RARE DISEASE
Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome
Drug discovery
5
drugs
With orphan designations
Overview
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder targeting presynaptic voltage-gated calcium channels at the neuromuscular junction, impairing acetylcholine release and causing proximal muscle weakness, hyporeflexia, and autonomic dysfunction [1][6][7]. Approximately 50-60% of cases are paraneoplastic, typically associated with small-cell lung cancer (SCLC) [1][6]. Diagnosis involves antibody testing, electromyography, and cancer screening [7][15].
Burden
Health-related quality of life (HRQoL): Significantly lower than in myasthenia gravis and the general population, with impaired physical function (SF-36 score 34.2 vs. 78.6 in genP) [5][9][13].
Diagnostic delays: 58% initially misdiagnosed, often as myasthenia gravis or depression [10][12].
Disability: 25% require wheelchair use; prolonged disease duration in AI-LEMS (median 7.5 years) [10][16].
Therapies
First-line: 3,4-diaminopyridine (amifampridine) to enhance neuromuscular transmission [3][15].
Immunotherapy: IVIG, plasma exchange, or immunosuppressants (e.g., prednisone, azathioprine) for refractory cases [8][14].
Paraneoplastic: Tumor-directed therapy (e.g., chemotherapy for SCLC) improves LEMS outcomes [1][19].
Categories: rare neurological diseases
Research Papers
338 drug discovery papers about Lambert-Eaton myasthenic syndrome, with 1 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
338 drug discovery papers about Lambert-Eaton myasthenic syndrome, with 1 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-17 | Longitudinal overview of symptomatic and immunosuppressive drugs in LEMS.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder characterized by muscle weakness and autonomic dysfunction. While amifampridine is the established first-line symptomatic treatment, longitudinal data regarding the evolution of therapeutic regimens over time and the use of immunosuppressive therapies remain limited. This retrospective study analyzed 70 LEMS patients treated at the Leiden University Medical Center (LUMC) between 1992 and 2023. Treatment was evaluated and a four-point "leg score" was developed and used to retrospectively quantify functional impairment and response to amifampridine. Sixty-six percent of the cohort was female, the median age of diagnosis was 54 years and non-tumor LEMS was more prevalent (77%). All patients used amifampridine at some point, and 91% initiated it within six months of diagnosis. Amifampridine improved leg scores in 57% of patients. Although 58% of patients reported side effects (mostly paresthesia), discontinuation was rare (7%). Pyridostigmine was used in 81% of patients. Immunosuppressive drug use-predominantly prednisolone and azathioprine -increased over time, reaching 44% after five years. Conversely, azathioprine, prednisolone and pyridostigmine were discontinued by 50%, 38% and 32% of patients, respectively, often due to adverse effects. In conclusion, amifampridine provides significant clinical benefits and remains the cornerstone of LEMS therapy. Immunomodulatory therapies were introduced gradually and their use increased over time. Compared with autoimmune myasthenia gravis, immunomodulatory therapy was used less frequently during the early disease course of LEMS.
2026-07-16 | Clinical approach to neurological paraneoplastic syndromes.
Neurological paraneoplastic syndromes are immune-mediated disorders. The diagnosis of paraneoplastic syndromes is often difficult because they are rare and the onset of symptoms usually precedes detection of the underlying malignancy. Accurate diagnosis depends on recognition of the clinical phenotypes likely to be associated with a paraneoplastic aetiology and detection of an anti-neuronal antibody. Clinical phenotypes associated with a high risk of a paraneoplastic cause are limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus syndrome, subacute sensory neuronopathy, enteric neuropathy and Lambert Eaton myasthenic syndrome. Clinical phenotypes with an intermediate risk of a paraneoplastic aetiology are brainstem encephalitis, myelopathy, stiff person syndrome, Morvan syndrome and retinopathy. Anti-neuronal antibodies are extremely useful in the diagnosis of paraneoplastic neurological syndromes, but false-negative results can occur when only serum or cerebrospinal fluid (CSF) is tested. Commercial antibody panels do not include all antibodies associated with paraneoplastic syndromes, and if this diagnosis is strongly suspected, serum and CSF should be sent to a research laboratory. The risk of a false-positive result is increased if antibody tests are requested when there is a low pre-test probability of a paraneoplastic syndrome or if an antibody is detected in low titre.
2026-07-01 | Physiotherapy Management of an Older Adult with LambertEaton Myasthenic Syndrome Presenting with Proximal Limb Weakness and Autonomic Dysfunction: A Case Report
Introduction: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune presynaptic disorder of the neuromuscular junction, with an estimated prevalence of approximately 2.6 to 10 cases per million population.1,2 It is frequently under-recognized in physiotherapy settings because its insidious, fatigable proximal weakness can mimic deconditioning, lumbar radiculopathy, or age-related sarcopenia in older adults. This report describes the physiotherapy assessment and rehabilitation of a 60-year-old retired male with autoimmune LEMS, with particular attention to the use of low-intensity, fatigue-monitored exercise progression — an approach with limited prior documentation in the physiotherapy literature, as no controlled trials of physiotherapy specifically in LEMS currently exist. Case presentation: A 60-year-old retired male presented with a six-month history of progressive bilateral proximal lower limb weakness, difficulty rising from a chair and climbing stairs, dry mouth, and mild ptosis that worsened through the day and partially recovered with brief exertion. Tendon reflexes were diminished but augmented following sustained contraction. Management and outcomes: Diagnosis was confirmed by repetitive nerve stimulation showing post-tetanic facilitation and positive P/Q-type voltage-gated calcium channel (VGCC) antibodies, with no malignancy detected on staging investigations. Medical management with pyridostigmine and graded immunotherapy was combined with a physiotherapy programme emphasising submaximal aerobic and resistance exercise, energy conservation education, balance retraining, and fatigue self-monitoring. Over 12 weeks, the patient demonstrated improved manual muscle testing grades, a clinically meaningful reduction in Timed Up and Go time, and improved scores on the Myasthenia Gravis Quality of Life scale, without provoking overwork weakness. Conclusion: Individually tailored, fatigue-monitored physiotherapy can be safely incorporated alongside immunomodulatory and symptomatic pharmacological treatment in LEMS, supporting functional independence in an older adult. Close collaboration between neurology and physiotherapy, with vigilance for overwork weakness and underlying malignancy, is essential.
2026-05-20 | Nanotechnology-driven therapeutic strategies for lambert–eaton myasthenic syndrome: Emerging drug delivery and immunomodulatory approaches
Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by impaired acetylcholine release due to autoantibody-mediated targeting of presynaptic P/Q-type voltage-gated calcium channels. Although symptomatic therapies such as amifampridine and immunomodulatory agents provide clinical benefit, their efficacy is limited by short half-life, fluctuating plasma concentrations, systemic toxicity, and dose-dependent adverse effects, including seizures. These limitations highlight the need for advanced drug delivery systems. Recent advances in nanotechnology offer promising strategies to enhance therapeutic precision, bioavailability, and safety in LEMS management. Nanoparticle-based platforms including polymeric nanoparticles and lipid-based nanocarriers enable controlled drug release and improved pharmacokinetic stability, which may help maintain sustained plasma concentrations and thereby enhance drug availability at the neuromuscular junction. In addition, nanocarriers may facilitate improved transport across physiological barriers such as the Blood Nerve Barrier, potentially increasing drug accumulation at presynaptic terminals. Intranasal nanoformulations are explored as a non-invasive systemic delivery strategy, leveraging the highly vascularized nasal mucosa to enhance drug absorption and bypass hepatic first-pass metabolism, thereby improving systemic exposure rather than enabling direct central nervous system targeting. Furthermore, nano-enabled immunomodulation may allow selective suppression of pathogenic autoantibodies while minimizing systemic immunosuppression. This review provides a comprehensive overview of LEMS pathophysiology and current therapies, with a focused discussion on nanotechnology-driven approaches that may overcome existing pharmacological limitations. Future perspectives in targeted delivery, nano-immunotherapy, and biomarker-guided treatment strategies are also highlighted.
2026-04-29 | Lambert-Eaton Myasthenic Syndrome During Immunotherapy in Extensive-Stage Small-Cell Lung Cancer: A Case Report.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction that is frequently associated with small-cell lung cancer (SCLC). It is characterized by proximal muscle weakness, reduced deep tendon reflexes, and autonomic symptoms, all of which can significantly impair quality of life and complicate oncologic management. Early recognition and timely intervention are crucial to improving clinical outcomes. We report a case of a 76-year-old man with extensive-stage SCLC and chronic renal insufficiency whose LEMS worsened during durvalumab immunotherapy. Despite continued chemotherapy and immunotherapy, his symptoms progressively worsened. Chemotherapy failed to improve his neurological condition, with subsequent recurrent episodes of muscle weakness. Subsequent administration of intravenous immunoglobulin (IVIG) combined with pyridostigmine led to marked neurological improvement and restoration of muscle strength to grade 5, enabling continuation of antitumor therapy. The patient subsequently received three cycles of second-line lurbinectedin chemotherapy, during which inflammatory responses, anemia, and venous thrombosis developed but were effectively managed with supportive treatment. Following chemotherapy and immunotherapy, the patient's limb muscle strength recovered to grade 5, followed by recurrent muscle weakness symptoms. Hematologic and biochemical parameters gradually normalized, and inflammatory markers returned to baseline. At discharge, his clinical condition was stable. This case highlights the importance of early recognition and standardized management of paraneoplastic LEMS in enhancing functional recovery and enabling the safe continuation of antitumor therapy.
cell therapies
2026-09-01 | Chimeric antigen receptor T cell therapy in autoimmune neurological disease: current status of efficacy and safety
Autoimmune neurological diseases affecting the central nervous system, peripheral nervous system and neuromuscular junction are frequently refractory to conventional B-cell-depleting therapies such as CD20-directed monoclonal antibodies, highlighting a need for more effective treatment approaches. Chimeric antigen receptor T (CAR-T) cell therapy, initially developed for haematological malignancy, has been repurposed to more comprehensively deplete pathogenic B-cell and plasma cell populations in autoimmune disease, raising the possibility of durable, treatment-free remission. This scoping review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-ScR guidelines, examined published clinical studies from January 2023 to January 2026 in which CAR-T cells targeting CD19, CD20 or B-cell maturation antigen were used to treat autoimmune neurological disease, identifying 19 eligible studies. Efficacy signals were most consistent in refractory acetylcholine receptor antibody-positive generalised myasthenia gravis and Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, with encouraging but more preliminary results reported in multiple sclerosis, Lambert-Eaton myasthenic syndrome, myelin oligodendrocyte glycoprotein antibody-associated disease, chronic inflammatory demyelinating polyneuropathy, stiff-person syndrome and autoimmune encephalitis. Relapse was reported across several conditions, with follow-up generally limited to under two years. The safety profile compared favourably with that seen in oncological CAR-T use, with lower rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, although cytopenias, infection and prolonged hypogammaglobulinaemia remain clinically significant, and local immune effector cell-associated toxicity syndrome is an emerging concern not yet formally reported in this population. Current evidence remains limited to small, largely uncontrolled studies with heterogeneous outcome reporting. Adequately powered, longer-term controlled trials are needed before CAR-T therapy can be recommended more broadly in the management of refractory autoimmune neurological disease.
2026-08-19 | Plasma Exchange-Responsive Bulbar Dysfunction in Thymoma-Associated Myasthenia Gravis with Concomitant Lambert-Eaton Myasthenic Syndrome.
The coexistence of thymoma-associated myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) is rare, and no established therapeutic strategy exists for this condition. We herein report a case of MG-LEMS overlap syndrome (MLOS) in which plasma exchange (PE) effectively treated severe bulbar dysfunction refractory to intravenous immunoglobulin (IVIg). Sequential electrophysiological testing demonstrated an improvement in the low compound muscle action potential amplitudes and post-exercise increments, reflecting LEMS activity. This case highlights that PE may be more efficacious than IVIg for bulbar symptoms in MLOS, particularly with prominent presynaptic involvement, and supports electrophysiological assessment to guide treatment.
2026-04-24 | Cellular therapies in autoimmune neuromuscular disorders: the new frontier.
Antibody-mediated humoral immunity plays a vital role in a number of autoimmune neuromuscular disorders (AINMD), such as myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), stiff-person syndrome (SPS), and autoimmune myositides. Although biologics based B cell and plasma cell depletion (BCDT) therapy effectively treats some AINMDs, its variable success highlights the limitations of this therapeutic modality. B cell directed cellular therapy (BCDcT) targeting a wide array of B cell lineages, including short-lived plasma cells, has emerged as an effective treatment modality in hematological malignancies, resulting in impressive reductions in tumor burden, relapse rates, and mortality. Despite the impressive success of BCDcT, especially in hematological malignancies, its initial use was limited to last-resort cases due to the high morbidity associated with cytokine release syndrome (CRS) and immune cell-associated neurological toxicity (ICANS). Recent improvements in the safety profile of BCDcTs and better clinical management have lowered the incidences of CRS and ICANS, leading to its earlier use in some cancers. The success of BCDcT in B cell malignancies has promoted strong interest in applying this therapeutic approach to autoimmune disorders, particularly AINMD. This review will cover cell therapy fundamentals, limitations of current BCDTs, experiences with cell therapy in AINMD, and both ongoing and planned trials in this field.
2026-03-13 | CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy.
Chimeric antigen receptor (CAR) T cell therapy is emerging as a promising approach for B cell-driven neurological autoimmune disorders, particularly those characterized by pathogenic autoantibodies that target key neural structures. These conditions, including neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis, can be categorized based on their primary autoantigens into (1) extracellular antigen-associated (e.g., AQP4, AChR, NMDAR, MOG, VGCC), (2) intracellular antigen-associated (e.g., GAD65, DAGLA), or (3) unidentified antigenic origin (as seen in multiple sclerosis). This distinction is essential for guiding therapeutic strategies and exploring novel principles represented in distinct treatment approaches and their corresponding therapeutic outcomes. In this review, we propose a classification of CAR T cell therapies designed for different target antigens, including: CD19/20/BCMA-directed CAR T cells targeting general B cell-mediated pathogenesis, regulatory T cells modified with CARs, and the design of chimeric autoantibody receptors (CAARs) to selectively deplete pathogenic B cells directly associated with disease progression while preserving immune tolerance. We further discuss preclinical and clinical advancements, key challenges such as safety concerns and neurotoxicity, and the future landscape of CAR T applications in neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis according to the latest research, case and trial data. CAR T cell therapy potentially offers a highly specific and effective method with thorough elimination of autoreactive B cells, representing a rapidly evolving field with the potential to transform the treatment of autoimmune neurological disorders. As CAR T technology advances, it holds the potential to become a groundbreaking immunoablative strategy with so-far disclosed controllable side effects; however, further long-term follow-up data are still needed to validate its application in autoimmune disorders.
2025-06-27 | A Rare Case of Lambert-Eaton Myasthenia Syndrome With Dysphasia and Dysarthria.
Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder resulting in muscle weakness. LEMS typically presents with progressive proximal muscle weakness, especially in the lower extremities, areflexia, and autonomic dysfunction. Bulbar involvement and respiratory compromise tend to occur later in the disease course and usually in severe, advanced cases. We report a unique case of a 50-year-old male with a known history of LEMS, autoimmune retinopathy, erectile dysfunction, and prediabetes who presented with progressive bulbar symptoms - slurred speech and difficulty swallowing - without accompanying weakness in the upper or lower extremities. Despite receiving four doses of intravenous immunoglobulin (IVIG) prior to admission with no improvement, he showed a significant clinical response to six sessions of plasmapheresis. Notably, the absence of limb weakness and preserved motor strength throughout his hospital stay raised diagnostic uncertainty, prompting evaluation for myasthenia gravis, which was ruled out through negative acetylcholine receptor antibody testing and reaffirmed voltage-gated calcium channel (VGCC) antibody positivity. Chest imaging showed no underlying malignancy. This case illustrates an atypical LEMS presentation dominated by severe bulbar dysfunction in the absence of limb involvement or respiratory failure, which is uncommon and may mimic other neuromuscular junction disorders such as myasthenia gravis. The favorable response to plasmapheresis emphasizes the importance of early recognition and aggressive immunomodulatory treatment in preventing clinical deterioration. Clinicians should maintain a high index of suspicion for LEMS even in unusual presentations to ensure timely and appropriate management.
antibodies
2026-09-28 | Case Report: Efgartigimod in refractory non-tumor Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder, associated with neoplastic disease in 50-60% of cases. In severe cases, currently available immunomodulatory therapies frequently fail to achieve adequate control. We report a 20-year-old woman with non-tumor LEMS refractory to 3,4-diaminopyridine, sequential immunosuppression with prednisone, azathioprine, mycophenolate mofetil and rituximab and plasma exchange, who remained severely disabled after two years of progressive disease. Off-label efgartigimod (1000mg subcutaneously weekly for four weeks, with the interval between cycles initially adjusted according to symptom recurrence), produced rapid and sustained clinical improvement, including recovery from a respiratory decompensation episode. The Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased from a baseline of 5–9 to a minimum of 2, and the Quantitative Myasthenia Gravis (QMG) score improved from 13–18 to 8-11. Symptoms consistently recurred toward the end of the third week of each treatment-free interval, prompting a fixed two-week interval, which stabilized clinical response and reduced fluctuation severity. This is, to our knowledge, the first report of sustained clinical benefit from FcRn inhibition in non-paraneoplastic, long-standing refractory LEMS. As in myasthenia gravis, LEMS is mediated by pathogenic circulating IgG antibodies, and these findings support FcRn inhibition as a rational treatment strategy in refractory LEMS regardless of tumor association.
2026-09-17 | Decrement on Low-Frequency Repetitive Nerve Stimulation Is Not Synonymous With Myasthenia Gravis.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic neuromuscular junction disorder that may be mistaken for peripheral neuropathy, radiculopathy, inflammatory myopathy, or myasthenia gravis. We report a female in her early 40s with two months of progressive, predominantly proximal lower-limb weakness, areflexia, and dry mouth, without ocular or bulbar symptoms. Routine laboratory testing and creatine kinase were unremarkable, while spinal imaging showed degenerative abnormalities that did not explain the clinical pattern. Nerve conduction studies demonstrated low compound muscle action potential amplitudes with preserved sensory responses and no demyelinating features. Low-frequency repetitive nerve stimulation produced a decrement, whereas brief exercise caused a marked increase in compound muscle action potential amplitude. Serum P/Q-type voltage-gated calcium channel antibodies were positive, confirming LEMS. Pyridostigmine produced partial symptomatic improvement. Amifampridine was subsequently initiated, followed by intravenous immunoglobulin, after which the patient demonstrated marked improvement in lower-limb strength and walking ability. Initial malignancy screening was negative, and longitudinal surveillance was planned. This case emphasizes that a decrement on low-frequency stimulation is not specific for myasthenia gravis and that low resting motor amplitudes with marked post-exercise facilitation strongly indicate a presynaptic neuromuscular junction disorder.
2026-08-21 | Rituximab for autoimmune myasthenic syndromes: a retrospective cohort study in myasthenia gravis and Lambert-Eaton myasthenic syndrome
Abstract INTRODUCTION Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune diseases of the neuromuscular junction resulting in fatigable muscle weakness. Rituximab (RTX) is used to treat patients refractory to standard immunosuppression, but evidence for its efficacy remains inconsistent. Here, we analyzed real-world data on the clinical course and side effects of RTX in MG and LEMS patients. METHODS This was a single-center study of all patients diagnosed with MG (n=64) or LEMS (n=5) treated with RTX from 2011 until 2021. Outcomes of RTX treatment were recorded retrospectively with Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), number of rescue therapies, myasthenic crises, and steroid dose at 1-year and 2-year follow-ups. RESULTS MGFA-PIS improved at both 1-year (y) and 2-y follow-up compared with baseline. Incidence rates of rescue therapies per 100 person-months (95% CI) decreased from 15.0 (11.8–18.8) at baseline to 7.5 (4.7–12.3) at 1-y and 4.3 (2.5–7.8) at 2y-follow-up. The number of patients without myasthenic crises within one year increased from baseline (49, 86.0%) to 1y-follow-up (55, 96.5%). Median (IQR) daily steroid dose decreased from 10 (5– 22.5) mg/d at baseline to 4 (0–10) mg/d at 1y-follow-up, and to 2.5 (0–10) mg/d at 2y-follow-up. CONCLUSION This study indicates that RTX was associated with a stabilized clinical course and decreased steroid use in patients with autoimmune myasthenic syndromes, including those with thymoma-associated MG. Our data suggest that therapeutic benefit is apparent within the first year of treatment and is maintained through two years.
2026-08-19 | Early Induction of IVIg Improved the Performance Status and Enabled Chemotherapy Initiation in PCD-LEMS: A Case Report.
A 73-year-old man developed progressive gait disturbance and diplopia over two weeks concomitant with rapidly enlarging pulmonary lesions. Examination revealed proximal lower limb weakness, diminished deep tendon reflexes, ataxic dysarthria, limb and truncal ataxia, and orthostatic hypotension. Nerve conduction studies revealed reduced compound muscle action potentials with postexercise facilitation. Elevated anti-P/Q-type voltage-gated calcium channel antibodies confirmed paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome (LEMS). Bronchoscopy revealed small-cell lung cancer. Although a poor performance status (PS) initially precluded chemotherapy, high-dose intravenous immunoglobulin therapy improved the PS, enabling cancer treatment. Immunotherapy should be considered when a PCD-LEMS-related poor PS prevents cancer therapy.
2026-01-24 | Clinical Spectrum and Outcomes of SOX1 Antibody-Associated Paraneoplastic Neurological Syndromes: A Chinese Cohort Study.
SOX1 antibody-positive paraneoplastic neurological syndromes (PNS) exhibit significant population-specific clinical heterogeneity. While Western cohorts predominantly manifest Lambert-Eaton myasthenic syndrome (65%-80%), comprehensive clinical characterization and treatment response data in Asian populations remain critically limited. We conducted a single-center retrospective case series analyzing 13 consecutive patients with SOX1 antibody-positive PNS treated at Guangdong Sanjiu Brain Hospital from January 2019 to December 2024. SOX1 antibodies were confirmed using commercial immunoblot assay. Primary endpoints included treatment response (≥ 1-point improvement on modified Rankin Scale [mRS]) and functional recovery (mRS ≤ 2). Statistical analyses employed Fisher's exact tests and Mann-Whitney U tests. Among 13 patients (median age 61 years [IQR 56-67], 53.8% female), neuropsychiatric presentations predominated, including seizures (46.2%) and psychiatric symptoms (30.8%), with combined neuropsychiatric manifestations occurring in 53.8% of patients. Co-existing neuronal antibodies were identified in 15.4% of cases (GABAB receptor, LGI1). Malignancy was confirmed in 30.8% of patients. Immunotherapy recipients (n = 7) demonstrated significantly superior functional outcomes compared to non-treated patients: median 3-month mRS 0 (IQR 0-0) versus 3 (IQR 3-3), p = 0.03. Treatment response rates were 85.7% versus 33.3% (p = 0.103). Chinese patients with SOX1 antibody-positive PNS demonstrate a neuropsychiatric-predominant phenotype (53.8%), contrasting markedly with Western cohorts. Early immunotherapy administration was associated with superior functional outcomes (median 3-month mRS: 0 vs. 3, p = 0.03). These findings support comprehensive neuronal antibody profiling and early immunotherapy consideration in patients presenting with neuropsychiatric manifestations.
combination
2025-10-09 | A Rare Case of Autoimmune Enteropathy Associated With Lambert-Eaton Myasthenic Syndrome and a Literature Review.
Autoimmune enteropathy is a rare intestinal disease characterized by chronic diarrhea and severe malabsorption in the presence of circulating autoantibodies against enterocytes and goblet cells, typically affecting children or young adults. Lambert-Eaton myasthenic syndrome (LEMS) is also a rare autoimmune neuromuscular junction disorder characterized by muscle weakness due to antibodies against the P/Q-type voltage-gated calcium channels (VGCCs) on the presynaptic nerve terminals. We report a case of concurrent diagnoses of autoimmune enteropathy and LEMS in a 24-year-old female patient with a history of autoimmune thyroiditis and vitiligo. The diagnosis of LEMS was established by the typical electromyographic findings and positive antibodies against P/Q-type VGCCs. After malignancies were excluded, treatment with rituximab in combination with intravenous immunoglobulin led to improvement. Within two months of the LEMS diagnosis, the patient presented with severe muscle weakness, chronic diarrhea, vomiting, and weight loss. After a thorough work-up, the diagnosis of autoimmune enteropathy was made, based on severe villous atrophy with a dense inflammatory infiltrate in duodenal biopsies and the exclusion of other causes of chronic diarrhea and non-celiac enteropathy. The patient was treated successfully with total parenteral nutrition, corticosteroids, and azathioprine. To our knowledge, this is one of the first reports of autoimmune enteropathy associated with LEMS.
small molecules
2026-08-17 | Longitudinal overview of symptomatic and immunosuppressive drugs in LEMS.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder characterized by muscle weakness and autonomic dysfunction. While amifampridine is the established first-line symptomatic treatment, longitudinal data regarding the evolution of therapeutic regimens over time and the use of immunosuppressive therapies remain limited. This retrospective study analyzed 70 LEMS patients treated at the Leiden University Medical Center (LUMC) between 1992 and 2023. Treatment was evaluated and a four-point "leg score" was developed and used to retrospectively quantify functional impairment and response to amifampridine. Sixty-six percent of the cohort was female, the median age of diagnosis was 54 years and non-tumor LEMS was more prevalent (77%). All patients used amifampridine at some point, and 91% initiated it within six months of diagnosis. Amifampridine improved leg scores in 57% of patients. Although 58% of patients reported side effects (mostly paresthesia), discontinuation was rare (7%). Pyridostigmine was used in 81% of patients. Immunosuppressive drug use-predominantly prednisolone and azathioprine -increased over time, reaching 44% after five years. Conversely, azathioprine, prednisolone and pyridostigmine were discontinued by 50%, 38% and 32% of patients, respectively, often due to adverse effects. In conclusion, amifampridine provides significant clinical benefits and remains the cornerstone of LEMS therapy. Immunomodulatory therapies were introduced gradually and their use increased over time. Compared with autoimmune myasthenia gravis, immunomodulatory therapy was used less frequently during the early disease course of LEMS.
2026-07-16 | Clinical approach to neurological paraneoplastic syndromes.
Neurological paraneoplastic syndromes are immune-mediated disorders. The diagnosis of paraneoplastic syndromes is often difficult because they are rare and the onset of symptoms usually precedes detection of the underlying malignancy. Accurate diagnosis depends on recognition of the clinical phenotypes likely to be associated with a paraneoplastic aetiology and detection of an anti-neuronal antibody. Clinical phenotypes associated with a high risk of a paraneoplastic cause are limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus syndrome, subacute sensory neuronopathy, enteric neuropathy and Lambert Eaton myasthenic syndrome. Clinical phenotypes with an intermediate risk of a paraneoplastic aetiology are brainstem encephalitis, myelopathy, stiff person syndrome, Morvan syndrome and retinopathy. Anti-neuronal antibodies are extremely useful in the diagnosis of paraneoplastic neurological syndromes, but false-negative results can occur when only serum or cerebrospinal fluid (CSF) is tested. Commercial antibody panels do not include all antibodies associated with paraneoplastic syndromes, and if this diagnosis is strongly suspected, serum and CSF should be sent to a research laboratory. The risk of a false-positive result is increased if antibody tests are requested when there is a low pre-test probability of a paraneoplastic syndrome or if an antibody is detected in low titre.
2026-07-01 | Physiotherapy Management of an Older Adult with LambertEaton Myasthenic Syndrome Presenting with Proximal Limb Weakness and Autonomic Dysfunction: A Case Report
Introduction: Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune presynaptic disorder of the neuromuscular junction, with an estimated prevalence of approximately 2.6 to 10 cases per million population.1,2 It is frequently under-recognized in physiotherapy settings because its insidious, fatigable proximal weakness can mimic deconditioning, lumbar radiculopathy, or age-related sarcopenia in older adults. This report describes the physiotherapy assessment and rehabilitation of a 60-year-old retired male with autoimmune LEMS, with particular attention to the use of low-intensity, fatigue-monitored exercise progression — an approach with limited prior documentation in the physiotherapy literature, as no controlled trials of physiotherapy specifically in LEMS currently exist. Case presentation: A 60-year-old retired male presented with a six-month history of progressive bilateral proximal lower limb weakness, difficulty rising from a chair and climbing stairs, dry mouth, and mild ptosis that worsened through the day and partially recovered with brief exertion. Tendon reflexes were diminished but augmented following sustained contraction. Management and outcomes: Diagnosis was confirmed by repetitive nerve stimulation showing post-tetanic facilitation and positive P/Q-type voltage-gated calcium channel (VGCC) antibodies, with no malignancy detected on staging investigations. Medical management with pyridostigmine and graded immunotherapy was combined with a physiotherapy programme emphasising submaximal aerobic and resistance exercise, energy conservation education, balance retraining, and fatigue self-monitoring. Over 12 weeks, the patient demonstrated improved manual muscle testing grades, a clinically meaningful reduction in Timed Up and Go time, and improved scores on the Myasthenia Gravis Quality of Life scale, without provoking overwork weakness. Conclusion: Individually tailored, fatigue-monitored physiotherapy can be safely incorporated alongside immunomodulatory and symptomatic pharmacological treatment in LEMS, supporting functional independence in an older adult. Close collaboration between neurology and physiotherapy, with vigilance for overwork weakness and underlying malignancy, is essential.
2026-05-20 | Nanotechnology-driven therapeutic strategies for lambert–eaton myasthenic syndrome: Emerging drug delivery and immunomodulatory approaches
Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by impaired acetylcholine release due to autoantibody-mediated targeting of presynaptic P/Q-type voltage-gated calcium channels. Although symptomatic therapies such as amifampridine and immunomodulatory agents provide clinical benefit, their efficacy is limited by short half-life, fluctuating plasma concentrations, systemic toxicity, and dose-dependent adverse effects, including seizures. These limitations highlight the need for advanced drug delivery systems. Recent advances in nanotechnology offer promising strategies to enhance therapeutic precision, bioavailability, and safety in LEMS management. Nanoparticle-based platforms including polymeric nanoparticles and lipid-based nanocarriers enable controlled drug release and improved pharmacokinetic stability, which may help maintain sustained plasma concentrations and thereby enhance drug availability at the neuromuscular junction. In addition, nanocarriers may facilitate improved transport across physiological barriers such as the Blood Nerve Barrier, potentially increasing drug accumulation at presynaptic terminals. Intranasal nanoformulations are explored as a non-invasive systemic delivery strategy, leveraging the highly vascularized nasal mucosa to enhance drug absorption and bypass hepatic first-pass metabolism, thereby improving systemic exposure rather than enabling direct central nervous system targeting. Furthermore, nano-enabled immunomodulation may allow selective suppression of pathogenic autoantibodies while minimizing systemic immunosuppression. This review provides a comprehensive overview of LEMS pathophysiology and current therapies, with a focused discussion on nanotechnology-driven approaches that may overcome existing pharmacological limitations. Future perspectives in targeted delivery, nano-immunotherapy, and biomarker-guided treatment strategies are also highlighted.
2026-04-29 | Lambert-Eaton Myasthenic Syndrome During Immunotherapy in Extensive-Stage Small-Cell Lung Cancer: A Case Report.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction that is frequently associated with small-cell lung cancer (SCLC). It is characterized by proximal muscle weakness, reduced deep tendon reflexes, and autonomic symptoms, all of which can significantly impair quality of life and complicate oncologic management. Early recognition and timely intervention are crucial to improving clinical outcomes. We report a case of a 76-year-old man with extensive-stage SCLC and chronic renal insufficiency whose LEMS worsened during durvalumab immunotherapy. Despite continued chemotherapy and immunotherapy, his symptoms progressively worsened. Chemotherapy failed to improve his neurological condition, with subsequent recurrent episodes of muscle weakness. Subsequent administration of intravenous immunoglobulin (IVIG) combined with pyridostigmine led to marked neurological improvement and restoration of muscle strength to grade 5, enabling continuation of antitumor therapy. The patient subsequently received three cycles of second-line lurbinectedin chemotherapy, during which inflammatory responses, anemia, and venous thrombosis developed but were effectively managed with supportive treatment. Following chemotherapy and immunotherapy, the patient's limb muscle strength recovered to grade 5, followed by recurrent muscle weakness symptoms. Hematologic and biochemical parameters gradually normalized, and inflammatory markers returned to baseline. At discharge, his clinical condition was stable. This case highlights the importance of early recognition and standardized management of paraneoplastic LEMS in enhancing functional recovery and enabling the safe continuation of antitumor therapy.
cell therapies
2026-09-01 | Chimeric antigen receptor T cell therapy in autoimmune neurological disease: current status of efficacy and safety
Autoimmune neurological diseases affecting the central nervous system, peripheral nervous system and neuromuscular junction are frequently refractory to conventional B-cell-depleting therapies such as CD20-directed monoclonal antibodies, highlighting a need for more effective treatment approaches. Chimeric antigen receptor T (CAR-T) cell therapy, initially developed for haematological malignancy, has been repurposed to more comprehensively deplete pathogenic B-cell and plasma cell populations in autoimmune disease, raising the possibility of durable, treatment-free remission. This scoping review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-ScR guidelines, examined published clinical studies from January 2023 to January 2026 in which CAR-T cells targeting CD19, CD20 or B-cell maturation antigen were used to treat autoimmune neurological disease, identifying 19 eligible studies. Efficacy signals were most consistent in refractory acetylcholine receptor antibody-positive generalised myasthenia gravis and Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder, with encouraging but more preliminary results reported in multiple sclerosis, Lambert-Eaton myasthenic syndrome, myelin oligodendrocyte glycoprotein antibody-associated disease, chronic inflammatory demyelinating polyneuropathy, stiff-person syndrome and autoimmune encephalitis. Relapse was reported across several conditions, with follow-up generally limited to under two years. The safety profile compared favourably with that seen in oncological CAR-T use, with lower rates of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, although cytopenias, infection and prolonged hypogammaglobulinaemia remain clinically significant, and local immune effector cell-associated toxicity syndrome is an emerging concern not yet formally reported in this population. Current evidence remains limited to small, largely uncontrolled studies with heterogeneous outcome reporting. Adequately powered, longer-term controlled trials are needed before CAR-T therapy can be recommended more broadly in the management of refractory autoimmune neurological disease.
2026-08-19 | Plasma Exchange-Responsive Bulbar Dysfunction in Thymoma-Associated Myasthenia Gravis with Concomitant Lambert-Eaton Myasthenic Syndrome.
The coexistence of thymoma-associated myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) is rare, and no established therapeutic strategy exists for this condition. We herein report a case of MG-LEMS overlap syndrome (MLOS) in which plasma exchange (PE) effectively treated severe bulbar dysfunction refractory to intravenous immunoglobulin (IVIg). Sequential electrophysiological testing demonstrated an improvement in the low compound muscle action potential amplitudes and post-exercise increments, reflecting LEMS activity. This case highlights that PE may be more efficacious than IVIg for bulbar symptoms in MLOS, particularly with prominent presynaptic involvement, and supports electrophysiological assessment to guide treatment.
2026-04-24 | Cellular therapies in autoimmune neuromuscular disorders: the new frontier.
Antibody-mediated humoral immunity plays a vital role in a number of autoimmune neuromuscular disorders (AINMD), such as myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), stiff-person syndrome (SPS), and autoimmune myositides. Although biologics based B cell and plasma cell depletion (BCDT) therapy effectively treats some AINMDs, its variable success highlights the limitations of this therapeutic modality. B cell directed cellular therapy (BCDcT) targeting a wide array of B cell lineages, including short-lived plasma cells, has emerged as an effective treatment modality in hematological malignancies, resulting in impressive reductions in tumor burden, relapse rates, and mortality. Despite the impressive success of BCDcT, especially in hematological malignancies, its initial use was limited to last-resort cases due to the high morbidity associated with cytokine release syndrome (CRS) and immune cell-associated neurological toxicity (ICANS). Recent improvements in the safety profile of BCDcTs and better clinical management have lowered the incidences of CRS and ICANS, leading to its earlier use in some cancers. The success of BCDcT in B cell malignancies has promoted strong interest in applying this therapeutic approach to autoimmune disorders, particularly AINMD. This review will cover cell therapy fundamentals, limitations of current BCDTs, experiences with cell therapy in AINMD, and both ongoing and planned trials in this field.
2026-03-13 | CAR T cell therapy in autoantibody-mediated neurological disorders: a promising strategy.
Chimeric antigen receptor (CAR) T cell therapy is emerging as a promising approach for B cell-driven neurological autoimmune disorders, particularly those characterized by pathogenic autoantibodies that target key neural structures. These conditions, including neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis, can be categorized based on their primary autoantigens into (1) extracellular antigen-associated (e.g., AQP4, AChR, NMDAR, MOG, VGCC), (2) intracellular antigen-associated (e.g., GAD65, DAGLA), or (3) unidentified antigenic origin (as seen in multiple sclerosis). This distinction is essential for guiding therapeutic strategies and exploring novel principles represented in distinct treatment approaches and their corresponding therapeutic outcomes. In this review, we propose a classification of CAR T cell therapies designed for different target antigens, including: CD19/20/BCMA-directed CAR T cells targeting general B cell-mediated pathogenesis, regulatory T cells modified with CARs, and the design of chimeric autoantibody receptors (CAARs) to selectively deplete pathogenic B cells directly associated with disease progression while preserving immune tolerance. We further discuss preclinical and clinical advancements, key challenges such as safety concerns and neurotoxicity, and the future landscape of CAR T applications in neuromyelitis optica spectrum disorder, myasthenia gravis, Lambert-Eaton myasthenic syndrome, MOG antibody-associated disease, anti-NMDA receptor encephalitis, Diacylglycerol lipase alpha antibody associated encephalitis, stiff person syndrome, and multiple sclerosis according to the latest research, case and trial data. CAR T cell therapy potentially offers a highly specific and effective method with thorough elimination of autoreactive B cells, representing a rapidly evolving field with the potential to transform the treatment of autoimmune neurological disorders. As CAR T technology advances, it holds the potential to become a groundbreaking immunoablative strategy with so-far disclosed controllable side effects; however, further long-term follow-up data are still needed to validate its application in autoimmune disorders.
2025-06-27 | A Rare Case of Lambert-Eaton Myasthenia Syndrome With Dysphasia and Dysarthria.
Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder resulting in muscle weakness. LEMS typically presents with progressive proximal muscle weakness, especially in the lower extremities, areflexia, and autonomic dysfunction. Bulbar involvement and respiratory compromise tend to occur later in the disease course and usually in severe, advanced cases. We report a unique case of a 50-year-old male with a known history of LEMS, autoimmune retinopathy, erectile dysfunction, and prediabetes who presented with progressive bulbar symptoms - slurred speech and difficulty swallowing - without accompanying weakness in the upper or lower extremities. Despite receiving four doses of intravenous immunoglobulin (IVIG) prior to admission with no improvement, he showed a significant clinical response to six sessions of plasmapheresis. Notably, the absence of limb weakness and preserved motor strength throughout his hospital stay raised diagnostic uncertainty, prompting evaluation for myasthenia gravis, which was ruled out through negative acetylcholine receptor antibody testing and reaffirmed voltage-gated calcium channel (VGCC) antibody positivity. Chest imaging showed no underlying malignancy. This case illustrates an atypical LEMS presentation dominated by severe bulbar dysfunction in the absence of limb involvement or respiratory failure, which is uncommon and may mimic other neuromuscular junction disorders such as myasthenia gravis. The favorable response to plasmapheresis emphasizes the importance of early recognition and aggressive immunomodulatory treatment in preventing clinical deterioration. Clinicians should maintain a high index of suspicion for LEMS even in unusual presentations to ensure timely and appropriate management.
antibodies
2026-09-28 | Case Report: Efgartigimod in refractory non-tumor Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder, associated with neoplastic disease in 50-60% of cases. In severe cases, currently available immunomodulatory therapies frequently fail to achieve adequate control. We report a 20-year-old woman with non-tumor LEMS refractory to 3,4-diaminopyridine, sequential immunosuppression with prednisone, azathioprine, mycophenolate mofetil and rituximab and plasma exchange, who remained severely disabled after two years of progressive disease. Off-label efgartigimod (1000mg subcutaneously weekly for four weeks, with the interval between cycles initially adjusted according to symptom recurrence), produced rapid and sustained clinical improvement, including recovery from a respiratory decompensation episode. The Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased from a baseline of 5–9 to a minimum of 2, and the Quantitative Myasthenia Gravis (QMG) score improved from 13–18 to 8-11. Symptoms consistently recurred toward the end of the third week of each treatment-free interval, prompting a fixed two-week interval, which stabilized clinical response and reduced fluctuation severity. This is, to our knowledge, the first report of sustained clinical benefit from FcRn inhibition in non-paraneoplastic, long-standing refractory LEMS. As in myasthenia gravis, LEMS is mediated by pathogenic circulating IgG antibodies, and these findings support FcRn inhibition as a rational treatment strategy in refractory LEMS regardless of tumor association.
2026-09-17 | Decrement on Low-Frequency Repetitive Nerve Stimulation Is Not Synonymous With Myasthenia Gravis.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic neuromuscular junction disorder that may be mistaken for peripheral neuropathy, radiculopathy, inflammatory myopathy, or myasthenia gravis. We report a female in her early 40s with two months of progressive, predominantly proximal lower-limb weakness, areflexia, and dry mouth, without ocular or bulbar symptoms. Routine laboratory testing and creatine kinase were unremarkable, while spinal imaging showed degenerative abnormalities that did not explain the clinical pattern. Nerve conduction studies demonstrated low compound muscle action potential amplitudes with preserved sensory responses and no demyelinating features. Low-frequency repetitive nerve stimulation produced a decrement, whereas brief exercise caused a marked increase in compound muscle action potential amplitude. Serum P/Q-type voltage-gated calcium channel antibodies were positive, confirming LEMS. Pyridostigmine produced partial symptomatic improvement. Amifampridine was subsequently initiated, followed by intravenous immunoglobulin, after which the patient demonstrated marked improvement in lower-limb strength and walking ability. Initial malignancy screening was negative, and longitudinal surveillance was planned. This case emphasizes that a decrement on low-frequency stimulation is not specific for myasthenia gravis and that low resting motor amplitudes with marked post-exercise facilitation strongly indicate a presynaptic neuromuscular junction disorder.
2026-08-21 | Rituximab for autoimmune myasthenic syndromes: a retrospective cohort study in myasthenia gravis and Lambert-Eaton myasthenic syndrome
Abstract INTRODUCTION Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune diseases of the neuromuscular junction resulting in fatigable muscle weakness. Rituximab (RTX) is used to treat patients refractory to standard immunosuppression, but evidence for its efficacy remains inconsistent. Here, we analyzed real-world data on the clinical course and side effects of RTX in MG and LEMS patients. METHODS This was a single-center study of all patients diagnosed with MG (n=64) or LEMS (n=5) treated with RTX from 2011 until 2021. Outcomes of RTX treatment were recorded retrospectively with Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), number of rescue therapies, myasthenic crises, and steroid dose at 1-year and 2-year follow-ups. RESULTS MGFA-PIS improved at both 1-year (y) and 2-y follow-up compared with baseline. Incidence rates of rescue therapies per 100 person-months (95% CI) decreased from 15.0 (11.8–18.8) at baseline to 7.5 (4.7–12.3) at 1-y and 4.3 (2.5–7.8) at 2y-follow-up. The number of patients without myasthenic crises within one year increased from baseline (49, 86.0%) to 1y-follow-up (55, 96.5%). Median (IQR) daily steroid dose decreased from 10 (5– 22.5) mg/d at baseline to 4 (0–10) mg/d at 1y-follow-up, and to 2.5 (0–10) mg/d at 2y-follow-up. CONCLUSION This study indicates that RTX was associated with a stabilized clinical course and decreased steroid use in patients with autoimmune myasthenic syndromes, including those with thymoma-associated MG. Our data suggest that therapeutic benefit is apparent within the first year of treatment and is maintained through two years.
2026-08-19 | Early Induction of IVIg Improved the Performance Status and Enabled Chemotherapy Initiation in PCD-LEMS: A Case Report.
A 73-year-old man developed progressive gait disturbance and diplopia over two weeks concomitant with rapidly enlarging pulmonary lesions. Examination revealed proximal lower limb weakness, diminished deep tendon reflexes, ataxic dysarthria, limb and truncal ataxia, and orthostatic hypotension. Nerve conduction studies revealed reduced compound muscle action potentials with postexercise facilitation. Elevated anti-P/Q-type voltage-gated calcium channel antibodies confirmed paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome (LEMS). Bronchoscopy revealed small-cell lung cancer. Although a poor performance status (PS) initially precluded chemotherapy, high-dose intravenous immunoglobulin therapy improved the PS, enabling cancer treatment. Immunotherapy should be considered when a PCD-LEMS-related poor PS prevents cancer therapy.
2026-01-24 | Clinical Spectrum and Outcomes of SOX1 Antibody-Associated Paraneoplastic Neurological Syndromes: A Chinese Cohort Study.
SOX1 antibody-positive paraneoplastic neurological syndromes (PNS) exhibit significant population-specific clinical heterogeneity. While Western cohorts predominantly manifest Lambert-Eaton myasthenic syndrome (65%-80%), comprehensive clinical characterization and treatment response data in Asian populations remain critically limited. We conducted a single-center retrospective case series analyzing 13 consecutive patients with SOX1 antibody-positive PNS treated at Guangdong Sanjiu Brain Hospital from January 2019 to December 2024. SOX1 antibodies were confirmed using commercial immunoblot assay. Primary endpoints included treatment response (≥ 1-point improvement on modified Rankin Scale [mRS]) and functional recovery (mRS ≤ 2). Statistical analyses employed Fisher's exact tests and Mann-Whitney U tests. Among 13 patients (median age 61 years [IQR 56-67], 53.8% female), neuropsychiatric presentations predominated, including seizures (46.2%) and psychiatric symptoms (30.8%), with combined neuropsychiatric manifestations occurring in 53.8% of patients. Co-existing neuronal antibodies were identified in 15.4% of cases (GABAB receptor, LGI1). Malignancy was confirmed in 30.8% of patients. Immunotherapy recipients (n = 7) demonstrated significantly superior functional outcomes compared to non-treated patients: median 3-month mRS 0 (IQR 0-0) versus 3 (IQR 3-3), p = 0.03. Treatment response rates were 85.7% versus 33.3% (p = 0.103). Chinese patients with SOX1 antibody-positive PNS demonstrate a neuropsychiatric-predominant phenotype (53.8%), contrasting markedly with Western cohorts. Early immunotherapy administration was associated with superior functional outcomes (median 3-month mRS: 0 vs. 3, p = 0.03). These findings support comprehensive neuronal antibody profiling and early immunotherapy consideration in patients presenting with neuropsychiatric manifestations.
combination
2025-10-09 | A Rare Case of Autoimmune Enteropathy Associated With Lambert-Eaton Myasthenic Syndrome and a Literature Review.
Autoimmune enteropathy is a rare intestinal disease characterized by chronic diarrhea and severe malabsorption in the presence of circulating autoantibodies against enterocytes and goblet cells, typically affecting children or young adults. Lambert-Eaton myasthenic syndrome (LEMS) is also a rare autoimmune neuromuscular junction disorder characterized by muscle weakness due to antibodies against the P/Q-type voltage-gated calcium channels (VGCCs) on the presynaptic nerve terminals. We report a case of concurrent diagnoses of autoimmune enteropathy and LEMS in a 24-year-old female patient with a history of autoimmune thyroiditis and vitiligo. The diagnosis of LEMS was established by the typical electromyographic findings and positive antibodies against P/Q-type VGCCs. After malignancies were excluded, treatment with rituximab in combination with intravenous immunoglobulin led to improvement. Within two months of the LEMS diagnosis, the patient presented with severe muscle weakness, chronic diarrhea, vomiting, and weight loss. After a thorough work-up, the diagnosis of autoimmune enteropathy was made, based on severe villous atrophy with a dense inflammatory infiltrate in duodenal biopsies and the exclusion of other causes of chronic diarrhea and non-celiac enteropathy. The patient was treated successfully with total parenteral nutrition, corticosteroids, and azathioprine. To our knowledge, this is one of the first reports of autoimmune enteropathy associated with LEMS.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
5 orphan drug designations for Lambert-Eaton myasthenic syndrome, including 1 approved therapy.
5 orphan drug designations for Lambert-Eaton myasthenic syndrome, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
3,4 diaminopyridine and choline bitartrate | small molecules | FDA | — | MS Therapeutics Limited |
amifampridine [Firdapse] | small molecules | FDA | Approved | Catalyst Pharmaceuticals, Inc. |
Amifampridine phosphate [Firdapse] | small molecules | EMA | Biomarin International Limited | |
amifampridine | small molecules | FDA | Catalyst Pharmaceuticals, Inc. | |
Dynamine | small molecules | FDA | Mayo Foundation |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.