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• #1 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. […] 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. […] In 40% of patients with LEMS, cancer is present when the weakness begins or is found later. This is usually a small cell lung cancer (SCLC), although LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder.

• #1 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.

• #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 that may present as a paraneoplastic syndrome or a primary autoimmune disorder. The majority of cases are associated with small-cell lung cancer (SCLC). […] LEMS is categorized as either paraneoplastic or non-paraneoplastic, the latter being referred to as non-tumor LEMS (NT-LEMS). NT-LEMS is characterized by its absence of association with malignancies. Approximately 60% of LEMS patients have an underlying tumor, with the paraneoplastic form predominantly associated with SCLC. […] LEMS is also associated with other malignancies, such as non-SCLC, mixed lung carcinoma, prostate cancer, thymoma, and lymphoproliferative disorders. Research has shown that the diagnosis of LEMS can precede the diagnosis of SCLC by 5 to 6 years. Furthermore, a significant risk factor for LEMS is having a history of smoking. The genetic association with HLAB8DR3 haplotype is present in about 65% of young patients with NTLEMS.

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

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

  For many years, clinical observations suggested an autoimmune etiology for Lambert-Eaton myasthenic syndrome (LEMS). Such observations included the following: LEMS is frequently associated with known autoimmune diseases. […] More direct evidence has been accumulated supporting the autoimmune etiology of LEMS. […] Small cell lung cancer (SCLC) cells originate from neuroectoderm, share a number of antigens with peripheral nervous system tissue, and contain high concentrations of VGCCs. […] In patients with LEMS who have SCLC or other cancer, cancer cells presumably contain antigens that mimic VGCCs and induce production of VGCC antibodies. […] In patients who have LEMS without cancer, an antibody response to domain IV of the 1A subunit of P/Q-type VGCCs is more common than in patients who have LEMS with cancer.

• #1 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.

• #1 Understanding Lambert-Eaton Syndrome: A Rare Disorder – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/understanding-lambert-eaton-syndrome-a-rare-disorder/

  Lambert-Eaton syndrome (LEMS) is a rare disorder that occurs as a result of an immune system attack on the neuromuscular junction (a point where nerves send signals to your muscles). […] This condition is often referred to as Lambert-Eaton myasthenic syndrome due to the similarities of its symptoms to myasthenia gravis (a type of neuromuscular junction disorder). […] Researchers believe the immune system is the driving factor behind the onset of LEMS. Moreover, in 50% to 60% of the cases, this disease is also found to be highly associated with certain types of cancers, in particular small cell lung cancer (SCLC). […] It is theorized that when the immune system fights cancer cells, it also mistakenly attacks the nerve endings since cancer cells contain some of the same proteins that are also present in nerve endings. This mixup is coined “paraneoplastic syndrome,” which can manifest as LEMS. […] However, not all cancers cause LEMS. The trigger for LEMS without cancer is currently unknown; however, it is theorized genes linked to autoimmunity may be the cause.

• #1 Lambert-Eaton Myasthenic Syndrome (LEMS) Clinical Presentation: History, Physical Examination

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

  Cancer is present or subsequently discovered in 50-70% of patients with LEMS. […] Smoking and age at onset are major risk factors for cancer in patients with LEMS. […] Duration of symptoms is also a factor. If a tumor is not found within the first 2 years after symptom onset, cancer is unlikely. […] On the other hand, a long-term smoker with LEMS onset after age 50 years probably has underlying lung cancer.

• #1 Lambert-Eaton Myasthenic Syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6690495/

  Tumor association is reported in about 60% of patients with LEMS. Most patients have SCLC, a smoking-related lung carcinoma with neuroendocrine characteristics, but other malignancies have been described (nonsmall cell and mixed lung carcinomas, prostate carcinoma, thymoma, and lymphoproliferative disorders). […] The diagnosis of LEMS usually precedes the diagnosis of cancer by many months and even up to 2 years. […] The genetic association with HLA-B8-DR3 haplotype is linked to autoimmunity and is present in around 65% of patients with young onset of NT-LEMS. […] P/Q VGCC antibodies are present in 80% to 90% of patients with LEMS. P/Q-type VGCCs antibodies have been reported in up to 100% of patients with LEMS who have small cell lung cancer and in up to 90% of patients with LEMS who do not have underlying malignancy.

• #1 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. […] Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer (SCLC); it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body). […] LEMS is often associated with lung cancer (50-70%), specifically small-cell carcinoma, making LEMS a paraneoplastic syndrome. […] Of the people with small-cell lung cancer, 13% have LEMS. […] LEMS may also be associated with endocrine diseases, such as hypothyroidism (an underactive thyroid gland) or diabetes mellitus type 1. […] HLA-DR3-B8 (an HLA subtype), in particular, seems to predispose to LEMS.

• #1 Lambert-Eaton myasthenic syndrome | Lima Memorial Health System

  https://www.limamemorial.org/health-library/HIE%20Multimedia/1/000710

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder in which faulty communication between nerves and muscles leads to muscle weakness. […] LEMS is an autoimmune disorder. This means your immune system mistakenly targets healthy cells and tissues in the body. With LEMS, antibodies produced by the immune system attack nerve cells. This makes nerves cells unable to release enough of a chemical called acetylcholine. This chemical transmits impulses between nerves and muscles. The result is muscle weakness. […] LEMS may occur with cancers such as small cell lung cancer or autoimmune disorders such as vitiligo, which leads to a loss of skin pigment.

• #1 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

  Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune conditions. This means the immune system attacks your own healthy cells. […] 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. […] About 3 out of 5 people with LEMS also have small cell lung cancer (SCLC). When this is the case, it is believed the immune system mistakenly attacks nerve cells when trying to attack the cancer. […] The other 2 out of every 5 people with LEMS often do not have cancer. This type of LEMS usually develops when the person is around 35 years old. Personal or family history of autoimmune conditions increases the risk.

• #1 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. […] LEMS occurs either as a paraneoplastic disorder in association with an underlying cancer (CA-LEMS), or without cancer and as part of a more general autoimmune state (NCA-LEMS). […] Over 40% of patients with LEMS have underlying cancer, usually small cell lung cancer. […] 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. […] Risk factors include underlying small cell lung cancer or other malignancy, coexisting autoimmune disorder, cigarette smoking, and family history of autoimmune disease.

• #1 Lambert-Eaton Syndrome Signs, Symptoms, and Causes | Baptist Health

  https://www.baptisthealth.com/care-services/conditions-treatments/lamberteaton-syndrome

  LES is an autoimmune disease in which your bodys defenses against intrusive infection begin attacking some aspect of your internal chemistry instead. […] In the case of LES, antibodies damage the calcium channels associated with nerve endings in the muscles. […] There is a second important cause of LES. In about 60 percent of cases, a person with LES will have also developed small cell lung cancer. […] In fact, LES may be one of the side effects of your bodys ongoing battle with this disease. […] Individuals with LES and no cancer typically see LES emerge around 35 years of age. […] There may be a genetic factor in play with this latter version of LES.

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

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

  VGCC antibody levels do not correlate with disease severity among patients with LEMS. However, antibody levels do fall in individual patients if the disease improves after cancer therapy or immunosuppression. […] All patients with LEMS who have associated SCLC have a history of long-term smoking. Only half of patients with autoimmune LEMS are long-term smokers.

• #1 Lambert-Eaton myasthenic syndrome

  https://www.nhs.uk/conditions/lambert-eaton-myasthenic-syndrome/

  LEMS is caused by the body’s natural defences (the immune system) mistakenly attacking and damaging the nerves. […] It’s not known what triggers the immune system to attack the nerves. It’s often associated with lung cancer, but can occur in people without cancer.

• #1 OBM Neurobiology | Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

  https://www.lidsen.com/journals/neurobiology/neurobiology-05-01-086

  Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). […] Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. […] The etiology of our patients LEMS remains unclear. The presence of P/Q-type VGCC antibodies and lack of steroid response might argue for a paraneoplastic cause while the delayed onset of symptoms favors ICI-related LEMS. Further complicating the case, although her AchR antibodies were negative, she had shortness of breath and diplopia (atypical for LEMS), raising the possibility of concurrent ICI-related antibody negative MG which would also be treated with IVIg and corticosteroids.

• #1

  https://link.springer.com/article/10.1007/s00415-024-12206-6

  Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disorder leading to muscle weakness, autonomic dysregulation and hyporeflexia. […] Epidemiological studies estimate LEMS to be associated to carcinoma in up to 60% of cases. […] For paraneoplastic LEMS (pLEMS) small cell lung cancer (SCLC) is the leading tumour entity, however further tumours have been described to be associated with LEMS including Merkel cell carcinoma, neuroendocrine tumours, prostate cancer and lymphomas. […] Antibodies targeted against the presynaptic voltage-gated calcium channels (VGCC) are detected in about 90% of patients. […] Life expectancy of LEMS patients without neoplasia is comparable to the general population. […] Most LEMS patients reach maximum disease severity before or within the first year of diagnosis.

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

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

  All people with LEMS are tested for the presence of antibodies in their blood directed against calcium channels, and 85 to 90 percent of those diagnosed with LEMS do have measurable antibodies to calcium channels present. A small percentage of people who are diagnosed with LEMS do not have measurable antibodies to calcium channels. These individuals are referred to as sero-negative LEMS patients, and they have antibodies to other proteins that are important for ACh release from nerve endings. Along these lines, all people with LEMS likely have antibodies to other nerve ending proteins in addition to antibodies to calcium channels. Lastly, some people who test positive for calcium channel antibodies do not have clinical signs of LEMS. This may be because the levels of those antibodies are very low.

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

  https://thejcn.com/DOIx.php?id=10.3988/jcn.2012.8.4.305

  Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder that is most frequently associated with small-cell lung cancer (SCLC). The etiology of LEMS is the reduced exocytosis of acetylcholine from nerve endings by antibodies against voltage-gated calcium channels (VGCC-abs), increases in the titers of which are observed in more than 90% of patients with LEMS. […] It has been reported that titer of muscle anti-acetylcholine-receptor-binding antibodies (AChR-abs), which are more specific for myasthenia gravis (MG), is also increased in a small percentage of patients with LEMS (7%), although there are no detailed data or clinical information to corroborate this finding. […] One unanswered question in this case is the clinical significance of the transiently increased titer of AChR-abs at the first evaluation. […] Finally, we hypothesize that the transient 'nonpathologic epiphenomenon’ of raised AChR-abs titer in SCLC with LEMS is more appropriate than true MG with spontaneous remission in this case.

• #1

  https://journals.lww.com/nsan/fulltext/2024/04000/truncal_ataxia__an_overlooked_symptom_in_patients.1.aspx

  Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic myasthenic syndrome characterized by muscle weakness predominantly in the lower extremities, dysautonomia (dry eyes, dry mouth, and erectile dysfunction), and areflexia. Approximately, 50% of cases are paraneoplastic, with small cell lung cancer (SCLC) being the most common cancer association. […] Voltage-gated calcium channel (VGCC) antibodies of the P/Q type have been detected in up to 100% of LEMS patients with small-cell lung carcinoma and in up to 90% of LEMS patients without underlying malignancy. The autoantibodies bind to the presynaptic motor nerve terminal and block depolarization-induced calcium flow, reducing the release of acetylcholine at the neuromuscular junction and resulting in LEMS weakness. […] Although the pathogenic effects of P/Q-type VGCCs antibodies leading to disruption of neuromuscular transmission (and thus muscle weakness) and autonomic dysfunction are well established as major features of LEMS, the processes by which these paraneoplastic antibodies cause truncal ataxia are less well understood.

• #1 Lambert-Eaton myasthenic syndrome: Treatment and prognosis – UpToDate

  https://www.uptodate.com/contents/lambert-eaton-myasthenic-syndrome-treatment-and-prognosis

  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 of LEMS is particularly important because of its strong association with small cell lung cancer (SCLC). […] Although LEMS can occur at any point in the course of SCLC, it may serve as a marker for early disease and thus allow more effective treatment of this malignancy. […] The first priority in the management of LEMS is to evaluate for a primary underlying malignancy. […] Treatment of the underlying malignancy may be the only intervention necessary to produce improvement in neurologic symptoms.

• #1 Simulations Suggest that Muscle Disease Cause Is Complex, May Need Multiple Treatments – Mellon College of Science – Carnegie Mellon University

  https://www.cmu.edu/mcs/news-events/2023/1215_psc-degenerative-disease.html

  In Lambert-Eaton myasthenic syndrome (LEMS), patients’ immune systems attack a critical nerve cell protein, causing muscle weakness and degeneration. […] LEMS is caused by the immune systems own antibodies attacking the neuromuscular junction (NMJ) between nerve cells and the muscle cells they are meant to signal. […] In most patients with LEMS, their antibodies attack the calcium channel protein. […] One prevailing theory was that blocking calcium channel activity and the signal to the muscle cell caused LEMS. […] 10 to 15% of patients with LEMS don’t have measurable levels of anti-calcium-channel antibodies. […] The results supported researchers’ suspicions that individual patients’ LEMS symptoms arise from different combinations of factors, stemming from their particular mix of autoimmune antibodies. […] It reveals that LEMS is more complex than doctors would have liked.

• #2 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 that may present as a paraneoplastic syndrome or a primary autoimmune disorder. The majority of cases are associated with small-cell lung cancer (SCLC). […] LEMS is categorized as either paraneoplastic or non-paraneoplastic, the latter being referred to as non-tumor LEMS (NT-LEMS). NT-LEMS is characterized by its absence of association with malignancies. Approximately 60% of LEMS patients have an underlying tumor, with the paraneoplastic form predominantly associated with SCLC. […] LEMS is also associated with other malignancies, such as non-SCLC, mixed lung carcinoma, prostate cancer, thymoma, and lymphoproliferative disorders. Research has shown that the diagnosis of LEMS can precede the diagnosis of SCLC by 5 to 6 years. Furthermore, a significant risk factor for LEMS is having a history of smoking. The genetic association with HLAB8DR3 haplotype is present in about 65% of young patients with NTLEMS.

• #2 Myasthenia Gravis & Lambert-Eaton Myasthenic Syndrome – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/myasthenia-gravis-lambert-eaton-myasthenic-syndrome

  Lambert-Eaton myasthenic syndrome (LEMS) arises when IgG autoantibodies specifically attack the presynaptic P/Q-type voltage-gated calcium channels, resulting in a disruption in the transport of acetylcholine (ACh) vesicles to the membrane. This disruption causes a significant decrease in ACh within the synapse, culminating in muscle weakness. […] LEMS originates from IgG autoantibodies against presynaptic P/Q-type voltage-gated calcium channels, curtailing ACh release and causing muscle weakness. LEMS typically exhibits symmetric muscle weakness in the proximal lower extremities and, in some instances, is linked to small cell lung cancer.

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

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

  Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder. […] In this condition, your body’s own immune system attacks the contact point between motor nerves and muscles the so-called neuromuscular junction. […] About 60% of cases happen in people who have an underlying malignancy. The most common is small-cell lung cancer. […] While small-cell lung cancer is the most common malignancy associated with LEMS, other cancers have also been associated with the development of LEMS, including prostate cancer, thymoma and lymphoproliferative disorders. […] Scientists think there may be a genetic link to autoimmune diseases in general. Lambert-Eaton myasthenic syndrome is an autoimmune disease. […] Lambert-Eaton myasthenic syndrome is an autoimmune disorder. This means your body’s natural defenders (antibodies) attack your own healthy tissue. In LEMS, your antibodies attack where nerve cells meet muscle fibers (neuromuscular junction); more specifically, at calcium channels that are critical in signaling at this contact point. […] Scientists think the cause of LEMS in people who don’t have lung cancer is an immune response that simply goes awry. It remains unclear why this happens.

• #2 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. […] LEMS occurs either as a paraneoplastic disorder in association with an underlying cancer (CA-LEMS), or without cancer and as part of a more general autoimmune state (NCA-LEMS). […] Over 40% of patients with LEMS have underlying cancer, usually small cell lung cancer. […] 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. […] Risk factors include underlying small cell lung cancer or other malignancy, coexisting autoimmune disorder, cigarette smoking, and family history of autoimmune disease.

• #2 Paraneoplastic syndromes of the nervous system – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/paraneoplastic-syndromes/symptoms-causes/syc-20355687

  Lambert-Eaton myasthenic syndrome is caused by disrupted communication between nerves and muscles. Symptoms include muscle weakness in the pelvis and legs, and fatigue. It also may cause trouble swallowing and speaking, irregular eye movement, and double vision. Other symptoms may include dry mouth and erectile dysfunction. […] When it occurs as a paraneoplastic syndrome, Lambert-Eaton myasthenic syndrome is typically associated with lung cancer. […] Paraneoplastic syndromes of the nervous system are not caused by cancer cells directly or by the cancer spreading, known as metastasis. They’re also not caused by other complications, such as infections or treatment side effects. Instead, the syndromes occur alongside the cancer as a result of the activation of your immune system. […] Researchers believe that paraneoplastic syndromes of the nervous system are caused by cancer-fighting abilities of the immune system. In particular, antibodies and certain white blood cells, known as T cells, are thought to be involved. Instead of attacking only the cancer cells, these immune system agents also attack the healthy cells of the nervous system.

• #2 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.

• #2 Lambert-Eaton Myasthenic Syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6690495/

  Tumor association is reported in about 60% of patients with LEMS. Most patients have SCLC, a smoking-related lung carcinoma with neuroendocrine characteristics, but other malignancies have been described (nonsmall cell and mixed lung carcinomas, prostate carcinoma, thymoma, and lymphoproliferative disorders). […] The diagnosis of LEMS usually precedes the diagnosis of cancer by many months and even up to 2 years. […] The genetic association with HLA-B8-DR3 haplotype is linked to autoimmunity and is present in around 65% of patients with young onset of NT-LEMS. […] P/Q VGCC antibodies are present in 80% to 90% of patients with LEMS. P/Q-type VGCCs antibodies have been reported in up to 100% of patients with LEMS who have small cell lung cancer and in up to 90% of patients with LEMS who do not have underlying malignancy.

• #2 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 a rare autoimmune disorder that affects the neuromuscular junction, leading to progressive muscle weakness and decreased reflexes. […] LEMS is primarily linked to small-cell lung cancer (SCLC) and can also be associated with other malignancies such as non-Hodgkin lymphoma and thymoma. […] The condition arises when antibodies disrupt the release of acetylcholine, a neurotransmitter essential for muscle contraction. […] 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. […] 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.

• #2 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

  LEMS is an autoimmune disorder. Autoimmune disorders occur when the body’s natural defenses against „foreign” or invasive organisms (for example, antibodies) begin to attack healthy tissue for unknown reasons. LEMS occurs because the antibodies damage the voltage-gated calcium channels (VGCCs) in the motor nerve membrane at the junction of the muscle nerve. These channels normally carry calcium to the nerves, releasing a chemical called acetylcholine. Acetylcholine helps connect nerve cells and muscles and is groups of chemicals known as neurotransmitters that help transmit nerve impulses. Antibodies attack the VGCC, resulting in decreased acetylcholine secretion. […] 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. Smoking is one of the most important risk factors for SCLC, and in patients with LEMS associated with cancer, a long history of smoking is also an important factor.

• #2

  https://journals.lww.com/nsan/fulltext/2024/04000/truncal_ataxia__an_overlooked_symptom_in_patients.1.aspx

  Several other neurological symptoms may be associated with VGCC autoantibodies, including ataxia. The high expression of VGCC-P/Q in the Purkinje and molecular layers of the cerebellum and the detection of VGCC antibodies in patients with autoimmune ataxia draw attention to the association between LEMS and ataxia. […] Several neurologic paraneoplastic disorders are thought to be caused by an autoimmune response to an antigen or antigens expressed in common by tumor cells and neurons. Among paraneoplastic syndromes, this is true of Lambert-Eaton myasthenic syndrome (LEMS), in which autoantibodies downregulate P/Q-type VGCCs in the presynaptic nerve terminal. […] The role of VGCC antibodies in LEMS immunopathogenesis is known, but their role in cerebellar degeneration is unclear. Determining the effect of VGCC antibodies on the pathogenesis of cerebellar degeneration may help develop more effective treatment strategies. […] We found that ataxia was the first complaint in most of the LEMS patients we followed in our series, which raises the question of whether truncal ataxia is an early finding in LEMS.

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

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

  VGCC antibody levels do not correlate with disease severity among patients with LEMS. However, antibody levels do fall in individual patients if the disease improves after cancer therapy or immunosuppression. […] All patients with LEMS who have associated SCLC have a history of long-term smoking. Only half of patients with autoimmune LEMS are long-term smokers.

• #2 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. […] One of the major risk factors for SCLC is smoking, and in patients who have LEMS associated with cancer, a long history of smoking is also a major contributing factor. […] 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.

• #2 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. […] In about 50 to 60 percent of cases, LEMS is associated with an underlying disease, particularly small cell lung cancer. It is thought that the body’s attempt to fight the cancer inadvertently causes it to attack nerve endings because cancer cells share some of the same proteins as nerve endings. […] In the other 40 to 50 percent of cases, the cause is unknown. […] 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.

• #2 Neuro-Ophthalmic Manifestations of Lambert-Eaton Myasthenic Syndrome – EyeWiki

  https://eyewiki.org/Neuro-Ophthalmic_Manifestations_of_Lambert-Eaton_Myasthenic_Syndrome

  Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder characterized by presynaptic autoantibodies against voltage-gated calcium channels (VGCCs) and limb weakness that improves after repetitive voluntary muscle movement. […] LEMS is an acquired autoimmune disease secondary to a paraneoplastic syndrome or associated with an underlying autoimmune disease risk. […] Around 60% of LEMS have an associated underlying tumor, and small cell lung cancer (SCLC) is the most common malignancy seen in LEMS. […] A proposed mechanism for autoantibody development is the cross-reactivity of antibodies against VGCCs expressed in high concentrations on SCLC tumor cells. […] VGCC antibodies may develop in the absence of cancer. This is known as non-tumor LEMS (NT-LEMS). […] The incidence of SCLC is less common in seronegative (12%) vs. seropositive (60-70%) patients.

• #2 Lambert-Eaton myasthenic syndrome | Lima Memorial Health System

  https://www.limamemorial.org/health-library/HIE%20Multimedia/1/000710

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder in which faulty communication between nerves and muscles leads to muscle weakness. […] LEMS is an autoimmune disorder. This means your immune system mistakenly targets healthy cells and tissues in the body. With LEMS, antibodies produced by the immune system attack nerve cells. This makes nerves cells unable to release enough of a chemical called acetylcholine. This chemical transmits impulses between nerves and muscles. The result is muscle weakness. […] LEMS may occur with cancers such as small cell lung cancer or autoimmune disorders such as vitiligo, which leads to a loss of skin pigment.

• #2 Lambert-Eaton Disease: Symptoms, Causes and Treatment

  https://lonestarneurology.net/blog/lambert-eaton-disease/

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder affecting signals transmitted from the nerves to the muscles. The syndrome is caused by a mutation in the genes of the proteins responsible for muscle contractions. The syndrome occurs in the presence of malignant tumors (stomach, bronchi, ovaries, prostate, colon (colorectal cancer)) and autoimmune processes in the body (autoimmune thyroiditis, rheumatoid arthritis, Sjgrens disease, systemic lupus erythematosus, etc.). The pathogenetic substrate of the syndrome is autoimmune mechanisms. […] The main factors in developing LEMS may be malignant neoplasia or an autoimmune process. In autoimmune diseases, the immune system mistakes your body for a foreign object. Your immune system produces antibodies that attack your body.

• #2 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

  Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune conditions. This means the immune system attacks your own healthy cells. […] 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. […] About 3 out of 5 people with LEMS also have small cell lung cancer (SCLC). When this is the case, it is believed the immune system mistakenly attacks nerve cells when trying to attack the cancer. […] The other 2 out of every 5 people with LEMS often do not have cancer. This type of LEMS usually develops when the person is around 35 years old. Personal or family history of autoimmune conditions increases the risk.

• #2 OBM Neurobiology | Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

  https://www.lidsen.com/journals/neurobiology/neurobiology-05-01-086

  In this setting, determining the LEMS etiology (i.e. paraneoplastic vs. irAE) is critical to enact the right treatment plan. […] Over 60% of cases occur as a paraneoplastic disorder that is most frequently associated with SCLC. […] The mainstay of therapy for classic LEMS is treatment of the underlying malignancy and 3,4 DAP, which augments acetylcholine release at the neuromuscular junction. […] There are limited reports of ICI-related LEMS and no consensus on optimal treatment. […] In cases of LEMS in ICI SCLC patients, the etiology matters because LEMS treatment may have effects on the efficacy and selection of ongoing cancer treatment for two reasons. […] We predict that as other cases are described, it may remain difficult to determine the etiology of LEMS in SCLC patients treated with ICI therapy.

• #2

  https://link.springer.com/article/10.1007/s00415-024-12206-6

  Functional impairment typically improves within 1 year after diagnosis for both autoimmune LEMS (aiLEMS) and pLEMS patients, though pLEMS patients report higher levels of functional impairment throughout the disease course. […] In LEMS patients, effects of age on domains such as physical functioning and emotional well-being were higher than in the genP. […] However, it is likely that some of the tumours reported, especially with unclear temporal connection, had no causative connection to LEMS and led to overestimation of pLEMS in our cohort.

• #2 Simulations Suggest that Muscle Disease Cause Is Complex, May Need Multiple Treatments – Mellon College of Science – Carnegie Mellon University

  https://www.cmu.edu/mcs/news-events/2023/1215_psc-degenerative-disease.html

  In Lambert-Eaton myasthenic syndrome (LEMS), patients’ immune systems attack a critical nerve cell protein, causing muscle weakness and degeneration. […] LEMS is caused by the immune systems own antibodies attacking the neuromuscular junction (NMJ) between nerve cells and the muscle cells they are meant to signal. […] In most patients with LEMS, their antibodies attack the calcium channel protein. […] One prevailing theory was that blocking calcium channel activity and the signal to the muscle cell caused LEMS. […] 10 to 15% of patients with LEMS don’t have measurable levels of anti-calcium-channel antibodies. […] The results supported researchers’ suspicions that individual patients’ LEMS symptoms arise from different combinations of factors, stemming from their particular mix of autoimmune antibodies. […] It reveals that LEMS is more complex than doctors would have liked.

• #2 Lambert-Eaton myasthenic syndrome: Treatment and prognosis – UpToDate

  https://www.uptodate.com/contents/lambert-eaton-myasthenic-syndrome-treatment-and-prognosis

  Small cell lung cancer (SCLC) is the most common associated tumor in patients with LEMS. […] Population studies have consistently shown that approximately one-half of LEMS cases are associated with a malignancy, which is usually SCLC. […] The other malignancies most convincingly associated with LEMS are lymphoproliferative disorders, including Hodgkin lymphoma.

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

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

  All people with LEMS are tested for the presence of antibodies in their blood directed against calcium channels, and 85 to 90 percent of those diagnosed with LEMS do have measurable antibodies to calcium channels present. A small percentage of people who are diagnosed with LEMS do not have measurable antibodies to calcium channels. These individuals are referred to as sero-negative LEMS patients, and they have antibodies to other proteins that are important for ACh release from nerve endings. Along these lines, all people with LEMS likely have antibodies to other nerve ending proteins in addition to antibodies to calcium channels. Lastly, some people who test positive for calcium channel antibodies do not have clinical signs of LEMS. This may be because the levels of those antibodies are very low.

• #3 Lambert-Eaton Myasthenic Syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6690495/

  Tumor association is reported in about 60% of patients with LEMS. Most patients have SCLC, a smoking-related lung carcinoma with neuroendocrine characteristics, but other malignancies have been described (nonsmall cell and mixed lung carcinomas, prostate carcinoma, thymoma, and lymphoproliferative disorders). […] The diagnosis of LEMS usually precedes the diagnosis of cancer by many months and even up to 2 years. […] The genetic association with HLA-B8-DR3 haplotype is linked to autoimmunity and is present in around 65% of patients with young onset of NT-LEMS. […] P/Q VGCC antibodies are present in 80% to 90% of patients with LEMS. P/Q-type VGCCs antibodies have been reported in up to 100% of patients with LEMS who have small cell lung cancer and in up to 90% of patients with LEMS who do not have underlying malignancy.

• #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. […] Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer (SCLC); it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body). […] LEMS is often associated with lung cancer (50-70%), specifically small-cell carcinoma, making LEMS a paraneoplastic syndrome. […] Of the people with small-cell lung cancer, 13% have LEMS. […] LEMS may also be associated with endocrine diseases, such as hypothyroidism (an underactive thyroid gland) or diabetes mellitus type 1. […] HLA-DR3-B8 (an HLA subtype), in particular, seems to predispose to LEMS.

• #3 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 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 most common associated malignancy is small cell lung carcinoma (SCLC), although nonsmall cell lung carcinoma, prostate carcinoma, and lymphoproliferative disorders have been described to be less commonly associated with LEMS. […] There is a strong association with cancer, with more than half of LEMS cases being paraneoplastic in etiology, which renders serial cancer screening of critical importance.

• #3 Lambert-Eaton Myasthenic Syndrome (LEMS) Clinical Presentation: History, Physical Examination

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

  Cancer is present or subsequently discovered in 50-70% of patients with LEMS. […] Smoking and age at onset are major risk factors for cancer in patients with LEMS. […] Duration of symptoms is also a factor. If a tumor is not found within the first 2 years after symptom onset, cancer is unlikely. […] On the other hand, a long-term smoker with LEMS onset after age 50 years probably has underlying lung cancer.

• #3 Lambert-Eaton myasthenic syndrome | MedLink Neurology

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

  The HLA-B8 histocompatibility antigen is overrepresented among patients with nonparaneoplastic Lambert-Eaton myasthenic syndrome but not in patients with small cell lung cancer and Lambert-Eaton myasthenic syndrome. […] Voltage-gated calcium channels may not be the sole targets of autoimmunity in Lambert-Eaton syndrome. […] Antibodies against the SOX1 transcription factor are present in nearly two thirds of patients with Lambert-Eaton myasthenic syndrome associated with small cell lung cancer but are only identified in 5% of patients with nonparaneoplastic Lambert-Eaton myasthenic syndrome.

• #3 Lambert-Eaton Disease: Symptoms, Causes and Treatment

  https://lonestarneurology.net/blog/lambert-eaton-disease/

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder affecting signals transmitted from the nerves to the muscles. The syndrome is caused by a mutation in the genes of the proteins responsible for muscle contractions. The syndrome occurs in the presence of malignant tumors (stomach, bronchi, ovaries, prostate, colon (colorectal cancer)) and autoimmune processes in the body (autoimmune thyroiditis, rheumatoid arthritis, Sjgrens disease, systemic lupus erythematosus, etc.). The pathogenetic substrate of the syndrome is autoimmune mechanisms. […] The main factors in developing LEMS may be malignant neoplasia or an autoimmune process. In autoimmune diseases, the immune system mistakes your body for a foreign object. Your immune system produces antibodies that attack your body.

• #3 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. […] In about 50 to 60 percent of cases, LEMS is associated with an underlying disease, particularly small cell lung cancer. It is thought that the body’s attempt to fight the cancer inadvertently causes it to attack nerve endings because cancer cells share some of the same proteins as nerve endings. […] In the other 40 to 50 percent of cases, the cause is unknown. […] 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.

• #4 Lambert-Eaton Myasthenic Syndrome

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6690495/

  Tumor association is reported in about 60% of patients with LEMS. Most patients have SCLC, a smoking-related lung carcinoma with neuroendocrine characteristics, but other malignancies have been described (nonsmall cell and mixed lung carcinomas, prostate carcinoma, thymoma, and lymphoproliferative disorders). […] The diagnosis of LEMS usually precedes the diagnosis of cancer by many months and even up to 2 years. […] The genetic association with HLA-B8-DR3 haplotype is linked to autoimmunity and is present in around 65% of patients with young onset of NT-LEMS. […] P/Q VGCC antibodies are present in 80% to 90% of patients with LEMS. P/Q-type VGCCs antibodies have been reported in up to 100% of patients with LEMS who have small cell lung cancer and in up to 90% of patients with LEMS who do not have underlying malignancy.

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