Voltage-gated Calcium Channel Antibodies Research Articles

Initial screening for neuronal autoantibodies and their putative impact on survival in patients with small-cell lung cancer.

Small-cell lung cancer (SCLC) may be associated with neuronal autoantibodies and paraneoplastic neurological syndromes. It has been suggested that neuronal autoantibodies, especially antineuronal nuclear antibody type 1 (Hu) autoantibodies, are associated with longer survival of patients with SCLC. The objective of this study was to determine the frequency and distribution of neuronal autoantibodies at the time of diagnosis of SCLC patients and assess survival rates in relation to autoimmunity. In this retrospective study, serum from 40 patients with biopsy-proven SCLC at the time of diagnosis was studied prior to treatment. The sera originated from a cancer registry at the Oncology Department, Vejle Hospital from 2007 to 2010. The sera were analyzed blindly to clinical status for the presence of neuronal autoantibodies. Medical records were reviewed for neurological symptoms. Neuronal autoantibodies were detected in 22/40 (55%) of the SCLC patients. A broad range of neurological symptoms was recorded in 28/40 (70%) patients, of which 14/28 (50%) were positive for neuronal autoantibodies. The most frequently detected autoantibodies were Hu (7/40, 17.5%) followed by GAD65 (6/22, 15.0%). Striational and P/Q- or N-type voltage-gated calcium channel antibodies were less common, with each found in five patients (12.5%). Eight patients (20%) had coexisting autoantibodies. Autoantibody-positivity was not associated with survival. Neuronal autoantibodies were at time of diagnosis found in approximately half of the treatment-naïve SCLC patients. Neither autoantibody positivity at diagnosis nor neurological manifestations correlated with survival and their clinical importance requires further studies in larger, prospective cohorts.

Diagnosis and Treatment of Lambert-Eaton Myasthenic Syndrome

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

Blood-brain barrier breakdown and autoimmune cerebellar ataxia

Autoimmune cerebellar ataxia is a disease entity that affects the cerebellum and is induced by autoimmune mechanisms. The disease is classified into several etiologies, including gluten ataxia, anti-glutamate decarboxylase (GAD) ataxia, paraneoplastic cerebellar degeneration, primary autoimmune cerebellar ataxia and postinfectious cerebellar ataxia. The autoimmune response in the periphery cross-reacts with similar antigens in the cerebellum due to molecular mimicry. Breakdown of the blood‒brain barrier (BBB) could potentially explain the vulnerability of the cerebellum during the development of autoimmune cerebellar ataxia, as it gives rise to the entry of pathogenic autoantibodies or lymphocytes into the cerebellum. In this review, the maintenance of the BBB under normal conditions and the molecular basis of BBB disruption under pathological conditions are highlighted. Next, the pathomechanism of BBB breakdown in each subtype of autoimmune cerebellar ataxia is discussed. We recently identified glucose-regulated protein (GRP) 78 antibodies in paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome, and GRP78 antibodies induced by cross-reactivity with tumors can disrupt the BBB and penetrate anti-P/Q type voltage-gated calcium channel (VGCC) antibodies into the cerebellum, thus leading to cerebellar ataxia in this disease.

A MIDDLE-AGED PATIENT WITH BILATERAL VISION LOSS AND NYCTALOPIA.

Purpose: To report a case of nonparaneoplastic autoimmune retinopathy in a patient with diagnosis of Lambert Eaton Myasthenic Syndrome. 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 work up are also presented. 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 (LEMS), confirmed by positive voltage-gated calcium channel (VGCC) antibodies, and thymectomy reported as thymic follicular hyperplasia. OCT showed bilateral diffuse outer retinal atrophy and ellipsoid zone loss. Fundus autofluorescence displayed a bull's pattern of hyperautofluorescence around each fovea. Full field ERG showed an extinguished rod response and a severely depressed cone response in each eye. We describe a case of nonparaneoplastic autoimmune retinopathy in a patient with Lambert Eaton Myasthenic Syndrome. Multimodal retinal imaging and ERG confirmed the presence of autoimmune retinopathy with severe rod-cone degeneration. The association of this myasthenic syndrome with AIR is novel.

A Case of Hydroxychloroquine-Induced Neuromyopathy Causing Severe Ventilatory Failure (P9-8.013)

<h3>Objective:</h3> We present a case of HCQ-induced neuromyopathy culminating in reversible respiratory failure. <h3>Background:</h3> Hydroxychloroquine (HCQ) induced neuromyopathy is a well-documented but rare side effect of HCQ. Here, we discuss a case of HCQ-induced neuromyopathy culminating in respiratory failure. There are few documented cases of fulminant respiratory failure requiring mechanical ventilation due to this severe neuromuscular complication of HCQ. <h3>Design/Methods:</h3> A 58-year-old female with systemic lupus erythematous on HCQ for 15 years presented with peripheral edema and acute respiratory failure requiring intubation. She was admitted to the cardiovascular ICU for acute heart failure workup. Neurology was involved to help consider neuromuscular etiologies given the slightly restrictive pattern of respiratory failure. On exam, she had facial weakness and MRC grade 4/5 throughout without clear proximal or distal pattern. Reflexes were 1+ throughout. Acetylcholine receptor antibodies, anti-muscle-specific kinase antibodies, and voltage gated calcium channel antibodies were normal. Creatine kinase and aldolase were slightly elevated at 228 U/L and 9.1 U/L respectively. Concentric needle electromyography of the left vastus lateralis demonstrated low amplitude motor units of increased complexity but without early recruitment. <h3>Results:</h3> Muscle biopsy demonstrated internal accumulation of lysosomal vacuoles and glycogen in many myofibers. Electron microscopy showed curvilinear bodies, a characteristic finding in HCQ-induced myopathy. Testing for other causes of lysosomal storage diseases, which can have similar histologic findings, was negative. HCQ was discontinued. Within weeks of discontinuing HCQ the patient was weaned from mechanical ventilation and was ambulating with a walker. <h3>Conclusions:</h3> Our case underscores the importance of a high clinical suspicion for HCQ toxicity in the setting of respiratory failure in patients with risk factors. Increased awareness of HCQ neuromuscular toxicity marked by muscle weakness with possible ventilatory failure may lead to early recognition and treatment of a reversible condition. Furthermore, thorough evaluation of a patient’s pharmacopeia, including longstanding, previously tolerated medications, is paramount. <b>Disclosure:</b> Dr. Juster-Switlyk has nothing to disclose. Dr. Crane has nothing to disclose. Joshua M Klonoski has nothing to disclose. The institution of Dr. Mahoney has received research support from Viela Bio.

Pre-existing Lambert-Eaton Myasthenic Syndrome and Scleroderma in a Patient with Neuroendocrine Tumor undergoing Immune Checkpoint Inhibitor Cancer Immunotherapy (P4-5.029)

<h3>Objective:</h3> To illustrate the diagnostic and therapeutic challenges regarding paraneoplastic Lambert-Eaton Myasthenic Syndrome (LEMS) in patients with malignancy on immune checkpoint inhibitor (ICI). <h3>Background:</h3> Paraneoplastic syndromes often co-exist and can worsen with ICI cancer immunotherapy. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> We report a case of a 66-year-old female with progressive weakness and dry eyes and mouth diagnosed with LEMS based on P/Qtype voltage-gated calcium channel (VGCC) antibody positivity (0.11 nmol/L initially). She was diagnosed with neuroendocrine tumor and treated with weekly IVIg, chemotherapy (carboplatin and etoposide) and radiation with some improvement. A year into her disease she developed Raynaud’s and tightness of her fingers, legs, back and skin compatible with scleroderma with RNA Polymerase III antibody positivity. Due to cancer progression, she was treated with ICIs (ipilimumab and nivolumab) with concomitant IVIg. Due to colitis and thyroiditis, ipilimumab was discontinued. She was stable for eight months but then developed progressive weakness, dropped head, dysphagia and increased shortness of breath. Two hertz repetitive nerve stimulation of the ulnar and spinal accessory nerve demonstrated facilitation of 223% and 128% respectively after a baseline decrement, confirming a presynaptic disorder of the neuromuscular junction with diffuse myopathic changes without fibrillation potentials on electromyography. Repeat P/Q-type-VGCC-IgG was 0.89 nmol/L; creatinine kinase levels were normal. Nivolumab was stopped, and she was treated with 3,4-diaminopyridine and weekly IVIg; corticosteroid use was limited by her scleroderma, and plasma exchange due to infection. The patient had cancer progression and died within three weeks. <h3>Conclusions:</h3> This patient with pre-existing paraneoplastic LEMS and scleroderma was stable for 8 months while on ICI. Her clinical presentation upon progression with dropped head could be related to LEMS with secondary myopathic change or an ICI-triggered-myopathy. This patient illustrates the complexity of therapeutic decision making in these patients and the necessity of a multidisciplinary approach. <b>Disclosure:</b> Dr. Vorasoot has nothing to disclose. Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TerSera. Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Terumo. The institution of Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. The institution of Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Advanced Accelerator Applications. The institution of Dr. Halfdanarson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Isotopen Technologien Muenchen (ITM). The institution of Dr. Halfdanarson has received research support from Advanced Accelerator Applications. The institution of Dr. Halfdanarson has received research support from Thermo-Fisher Scientific. The institution of Dr. Halfdanarson has received research support from Camurus. Dr. Madigan has nothing to disclose. Dr. Thanarajasingam has nothing to disclose. The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.

Testing for N-type Voltage Gated Calcium Channel Antibody has Limited Utility in Evaluating Patients With Suspected Lambert-Eaton Myasthenic Syndrome

Objective To determine if testing for N-type voltage-gated calcium channel antibody improves diagnostic performance of serological testing for Lambert-Eaton Myasthenic Syndrome. Background Patients with suspected autoimmune neuromuscular junction transmission disorders are commonly tested for both P/Q-type (VGCC-P/Q) and N-type (VGCC-N) voltage-gated calcium channel antibodies to aid the diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). Design/Methods This retrospective cross-sectional study included 93 patients diagnosed at Mayo Clinic with LEMS based on electrodiagnostic findings, clinical presentation and positive serology for VGCC-P/Q and/or VGCC-N. Results Forty-five patients (48.4%) were female, of median age 61 years (range 11- 99). Twenty-five (26.9%) were positive for both VGCC antibody types (reference interval &lt;0.04 nmol/L [VGCC-N] and &lt;0.03 nmol/L [VGCC-P/Q]); 67 (72.0%) were positive for VGCC-P/Q only and one (1.1%) was positive for VGCC-N only. The single VGCC-N positive only result [VGCC-N = 0.10 nmol/L; VGCC-PQ = 0.02 nmol/L] was from a patient with classic LEMS presentation and no evidence of malignancy by Chest CT. The prevalence of VGCC-N only positivity was lower than in the healthy population or other disease control populations. VGCC-P/Q antibody titers were higher in patients who had detectable co-existing VGCC-N antibody (median titer 1.58 versus 0.39 nmol/L, P = 0.02) and there was a positive correlation (r = 0.762, P &lt; 0.001) between VGCC-N and VGCC-P/Q titers in double positive cases. Dual positivity did not significantly increase the likelihood of an underlying cancer (40.9% versus 30.1%, P = 0.33). Conclusions Testing for VGCC-P/Q antibodies alone is sufficient in the serological evaluation of suspected LEMS cases. Inclusion of VGCC-N antibody testing does not improve diagnostic performance. A positive VGCC-N antibody did not significantly increase the risk of paraneoplastic LEMS.

Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert-Eaton myasthenic syndrome: A case report.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mechanoreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenomenon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67-year-old man presenting with progressive proximal muscle weakness, autonomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage-gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radiotherapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduction. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.

IVIG treatment in non-paraneoplastic Lambert- Eaton myasthenic syndrome with elevated voltage- gated calcium channels antibodies and subacute cerebellar ataxia

Non paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) is rare and only very few cases have been reported to date. Besides that, LEMS is rarely associated with cerebellar ataxia. Here, we described a case of middle age gentleman who presented with subacute onset of cerebellar ataxia and subsequently found to have remarkably elevated voltage-gated calcium channels (VGCC) antibodies serum titre and LEMS. Repeated screenings for malignancies remained negative. He improved significantly with intravenous immunoglobulin (IVIG) treatment. In conclusion, even with negative malignancy screen, investigation for LEMS and measurement of VGCC level should be considered in patients with subacute cerebellar ataxia. Our case demonstrated good initial response towards IVIG treatment and hence early and timely initiation of treatment with IVIG may lead to clinical improvement. However, more clinical trials will be required in the future to further determine the long term prognosis of non-paraneoplastic cerebellar ataxia and LEMS towards IVIG treatment.

The European Lambert-Eaton Myasthenic Syndrome Registry: Long-Term Outcomes Following Symptomatic Treatment.

IntroductionLambert–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.MethodsThirty 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.ResultsAmong 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.ConclusionNo new safety signals were observed following long-term management of LEMS with 3,4-DAPP.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00354-8.

A Diagnostic Dilemma: Normal Repetitive Nerve Stimulation in Lambert-Eaton Myasthenic Syndrome

It is important for the diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) to confirm the incremental response at high-rate stimulation or after brief exercise in the repetitive nerve stimulation (RNS) test. Therefore, it may be difficult to diagnose LEMS if the RNS test is normal initially. We report a patient with LEMS whose diagnosis was delayed due to normal RNS findings. We believe that anti-P/Q-type voltage-gated calcium channel antibody testing is crucial in the diagnosis of LEMS.

Performance evaluation of a radioimmunoprecipitation assay for the detection of N-type voltage-gated calcium channel antibodies

BackgroundIn this study, we assessed the performance characteristics of a laboratory-developed radioimmunoassay (RIA) to detect N-type voltage-gated calcium channel (N-VGCC) antibodies found in several autoimmune neurologic diseases. MethodsFour hundred and forty-five (n = 445) sera were evaluated, including 156 sera (50 positive and 106 negative for N-VGCC antibodies) previously tested at Mayo Clinic Laboratories (MCL) and 289 controls (n = 187 disease and n = 102 healthy). Specimens were analyzed with the RIA using N-VGCC labeled with 125I-ω-conotoxin GVIA. The RIA was compared to the predicate MCL assay using a tiered positive predictive value (PPV) approach. Other performance characteristics evaluated included specificity, precision, interference, and stability. ResultsQualitative inter-laboratory agreement based on tiered PPVs was 100% for results >1.00 nmol/L (71% PPV), 48% for results of 0.10–0.99 nmol/L (24% PPV) and 22% for results of 0.04–0.10 nmol/L (19% PPV). Negative results showed 90% agreement (n = 106). Specificity in controls positive for other neural autoantibodies and healthy controls were 87% and 100%, respectively. Acceptable results were observed for other performance characteristics. ConclusionsInter-laboratory correlations demonstrate equivalence between assays with some discrepancies between low positive results. Collaborative efforts aimed at assessing the clinical spectrum associated with these antibodies and consensus for harmonizing test performance are required for optimal categorization of patients.

P-PN007. A case presenting with clinical and laboratory characteristics of fisher syndrome and lambert-eaten myasthenic syndrome (LEMS)

Introduction . Although Fisher syndrome and LEMS are classified into autoimmune neuromuscular diseases, we cannot find the coincidence of them in a single patient in the previous literature. Results . A 70-year-old female was admitted to our hospital because of bilateral hand numbness, double vision and unsteadiness which had developed 2 weeks. She had no history of preceding infection and/or related illness. On admission, her condition was characterized by mydriasis, extraocular muscle weakness, mild proximal muscle weakness and truncal ataxia. In addition, the tendon reflexes were absent at rest, and improved with brief exercise. Motor nerve conduction studies showed significantly low compound muscle action potentials (CMAPs) and increments of more than 200% after brief exercise (post-exercise facilitation) in several nerves. Sensory nerve conduction studies showed significantly low sensory nerve action potential (SNAPs) of median and ulnar nerves, and normal SNAPs of sural nerves. We also demonstrated the impairment of neuromuscular transmission in several muscles based on abnormal decrements in the repetitive nerve stimulation (RNS) test and abnormal jitter in the single-fiber electromyography (SFEMG). Both anti-GQ1b and GT1a ganglioside antibodies and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in her sera. Her conditions improved spontaneously. She accomplished walking alone in six weeks, and paralysis of the eye muscles recovered in five months. Median and ulnar SNAPs returned to normal in accordance with recovery of clinical findings. On the other hand, low CMAPs with post-exercise facilitation remained after complete recovery. Positron emission tomography and gastrointestinal endoscopy did not show any malignancy. Conclusion . Some electrophysiological studies revealed the impairment of neuromuscular transmission using RNS and/or SFEMG in patients with Fisher syndrome. Also, it has been known that autoimmune neurological phenotypes are diverse among patients with P/Q-type VGCC antibodies. This may be the first case who showed clinical and laboratory characteristics of Fisher syndrome and LEMS simultaneously.

Neuromuscular junction disorders beyond myasthenia gravis.

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

Neuromyotonia and encephalopathy with neuronal-type voltage-gated calcium channel antibodies and prostate adenocarcinoma (2652)

Neuromyotonia and encephalopathy with neuronal-type voltage-gated calcium channel antibodies and prostate adenocarcinoma (2652)

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

Case Report of Lambert Eaton Myasthenic Syndrome in a Patient with Small Cell Lung Cancer on Immune Checkpoint Inhibitor Therapy

Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder involving loss of functional pre-synaptic P/Q-type voltage-gated calcium channels. Many cases occur as a paraneoplastic disorder, often in small cell lung cancer (SCLC). Recently, immune checkpoint inhibitors (ICI) have emerged as treatment of choice for various malignancies. While generally well tolerated, certain ICI-treated patients experience neurologic immune-related adverse events (irAEs). Here, we explore therapeutic and diagnostic conundrums from the unclear etiology (paraneoplastic vs. irAE) of a case of LEMS in a patient with SCLC treated with ICI therapy. A 62-year-old female patient with SCLC was referred to EMG laboratory with 7 weeks of progressive weakness, shortness of breath and dysphagia. Due to tumor progression, immunotherapy with pembrolizumab was initiated five months prior to presentation. On examination, she had mild non-fatigable right-sided ptosis and diplopia, normal bulbar strength, and proximal greater than distal weakness of lower greater than upper extremities. Her reflexes were 2-/4 throughout, with left biceps reflex facilitating after 30 seconds of exercise. On nerve conduction studies (NCS), there was an amplitude increase in multiple nerves including the left median nerve (160%) and left ulnar nerve (370%) after 10 seconds of exercise. Paraneoplastic panel came back with elevated LEMS-related anti-P/Q-type voltage gated calcium channel antibodies at 0.19nmol/L (normal: ≤0.02nmol/L). This case illustrates the diagnostic and therapeutic challenges that surround LEMS in SCLC patients on immunotherapy. Diagnosis hinges on clinical presentation, motor NCS, and antibody testing while determination of the etiology (paraneoplastic vs ICI related LEMS) is more complex and may affect selection of the correct treatment. Therapy for ICI-related neuromuscular irAEs depends on symptom severity, but typically should include holding immunotherapy and administration of high dose corticosteroids as first line treatment with possible addition of IVIg and plasmapheresis. This differs from the common first line treatment for paraneoplastic LEMS, highlighting the importance of understanding of the etiology. Further research is needed to better understand optimal management.

長期経過を観察できた抗voltage–gated calcium channel抗体陽性傍腫瘍性小脳変性症の1例

長期経過を観察できた抗voltage–gated calcium channel抗体陽性傍腫瘍性小脳変性症の1例

Presence of P/Q Voltage-gated Calcium Channel (VGCC) Antibodies in Pediatric Autoimmune Encephalitis (1336)

Presence of P/Q Voltage-gated Calcium Channel (VGCC) Antibodies in Pediatric Autoimmune Encephalitis (1336)

Performance Evaluation of a Radioimmunoprecipitation Assay for the Detection of N-Type Voltage-gated Calcium Channel Antibodies in Patient and Control Groups (4968)

Performance Evaluation of a Radioimmunoprecipitation Assay for the Detection of N-Type Voltage-gated Calcium Channel Antibodies in Patient and Control Groups (4968)