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Background: Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the presynaptic neuromuscular junction associated with antibody mediated dysfunction of voltage-gated calcium channels (VGCCs). LEMS can exist as a paraneoplastic syndrome, paraneoplastic-LEMS (P-LEMS), when associated with tumors, most commonly, small cell lung carcinoma (SCLC) or as a non-paraneoplastic condition (NP-LEMS) when no malignancies are detected. Methods: A retrospective chart review was conducted in 3 tertiary hospitals in Saudi Arabia for patients diagnosed with LEMS between January 2010 and January 2020. Patients meeting all the following criteria were included: (1) weakness or fatigability of one or more extremity or oculo-bulbar muscles, (2) 60% or higher increment of compound muscle action potential (CMAP) amplitudes immediately following isometric exercise, and (3) positive serum P/Q type VGCC antibodies. Clinical, laboratory, and electrophysiologic features, as well as radiologic imaging modalities performed for tumor screening were reviewed. Results: The study included six patients diagnosed with LEMS, split evenly between P-LEMS and NP-LEMS. Fatigability, particularly in the lower extremities, and dyspnea on exertion were commonly reported symptoms. Low CMAP amplitudes were more frequently seen in NP-LEMS as compared to P-LEMS when recorded from both abductor pollicis brevis and abductor digiti minimi muscles. An incremental response above 60% in post activation CMAPs was detected at similar rates following variable durations of isometric exercise (10, 15, and 20 s). Tumor types detected in 3 patients with P-LEMS are SCLC, breast carcinoma, colon adenocarcinoma, and prostate acinar adenocarcinoma. Triple malignancy was detected in one patient. Conclusion: This is the first study to describe clinical and electrophysiologic features of LEMS in an Arab ethnic cohort. Early recognition of LEMS has a significant impact on prognosis, especially given the aggressive nature of associated cancers such as SCLC. [ABSTRACT FROM AUTHOR]

Neuromuscular junction (NMJ) disorders represent a heterogenous group of acquired and congenital disorders that present in variable and distinctive ways. The diagnosis is typically reached through a combination of clinical, serological, pharmacological and electrophysiological evaluation. While the diagnosis can be fairly straightforward in some cases, the overlap with other neurological disorders can make diagnosis challenging, particularly in pure ocular presentations and in seronegative patients. The over-reliance on serological tests and electrophysiological evaluation in isolation can lead to misdiagnosis. In this article, we provide an overview of the NMJ disorders, discuss red flags for the key differential diagnoses (mimics) and report the atypical ways in which NMJ disorders may present (chameleons). [ABSTRACT FROM AUTHOR]

Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic neurological syndrome complication of small cell lung cancer (SCLC). The clinical symptoms of LEMS overlap with those of myasthenia gravis (MG), leading to misdiagnosis. Herein, we report two cases of SCLC with LEMS-like disease that were difficult to distinguish from MG because of atypical electromyographic findings without waxing patterns on high-frequency stimulation. Both patients responded poorly to oral pyridostigmine and intravenous immunoglobulin, and were reported to be positive for the anti-P/Q-type voltage-gated calcium channel antibody characteristic of LEMS. Differentiating between LEMS and MG based on clinical symptoms and EMG findings can be difficult. [ABSTRACT FROM AUTHOR]

Abstract This is an unusual case of voltage gated calcium channel (VGCC) antibodies leading to two distinct and chronologically separated neurologic syndromes without the presence of an underlying neoplasm. Lambert Eaton Myasthenic Syndrome (LEMS) presented five years prior to cerebellar ataxia. Both LEMS and cerebellar ataxia were responsive to treatment, but not the same therapy. He was diagnosed with LEMS through history, exam, electromyography/nerve conduction studies (EMG/NCS) with repetitive nerve stimulation (RNS) and antibody testing. He was treated with 3,4 diaminopyridine (3,4 DAP) with an excellent response. Five years later, he developed acute ataxia. The patient required months of intensive and continued immunomodulating therapy.

Objective To summarize the electrophysiological and muscle pathological characteristics of Lambert - Eaton myasthenic syndrome (LEMS). Methods and Results Twelve LEMS patients referred to China - Japan Friendship Hospital between January 2010 and December 2021 were included. Clinically, they all showed proximal muscle weakness and reduced or disappeared tendon reflexes. Electrophysiologically, all 12 patients showed decreased compound muscle action potential (CMAP) amplitudes, normal distal motor latency (DML), and normal motor and sensory conduction velocities. Ten patients underwent repetitive nerve stimulation (RNS) test: all had amplitude increments of more than 100% at high - frequency RNS, and 8 had amplitude decrements of more than 15% at low - frequency RNS. Three patients completed the post-exercise facilitation (PEF) test: the ulnar nerve CMAP amplitude reached a peak immediately after maximum voluntary contraction of the abductor digiti minimi for 5-10 s and then gradually decreased to near baseline level after contraction for 60 s; the ulnar nerve CMAP amplitude reached a peak immediately after maximum voluntary contraction for 10 s, and then rapidly decreased to near baseline level after 15 s. On needle EMG, 8 patients showed normal motor unit action potential (MUAP), 3 showed short - duration MUAP mimicking myopathy, and one showed long - duration MUAP mimicking neuropathy. Two patients with normal MUAP underwent biceps biopsy, which showed selective type Ⅱ fiber atrophy. Conclusions Electrophysiologically, CMAP amplitudes of LEMS patients are usually diffusely low or borderline. LEMS patients have amplitude increments of more than 100% at high-frequency RNS, and some have amplitude decrements of more than 15% at low-frequency RNS. PEF test shows a transient but significant CMAP amplitude increase after 5-10 s maximum voluntary contraction. Needle EMG is usually normal, but some show myogenic lesions, and some show neurogenic lesions. Muscle biopsy shows selective type Ⅱ fiber atrophy. Needle EMG myogenic lesion may not be associated with pathologically selective type Ⅱ fiber atrophy.

Introduction. Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the symptomatic treatment of LEMS. Aim of study. To assess the effectiveness and safety of treatment in the real world. Material and methods. 14 patients with non-neoplastic LEMS treated with amifampridine were enrolled in the study (female 42.9%, mean age 48.8 ± 11.4 years). The patients were assessed using the Quantitative Myasthenia Gravis (QMG) scale, QMG limb domain (LD) score, spirometry, Hand Grip Strength (GRIP) test, and repetitive nerve stimulation study (RNS) at baseline and at the end of follow-up. Diagnostic delay since first symptoms was from seven months up to 22 years. Treatment delay ranged from one to 26 years. The patients were treated and reevaluated after 21.1 ± 12.0 weeks (range 13-48). Results. All of the patients improved in QMG score. Mean improvement was 5.1 ± 2.0 (range 1-8) points (p < 0.001) and this showed no correlation with the duration of the disease before treatment (p = 0.477). 85.7% of patients (n = 12) improved = 3 points (clinically meaningful) in QMG. 78.6% of the patients improved in QMG LD [mean 2.2 ± 1.6 points (p < 0.001)]. Also, forced vital capacity (FVC) improved after treatment (p = 0.031). Mean improvement in GRIP test was 7.0 ± 7.1 kg in the right hand and 5.2 ± 7.5 kg in the left hand (p < 0.001). In RNS before treatment, facilitation (> 100%) was observed in 78.6% (n = 11) of patients, and was higher before treatment (p < 0.001). Compound muscle action potential (CMAP) amplitude was higher after treatment (p < 0.001). Mean increase of CMAP amplitude was 2.1 ± 1.6 times. In 64.3% (n = 9) of patients lowering of corticosteroid dose was achieved. Conclusions. Amifampridine is an effective treatment in non-neoplastic LEMS patients, regardless of disease duration. The treatment is well-tolerated and allows to reduce dose of corticosteroids in the majority of patients. [ABSTRACT FROM AUTHOR]

BackgroundLambert–Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the presynaptic neuromuscular junction associated with antibody mediated dysfunction of voltage-gated calcium channels (VGCCs). LEMS can exist as a paraneoplastic syndrome, paraneoplastic-LEMS (P-LEMS), when associated with tumors, most commonly, small cell lung carcinoma (SCLC) or as a non-paraneoplastic condition (NP-LEMS) when no malignancies are detected.MethodsA retrospective chart review was conducted in 3 tertiary hospitals in Saudi Arabia for patients diagnosed with LEMS between January 2010 and January 2020. Patients meeting all the following criteria were included: (1) weakness or fatigability of one or more extremity or oculo-bulbar muscles, (2) 60% or higher increment of compound muscle action potential (CMAP) amplitudes immediately following isometric exercise, and (3) positive serum P/Q type VGCC antibodies. Clinical, laboratory, and electrophysiologic features, as well as radiologic imaging modalities performed for tumor screening were reviewed.ResultsThe study included six patients diagnosed with LEMS, split evenly between P-LEMS and NP-LEMS. Fatigability, particularly in the lower extremities, and dyspnea on exertion were commonly reported symptoms. Low CMAP amplitudes were more frequently seen in NP-LEMS as compared to P-LEMS when recorded from both abductor pollicis brevis and abductor digiti minimi muscles. An incremental response above 60% in post activation CMAPs was detected at similar rates following variable durations of isometric exercise (10, 15, and 20 s). Tumor types detected in 3 patients with P-LEMS are SCLC, breast carcinoma, colon adenocarcinoma, and prostate acinar adenocarcinoma. Triple malignancy was detected in one patient.ConclusionThis is the first study to describe clinical and electrophysiologic features of LEMS in an Arab ethnic cohort. Early recognition of LEMS has a significant impact on prognosis, especially given the aggressive nature of associated cancers such as SCLC.

This is an unusual case of voltage gated calcium channel (VGCC) antibodies leading to two distinct and chronologically separated neurologic syndromes without the presence of an underlying neoplasm. Lambert Eaton Myasthenic Syndrome (LEMS) presented five years prior to cerebellar ataxia. Both LEMS and cerebellar ataxia were responsive to treatment, but not the same therapy. He was diagnosed with LEMS through history, exam, electromyography/nerve conduction studies (EMG/NCS) with repetitive nerve stimulation (RNS) and antibody testing. He was treated with 3,4 diaminopyridine (3,4 DAP) with an excellent response. Five years later, he developed acute ataxia. The patient required months of intensive and continued immunomodulating therapy. [ABSTRACT FROM AUTHOR]

Background: The classic triad in LEMS is proximal muscle weakness, areflexia, and autonomic dysfunction. We have frequently observed truncal ataxia as the first complaint in LEMS patients. In this study, we aimed to show the presence of ataxia in 10 newly diagnosed LEMS patients in the past 3 years and what factors influence it. Methods: We present the clinical findings, voltage-gated calcium channels antibody positivity, and electrophysiologic findings of newly diagnosed LEMS patients who presented to our tertiary care center during the past 3 years. Results: Of the 10 LEMS patients examined, 60% (6) were males and 40% (4) were females. The first and most dysfunctional symptoms were gait disorder and loss of balance in seven of the patients. These patients had ataxia, a gait disturbance that was disproportionate to the proximal weakness. Although the patients had mild proximal weakness in the lower extremities, they had considerable difficulty walking. Proximal muscle weakness was present in six patients, speech disorders in three patients, dysphagia in three patients, dry mouth in three patients, ptosis in two patients, diplopia in two patients, and nystagmus in one patient. Conclusion: We believe that more caution is needed in patients with truncal ataxia when LEMS is suspected. This is because we have seen that the first complaints in 7 out of 10 LEMS patients were truncal ataxia, loss of balance, and gait disturbance.

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lambert–Eaton myasthenic syndrome (G73.1 according to ICD-10) is a rare autoimmune disease associated with a presynaptic impairment of neuromuscular transmission due to the production of antibodies to voltage-gated calcium channels. The peculiarity of Lambert–Eaton myasthenic syndrome is manifested in a combination of increased muscle weakness and fatigue with the phenomenon of «working in» — an increase in the muscle strength against the background of muscle load after a short-term maximum contraction. Lambert-Eaton myasthenic syndrome is often associated with small cell lung cancer and very rarely develops with tumors of another localization. CLINICAL CASE DESCRIPTION: We observed an 80-year-old patient with complaints of weakness and pain in the hips, shoulders, pelvic region, and half-ptosis of the eyelids. For half-ptosis of the eyelids, a differential diagnosis was conducted with myasthenia gravis. Stimulation electromyography revealed the M-response increment, i.e. the phenomenon of “working in”, which is typical for this syndrome. The examination revealed papillary thyroid cancer, which was later treated surgically. CONCLUSION: This case illustrates Lambert–Eaton’s paraneoplastic myasthenic syndrome, a rare tumor form associated with thyroid cancer.

Several review articles on voltage‐gated calcium channels (VGCCs) classify VGCCs into five electrophysiological types and 10 genotypes. Each VGCC is distributed in different organs and specialized cells, and various organ‐specific human genetic diseases have been reported. Most of the human diseases caused by abnormalities in the VGCCs are genetic diseases. To the best of our knowledge, Lambert–Eaton myasthenic syndrome (LEMS) appears to be the only autoimmune disease for VGCCs. Approximately 90% of LEMS patients are positive for autoantibodies against P/Q‐VGCCs in the active zone of nerve endings. On the other hand, about 50% of LEMS patients a tumor‐associated neurological syndrome with small cell lung cancer. Neurological symptoms in LEMS patients include weakness of proximal limb muscles, reduced tendon reflexes, autonomic neuropathy, and in 9%–14% of patients, cerebellar ataxia, and paraneoplastic cerebellar degeneration. In the second half of this manuscript, we provide a clinical review with reference to the recently published Practical Guideline for Myasthenia gravis and LEMS 2022 in Japan. [ABSTRACT FROM AUTHOR]

Background: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disorder leading to muscle weakness, autonomic dysregulation and hyporeflexia. Psychosocial well-being is affected. Previously, we assessed burden of disease for Myasthenia gravis (MG). Here, we aim to elucidate burden of disease by comparing health-related quality of life (HRQoL) of patients with LEMS to the general population (genP) as well as MG patients. Methods: A questionnaire-based survey included sociodemographic and clinical data along with standardized questionnaires, e.g. the Short Form Health (SF-36). HRQoL was evaluated through matched-pairs analyses. Participants from a general health survey served as control group. Results: 46 LEMS patients matched by age and gender were compared to 92 controls from the genP and a matched cohort of 92 MG patients. LEMS participants showed lower levels of physical functioning (SF-36 mean 34.2 SD 28.6) compared to genP (mean 78.6 SD 21.1) and MG patients (mean 61.3 SD 31.8). LEMS patients showed lower mental health sub-scores compared to genP (SF-36 mean 62.7 SD 20.2, vs. 75.7 SD 15.1) and MG patients (SF-36 mean 62.7 SD 20.2, vs. 66.0 SD 18.). Depression, anxiety and fatigue were prevalent. Female gender, low income, lower activities of daily living, symptoms of depression, anxiety and fatigue were associated with a lower HRQoL in LEMS. Discussion: HRQoL is lower in patients with LEMS compared to genP and MG in a matched pair-analysis. The burden of LEMS includes economic and social aspects as well as emotional well-being. Trial Registration Information: drks.de: DRKS00024527, submitted: February 02, 2021, https://drks.de/search/en/trial/DRKS00024527. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spontaneous regression (SR) of cancer is very rare, especially of small cell lung cancer (SCLC). Recently, an association of paraneoplastic neurological syndrome (PNS) has been reported as a cause of SR of cancer, and onconeural antibodies are a possible factor in the SR of cancer associated with PNS. We herein report the first case of SR of SCLC combined with anti-P/Q-type of voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS), a subtype of PNS. This case report suggests that SCLC may be spontaneously reduced by an autoimmune response induced by VGCC antibodies associated with LEMS. Our finding may help elucidate the mechanisms that inhibit tumor growth and cause the regression of tumors.

Introduction: Lambert-Eaton myasthenia syndrome (LEMS) is a rare autoimmune disorder characterized by autoantibodies targeting presynaptic neuromuscular junctions. It results in muscle weakness and autonomic dysfunction. LEMS can be idiopathic or associated with neoplastic diseases, often small-cell lung cancer. This case report describes a rare instance of paraneoplastic LEMS in a man with non-Hodgkin lymphoma. Case Presentation: A 57-year-old male with non-Hodgkin lymphoma presented with progressive muscle weakness, diminished reflexes, and autonomic symptoms. Diagnosis revealed LEMS with autoantibodies against voltage-gated calcium channels. Immunosuppressive therapy and lymphoma treatment led to significant improvement in his condition. Conclusion: This case highlights the rare occurrence of paraneoplastic LEMS in a patient with non-Hodgkin lymphoma. Recognition and timely management of LEMS alongside lymphoma treatment can lead to significant clinical improvement, emphasizing the need for increased awareness of such complex associations.

Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline 'Diagnostics and therapy of myasthenic syndromes' has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity. [ABSTRACT FROM AUTHOR]

A 57‐year‐old man presented with progressive muscle weakness in the lower limbs, with elevated anti‐P/Q‐type voltage‐gated calcium channel antibody levels. A repetitive stimulation test showed waxing with high‐frequency stimulation. He was diagnosed with Lambert–Eaton myasthenic syndrome (LEMS) and small‐cell lung cancer. After four courses of cisplatin and etoposide, computed tomography showed a decrease in tumor size and muscle weakness improved. After 3 months, the patient presented with progressive ataxic gait and dysarthria and was admitted to our hospital. Magnetic resonance imaging revealed slight cerebellar atrophy. We diagnosed the patient with paraneoplastic cerebellar degeneration (PCD)‐LEMS. The patient received intravenous immunoglobulin therapy, steroid pulse therapy, and plasmapheresis. The patient's cerebellar ataxia then improved. This represents a rare case of PCD‐LEMS after improvement of LEMS. [ABSTRACT FROM AUTHOR]

Robert M Pascuzzi, Cynthia L Bodkin Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USACorrespondence: Robert M Pascuzzi, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, 46202, USA, Email rpascuzz@iupui.eduAbstract: “Myasthenia Gravis is, like it or not, the neurologist’s disease!” (Thomas Richards Johns II, MD Seminars in Neurology 1982). The most common disorders in clinical practice involving defective neuromuscular transmission are myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). The hallmark of weakness related to malfunction of the neuromuscular junction (NMJ) is variability in severity of symptoms from minute to minute and hour to hour. Fatigable weakness and fluctuation in symptoms are common in patients whether the etiology is autoimmune, paraneoplastic, genetic, or toxic. Autoimmune MG is the most common disorder of neuromuscular transmission affecting adults with an estimated prevalence of 1 in 10,000. While LEMS is comparatively rare, the unique clinical presentation, the association with cancer, and evolving treatment strategies require the neurologist to be familiar with its presentation, diagnosis, and management. In this paper we provide a summary of the meaningful recent clinical developments in the diagnosis and treatment of both MG and LEMS.Keywords: Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome, disorders of neuromuscular transmission

Purpose: To report a case of nonparaneoplastic autoimmune retinopathy in a patient with a diagnosis of Lambert–Eaton myasthenic syndrome. Methods: Case report. Main outcome measures included findings on retinal examination and analysis of fundus autofluorescence, spectral-domain optical coherence tomography, and full-field electroretinogram. Vitamin A levels and results of antiretinal antibody testing and paraneoplastic workup are also presented. Results: A 47-year-old male presented with a 1-year history of bilateral vision loss and nyctalopia. Past medical history was significant for Lambert–Eaton myasthenic syndrome, confirmed by positive voltage-gated calcium channel antibodies, and thymectomy reported as thymic follicular hyperplasia. Optical coherence tomography showed bilateral diffuse outer retinal atrophy and ellipsoid zone loss. Fundus autofluorescence displayed a bull's pattern of hyperautofluorescence around each fovea. Full-field electroretinogram showed an extinguished rod response and a severely depressed cone response in each eye. Conclusion: We describe a case of nonparaneoplastic autoimmune retinopathy in a patient with Lambert–Eaton myasthenic syndrome. Multimodal retinal imaging and electroretinogram confirmed the presence of autoimmune retinopathy with severe rod–cone degeneration. The association of this myasthenic syndrome with AIR is novel. [ABSTRACT FROM AUTHOR]

Abstract Background The Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder characterized by proximal muscle weakness and autonomic dysfunction due to involvement of the neuromuscular junction A case of delayed unilateral recovery from spinal anesthesia in a patient with LEMS undergoing open cholecystectomy is described. Case presentation A 42-year-old lady, on treatment for LEMS with pyridostigmine, prednisolone, and azathioprine presented with cholelithiasis and was scheduled for open cholecystectomy. Neuraxial anesthesia combined with a light plane of general anesthesia provided adequate muscle relaxation without the use of neuromuscular blocking drugs. In spite of perioperative continuation of anticholinesterases, the patient required 12 h post-surgery for complete bilateral motor recovery from spinal anesthesia. Conclusions A combination of spinal anesthesia with a light plane of general anesthesia appears to be a safe anesthetic technique for managing patients with Lambert-Eaton myasthenic syndrome undergoing open cholecystectomy. However, neurologically asymptomatic patients with good treatment compliance may also show an unusual delay in recovery from neuraxial anesthesia.

Lambert‐Eaton myasthenic syndrome (LEMS) is an autoimmune paraneoplastic syndrome with proximal muscle weakness, that often complicates small cell lung cancer. It is known that neurological symptoms do not improve with malignancy treatment alone in many LEMS patients, therefore treatment is often difficult. Since Lambert‐Eaton myasthenic syndrome is a rare disease with a frequency of about 1/100 that of myasthenia gravis, there are only a few case reports on malignancy complications other than small cell lung cancer. We report a LEMS patient in his 40s who was found to have an anterior mediastinal mass. We performed surgical resection and confirmed the diagnosis of primary thymic marginal zone B‐cell lymphoma by pathological diagnosis using immunostaining. Thymectomy and malignant lymphoma treatment with rituximab had no effect on neurological symptoms. The neurological symptoms improved only after we provided comprehensive care with the haematology, neurology, and rehabilitation department. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical associations of SOX1 antibodies (SOX1-Abs), determine the accuracy of various detection techniques, and propose laboratory criteria to identify definite paraneoplastic neurological syndromes (PNS) associated with SOX1-Abs. Methods: Single-center, retrospective study of patients referred to the French Reference Center between 2009 and 2019 for confirmation of SOX1-Ab positivity, without concurrent neural antibodies. Patients were classified according to the updated diagnostic PNS criteria; biological samples were systematically retested with three distinct techniques (line blot, cell-based assay, indirect immunofluorescence). Results: Among 77 patients with isolated SOX1-Ab positivity, 23 (29.9%) fulfilled the criteria for definite PNS; all of them had lung cancer (mostly small-cell) and presented mainly with Lambert-Eaton myasthenic syndrome (10/23) and rapidly progressive cerebellar ataxia (6/23). SOX1-Ab positivity varied depending on the laboratory methods which were used, and a single technique was not sufficient to draw conclusions about the PNS diagnosis. The combination of an antigen-specific test (line blot and/or cell-based assay) and immunofluorescence showed the highest accuracy (81.5%, 95% CI 70.0–90.1) in identifying definite PNS. Moreover, when the PNS-Care score was recalculated assigning three points at the laboratory-level only to patients with positive "antigenic-specific test + immunofluorescence" and 0 points to the remaining cases, a higher certainty for definite and non-PNS was achieved (from 41/77, 53.2%, to 60/77, 77.9%; p < 0.001). Conclusion: SOX1-Abs should be considered high-risk antibodies only when detected with a positive antigenic-specific test and immunofluorescence. Other laboratory results and clinical associations different from Lambert-Eaton myasthenic syndrome and rapidly progressive cerebellar ataxia should be carefully reassessed to rule out false positivity and alternative diagnoses. [ABSTRACT FROM AUTHOR]

• In selected cases, with high index of suspicion for paraneoplastic syndromes, cancer screening should be prolonged beyond the current recommendations. • The long disease course may be related to the anti-tumour effect of anti-VGCC Abs that slowed neoplasm growth. • DELTA-P score is a highly sensitive tool to discriminate between SCLC-LEMS and nontumour LEMS, by contrast anti-SOX1 antibodies have limited value as paraneoplastic biomarkers in clinical practice. 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. [ABSTRACT FROM AUTHOR]

The revised Japanese clinical guidelines for myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome (LEMS) were published in 2022. The notable points in these guidelines (GLs) are as follows: (i) these are the first Japanese GLs to include a description of LEMS; (ii) diagnostic criteria of MG are revised to lessen the incidence of false negative patients; (iii) MG is divided into six clinical subtypes; (iv) a high‐dose oral steroid regimen with escalation and de‐escalation schedule is not recommended by the GLs; (v) the GLs promote the early fast‐acting treatment strategy initially proposed in the previous GLs; (vi) refractory MG is defined; (vii) the use of molecular targeted drugs is included; (viii) diagnostic criteria of LEMS are proposed; and (ix) treatment algorithms for both MG and LEMS are presented. These new GLs are expected to improve the patients' quality of life and will serve to bridge the present era with the molecular targeted treatment eras. [ABSTRACT FROM AUTHOR]

Introduction: Myasthenia gravis disease (MGD) and inflammatory myopathy (IM) are commonly reported in the literature and usually appear with thymic pathology. Lambert-Eton myasthenic syndrome (LEMS) associated with IM is extremely rare. Case Presentation: We report a 42-year-old female patient who presented with proximal muscle weakness of the upper and lower limbs, normal creatinine kinase (CK) level, and positive acetylcholine and voltage-gated calcium channel receptor antibodies. There were no oculobulbar symptoms and no history of thymoma, and the electrophysiological tests were unremarkable. Muscle biopsy revealed focal perimysial and perivascular inflammation, predominantly B-cell lymphocytes, in a non-necrotizing muscle. Conclusions: LEMS associated with IM, particularly B-cell inflammation, has never been reported in the absence of cancer history. Clinical investigations and myopathological features can help establish the diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Lambert-Eaton myasthenia syndrome (LEMS) is a rare autoimmune disorder characterized by autoantibodies targeting presynaptic neuromuscular junctions. It results in muscle weakness and autonomic dysfunction. LEMS can be idiopathic or associated with neoplastic diseases, often small-cell lung cancer. This case report describes a rare instance of paraneoplastic LEMS in a man with non-Hodgkin lymphoma. Case Presentation: A 57-year-old male with non-Hodgkin lymphoma presented with progressive muscle weakness, diminished reflexes, and autonomic symptoms. Diagnosis revealed LEMS with autoantibodies against voltage-gated calcium channels. Immunosuppressive therapy and lymphoma treatment led to significant improvement in his condition. Conclusion: This case highlights the rare occurrence of paraneoplastic LEMS in a patient with non-Hodgkin lymphoma. Recognition and timely management of LEMS alongside lymphoma treatment can lead to significant clinical improvement, emphasizing the need for increased awareness of such complex associations. [ABSTRACT FROM AUTHOR]

BackgroundWhile immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of cancer, their administration has been associated with a variety of immune-related adverse events (irAEs), including myasthenia gravis (MG), and Lambert-Eaton myasthenic syndrome (LEMS).ObjectiveTo provide a comprehensive synthesis of the evidence supporting an etiological role for ICIs in MG and LEMS in patients with no prior history of autoimmune disease.HypothesisICIs may trigger MG and LEMS in patients with no prior susceptibility to autoimmune disease.MethodsRelevant primary research on Medline was interrogated using a series of search algorithms. Search terms were constructed based on the PICOS tool endorsed by the Cochrane Collaboration, which describes population, intervention, comparison, outcomes, and study design. Papers were screened according to inclusion and exclusion criteria. Additional papers were retrieved from the reference lists of screened papers. Each paper included in the qualitative synthesis was assigned an integrated metric of evidence (IME) value, ranging from 0 to 7, based on study design, quality of data, likelihood of a causal link between the immune checkpoint inhibitor(s) and MG/LEMS, confidence of MG/LEMS diagnosis, and the number of patients treated with an ICI prior to MG/LEMS diagnosis.ResultsNinety-four papers describing at least one patient treated with ICI(s) prior to the onset of MG and/or LEMS were documented. Overall evidence for a causal link between ICI administration and MG/LEMS was low, with a median IME value of 2.88 (range 2.05–6.61).ConclusionsThere is a paucity of evidence in support of an etiological relationship between ICIs and MG/LEMS, due largely to the lack of mechanistic studies and/or prospective clinical trials with relevant study endpoints. The current literature is dominated by case reports and retrospective cohort studies, which inherently yield only low-level evidence, supporting the need for further work in this area. A role of ICIs in the etiology of MG/LEMS remains plausible, arguing for continued vigilance for irAEs in patients treated with these drugs. We argue that there is a need for future mechanistic, high quality, large-scale studies specifically investigating the possible etiological role of ICIs in MG/LEMS.

Paraneoplastic syndrome is a group of clinical symptoms that occur in the state of systemic malignant tumors. Paraneoplastic syndrome of the nervous system can affect any part of the central and peripheral nervous system and may also affect the eyes. In neuroophthalmology, paraneoplastic syndrome has a variety of manifestations that can affect both the afferent and efferent visual systems. The afferent system may involve the optic nerve, retina and uvea; the efferent system may involve eye movement, neuromuscular joints or involuntary eye movements and pupil abnormalities and may also have other neurological symptoms outside the visual system. This article discusses the clinical manifestations, pathological mechanisms, detection methods and treatment methods of paraneoplastic syndrome in neuroophthalmology. The performance of paraneoplastic syndrome is diverse, the diagnosis is difficult, and the treatment should be considered systematically. Differential diagnosis, optimal evaluation and management of these manifestations is not only the key to treatment but also a challenge. [ABSTRACT FROM AUTHOR]

However, the Orphan Drug Act is intended to increase I approvals i for treatments for orphan diseases, and it appears that Catalyst just may have served the intent of the ODA by being the first company to take and complete the path that the ODA created for that very purpose. FDA took the unique approach (FDA's admission) of "administratively dividing" Jacobus's NDA into pediatric and adult populations. It is not clear why Jacobus required 27 years (1990-2017) from the grant of orphan drug status to file its initial NDA, but Jacobus apparently had been selling its product under FDA's compassionate use exemption for 25 years (1993-2018) before Catalyst finally got official FDA approval (thereby cutting Jacobus out of its market). [Extracted from the article]

Introduction: Lambert–Eaton myasthenic syndrome (LEMS) is characterized by autoantibodies against voltage-gated calcium channels (VGCC) at the neuromuscular junction causing proximal muscle weakness, decreased tendon reflexes, and autonomic changes. The European LEMS registry aimed to collate observational safety data for 3,4-diaminopyridine phosphate (3,4-DAPP) and examine long-term outcomes for patients with LEMS. Methods: Thirty centers across four countries participated in the non-interventional European LEMS registry. Any patients diagnosed with LEMS by means of clinical assessment and abnormal neurophysiological testing, or clinical assessment and positive for VGCC antibodies were eligible to participate. Patients were monitored using standard assessments for LEMS-related clinical manifestations. Results: Among 96 evaluable participants, 50 (52.1%) were being treated with 3,4-DAPP, 21 (21.9%) with 3,4-diaminopyridine (3,4-DAP), and 25 (26.0%) with other treatments (e.g., pyridostigmine, corticosteroids, immunoglobulins, and azathioprine); 74 participants (77.1%) were exposed to 3,4-DAPP at any time. Quantitative myasthenia gravis scores were similar across treatment groups. Muscle strength was generally good and maintained during follow-up. Cerebellar ataxia, defined as a negative Romberg's test and at least one other positive ataxia test, was observed in 30 (56.6%) patients. Most participants had reduced reflex tone and limited functioning. Sustained or improved functioning was observed in participants administered 3,4-DAPP. Inconsistent and sporadic functional improvement and regression was observed with 3,4-DAP and other treatments. Fifty-five treatment-related adverse events (AEs) were reported by 32 (33.3%) participants. Eight (8.3%) participants reported nine treatment-related serious AEs. No new safety signals were identified. Conclusion: No new safety signals were observed following long-term management of LEMS with 3,4-DAPP. [ABSTRACT FROM AUTHOR]