[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.

[A case of myasthenia gravis with coexistence of anti-acetylcholine receptor antibodies and anti-P/Q-type VGCC antibodies].

A 79-year-old woman who presented ptosis and dysphagia were admitted to our hospital. Anti-acetylcholine receptor antibodies and anti-P/Q-type VGCC antibodies were both positive. Electrophysiological examination showed postsynaptic pattern which supported myasthenia gravis. She did not meet the diagnostic criteria for Lambert-Eaton myasthenic syndrome (LEMS). In cases which these antibodies coexist, careful electrophysiological evaluation is required for the diagnosis. In addition, although anti-P/Q-type VGCC antibodies have been specific to LEMS, patients with these antibodies represent various symptoms other than LEMS. Low and middle titer of the antibodies may be not specific to LEMS.

Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disease characterized by proximal muscle weakness, loss of tendon reflexes, and autonomic dysfunction. Muscle weakness usually starts in the upper legs and can progress to oculobulbar and in severe cases respiratory muscles. P/Q-type voltage-gated calcium channels (VGCCs) localized in the presynaptic motor nerve terminal and in the autonomic nervous system are targeted by antibodies in LEMS patients. These antibodies can be detected in about 90% of patients, and the presence of decrement and increment upon repetitive nerve stimulation is also a highly sensitive diagnostic test. Rapid diagnosis is important because of the association with SCLC in 50%-60% of patients, which stresses the need for vigorous tumor screening after diagnosis. Clinical parameters can predict tumor probability and guide frequency of tumor screening. Treatment of the tumor as well as symptomatic treatment and immunosuppression can effectively control symptoms in the majority of patients.

SOX-1 antibodies positive Lambert-Eaton myasthenic syndrome with occult small cell lung cancer: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.

[Diagnosis and Treatment of Lambert-Eaton Myasthenic Syndrome].

Approximately 90% of patients with Lambert-Eaton myasthenic syndrome (LEMS) show positive P/Q-type voltage-gated calcium channels antibodies, which can be broadly classified clinically as paraneoplastic, particularly with small cell lung carcinoma and non-paraneoplastic without cancer. The first Japanese guideline for LEMS was developed in May 2022 as MG/LEMS Practice Guideline 2022. This article describes the epidemiology, symptoms, diagnosis, examination, treatment, and prognosis of this condition, based on the LEMS guidelines.

[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.

Electrophysiological evaluation of the neuromuscular junction: a brief review.

The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability ("jiggle") due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.

O nervo terminal e a membrana muscular compõem a junção neuromuscular. Após a abertura dos canais de cálcio dependentes de voltagem, os potenciais de ação do axônio motor provocam uma cascata de eventos que libera acetilcolina das vesículas para a fenda sináptica, ligando-se ao receptor na membrana muscular para despolarização. O potencial de ação muscular composto de baixa amplitude ocorre nas desordens pré-sinápticas, aumentando em mais de 100% após esforço de 10 segundos na síndrome miastênica de Lambert-Eaton e menos no botulismo. A eletromiografia pode mostrar potenciais de ação da unidade motora miopáticos e instabilidade morfológica ("jiggle") devido ao bloqueio do impulso. Estimulação nervosa repetitiva (ENR) de baixa frequência é útil nos distúrbios pós-sinápticos, como miastenia gravis e a maioria das síndromes miastênicas congênitas, quando há número reduzido de receptores de acetilcolina funcionantes. ENR de baixa frequência com decremento >10% é anormal comparando-se à amplitude do quarto com o primeiro potencial de ação muscular composto. ENR de alta frequência é útil nas doenças pré-sinápticas, como síndrome miastênica de Lambert-Eaton, botulismo e algumas síndromes miastênicas congênitas raras. ENR de alta frequência libera mais cálcio, aumenta acetilcolina, resultando em incremento do potencial de ação muscular composto. O eletrodo de agulha concêntrico registra potenciais de ação aparente de fibra única (PAAFU). Ativação voluntária mede jitter entre dois PAAFUs (duas junções neuromusculares). Ativação elétrica mede jitter de um PAAFU (uma junção neuromuscular). Jitter é o teste mais sensível para detectar disfunção de junção neuromuscular. A maioria dos distúrbios juncionais é responsiva ao tratamento.

[A 50 year old man with progressive weakness in lower limbs].

Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare neurological disorder caused by autoimmune antibodies attacking the presynaptic neuromuscular junction, in some cases caused by underlying cancer. The main clinical finding is fluctuating weakness of the extremities and a triad of symtoms can help physicians suspect the disease. A key to the diagnosis are the electrophysiological abnormalities seen in this group of diseases. Treatment with symtomatic and/or immunosuppressive therapy is important as well as a workup for possible malignancy. This article identifies the clinical features, diagnosis and treatment of this uncommon disease.

What Is in the Neuromuscular Junction Literature?

ABSTRACT: This update covers several articles on diagnosis and misdiagnosis of myasthenia gravis (MG), the role of complement in MG, and then an impressive number of recent treatment trials. There is a negative study on any corticosteroid-sparing effect of intravenous immunoglobulin. A number of positive studies are reviewed. Open-label extension studies of phase 3 trials showed benefit regarding quality of life with efgartigimod and in functional measures with ravulizumab. The phase 3 RAISE trial of zilucoplan, a self-administered complement C5 inhibitor, is covered as well as the MyCarinG trial of rozanolixizumab. The notion of using fast-acting therapies early in the course of MG is addressed. The last sections center on MG and Lambert-Eaton myasthenic syndrome as a consequence of immune checkpoint inhibitor therapy.

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.

Cancer detection after a 9-year course of Lambert-Eaton myasthenic syndrome complicated by anti-Hu associated limbic encephalitis.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular junction disorder, paraneoplastic in 55% of cases and commonly associated with small-cell lung cancer (SCLC). We report the case of a 61-year-old man presented who with a 3-month history of lower limb proximal weakness, progressing to upper limbs, associated with dysphagia, xerostomia and erectile dysfunction. Electrodiagnostic studies and anti voltage-gated calcium channel (VGCC) antibodies (Abs) detection confirmed LEMS diagnosis. Contrast-enhanced thorax computed tomography (CT) scan and subsequently [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed no malignancy. Two years after the onset of LEMS, he was diagnosed with anti-Hu limbic encephalitis (LE). FDG-PET/CT scan remained negative for the following seven years. Nine years after LEMS onset, a hypermetabolic lesion of the left lung hilus was detected. This is a case of a paraneoplastic LEMS where the interval between the onset of neurological disease and tumour detection was as long as nine years.

[LEMS: Clinical Significance of Pathogenic Autoantibodies].

Approximately 90% of patients with Lambert-Eaton myasthenic syndrome (LEMS) are positive for P/Q-type voltage-gated calcium channels (VGCCs) antibodies, and can be broadly divided into two groups: paraneoplastic, especially with small cell lung carcinoma and, non-paraneoplastic, without cancer. Under the Japanese LEMS diagnostic criteria 2022, abnormal electrophysiological results is mandatory for diagnosis in addition to muscle weakness. Contrastingly, autoantibodies are useful for diagnosing the etiology and influence treatment strategies. We comprehensively reviewed the MG/LEMS 2022 practice guidelines. Moreover, we presented a case of PCD without LEMS that was positive for P/Q-type VGCCs antibodies_and discussed the clinical significance of the autoantibodies.

[A case of Lambert-Eaton myasthenic syndrome with exacerbation of respiratory failure triggered by acute myocardial infarction].

The patient, a 58-year-old man, experienced weakness of the proximal muscles in both lower extremities, and Lambert-Eaton myasthenic syndrome and small cell carcinoma of unknown primary origin were diagnosed. He received symptomatic treatment for myasthenia and radiochemotherapy for small cell carcinoma; once this regimen, the myasthenic symptoms improved. However, acute myocardial infarction occurred, after which type II respiratory failure developed, and the patient required ventilator management with tracheal intubation. Acute-phase treatment, such as plasma exchange, intravenous immune globulin therapy, and methylprednisolone pulse therapy, and intensification of symptomatic treatment allowed for extubation, and eventually the patient was able to walk independently. According to electrophysiological examination, compound muscle action potentials were larger at discharge than at the time of exacerbation.

Paraneoplastic Lambert-Eaton myasthenic syndrome: a diagnostic challenge.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder. Underlying small cell lung cancer is found in more than half of patients. Proximal muscle weakness, autonomic features and areflexia are typical manifestations. However, LEMS is often misdiagnosed. We report a rare case of paraneoplastic LEMS, identified amid admission due to a different diagnosis. Our patient was initially admitted due to aspiration pneumonia. Further investigation revealed clinical and electrophysiological manifestations of LEMS. High clinical suspicion and early diagnostic workup were paramount in the patient outcome. Nevertheless, paraneoplastic aetiology was difficult to confirm and revealed itself a difficult challenge. Clinical awareness is crucial to diagnose LEMS and urge cancer screening and early treatment.

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.

SOX-1 antibodies in a patient with Crohn's disease: a case report.

BACKGROUND: The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms. CASE PRESENTATION: A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure. CONCLUSIONS: Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.

[Diagnostics and treatment of clinically relevant paraneoplastic syndromes]. / Diagnostik und Therapie klinisch relevanter paraneoplastischer Syndrome.

Paraneoplastic syndromes (PS) are rare disorders with often complex clinical manifestations that occur in association with a tumor without being triggered by direct tumor invasion or compression. They arise from tumor secretions of hormones, peptides or cytokines or from immune cross-reactivity between malignant and healthy tissue. They are categorized into endocrine, neurological, dermatological, rheumatological, and hematological PS. The PS most commonly occurs in small cell lung carcinoma but also in association with other respiratory tract tumors, gynecological tumors, and hematological malignancies. The PS can precede a tumor diagnosis, therefore timely diagnosis can improve the prognosis of a malignant disease. The diagnostics are based on the clinical presentation as well as diagnostic methods depending on the underlying pathogenesis. The most important treatment approach involves the best possible treatment of the tumor and a targeted treatment is only sometimes possible. This review focuses on the clinically most frequently encountered PS.

Progressive motor quadriparesis with wasting: a diagnostic conundrum.

The case of a man in his early 30s, presenting with slowly progressive, asymmetrical onset, pure motor quadriparesis over 9 months with bulbar involvement, absence of upper motor neuron features and significant weight loss, is reported. In view of presentation with diffuse lower motor neuron involvement of short duration, the diagnostic possibilities are discussed. Apart from motor neuron disease, its mimics including muscle and neuromuscular junction disorders were also considered and evaluated for. Carefully assessed clinical and electrophysiological markers which finally clinched the diagnosis of the rare disorder Lambert-Eaton myasthenic syndrome are elaborated. In the present context, recognition of the oddities on clinical and laboratory evaluation is of paramount importance to rule in causes of pure motor quadriparesis.