lecturio.com/concepts/lambert-eaton-myasthenic-syndrome/

  In LEMS, antibodies are formed against VGCCs, which mediate the release of ACh. […] Due to a block in the VGCCs, the normal calcium flux leading to the release of ACh vesicles is blocked. […] Due to little or no ACh release, muscle contraction is minimal or none, which presents as muscle weakness. […] Chronic postsynaptic ACh deficiency leads to increased folding of the postsynaptic membrane (greater surface area) and a greater density of available ACh receptors. […] On initial presynaptic stimulation, limited ACh is available in the synaptic cleft. […] With repetitive stimulation, more ACh is released and binds to the increased population of available ACh receptors. […] Paraneoplastic LEMS: Small cell lung carcinoma cells express surface VGCCs. […] Antibodies form against surface VGCCs, causing cross-reaction with presynaptic VGCCs. […] Nonparaneoplastic LEMS: the specific trigger for the development of VGCC antibodies is unknown.

• #33 Synaptic Compensatory Mechanism and its Impairment in Autoimmune Myasthenic Diseases

  https://www.immunologyresearchjournal.com/articles/synaptic-compensatory-mechanism-and-its-impairment-in-autoimmune-myasthenic-diseases.html

  The fast-mode of endocytosis (clathrin-independent synaptic vesicle recycling) requires a large influx of external Ca2+ to compensate postsynaptic dysfunction. This homeostatic Ca2+ is promoted by phospholipase C (PLC) activation via the activation of G-protein-coupled receptor, such as the presynaptic M1-type muscarinic acetylcholine receptor (mAChR), and also via the interaction of brain-derived neurotrophic factor (BDNF) with receptor tyrosine kinase (TrkB). […] The mAChRs (M1 and M5) expressed in thymocytes and lymphocytes contribute to the regulation of pro-inflammatory cytokine production related to adaptive immunity.

• #34

  https://link.springer.com/article/10.1007/s12035-014-8887-2

  Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca2+ channels involved with neurotransmitter release. […] The underlying cause of LEMS in slightly more than half of all patients is small cell lung cancer, and cancer therapy is the priority for these patients. In the remaining cases, the cause of LEMS is unknown, and these patients often rely on symptomatic treatment options, as there is no cure. […] Recent studies introduced a novel Ca2+ channel agonist (GV-58) as a potential therapeutic alternative for LEMS. Additionally, this work has shown that GV-58 and 3,4-DAP interact in a supra-additive manner to completely restore the magnitude of neurotransmitter release at the NMJs of a LEMS mouse model. […] In this review, we discuss synaptic mechanisms for reliability at the NMJ and how these mechanisms are disrupted in LEMS.

• #35 Lambert-Eaton myasthenic syndrome – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1052

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction. […] In both types, LEMS is characterized by the presence of circulating antibodies against voltage-gated calcium channels; these impair neuromuscular transmission by inhibiting inward calcium current and subsequently the release of acetylcholine into the synaptic cleft. […] Serum P/Q-type voltage-gated calcium-channel antibodies are usually present. Electrophysiologic studies usually demonstrate decremental responses to low-frequency repetitive nerve stimulation, and may also exhibit postactivation facilitation of 100%. […] Over 40% of patients with LEMS have underlying cancer, usually small cell lung cancer. Effective treatment of underlying cancer frequently improves symptoms. […] Effective symptomatic and long-term treatment options include agents that augment neuromuscular transmission and immunomodulators. However, many patients have long-term disability due to weakness.

• #36 Lambert-Eaton Myasthenic Syndrome Versus Myasthenia GravisShare to Facebookprint pageBookmark for latercommentcaret iconcaret iconmore actionsFollow us on facebookFollow us on instagramFollow us on facebookFollow us on linkedincaret icon

  https://myasthenia-gravis.com/clinical/lems-symptom-differences

  LEMS is a very rare autoimmune condition. About 3,000 people in the United States have it. […] In LEMS, the immune system attacks the neuromuscular junction. This is where the nerve cells in charge of movement (motor neurons) contact your muscles. Antibodies in your immune system attack calcium channels in this area. This reduces the release of the neurotransmitter acetylcholine. Your muscles then cannot get fully activated. This leads to muscle weakness. […] Treatment for LEMS depends on whether you also have SCLC. Treating the underlying cancer can help treat LEMS. Cancer treatment can include chemotherapy, radiation, or surgery. The best treatment option for you depends on many personal factors. […] Treatment for LEMS also includes medicine to relieve symptoms. These drugs increase the amount of acetylcholine at the neuromuscular junction. The most effective is Firdapse (amifampridine). Firdapse is not a common treatment for MG. Another option is Mestinon (pyridostigmine). This may treat LEMS, but is more effective for MG. […] Treatment for LEMS may include immune-modulating treatments. These can reduce the activity of your immune system. For example, your doctor may suggest an immunosuppressant, such as prednisone.

• #37 Lambert-Eaton myasthenic syndrome (LEMS) – catalystpharma.com

  https://catalystpharma.com/lems/

  A diagnosis of LEMS is generally made on the basis of clinical symptoms during a physical examination, the degree of muscle weakness, your reflexes, and the function of your nervous system. Typically, people get electrodiagnostic tests, in which the nerves are stimulated electrically and the nerve impulses in the muscles are measured. Blood tests to check on the function of your immune system are also common. […] Currently, amifampridine is the only evidence-based, FDA-approved treatment for adult patients with Lambert-Eaton Myasthenic Syndrome (LEMS). […] Amifampridine, improves muscle function by stimulating the release of more acetylcholine into the synaptic cleft and enhancing neuromuscular transmission.

• #38 Profile of aminopyridines for Lambert–Eaton myasthenic syndrome | ODRR

  https://www.dovepress.com/profile-of-aminopyridines-for-lambertndasheaton-myasthenic-syndrome-peer-reviewed-fulltext-article-ODRR

  3,4-diaminopyridine (3,4-DAP) is an effective, symptomatic treatment for Lambert-Eaton myasthenic syndrome (LEMS). […] LEMS is an autoimmune disease mediated by antibodies to P/Q-type voltage-gated calcium channels at the motor nerve terminal. […] Given that LEMS is a presynaptic disorder characterized by impaired quantal release of acetylcholine, symptomatic treatment has utilized drugs that increase neurotransmitter release at the neuromuscular junction. […] The related aminopyridine 3,4-diaminopyridine (3,4-DAP) has become the mainstay of symptomatic treatment for LEMS in Europe, with the phosphate salt preparation amifampridine recently receiving a license for treatment in LEMS. […] 3,4-DAP has been shown in animals to be more potent in improving neuromuscular transmission and less convulsant than 4-AP.

• #39 Lambert-Eaton myasthenic syndrome (LEMS) | EBSCO Research Starters

  https://www.ebsco.com/research-starters/health-and-medicine/lambert-eaton-myasthenic-syndrome-lems

  Lambert-Eaton myasthenic syndrome is an autoimmune disease caused by antibodies acting at the neuromuscular junction. […] These antibodies target the area of the nerve fiber responsible for releasing acetylcholine, a chemical needed to stimulate normal muscle contraction. […] The antibodies cause too little acetylcholine to be released, and muscle contractions are weakened. […] In patients who have cancer (about 60 percent of LEMS cases), antibodies are thought to be released in response to cancer-cell growth, affecting the muscles and as secondary reactions. […] Lambert-Eaton myasthenic syndrome is uncommon. […] Between 50 and 70 percent of cases of LEMS are associated with small-cell lung cancer, but only about 3 percent of people with small-cell lung cancer develop LEMS. […] When Lambert-Eaton myasthenic syndrome has been diagnosed with underlying cancer, successful treatment of the cancer usually results in an improvement of LEMS. […] Immunosuppression therapy with corticosteroids or gamma globulin has proven to provide short-term relief. […] Several drugs, including Amifampridine (Firdapse), Guanidine, and 3,4-diaminopyridine, increase the release of acetylcholine and have been shown to decrease symptoms significantly.

• #40 Lambert-Eaton Myasthenic syndrome: early diagnosis is key | DNND

  https://www.dovepress.com/lambert-eaton-myasthenic-syndrome-early-diagnosis-is-key-peer-reviewed-fulltext-article-DNND

  Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon disorder of neuromuscular transmission with distinctive pathophysiological, clinical, electrophysiological and laboratory features. […] Approximately 90% of LEMS patients present antibodies against presynaptic membrane P/Q-type voltage-gated calcium channels (VGCC). These antibodies are directly implicated in the pathophysiology of the disorder, provoke reduced acetylcholine (ACh) at the nerve terminal and consequently lead to muscle weakness. […] LEMS is characterized by the presence of antibodies against presynaptic P/Q-type voltage-gated calcium channels (VGCC) that cause a reduction in the level of acetylcholine (ACh) released from the nerve terminal and consequent muscle weakness. […] Given that LEMS is uncommon but frequently a paraneoplastic disorder associated with cancer in the initial stages, awareness and a high degree of suspicion are essential factors for an early diagnosis that can lead to the optimal management of these patients.

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