[Lambert-Eaton Myasthenic Syndrome].

Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disorder that affects the neuromuscular junction, is characterized by proximal muscle weakness, reduction of tendon reflexes, and autonomic dysfunction. LEMS shows a prevalence of approximately 0.25-0.27 per 100,000 population. The characteristic muscle weakness observed in patients with LEMS is attributed to the role of pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal. Notably, 50-60% of patients with LEMS have an associated tumor, small-cell lung carcinoma (SCLC), which also expresses functional voltage-gated calcium channels (VGCC). The Japanese LEMS diagnostic criteria 2022 recommend documentation of typical electrophysiological abnormalities combined with myasthenic symptoms for accurate diagnosis. P/Q-type VGCC antibody positivity strongly supports the diagnosis. Treatment options are categorized as oncological treatment, immunotherapy, and symptomatic treatments. Effective treatment of the tumor can improve LEMS in patients with SCLC. Most patients benefit from 3,4-diaminopyridine administration for symptomatic treatment. A treatment algorithm is established by the clinical practice guidelines 2022.

Overview of treatment strategies in paraneoplastic neurological syndromes.

Treatment strategies in paraneoplastic neurological syndromes rely on the three pillars of tumor treatment, immunotherapy, and symptomatic treatment, the first one being by far the most important in the majority of patients and syndromes. Classically, antibodies against extracellular antigens are directly pathogenic, and patients with these syndromes are more responsive to immunomodulatory or immunosuppressive treatments than the ones with antibodies against intracellular targets. This chapter first discusses some general principles of tumor treatment and immunotherapy, followed by a closer look at specific treatment options for different clinical syndromes, focusing on symptomatic treatments.

[The Japanese Clinical Guidelines 2022 for Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: An Overview].

The new Japanese clinical guidelines for myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) were published in 2022. The Following are the salient features of these guidelines (GLs): (1)These are the first Japanese GLs that include a description of LEMS. (2)Diagnostic criteria for both MG and LEMS are described. (3)A high-dose oral steroid regimen with an escalation and de-escalation schedule is not recommended. (4)Refractory MG is defined. (5)The use of molecular-targeted drugs is included. (6)MG is subcategorized into six clinical subtypes. (7)Treatment algorithms for both MG and LEMS are discussed.

Undiagnosed Lambert-Eaton Myasthenic Syndrome in the Era of Sugammadex: A Case Report.

OBJECTIVE: In this case report, we discuss the rare manifestation of prolonged neuromuscular blockade in a patient with history of small cell lung cancer and undiagnosed Lambert-Eaton myasthenic syndrome (LEMS) who had previously received succinylcholine for general anesthesia without incident but subsequently exhibited prolonged neuromuscular blockade during a laparoscopic procedure. We aimed to emphasize the importance of reversal agent safety and precision as well as vigilant perioperative and postoperative care. METHODS: We used the patient's electronic medical record, direct patient care experiences, and comprehensive literature review for this case report. RESULTS: Sugammadex was administered with mild improvement. Suspecting undiagnosed LEMS, neostigmine was administered, yielding satisfactory muscle strength and successful extubation. In retrospect, the patient reported history of weakness when lifting weights that improved upon exertion. CONCLUSIONS: Sugammadex is an efficient and effective agent for reversal of neuromuscular blockade. However, proper monitoring of the depth and recovery of blockade is imperative to when using sugammadex with optimal safety and precision in all patients. Perioperative care teams must remain vigilant with a high index of suspicion for neuromuscular junction pathology to properly plan perioperative care for patients at risk, especially those with small cell lung cancer who may have undiagnosed LEMS.

[Transition of Japanese clinical guidelines for myasthenia gravis].

The Japanese clinical guidelines for myasthenia gravis (MG) were revised in 2022. The major revision points in these guidelines are as follows. 1) A description of Lambert-Eaton myasthenic syndrome (LEMS) was included for the first time. 2) Revised diagnostic criteria of both MG and LEMS are proposed. 3) A high-dose oral steroid regimen with escalation and de-escalation schedule is not recommended. 4) Refractory MG is defined. 5) The use of molecular-targeted drugs is included. 6) MG is divided into six clinical subtypes. 7) Treatment algorithms for both MG and LEMS are presented.

Lambert-Eaton myasthenic syndrome (LEMS) in a patient with lung cancer under treatment with pembrolizumab: a case study.

Pembrolizumab is an immune checkpoint inhibitor (ICI) against the programmed death-1 receptor. Herein, we introduce a rare adverse effect during using pembrolizumab. We present the case of an 80-year-old man with biopsy-proven unresectable double primary squamous cell carcinoma and large cell neuroendocrine carcinoma of the lung. After using pembrolizumab for 10 months, he complained of muscle weakness of both upper and lower extremities. In a nerve conduction study, the repetitive nerve stimulation test in the abductor digiti minimi was diagnostic of Lambert-Eaton myasthenic syndrome (LEMS): low in the amplitude of compound muscle action potential (1.4 mV), 28.6% decrement in the 5-Hz stimulation, and 579% increment in the 50-Hz stimulation. The disease did not progress after the discontinuation of pembrolizumab, even without any anti-cancer treatment for 12 months. We believe our clinical experience of this rare and unexpected adverse effect should be shared.

Lambert-Eaton Myasthenic Syndrome Recurrence Induced by Pembrolizumab in a Patient with Non-small-cell Lung Cancer.

A 73-year-old woman in complete remission from localized small-cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) 22 years earlier was referred to our hospital and diagnosed with non-small-cell lung cancer. After three courses of pembrolizumab, an immune checkpoint inhibitor, the patient complained of muscle weakness, fatigue, ptosis, and dysarthria. The anti-voltage-gated calcium channel antibody level was elevated, and waxing was observed on a high-frequency repetitive stimulation test using an electromyogram. We diagnosed her with recurrence of LEMS as an immune-related adverse event (irAE) induced by pembrolizumab. After intravenous immunoglobulin therapy, the patient's symptoms improved, and she was discharged.

Lambert-Eaton Myasthenic Syndrome and Botulism.

PURPOSE OF REVIEW: This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic disorders of neuromuscular transmission in which rapid diagnosis improves long-term outcomes. RECENT FINDINGS: Therapy for LEMS has seen significant advances in recent years due to the approval of amifampridine-based compounds. LEMS is likely still underdiagnosed, particularly when no underlying malignancy is identified. Clinicians must have a strong suspicion for LEMS in any patient presenting with proximal weakness and autonomic dysfunction. Botulism is another rare disorder of presynaptic neuromuscular transmission that is most commonly associated with improper storage or preservation of food products. Over the past 2 decades, wound botulism has been increasingly reported among users of black tar heroin. A high degree of clinical suspicion and electrodiagnostic studies can be beneficial in distinguishing botulism from other acute neurologic disorders, and early involvement of state and federal health authorities may assist in confirming the diagnosis and obtaining treatment. When botulism is suspected, electrodiagnostic studies can provide clinical evidence of disordered neuromuscular transmission in advance of serologic confirmation, and providers should not wait for confirmation of the diagnosis to initiate treatment. SUMMARY: A targeted clinical history and a thorough neurologic examination with support from serologic and electrodiagnostic studies are key to early diagnosis of LEMS and botulism. Early diagnosis of both conditions creates opportunities for therapy and improves outcomes.

Lambert-Eaton Myasthenic Syndrome Caused by Atezolizumab in a Patient with Small-cell Lung Cancer.

We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.

Neuromuscular junction disorders beyond myasthenia gravis.

PURPOSE OF REVIEW: To give an overview of the recent data on three autoimmune neuromuscular junction disorders with the recent Food Drug Administration (FDA) approval of amifampridine [3,4-Diaminopyridine (3,4-DAP) and 3,4-diaminopyridine phosphate (3,4-DAPP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). RECENT FINDINGS: In LEMS, the most important recent development is the introduction of FDA approved amifampridine for the symptomatic treatment. Randomized controlled studies showed an extremely effective improvement with amifampridine with daily dose of ≤ 80 mg with minimal side reactions. The next important development is in the electrodiagnostic criteria. Now 10 s exercise and an incremental response ≥ 60% either after 10 s exercise or at the high-rate stimulation in the repetitive nerve stimulation test are recommended as the standard tests.In 2016, myasthenia-gravis Lambert-Eaton overlap syndrome (MLOS) was coined as new syndrome for patients with myasthenia gravis and LEMS combined symptoms in same patients.In Isaacs syndrome, voltage gated calcium channel antibody order is no longer recommended because of low specificity for immunotherapy responsive disorders. Instead, ' leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated like-2 (CASPR2) autoantibody tests' are recommended. SUMMARY: In LEMS, amifampridine (3,4 DAP and 3,4-DAPP) is approved by the FDA as an effective symptomatic treatment. MLOS is coined as new syndrome recently. In Isaacs syndrome, LGI1 and CASPR2 antibody tests are recommended.

3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials.

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. METHODS: We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. RESULTS: Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. CONCLUSIONS: The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

[Lambert-Eaton myasthenic syndrome]. / Síndrome miasteniforme de Lambert-Eaton.

INTRODUCTION: Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce. AIM: This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published. PATIENTS AND METHODS: The medical records of 13 patients with LEMS with clinical findings, compatible electromyogram and/or positive antibodies were reviewed. Follow-up was performed until associated neoplasia was ruled out or confirmed according to the recommended algorithms. RESULTS: Four patients were diagnosed with T-LEMS, two of them with small-cell lung carcinoma. Of the nine patients with NT-LEMS, five had a DELTA-P score of 3 and 4. Nine patients presented with the classic clinical triad from the onset of the disease. All patients had electromyogram findings compatible with presynaptic neuromuscular plaque defect. Of the total, 70% improved symptomatically with pyridostigmine. CONCLUSIONS: The clinical findings, together with compatible neurophysiological studies, are sufficient for the diagnosis of LEMS. The relationship between the DELTA-P score and the risk of small-cell lung carcinoma could not be replicated. Symptomatic treatment with pyridostigmine represents an effective therapeutic alternative.

TITLE: Síndrome miasteniforme de Lambert-Eaton.Introducción. El síndrome miasteniforme de Lambert-Eaton (LEMS) es una patología paraneoplásica (T-LEMS) o idiopática autoinmunitaria (NT-LEMS) ocasionada por autoanticuerpos contra los canales de calcio dependientes del voltaje presinápticos de la unión neuromuscular. El 60% de los T-LEMS se asocia a carcinoma de pulmón de células pequeñas. Una puntuación Dutch-English LEMS Tumor Association Prediction (DELTA-P) mayor de 3 denota un riesgo elevado de dicha asociación. El diagnóstico precoz fundado en los hallazgos clínicos, estudios neurofisiológicos y dosificación de títulos de anticuerpos en el suero permite iniciar tempranamente el tratamiento sintomático y la búsqueda oncológica. Son escasos los informes de pacientes con LEMS en Latinoamérica. Objetivo. Describir las características de pacientes con LEMS de un centro privado de Buenos Aires, Argentina, y compararlas con las de otras series publicadas. Pacientes y métodos. Se revisaron historias clínicas de 13 pacientes con LEMS con hallazgos clínicos, electromiograma compatible y/o anticuerpos positivos. Se realizó seguimiento hasta descartar o confirmar una neoplasia asociada de acuerdo con los algoritmos recomendados. Resultados. Cuatro pacientes presentaron diagnóstico de T-LEMS, dos de ellos con carcinoma de pulmón de células pequeñas. De los nueve pacientes con NT-LEMS, cinco presentaron una puntuación DELTA-P de 3 y 4. Nueve pacientes presentaron la tríada clínica clásica desde el inicio. Todos los pacientes presentaron en el electromiograma hallazgos compatibles con defecto de placa neuromuscular presináptico. El 70% mejoró sintomáticamente con piridostigmina. Conclusiones. Los hallazgos clínicos, junto con los estudios neurofisiológicos compatibles, resultan suficientes para el diagnóstico de LEMS. No pudo replicarse la relación entre puntuación DELTA-P y riesgo de carcinoma de pulmón de células pequeñas. El tratamiento sintomático con piridostigmina representa una alternativa terapéutica eficaz.

Amifampridine to treat Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disabling neuromuscular disease caused by antibodies against presynaptic voltage-gated calcium channels. It reduces the quantal release of acetylcholine (Ach), causing muscle weakness, reduced or absent reflex and dysautonomia. About half of LEMS patients have associated small cell lung cancer. For symptomatic treatment, amifampridine (3,4-diaminopyridine [3,4-DAP]) is ideal because it increases the release of Ach at the presynaptic membrane. Since the first use of 3,4-DAP in LEMS patients in the 1980s, 136 LEMS patients were treated with amifampridines in the open-label studies and 208 patients in the eight randomized studies. These studies showed that amifampridine is the most effective drug for symptomatic treatment in LEMS. Now, 3,4-DAPP (3,4-DAP phosphate) is approved for adult LEMS patients and 3,4-DAP for pediatric patients. The recommended dose is 80 mg a day, divided 3 or 4 times a day. Side effects are usually mild, and the most frequently reported are paresthesia.

Aminopiridines in the treatment of multiple sclerosis and other neurological disorders.

Symptomatic treatment has a great relevance for the management of patients with neurologic diseases, since it reduces disease burden and improves quality of life. Aminopyridines (APs) are a group of potassium (K+) channel blocking agents that exert their activity both at central nervous system level and on neuromuscular junction. This review describes the use of APs for the symptomatic treatment of neurological conditions. We will describe trials leading to the approval of the extended-release 4-aminopyridine for MS and evidence in support of the use in other neurological diseases.

Successful treatment of advanced lung adenocarcinoma complicated with Lambert-Eaton myasthenic syndrome: A case report and literature review.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare disease characterized by involvement of the neuromuscular junction. Most cases have an underlying malignancy, especially small-cell lung cancer (SCLC), while adenocarcinoma is less common. Here, we report a rare case of metastatic lung adenocarcinoma complicated with LEMS. In this case, L858R mutation was detected in the 21st exon of the EGFR gene. First-line treatment with gefitinib was given, and the patient has survived for more than six years. Early diagnosis of LEMS and timely and effective treatment can result in a good prognosis. We also searched for "lung cancer", or "carcinoma of lung", or "adenocarcinoma of lung", or "Lambert-Eaton myasthenic syndrome" in PubMed until 1 December 2019. Seven cases of lung adenocarcinoma complicated with LEMS were found, most of which had a poor prognosis. KEY POINTS: This article reports a rare case of metastatic lung adenocarcinoma with EGFR mutation, complicated with LEMS. Gefitinib was given as first-line treatment, and resulted in a good prognosis.