Neuromuscular Junction Disorders Research Articles

Advancing the understanding of VAMP1-related congenital myasthenic syndrome: phenotypic insights, favorable response to 3,4-diaminopyridine, and clinical characterization of five new cases

Congenital myasthenic syndromes (CMS) are a group of inherited neuromuscular junction (NMJ) disorders arising from gene variants encoding diverse NMJ proteins. Recently, the VAMP1 gene, responsible for encoding the vesicle-associated membrane protein 1 (VAMP1), has been associated with CMS. This study presents a characterization of five new individuals with VAMP1-related CMS, providing insights into the phenotype.The individuals with VAMP1-related CMS exhibited early disease onset, presenting symptoms prenatally or during the neonatal period, alongside severe respiratory involvement and feeding difficulties. Generalized weakness at birth was a common feature, and none of the individuals achieved independent walking ability. Notably, all cases exhibited scoliosis. The clinical course remained stable, without typical exacerbations seen in other CMS types.The response to anticholinesterase inhibitors and salbutamol was only partial, but the addition of 3,4-diaminopyridine (3,4-DAP) led to significant and substantial improvements, suggesting therapeutic benefits of 3,4-DAP for managing VAMP1-related CMS symptoms. Noteworthy is the identification of the VAMP1 (NM_014231.5): c.340delA; p.Ile114SerfsTer72 as a founder variant in the Iberian Peninsula and Latin America.This study contributes valuable insights into VAMP1-related CMS, emphasizing its early onset, arthrogryposis, facial and generalized weakness, respiratory involvement, and feeding difficulties. Furthermore, the potential efficacy of 3,4-DAP as a useful therapeutic option warrants further exploration. The findings have implications for clinical management and genetic counseling in affected individuals. Additional research is necessary to elucidate the long-term outcomes of VAMP1-related CMS.

Pearls & Oy-sters: Thyroid-Associated Ophthalmopathy and Transient Neuromuscular Junction Disorder Due to Graves Disease.

The concomitant presentation of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis is well documented. In the course of Graves disease (GD), symptomatic transient neuromuscular junction disorder may occur due to the effect of thyroid hormones at the neuromuscular synapse. Diagnostic clues are the clinical and electrophysiologic remission synchronous with restoration of euthyroidism. Furthermore, the occurrence of thymic hyperplasia in GD poses further diagnostic and therapeutic considerations. These points are discussed in the case report of a 43-year-old male patient suffering from TAO and transient neuromuscular junction disorder due to GD.

Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.

The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.

Neurological autoimmunity in patients with non-pulmonary neuroendocrine neoplasms: clinical manifestations and neural autoantibody profiles.

Paraneoplastic neurological autoimmunity is well described with small-cell lung cancer, but information is limited for other neuroendocrine neoplasms (NENs). Adult patients with histopathologically confirmed non-pulmonary NENs, neurological autoimmunity within 5 years of NEN diagnosis, and neural antibody testing performed at the Mayo Clinic Neuroimmunology Laboratory (January 2008 to March 2023) were retrospectively identified. Control sera were available from patients with NENs without neurological autoimmunity (116). Thirty-four patients were identified (median age 68 years, range 31-87). The most common primary tumor sites were pancreas (nine), skin (Merkel cell, eight), small bowel/duodenum (seven), and unknown (seven). Five patients received immune checkpoint inhibitor (ICI) therapy before symptom onset; symptoms preceded cancer diagnosis in 62.1% of non-ICI-treated patients. The most frequent neurological phenotypes (non-ICI-treated) were movement disorders (12; cerebellar ataxia in 10), dysautonomia (six), peripheral neuropathy (eight), encephalitis (four), and neuromuscular junction disorders (four). Neural antibodies were detected in 55.9% of patients studied (most common specificities: P/Q-type voltage-gated calcium channel [seven], muscle-type acetylcholine receptor [three], anti-neuronal nuclear antibody type 1 [three], and neuronal intermediate filaments [two]), but in only 6.9% of controls. Amongst patients receiving cancer or immunosuppressive therapy, 51.6% had partial or complete recovery. Outcomes were unfavorable in 48.3% (non-ICI-treated) and neural autoantibody positivity was associated with poor neurological outcome. Neurological autoimmunity associated with non-pulmonary NENs is often multifocal and can be treatment responsive, underscoring the importance of rapid recognition and early treatment.

Clinical features of double seronegative ocular myasthenia gravis.

To clarify the clinical features of patients with Double seronegative (DS) ocular myasthenia gravis (OMG). Sixty-one patients diagnosed with DS OMG at the Department of Ophthalmology, Hyogo Medical University Hospital over a 5-year period from 2017 were included. Patients were classified into three groups based on the initial examination findings: group P (ptosis alone), group M (ocular motility disorder alone), and group PM (combination of both). We retrospectively reviewed the patients and clarified their clinical features. There were 32 males and 29 females, with a mean age of 49.8 ± 20.9:1-82years. Twenty-one patients (34.4%) were in group P, 23 (37.7%) in group M, and 17 (27.8%) in group PM. The proportion of males (73.9%) was significantly higher in group M compared with the other two groups. The diagnosis was proven by detection of neuromuscular junction (NMJ) disorder in 73.8%, oral pyridostigmine trial test in 13.1%, and eight patients (13.1%) in group M were diagnosed after surgical treatment. The clinical symptoms were resolved by oral pyridostigmine treatment in 54.1% of cases. About 30% of patients with DS OMG had no obvious NMJ disorder, and an oral pyridostigmine trial test was necessary to diagnose these patients. Although DS OMG is often considered as the mildest form of MG, its prognosis is not optimistic and it requires aggressive therapeutic intervention. Trial registration number: 202104-750, "2016/4/18," retrospectively registered.

Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes

Exploring the molecular basis of disease severity in rare disease scenarios is a challenging task provided the limitations on data availability. Causative genes have been described for Congenital Myasthenic Syndromes (CMS), a group of diverse minority neuromuscular junction (NMJ) disorders; yet a molecular explanation for the phenotypic severity differences remains unclear. Here, we present a workflow to explore the functional relationships between CMS causal genes and altered genes from each patient, based on multilayer network community detection analysis of complementary biomedical information provided by relevant data sources, namely protein-protein interactions, pathways and metabolomics. Our results show that CMS severity can be ascribed to the personalized impairment of extracellular matrix components and postsynaptic modulators of acetylcholine receptor (AChR) clustering. This work showcases how coupling multilayer network analysis with personalized -omics information provides molecular explanations to the varying severity of rare diseases; paving the way for sorting out similar cases in other rare diseases.

How should newer therapeutic agents be incorporated into the treatment of patients with myasthenia gravis?

Generalized myasthenia gravis (gMG) is a postsynaptic neuromuscular junction disorder that results in fatigable muscle weakness. The traditional treatment approach includes the use of acetylcholinesterase inhibitors, corticosteroids, and steroid-sparing immunosuppressant therapies (ISTs) for chronic management, whereas exacerbations and crises are managed with intravenous immunoglobulin (IVIg) and plasma exchange (PLEX). Over the past 6 years, four new therapeutic agents with novel immunological mechanisms of action-complement and neonatal Fc receptor (FcRn) inhibition-were approved as a result of clinically significant improvement in gMG symptoms of those treated with these newer agents in Phase 3 clinical trials. At present, it is unclear when and in whom to initiate these therapeutic agents and how to integrate them into the current treatment paradigm. When selecting a newer therapeutic agent, we use a simple equation: Value = Clinical Improvement/(Cost + Side Effects + Treatment Burden), which guides our decision-making. We consider using these novel therapeutic agents in two specific clinical situations. Firstly, the newer agents are fast-acting, suggesting they can be used in clinically unstable patients as "bridge therapy," and secondly, they provide additional options for those patients considered treatment-refractory. There are downsides, however, including treatment cost, unique side effect profiles, and intravenous and subcutaneous drug administration (though for some, this may be an advantage). As additional drugs enter the marketplace with unique mechanisms of action, routes of administration, and dosing schedules, the placement of the novel therapeutic agents in the gMG treatment algorithm will likely evolve.

Paraneoplastic Neurological Syndromes as Initial Presentation of Tumors: An Eight-Year Single-Center Experience

Background: Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue. Methods: A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria. Results: Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR (n = 4), anti-P/Q-VGCC (n = 3), anti-Hu (n = 3), anti-Yo (n = 1), anti-Ma (n = 1), anti-titin (n = 1), anti-IgLON5 (n = 1), and anti-GAD65 (n = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively. Conclusions: This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.

The Incidence of Myasthenia Gravis in the Province of Ferrara, Italy, in the Period of 2008-2022: An Update on a 40-Year Observation and the Influence of the COVID-19 Pandemic.

Myasthenia gravis (MG) is the most common neuromuscular junction disorder. We evaluated the MG incidence rate in the province of Ferrara, Northern Italy, over two time frames (2008-2018 and 2019-2022, i.e., the COVID-19 pandemic) and considered early-onset (EOMG), late-onset (LOMG), and thymoma- and non-thymoma-associated MG. Moreover, in the second period, we assessed its possible relationship with SARS-CoV-2 infection or COVID-19 vaccination. We used a complete enumeration approach to estimate the MG incidence and its temporal trend. For the period of 2008-18, 106 new cases were identified (mean incidence rate 2.7/100,000 people). The highest rates were observed for the over-70 age group and in rural areas, with 17% of thymoma-associated MG. During the COVID-19 period, 29 new cases were identified (average incidence rate 2.1/100,000 people), showing a marked (though not statistically significant) decrease in the mean annual incidence compared to the previous period. Again, the highest rate was observed for the over-70 age group. The first period was in line with our previous observations for the period between 1985 and 2007, highlighting a rising incidence of LOMG and a marked decrease in EOMG. During the COVID-19 period, incidence rates were lower in the first years whereas, when the pandemic ended, the previous trend was confirmed.

Tata Laksana Lambert Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular junction disorder resulting from a paraneoplastic or autoimmune reaction. More than half LEMS cases are associated with small cell lung carcinoma (SCLC). The main clinical manifestation is muscle weakness. The pathophysiology is due to the generation of the autoantibodies against voltage-gated calcium channels (VGCCs) on presynaptic nerve terminals leading to a decrease in neurotransmitter acethylcholine (ACh). Various treatments such as tumor treatments, immunomodulatory, and symptomatic treatment have been studied, but further research is needed.

Critical Understanding of Myasthenia Gravis on the Basis of Vyadhi Ghatak

Myasthenia gravis (MG) is an autoimmune neuromuscular junction (NMJ) disorder characterized by weakness and fatigability of skeletal muscles. Myasthenia gravis has prevalence as high 200 in 100,000. It affects individuals in all age groups, but peak incidences occur in women in their twenties and thirties and in men in their fifties and sixties. Overall, women are affected more frequently than men, in a ratio of 3:2. It has bimodal age distribution. In MG, the fundamental defect is a decrease in the number of available AChRs at the postsynaptic muscle membrane. It presents with fluctuating skeletal muscle weakness and fatigue most commonly affecting the ocular muscles, although any muscle may be affected. In modern science treatment of Myasthenia gravis include anti-cholinesterase medications, glucocorticoids and other immunosuppressive agents. Long term use of steroid and immune modulator drugs has many adverse effects on other system of body. Ayurvedic therapies can give much more promising results. Comparison between myasthenia gravis and diseases explained in Ayurveda is difficult and exact correlation is not possible. But based on critical understanding of Vyadhighataka, a probable diagnosis can be made and treated accordingly. In this article, attempt is made to understand the pathogenesis of myasthenia gravis by considering the concepts of Dosha (vitiated Dosha), Dushya (vitiated Dushya), Aama, Agnimandya, and Srotovaigunya. For any disease pathology to begin, all components must be present. Pathogenesis of any disease will not occur without these elements.

Remission of severe myasthenia gravis after autologous stem cell transplantation.

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG. As part of a pilot study of HDIT/HCT for patients with treatment-resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G-CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed. The patient had been diagnosed with AChR antibody-positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom-free. After HDIT/HCT, AChR-binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted. HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell-mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis.

Database Evaluation for Muscle and Nerve Diseases - DEMAND: An academic neuromuscular coding system

Background: A database which documents the diagnosis of neuromuscular patients is useful for determining the types of patients referred to academic centers and for identifying participants for clinical trials and other studies. The ICD-9 or ICD-10 numeric systems are insufficiently detailed for this purpose. Objective: To develop a database for neuromuscular diagnoses Methods: We developed a detailed diagnostic coding system for neuromuscular diseases called DEMAND: Database Evaluation for Muscle and Nerve Diseases that has been adopted by neuromuscular clinics at University of Texas Health Science Center San Antonio (UTHSCSA), Ohio State University (OSU), University of Kansas Medical Center (KUMC), and University of Texas Southwestern (UTSW). At the initial visit, patients are assigned a diagnostic code which can be revised later if appropriate. Fields include patient’s name, date of birth, and diagnostic code. The neuromuscular database consisted of 457 codes. Each code has a prefix (MUS or PNS) followed by a three-digit number. Depending on whether muscle or nerve is primarily involved, there are eight broad groups: motor neuron disease (MUS codes 100-139); neuromuscular junction disorders (MUS 200-217); acquired and hereditary myopathies (MUS 300-600s); acquired and hereditary polyneuropathies (PNS 100-400); mononeuropathies (PNS 500s); plexopathies (PNS 600s); radiculopathies (PNS 700s); and mononeuritis multiplex (PNS 800s). Results: During a period of 10 years, 17,163 of patients were entered (1,752 at UTHSCSA, 1,840 at OSU, 3,699 at KUMC, 9,872 at UTSW). The number of patients in several broad categories are: 3,080 motor neuron disease; 1,575 neuromuscular junction disease; 1,851 muscular dystrophies; 633 inflammatory myopathies; 1,090 hereditary neuropathies; 1,001 immune-mediated polyneuropathies; 620 metabolic/toxic polyneuropathies; 535 mononeuropathies; 296 plexopathies; and 769 radiculopathies. Conclusion: A detailed diagnostic neuromuscular database can be utilized at multiple academic centers. The database should be simple without too many fields to complete, to ensure compliance during busy clinic operations. This database has been very useful in identifying groups of patients for retrospective, observational studies and for prospective treatment studies including trials for Amyotrophic Lateral Sclerosis (ALS), Muscular Dystrophies (MD), Myasthenia Gravis (MG), and retrospective studies of Primary Lateral Sclerosis (PLS), chronic inflammatory demyelinating neuropathy (CIDP), etc.

New Therapeutic Agents in Myasthenia Gravis

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder characterized by fatigable muscle weakness. Mainstay therapies for MG include anticholinesterase inhibitor, thymectomy, corticosteroids, and non-specific immunotherapy, such as azathioprine, tacrolimus, mycophenolate mofetil, intravenous immunoglobulin, and plasma exchange. These therapeutic methods have significantly improved MG treatment in recent decades. However, there are still some patients with MG refractory to conventional treatments. In addition, long-term use of corticosteroids and non-specific immunosuppressants can lead to serious complications, including metabolic derangement, infections, malignancies, and systemic organ dysfunction. Recently, new therapeutic agents have been developed based on advancements in our understanding of the immunopathogenesis of MG. These agents are more specific and have a more rapid effect compared with conventional treatments. This article reviews novel therapeutic agents and their scientific basis.

In-Hospital Mortality among Patients of Severe Adult Tetanus Presenting with bad Prognostic Factors: A Tertiary Care Hospital Experience

Background: Tetanus caused by clostridium tetani, despite being a preventable disease, is still posing a significant health hazard to developing countries like Pakistan. Objective: To determine in-hospital mortality among patients of severe adult tetanus presenting with bad prognostic factors.Material and Methods: This cross-sectional study was conducted at the Department of Medicine, Medical Teaching Institution Lady Reading Hospital, Peshawar, Pakistan from July 13, 2017, to January 13, 2018, on 176 patients. All severe adult tetanus patients as per Ablett Classification with bad prognostic factors (incubation period <7 days, persistent fever >40o C, persistent tachycardia of >120/min, and no history of post-exposure prophylaxis) were included in the study. Patients with compromised renal functions (urea >108 mg/dl, reduced urine output <50 ml/hr) and already diagnosed neuromuscular junction disorders were excluded from the study. Written informed consent was obtained and patients were enrolled in the study. All patients were immediately worked up with detailed history and clinical examinations and were managed as per ICU protocols and followed within the hospital for mortality.Results: Mean age of study participants was 47±10.27 years. The majority of study subjects were males (n=102, 58%), un-immunized (n=88, 50%) or partially immunized (n=26, 15%), socioeconomically poor (n=84, 48%), illiterate (n=82, 47%) and from urban areas (n=114, 65%). In-hospital mortality was recorded in 109 (62%) of the study subjects. In hospital mortality was recorded highest in patients with an age range of 41-65 years (n=70/109, 64.22%), males (n=63/109, 57.8%), unimmunized (n=55/109, 50.45%), poor (n=52/109, 47.7%), illiterate (n=51/109, 46.78%) and urban (n=71/109, 65.14%). Conclusion: In-hospital mortality was high in patients with severe adult tetanus presenting with bad prognostic factors.Keywords: Clostridium tetani, Hospital Mortality, Severe adult tetanus, Tetanus, Tetanus Antitoxin, Tetanus Toxoid, Trismus, Prognostic Factors.

Epigenome-wide DNA methylation analysis of myasthenia gravis.

Myasthenia gravis (MG) is a common neuromuscular junction (NMJ) disorder and autoimmune disease mediated by several antibodies. Several studies have shown that genetic factors play an important role in MG pathogenesis. To gain insight into the epigenetic factors affecting MG, we report here genome-scale DNA methylation profiles of MG. DNA was extracted from 8 MG patients and 4 healthy controls for genome-wide DNA methylation analysis using the Illumina HumanMethylation 850K BeadChip. Verification of pyrosequencing was conducted based on differential methylation positions (DMPs). Subsequently, C2C12 and HT22 cell lines (derived from mouse) were treated with demethylation drugs. Transcribed mRNA of the screened differential genes were detected using quantitative Real-time PCR. The control and MG group were compared, and two key probe positions were selected. The corresponding genes were CAMK1D and CREB5 (P<0.05). Similarly, the myasthenic crisis (MC) and non-MC group were compared and four key probe positions were selected. The corresponding genes were SAV1, STK3, YAP1 and WWTR1 (P<0.05). Subsequently, pyrosequencing was performed for verification, revealing that hypomethylation of CAMK1D was significantly different between the MG and control group (P<0.001). Moreover, transcription of CREB5, PKD, YAP1 and STK3 genes in the C2C12 cells was downregulated (P<0.05) after drug treatment, but only YAP1 mRNA was downregulated in HT22 cells (P<0.05). This is the first study to investigate genome-scale DNA methylation profiles of MG using 850K BeadChip. The identified molecular markers of methylation may aid in the prevention, diagnosis, treatment and prognosis of MG.

PCR212 Correlation between Myasthenia Gravis Disease Severity and Impairment of Daily Living Activities of Real-World Patients in the United States and Five European Countries

Myasthenia Gravis (MG) is a neuro-muscular junction disorder caused by autoantibodies disrupting neuromuscular transmission resulting in impaired activities of daily living. The relationship between MG severity and ADL is not well understood. Using the MG-ADL score, a measure of MG impact on ADL, we assess how increased MG severity impacts ADL.

Application of a Validated Algorithm to Identify and Describe Contemporary Epidemiology of Privately Insured Myasthenia Gravis Patients in the United States (N6.002)

<h3>Objective:</h3> 1) To derive a cohort of patients with myasthenia gravis (MG) from a large United States (US) claims database using an algorithm previously validated in a Medicare population; 2) To describe epidemiology of this patient cohort. <h3>Background:</h3> Epidemiologic studies of MG using reliable case-ascertainment are lacking. A previously validated algorithm identified “definite” MG cases with sensitivity and positive predictive value of 80% among Medicare patients. To our knowledge, it has not been applied to other datasets. Analysis of contemporary care utilization for MG depends on accurate patient identification. <h3>Design/Methods:</h3> We performed a retrospective cohort study using years 2017–20 of Truven Marketscan, an administrative claims database. Adult patients with autoimmune MG were identified by presence of at least 2 MG-related ICD10 codes (G70.0, G70.00 and G70.01) associated with outpatient visits, separated by ≥ 4 weeks; OR ≥ 1 hospitalization and 1 outpatient visit using MG-related ICD codes, separated by ≥ 4 weeks, within 2 years. Exclusion criteria included other neuromuscular junction disorders. Annual incidence was calculated for 2019–20, using a 2 year wash-out period. We derived a non-MG comparison group from a random 1% sample of the total population. <h3>Results:</h3> Among 47,803,384 patients, we identified 12,121 (0.025%) with MG. MG patients were more likely female (56% vs 51%), age 40–64 (58% vs 46%) and with history of thymoma (2% vs 0.01%). Like the non-MG group, at least 11% lived in rural areas, but a lower proportion of MG patients lived in Western states (12% vs 17%). Total of 1,556/21,935,502 continuously enrolled patients had incident diagnosis of MG 2019–20 (0.007%). <h3>Conclusions:</h3> An algorithm validated in Medicare patients for MG identification was applied to a private insurer claims database. Incidence and prevalence of MG were calculated and are comparable to previous estimates. The cohort’s healthcare utilization data will be presented. <b>Disclosure:</b> Miss Hua has nothing to disclose. Dr. Semenov has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Regeneron. Dr. Semenov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Galderma. Dr. Semenov has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of the American Academy of Dermatology. The institution of Dr. Semenov has received research support from Dermatology Foundation. An immediate family member of Dr. Guidon has received personal compensation for serving as an employee of GE Healthcare. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Momenta. Dr. Guidon has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Guidon has received research support from MGFA. The institution of Dr. Guidon has received research support from Project Data Sphere. The institution of Dr. Guidon has received research support from MGNet. The institution of Dr. Guidon has received research support from MGNet. Dr. Guidon has received publishing royalties from a publication relating to health care.

Use of Efgartigimod in Treatment of Myasthenia Gravis Relapse after Possible Recurrence of Invasive Thymoma: A Case Report. (P1-5.011)

<h3>Objective:</h3> NA <h3>Background:</h3> Myasthenia gravis is an autoimmune neuromuscular junction disorder with established association with thymoma. There is no consensus on optimal treatment of recurrent thymoma post-resection. Efgartigimod is a first-in-class FcRn antagonist approved by the FDA in December 2021 for treatment of AChR-antibody-positive adults with generalized MG. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 53-year-old right-handed man presented to us in September 2020 with a 10-month history of recurrent diplopia, ptosis, dysarthria, dysphagia, and bilateral hand weakness. Workup for MG revealed blocking, binding, and modulating AChR antibodies. CT scan of his chest demonstrated an invasive anterior mediastinal mass. He started pyridostigmine, mycophenolate and prednisone, and underwent a sternotomy with thymectomy with sparing of the directly adjacent right phrenic nerve in October 2020. Histopathology revealed a locally invasive Masaoka stage IIIA, pT1bN0M0, WHO type B2 thymoma. He received adjuvant radiotherapy until January 2021. He was weaned off prednisone and pyridostigmine by May 2021. He remained asymptomatic for about 18 months post-thymectomy except for transient dysarthria in September 2021 attributed to missed mycophenolate doses. Patient noticed recrudescence of bulbar and respiratory symptoms around April 2022. Tests showed elevated AChR antibodies but surveillance chest CT scans did not demonstrate tumor recurrence or metastases. His cardiothoracic surgeon remained suspicious of residual thymoma. He started efgartigimod in July 2022 which he tolerated well, resulting in symptom resolution and objective improvement on MG-specific outcome measures (MG-ADL, MG-QoL15r and MGC). His symptoms recurred during a COVID-19 infection a month later, but he rapidly became asymptomatic after completing the second efgartigimod cycle in September 2022. <h3>Conclusions:</h3> Our patient with AChR antibody-positive, thymoma-associated, generalized MG with recurrent symptoms despite mycophenolate treatment, thymectomy and radiotherapy showed a dramatic response to initial cycles of efgartigimod therapy without significant adverse effects. We propose that efgartigimod be considered early in the management of MG patients with recurrent symptoms after thymectomy. <b>Disclosure:</b> Dr. Akemokwe has stock in CVS HEALTH CORP. Dr. Akemokwe has stock in LABORATORY CORP AMERICAN HOLDINGS. Dr. Coskun has nothing to disclose. Dr. Meyerson has nothing to disclose. Dr. Ebong has nothing to disclose.

Stimulated Jitter Analysis for the Evaluation of Neuromuscular Junction Disorders in Children (P7-8.004)

Stimulated Jitter Analysis for the Evaluation of Neuromuscular Junction Disorders in Children (P7-8.004)