Case Of Lambert-Eaton Myasthenic Syndrome Research Articles

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

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). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). 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. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

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). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). 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. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

Adenocarcinoma of Lung Presenting as Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic neuromuscular junction disorder. LEMS presents with muscular weakness and fatigability, mainly involving the proximal lower limbs. There are 2 types of LEMS depending on the etiology: paraneoplastic and idiopathic. The paraneoplastic form, which constitutes more than a half of the cases, is mostly associated with intrathoracic neoplasms. Most cases are seen in patients with small cell lung cancer; other subtypes of lung cancer are extremely rare. In this article, we report a case of LEMS as a rare association with adenocarcinoma of the lung.

CLINICAL CASE OF LAMBERT EATON MYASTHENIC SYNDROME ON THE BACKGROUND OF ASYMPTOMATIC SMALL CELL LUNG CARCINOMA

This paper presents a case of Lambert-Eaton myasthenic syndrome (LEMS) of a man 54 years old. Manifestation of LEMS at 8 months ahead of identifying asymptomatic developing central lung cancer. Combined influence on the neuromuscular autoimmune and neoplastic processes led to complete remission of the LEMS and the absence progression of cancer within the next 3 years of observation. The paper provides a detailed analysis of the electrophysiological characteristics of disorders of neuromuscular transmission, allowing differentiating myasthenia gravis from the LEMS; compared the sensitivity of various immunological and oncologic markers in the early diagnosis of lung tumor; immunohistochemical studies disclosed the possibility to clarify the histological types of lung cancer. Discussed etiologic relationship lung carcinoma and LEMS

Child Neurology: Diagnosis of Lambert-Eaton myasthenic syndrome in children

To report a case of Lambert-Eaton myasthenic syndrome (LEMS) in a child and review the existing literature of LEMS in children. We report a pediatric case of LEMS with the classic clinical triad of proximal weakness, autonomic dysfunction, and areflexia; the characteristic increment in compound motor action potential on high-frequency repetitive nerve stimulation; and positive serum P/Q-type voltage-gated calcium channel antibodies. Only 11 pediatric cases of LEMS have been reported in the literature. The patient's presentation with LEMS led to the diagnosis of occult neuroblastoma. Based on review of the existing pediatric literature, no consistent clinical or electrodiagnostic criteria exist to diagnose LEMS in children. There exists a need for consistent clinical criteria and electrodiagnostic testing for prompt diagnosis of LEMS in children. Prompt identification of LEMS will alert the physician to search for malignancy or another immune-mediated process.

Pseudomyopathic Changes in Needle Electromyography in Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of the neuromuscular junction in association with cancer and subsequently in cases in which no neoplasm has been detected (O'Neill et al., 1988). The diagnosis of LEMS is based on the combination of fluctuating muscle weakness, diminished or absent reflexes, and a more than 60% increment of compound muscle action potential (CMAP) amplitude after brief exercise or 50 Hz stimulation for 1 s in a repetitive nerve stimulation (RNS) test (Oh et al., 2005). On the other hand, needle electromyography (EMG) findings related to LEMS have not been well described. Here, we report a case of LEMS, which showed apparent myopathic changes in needle EMG findings. Furthermore, we retrospectively examined the needle EMG findings in 8 patients with LEMS. In six of the 8 patients, the EMG findings showed myopathy-like findings. Although the findings of needle EMG indicated myopathic changes at a glance, the motor unit potential (MUP) returned to normal after a sustained strong muscle contraction. We propose the name “pseudomyopathic changes” for this phenomenon.

A Case of Lambert-Eaton Myasthenic Syndrome with Small-Cell Lung Cancer and Transient Increase in Anti-Acetylcholine-Receptor-Binding Antibody Titer

BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a presynaptic neuromuscular junction disorder that is most frequently associated with small-cell lung cancer (SCLC). The titers of antibodies against voltage-gated calcium channels are frequently increased in LEMS, but only rarely is titer of anti-acetylcholine-receptor-binding antibodies (AChR-abs) increased.Case ReportA 57-year-old male was admitted to our hospital due to dry mouth and eyes and progressive proximal limb weakness of 2 months duration. The results of a repetitive nerve stimulation test disclosed all criteria for the electrophysiological LEMS pattern, and the patient's AChR-abs titer was 0.587 nmol/L. At a follow-up performed 5 years after successful treatment of SCLC and LEMS, his AChR-abs titer had decreased to 0.001 nmol/L.ConclusionsWe suggest that this was a case of transient pseudopositivity of AChR-abs in SCLC with LEMS.

Syndrome myasthénique de Lambert-Eaton associé à un carcinome épidermoïde de la corde vocale

Introduction Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune channelopathy in which patients produce autoantibodies directed against voltage-gated calcium channels. LEMS is paraneoplastic in 50% of patients, most frequently associated with small cell lung carcinoma. We describe a case of paraneoplastic LEMS associated with a vocal cord carcinoma. Observation A 64-year-old man developed in five months muscle weakness affecting gait. Clinical examination showed proximal muscular deficiency, areflexia and dysphonia. Electrophysiologic study showed potentiation greater than 500% after post exercise facilitation and 76 percent increment response at high-rate repetitive nerve stimulation (20 Hz). Diagnosis of LEMS was confirmed by electrophysiologic study and anti-voltage gated calcium channel antibodies (90 pM, positive value greater or equal to 70 pM). Left vocal cord lesion histology showed epidermoid carcinoma. A combination of vocal cord tumor removal by endoscopy and treatment by pyridostigmine, 3-4 diaminopyridine and intravenous human immunoglobulin improved neurological symptoms. Conclusion Paraneoplastic syndromes in association with cancers of the larynx and hypopharynx are unusual. Only two cases are reported with LEMS associated with larynx carcinoma. We describe an unusual case of LEMS associated with a left vocal cord carcinoma.

Intravenous Immunoglobulin Therapy for Neuromuscular Disorders

Treatment of specific immune-mediated neuromuscular disorders involves consideration of many factors including severity of illness, concurrent medical problems, supportive therapies, and immune-modulating therapies. Many immune-modulating therapies are available, including steroids, an increasing number of immunosuppressive drugs, plasmapheresis, and intravenous immunoglobulin (IVIG). Deciding on which immune-modulating therapy involves selecting from those with proven efficacy for a specific disorder and global considerations of which therapies are most appropriate for an individual patient's circumstances. IVIG has become a commonly used therapy as it is well tolerated, easily administered, and is often efficacious with a relatively rapid action. IVIG has become a first-line therapy for several immune-mediated demyelinating polyneuropathies and may play a role in treating exacerbations of myasthenia gravis and selected chronic treatment-refractory cases of Lambert-Eaton myasthenic syndrome, dermatomyositis, and polymyositis.

A Case of Lambert-Eaton Myasthenic Syndrome with Positive VGCC Antibodies Diagnosed in Small Cell Lung Cancer

Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neurological syndrome, is caused by defects in the secretion of acetylcholine from the presynaptic membrane, and is associated with the destruction of voltage gated calcium channels (VGCC) in the neuromuscular junction. LEMS can be confirmed by repetitive nerve stimulation and by the clinical symptoms, which are characterized by proximal muscle weakness in the lower extremities, decreased deep tendon reflexes and autonomic dysfunctions. In about 60% of patients with this disorder, underlying cancer-small cell lung cancer may be detected. Clinical symptoms may precede the diagnosis of malignancy, with the early diagnosis and treatment of the underlying malignancy being possible through the diagnosis of LEMS. A case of LEMS, with positive VGCC antibodies, in a 48-year-old man, which improved after chemotherapy of the underlying small cell lung cancer, is reported. (Tuberc Respir Dis 2005; 59: 427-431)

Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases

To compare the clinical features of patients with the Lambert-Eaton myasthenic syndrome (LEMS) associated with carcinoma, with patients having LEMS but no cancer, reports on LEMS patients were analyzed systematically. Cancer was detected (CD group) in 62% of the 227 included cases. This CD group showed a male predominance (70%). No sex difference was found in patients in whom no cancer was detected (NCD group). Median age at onset of LEMS in the CD group was higher than in the NCD group (58 and 49.5 years, P<0.01). Median interval between onset of symptoms and diagnosis of LEMS was longest in NCD cases ( P<0.001). CD patients had additional immunological disorders less frequently than NCD cases (6 and 27%, P<0.001). Symptoms distinguishing the CD group from the NCD group were weight loss ( P<0.001) and need for prolonged artificial ventilation after anaesthesia ( P<0.05). This analysis shows significant differences between CD and NCD cases of LEMS. The male predominance and higher age at onset in patients with a tumor probably reflects the characteristics of patients with small cell lung cancer. The high frequency of additional immunological disorders in patients without malignancy, together with the younger age at onset suggests a similar etiology as other non-paraneoplastic autoimmune diseases.

Apheresis Treatment in Lambert‐Eaton Myasthenic Syndrome

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies decrease the presynaptic release of acetylcholine at the neuromuscular junction and autonomic system. Recent results suggest that the antibodies to P/Q-type calcium channels are the principal pathogenic factors in LEMS. Here, we present our experience with cases of LEMS who are noncarcinomatous. We studied the efficacy of plasmapheresis, analyzing the clinical score, electrophysiological finding, and the titer of anti-P/Q-type voltage-gated calcium channel (P/Q-VGCC) antibody. The first case, a 72-year-old female presenting with leg weakness, was treated by plasma exchange (PE). However, clinical improvement was transient; intravenous immunoglobulin (IVIg) therapy was followed by additional PE. She had a clinical and electromyologic improvement, and her P/Q-VGCC antibody titers decreased. Her clinical status and CMAP amplitude correlated closely with the anti-P/Q-VGCC antibody titers. The second case, a 73-year-old male presenting with leg weakness, was treated by PE and double-filtration plasmapheresis. The P/Q-VGCC antibody titres decreased immediately after these aphereses, but recovered to the pretreatment levels 1 week after them. After the immunosuppressive drugs prednisolone and azathioprine were started, his clinical symptoms improved. His antibody titers decreased gradually after immunosuppressive therapy. It is speculated that no sufficient efficacious improvement could be obtained by apheresis alone because of a high rate of P/Q-VGCC antibody production. Considering our experiences and other literature, we discuss the indication of apheresis treatment of LEMS.

A Case of Lambert-Eaton Myasthenic Syndrome Improved after Surgical Resection for Diagnosis of Small Cell carcinoma of the Lung

Lambert Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome caused by defects in the secretion of acetylcholine from the presynaptic membrane of nerve terminals and is strongly associated with small cell lung carcinoma. The pathogenesis of LEMS is the destruction of voltage gated calcium channels by an autoimmune process resulting in clinical manifestations consisting of lower extremity weakness. decreased deep tendon reflexes and autonomic dysfunctions. The diagnosis can be confirmed by the characteristic clinical features and repetitive nerve stimulation. The neurological symptoms and signs of LEMS may manifest themselves months before the clinical manifestation of the underlying malignancy. Therefore early diagnosis and treatment of the primary malignancy may become possible through the diagnosis of this rare paraneoplastic syndrome. We report a case of a patient diagnosed with LEMS who upon further evaluation for an underlying malignancy was found to have a 0.2 cm sized nodular and infiltrative mass lesion at the bifurcation of the left apicoposterior segmental and anterior segmental bronchi by bronchoscopy. Although repeated bronchoscopic biopsies of the lesion was not able to disclose malignancy, under strong clinical suspicion left upper lobectomy was performed and subsequently the diagnosis of small cell carcinoma of the lung was confirmed. Muscle weakness began to improve starting from a week after the surgery, then reached a plateau 2 weeks later. Muscle weakness improved further after the trial of anticancer chemotherapy.

Lambert‐Eaton myasthenic syndrome presenting with severe respiratory failure

Two cases of Lambert-Eaton myasthenic syndrome (LEMS) who presented with primary respiratory failure are reported. In each case, although not initially suspected clinically, the electrophysiological findings, which included reduced compound muscle action potential amplitudes, decrement to 3-Hz stimulation, and potentiation after 40-Hz stimulation, led to the diagnosis in the critical care unit. Electrophysiological studies of the respiratory system, including repetitive nerve stimulation of the phrenic nerve, were extremely valuable in management. As shown by these cases, the severe respiratory failure in LEMS is reversible with treatment. Thus, LEMS should be considered in cases of unexplained respiratory failure, other clinical features of the disorder sought, and the electrophysiological hallmarks looked for, including studies of the respiratory system. © 1996 John Wiley & Sons, Inc.

Syndrome de Lambert-Eaton et cancer à petites cellules. Considérations étiopathogéniques à propos de deux observations

The authors report two cases of Lambert-Eaton myasthenic syndrome associated with small cell lung carcinoma. Following the observations, the clinical diagnosis of this syndrome is considered. We discuss the autoimmune pathogenesis and the relation between paraneoplastic syndrome and small cell cancer. This syndrome is caused by autoantibodies that block the voltage-dependent calcium channels at motor nerve terminals. Small cell carcinoma cells appear to express calcium channels, suggesting that autoantibody production may be triggered by tumor calcium channels determinants. The autoimmune paraneoplastic syndrome theory refers to cross-antigenicity.

Electrophysiological data in 23 cases of lambert-eaton myasthenic syndrome: B.Bady, G. Chauplannaz et C.Vial. EMG department, Hopital Neurologique, 59 Bd Pinel 69394 Lyon Cedex 03 France

Electrophysiological data in 23 cases of lambert-eaton myasthenic syndrome: B.Bady, G. Chauplannaz et C.Vial. EMG department, Hopital Neurologique, 59 Bd Pinel 69394 Lyon Cedex 03 France

Type 2 fiber predominance in lambert–eaton myasthenic syndrome

Serial muscle biopsies in a noncarcinomatous case of Lambert-Eaton myasthenic syndrome (LEMS) have shown progressive atrophy and loss of type 1 fibers, resulting in overwhelming type 2 predominance. A similar abnormality was found in a single biopsy from a second case of LEMS without associated carcinoma. Review of the literature suggests that type 2 fiber predominance has been observed in at least one other biopsied case. Interference with transmitter release caused by anti-voltage-gated calcium channel antibodies may deprive type 1 muscle fibers of the low frequency discharge necessary to maintain their metabolic properties.

A case of Lambert-Eaton myasthenic syndrome accompanied by a small cell carcinoma of the lung.

A 57-year-old man presented with muscle stiffness and weakness accompanied by small cell carcinoma of the lung. The electromyogram showed the characteristic pattern for a Lambert-Eaton myasthenic syndrome (LEMS). The tumor of the lung was reduced in size by one-half with chemotherapy, but the muscle weakness improved only a little.