Postexercise reflex facilitation in Lambert-Eaton myasthenic syndrome.

A 62-year-old woman had 6 months of proximal weakness, fatigue and occasional diplopia, symptoms normally suggesting myasthenia gravis or inflammatory myopathy. Postexercise reflex facilitation is a bedside clinical sign that points to a diagnosis of the rarer alternative, Lambert-Eaton myasthenic syndrome (LEMS). We confirmed this diagnosis using electrodiagnostic short exercise testing and serum assay for voltage-gated calcium channel antibodies. Further investigation identified a small cell neuroendocrine carcinoma of the gallbladder, not previously associated with LEMS. Postexercise reflex facilitation is an important bedside clinical finding that helps clinicians to distinguish LEMS from its mimics.

Unusual paraneoplastic syndromes in pancreatic cancer: a case report of Lambert-Eaton myasthenic syndrome (LEMS) associated with intraductal papillary mucinous cancer of the pancreas.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction. It can occur as a paraneoplastic disorder associated with various types of carcinomas, usually small cell lung cancer or as an autoimmune disease. LEMS can be misdiagnosed as myasthenia gravis or as an oncological sequela, causing delays in diagnosis. We present a rare case of a male adult with confirmed LEMS occurring with pancreatic carcinoma. Case Description: A 66-year-old man presented with a newly diagnosed pancreatic tumor. He had been experiencing weakness and fatigue in his lower extremities since the summer of 2020. Over time, the weakness progressed to include his proximal upper extremity muscles. Dysphonia, dysarthria, decreased appetite and significant weight loss were also observed. A computed tomography (CT) scan revealed a 3 cm locally resectable cystic tumor in the pancreatic head. Blood tests showed elevated carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels. A Whipple procedure was performed, which revealed a poorly differentiated pancreatic adenocarcinoma inside an intraductal pancreatic mucinous neoplasm. Postoperatively, the patient was admitted to the intensive care unit (ICU) because he had no spontaneous breathing and manifested areflexia signs. A train of four (TOF) monitoring of peripheral nerve stimulation was performed and pyridostigmine therapy was initiated, leading to an improvement in symptoms allowing the extubation and transfer to the peripheral ward. Further diagnostic tests revealed a LEMS and an intravenous therapy with cumulative 100 g immunoglobulin (Ig) G was initiated. Upon discharge, 10 days after starting LEMS treatment, the patient showed subjective and objective improvement in strength. Conclusions: Paraneoplastic syndromes are more common than expected, but rare in pancreatic adenocarcinoma. They can appear before abdominal symptoms, facilitating early diagnosis. Successful treatment of cancer may eliminate paraneoplastic symptoms. LEMS may reveal pancreatic cancer. Early recognition of paraneoplastic syndromes is important for pancreatic cancer management. Further investigation is needed to evaluate the diagnostic approach for LEMS in all patients with pancreatic cancer.

Dilated fixed pupils and respiratory failure: a rare clinical course of Lambert-Eaton myasthenic syndrome.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder and the clinical triad consists of proximal muscle weakness, autonomic symptoms and reduced tendon reflexes. Sluggish pupillary reflexes are common but dilated fixed pupils are rare. Case presentation: We report a patient with a rare clinical course of LEMS. The patient was hospitalised due to progressive dyspnoea. She was ambulant and independent of oxygen at hospitalisation. The following day she suffered an in-hospital cardiac arrest based on hypoxia due to sputum stasis. The neurology department was consulted since the patient did not trigger on the ventilator after cessation of sedation. On neurological examination, the patient had dilated and fixed pupils, severe muscle weakness and areflexia, but a normal consciousness. Finally, she was diagnosed with LEMS. In this case report, the clinical course and diagnostic workup including anti-VGCC antibody testing, imaging and the results of electrophysiological studies are discussed. We also emphasise the importance of malignancy screening since the conventional chest CT was negative for lung carcinoma, but PET-CT raised a high suspicion for small-cell lung carcinoma. Conclusions: A rare course of LEMS, with early respiratory failure and wide, fixed pupils. Regarding repetitive nerve stimulation, it is important to stimulate long enough to see the incremental response. Furthermore, this study illustrated the importance of malignancy screening with PET-CT when there is a high suspicion of small-cell lung carcinoma with negative conventional CT.

Total Plasma Exchange in Neuromuscular Junction Disorders-A Single-Center, Retrospective Analysis of the Efficacy, Safety and Potential Diagnostic Properties in Doubtful Diagnosis.

Neuromuscular junction disorders (NJDs) are a heterogeneous group of diseases including myasthenia gravis (MG). In some cases, patients are present with myasthenic symptoms without evidence of autoimmune antibodies, making diagnosis challenging. Total plasma exchange (TPE) has proven efficacy in NJDs. The objective is to describe the safety and efficacy of TPE in NJD patients with questionable disease activity or uncertain diagnosis in order to assess the diagnostic potential of TPE. We report an observational, retrospective cohort study of clinical routine data. All the data were derived from the electronic medical records of the Department of Neurology at University Hospital Essen. We searched for patients with NJDs between 1 July 2018 and 30 June 2021. Of the 303 patients who presented to the department with NJDs, 20 were treated with TPE; 9 patients did not show a measurable benefit from TPE (45%), 6 of whom were diagnosed with seronegative MG. Of these, 3 (50%) had long-standing ocular symptoms. There were decreases in the mean arterial pressure, hemoglobin, hematocrit and fibrinogen during treatment, which were not considered clinically relevant. In (seronegative) myasthenic patients, TPE may help to verify an uncertain diagnosis or to reveal possible muscle damage, allowing unnecessary therapy to be avoided.

Protecting people with multiple sclerosis through vaccination.

Vaccination is one of the most effective and cost-efficient methods for protecting people with multiple sclerosis (MS) from infections. However, use of vaccines has often been problematic because of misguided concerns that they may exacerbate the disease and/or that some disease-modifying therapies may influence the immune response to immunisations and/or their safety. People with MS risk higher morbidity and mortality from vaccine-preventable infections. It is, therefore, important to address any patient's reluctance to accept vaccination and to provide clear guidance for clinicians on which vaccinations to consider proactively. We have reviewed the current literature and provide recommendations regarding vaccines in adults with MS, including specific advice regarding vaccination safety in patients receiving-or going to receive-disease-modifying therapies, vaccination during pregnancy, pretravel counselling and patient education.

Validation of the triple timed up-and-go test in Lambert-Eaton myasthenia.

INTRODUCTION: There are no validated, practical, and quantitative measures of disease severity in Lambert-Eaton myasthenia (LEM). METHODS: Data from the Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (DAPPER) trial were analyzed to assess triple timed up-and-go (3TUG) reproducibility and relationships between 3TUG times and other measures of LEM severity. RESULTS: The coverage probability technique showed ≥0.90 probability for an acceptable 3TUG difference of ≤0.2, indicating that it is reproducible in LEM patients. The correlation between 3TUG times and lower extremity function scores was significant in subjects who continued and in those who were withdrawn from 3,4-diaminopyridine free base. Worsening patient-reported Weakness Self-Assessment Scale and Investigator Assessment of Treatment Effect scores corresponded with prolongation of 3TUG times. DISCUSSION: The 3TUG is reproducible, demonstrates construct validity for assessment of lower extremity function in LEM patients, and correlates with changes in patient and physician assessments. These findings, along with prior reliability studies, indicate 3TUG is a valid measure of disease severity in LEM.

Autoimmune Channelopathies at Neuromuscular Junction.

The neuromuscular junction, also called myoneural junction, is a site of chemical communication between a nerve fiber and a muscle cell. There are many types of channels at neuromuscular junction that play indispensable roles in neuromuscular signal transmission, such as voltage-gated calcium channels and voltage-gated potassium channels on presynaptic membrane, and acetylcholine receptors on post-synaptic membrane. Over the last two decades, our understanding of the role that autoantibodies play in neuromuscular junction disorders has been greatly improved. Antibodies against these channels cause a heterogeneous group of diseases, such as Lambert-Eaton syndrome, Isaacs' syndrome and myasthenia gravis. Lambert-Eaton syndrome is characterized by late onset of fatigue, skeletal muscle weakness, and autonomic symptoms. Patients with Isaacs' syndrome demonstrate muscle cramps and fasciculation. Myasthenia gravis is the most common autoimmune neuromuscular junction channelopathy characterized by fluctuation of muscle weakness. All these disorders have a high risk of tumor. Although these channelopathies share some common features, they differ for clinical features, antibodies profile, neurophysiological features, and treatments. The purpose of this review is to give a comprehensive insight on recent advances in autoimmune channelopathies at the neuromuscular junction.

Paraneoplastic Lambert-Eaton syndrome in a patient with disseminated metastatic cancer.

BACKGROUND: Neurological paraneoplastic syndromes are rare, occur in 0.01% of all cancer patients; like part of them, the Lambert-Eaton syndrome is an autoimmune presynaptic disorder of neuromuscular transmission characterized by muscle weakness and neurovegetative dysfunction, and often associated with small cell lung cancer. CASE REPORT: A 72 years old female with a family history of lung cancer and leukemia, with 7 months of dry cough and 3 months with waist and pelvic muscle weakness, oropharyngeal dysphagia, dry mouth, chronic constipation and weight loss of 10 kg. PHYSICAL EXAMINATION: patient prostrated; clinical muscle examination: pelvic muscles waist -3/5 and -4/5 the rest; diminished reflexes. Laboratory normal parathormone and hypercalcemia. With electrophysiological study and positive anti-voltage-gated calcium channel antibodies, confirming Lambert-Eaton syndrome and imaging studies with neoplastic condition in brain, liver and kidney, with unspecified primary origin.

ANTECEDENTES: Los síndromes paraneoplásicos neurológicos son poco frecuentes; se presentan en el 0.01% de todos los pacientes con cáncer. Uno de ellos es el síndrome de Lambert-Eaton, correspondiendo a un trastorno presináptico autoinmunitario de transmisión neuromuscular caracterizado por debilidad muscular y disfunción neurovegetativa, y asociado con frecuencia al carcinoma microcítico de pulmón. CASO CLÍNICO: Mujer de 72 años, con antecedentes heredofamiliares de cáncer de pulmón y leucemia, con tos seca de 7 meses, 3 meses con debilidad de los músculos de cintura pélvica, disfagia al inicio de la deglución, xerostomía, estreñimiento crónico y pérdida de peso de 10kg. Ala exploración física: paciente postrada; examen clínico muscular: músculos de cintura pélvica en −3/5, resto en −4/5; reflejos disminuidos. Pruebas de laboratorio indicando hipercalcemia y paratohormona normal. Estudio electrofisiológico y anticuerpos anticanales de calcio positivos, demostrando síndrome de Lamber-Eaton, y estudios de imagen con afectación neoplásica en cerebro, hígado y riñón, sin lograr especificar el origen primario.

Paraneoplastic Lambert-Eaton syndrome in a patient with disseminated metastatic cancer. / Síndrome paraneoplásico de Lambert-Eaton en paciente con cáncer metastásico diseminado

Background: Neurological paraneoplastic syndromes are rare, occur in 0.01% of all cancer patients; like part of them, the Lambert-Eaton syndrome is an autoimmune presynaptic disorder of neuromuscular transmission characterized by muscle weakness and neurovegetative dysfunction, and often associated with small cell lung cancer. Case report: A 72 years old female with a family history of lung cancer and leukemia, with 7 months of dry cough and 3 months with waist and pelvic muscle weakness, oropharyngeal dysphagia, dry mouth, chronic constipation and weight loss of 10 kg. Physical examination: patient prostrated; clinical muscle examination: pelvic muscles waist -3/5 and -4/5 the rest; diminished reflexes. Laboratory normal parathormone and hypercalcemia. With electrophysiological study and positive anti-voltage-gated calcium channel antibodies, confirming Lambert-Eaton syndrome and imaging studies with neoplastic condition in brain, liver and kidney, with unspecified primary origin.

Antecedentes: Los síndromes paraneoplásicos neurológicos son poco frecuentes; se presentan en el 0.01% de todos los pacientes con cáncer. Uno de ellos es el síndrome de Lambert-Eaton, correspondiendo a un trastorno presináptico autoinmunitario de transmisión neuromuscular caracterizado por debilidad muscular y disfunción neurovegetativa, y asociado con frecuencia al carcinoma microcítico de pulmón. Caso clínico: Mujer de 72 años, con antecedentes heredofamiliares de cáncer de pulmón y leucemia, con tos seca de 7 meses, 3 meses con debilidad de los músculos de cintura pélvica, disfagia al inicio de la deglución, xerostomía, estreñimiento crónico y pérdida de peso de 10 kg. A la exploración física: paciente postrada; examen clínico muscular: músculos de cintura pélvica en −3/5, resto en −4/5; reflejos disminuidos. Pruebas de laboratorio indicando hipercalcemia y paratohormona normal. Estudio electrofisiológico y anticuerpos anticanales de calcio positivos, demostrando síndrome de Lamber-Eaton, y estudios de imagen con afectación neoplásica en cerebro, hígado y riñón, sin lograr especificar el origen primario.

3,4-diaminopyridine base effectively treats the weakness of Lambert-Eaton myasthenia.

INTRODUCTION: 3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. METHODS: We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). RESULTS: Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P < 0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (P < 0.0001). Requirement for rescue and adverse events were more common in the placebo group. DISCUSSION: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM. Muscle Nerve 57: 561-568, 2018.

Calcium channel autoimmunity: Cerebellar ataxia and lambert-eaton syndrome coexisting.

INTRODUCTION: Neuronal calcium channel antibodies are a biomarker of Lambert-Eaton syndrome (LES) and cerebellar ataxia. We have encountered several patients with LES and cerebellar ataxia coexisting, and we sought to further define this association. METHODS: We reviewed records of patients at our institution with a diagnosis of "Lambert-Eaton syndrome" and "cerebellar ataxia." RESULTS: Seventeen patients were identified with LES and ataxia. Presenting symptoms were weakness (8), concurrent weakness and ataxia (4), ataxia (4), and other (1). Nine patients had small-cell lung carcinoma, 3 of whom had survival greater than 100 months. Immunotherapy responses were best among patients without cancer. Nine of 17 (53%) patients were alive at last follow-up (median survival 62 months; range, 8-240). DISCUSSION: Calcium channel autoimmunity should be considered in patients with coexisting cerebellar ataxia and myasthenic weakness. Affected patients may survive small-cell carcinoma or have immunotherapy-responsive neurological symptoms. Muscle Nerve, 2018.

Review of the Diagnostic Challenges of Lambert-Eaton Syndrome Revealed Through Three Case Reports.

Lambert-Eaton syndrome (LES) is a rare immune-mediated disorder characterized by proximal leg weakness, autonomic symptoms and hypoactive tendon reflexes. The paraneoplastic form is associated with small-cell lung cancer in 50-60% of cases, whereas the remaining cases are found in younger adults with a higher likelihood of coexisting autoimmune disease. The early recognition of LES is crucial for improving clinical outcomes but remains a major challenge. In this review, we analyze the clinical characteristics and diagnostic considerations in treating LES through a series of three case studies, one of which showed definitive response to pyridostigmine and corticosteroid combination therapy, followed by spontaneous remission. Patients were assessed by image-based screening, serological testing and electrophysiological evaluations, which included respiratory and autonomic testing. A better understanding of the common pitfalls in the clinical, serological and neurophysiologic diagnosis of LES through assessment of typical LES dysfunction throughout the nervous system should enable improved recognition and treatment of this syndrome.

Neurologic indications for therapeutic plasma exchange: 2013 update.

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review considers the most common neurologic indications for TPE. It focuses on Guillain-Barré syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy. As with any treatment, the proven efficacy, cost, side effects, and availability must be considered before initiation of therapy.

Is the decremental pattern in Lambert-Eaton syndrome different from that in myasthenia gravis?

OBJECTIVE: We reviewed our experience to determine if the decremental pattern during low frequency repetitive nerve stimulation (LF-RNS) distinguishes between the Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG). METHODS: LF-RNS studies were reviewed from 34 LEMS and 44 MG patients, 4 of whom had antibodies to muscle specific kinase (MuSK). In each train we calculated the ratio between the early and the later decrement. Receiver-operator characteristic curves were calculated to determine the ratio that best distinguished between LEMS and MG. RESULTS: The late decrement was more often greater in LEMS and the converse was true in MG, but with some overlap in values in individual patients. A late decrement more than 102% of the early decrement discriminated between LEMS and MG in 90% of studies. The decremental pattern in MG patients with MuSK antibodies resembled that in LEMS. CONCLUSION: When the decrement becomes progressively greater during low frequency RNS, the patient is more likely to have LEMS than MG, and in MG, is more likely to have MuSK antibodies. SIGNIFICANCE: A progressive decrement in patients otherwise felt to have MG should prompt further clinical, serological and electrodiagnostic tests. Further studies are needed to assess the decremental pattern in MuSK MG.

Long-term follow-up in infantile-onset lambert-eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome). Lambert-Eaton myasthenic syndrome is a very rare disorder in children younger than age 12 years. Herein, we report a 25-year-old man with NP-Lambert-Eaton myasthenic syndrome, which onset was at the age of 10 years. To date, this is the most long-term follow-up of NP-Lambert-Eaton myasthenic syndrome in childhood. In our patient, the only symptomatic treatment with 3,4-diaminopyridine phosphate has been sufficient to guarantee him a good quality of life. Our data remind physicians to keep in mind the diagnosis of Lambert-Eaton myasthenic syndrome in children with a proximal myopathic pattern and they confirm the specificity of compound muscle action potential incremental pattern after brief maximal effort in Lambert-Eaton myasthenic syndrome.

[Myasthenia, from the internist's point of view]. / La myasthénie du côté de l'interniste.

Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a neuromuscular transmission defect causing muscle fatigability. If onset of the disease may be at any age, myasthenia gravis concerns mostly young adults, in majority females. The disease characteristic features are the following: ocular symptoms (ptosis or diplopia) as main initial manifestation, extension to other muscles in 80 % of the cases, variability of the deficit, effort induced worsening, successive periods of exacerbation during the disease course, severity depending on respiratory and swallowing impairment (if rapid worsening, a myasthenic crisis is to be suspected), association with thymoma in 20 % of patients and with other various autoimmune diseases, most commonly hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical features, improvement with cholinesterase inhibitors, detection of specific autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by electrophysiological tests. The points concerning specifically the internist have been highlighted in this article: diagnostic traps, associated autoimmune diseases, including inflammatory myopathies that may mimic myasthenia gravis, adverse effects of medications commonly used in internal medicine, some of them inducing myasthenic syndromes. The treatment is well codified: the treatment is well codified: (1) respect of adverse drugs contra-indications, systematically use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or intravenous immunoglobulins for patients with myasthenic crisis.

Asymptomatic Lambert-Eaton syndrome.

INTRODUCTION: All descriptions of the Lambert-Eaton syndrome are based on symptomatic patients. We incidentally encountered electromyographic evidence of this syndrome in a patient being studied for another reason. The patient had controlled hypothyroidism and smoked for 9 pack-years but never had symptoms of weakness or had evidence of cancer. METHODS: Detailed electrophysiological and serological evaluations were undertaken in this study. RESULTS: Neuromuscular transmission tests were consistent with a presynaptic disorder. Autoantibodies specific for P/Q-type voltage-gated calcium channels (VGCC) were detected in the serum and persisted throughout 7 years of follow-up. Multiple IgG markers of thyrogastric autoimmunity also were detected. CONCLUSIONS: This demonstration of asymptomatic Lambert-Eaton syndrome persisting for 8 years provided novel insight into the natural history of the disorder. It is plausible that patients with a subclinical syndrome would have abrupt neuromuscular decompensation when challenged with medications that compromise the safety factor for synaptic transmission.