Neuromuscular Junction Disorders Research Articles

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)

Neuromuscular junction disorders: Experimental models and pathophysiological mechanisms.

Located between skeletal muscle fibers and motoneurons, the neuromuscular junction is a chemical synapse essential for the transmission of information from nervous system to skeletal muscle. There are many diseases related to neuromuscular junction dysfunction, including myasthenia gravis, Lambert‑Eaton myasthenic syndrome, congenital myasthenic syndromes, amyotrophic lateral sclerosis, and spinal muscular atrophy. The pathophysiological mechanisms of these diseases have been investigated using many animal models. Among them, mouse models are the most commonly used and have provided the majority of current data. Moreover, advances in human induced pluripotent stem cell technology has resulted in new opportunities to study neuromuscular junction disorders from both patients and healthy individuals. Currently, patient‑specific induced pluripotent stem cells derived from motor neurons have begun to be studied. These studies will help us achieve a more comprehensive understanding of diseases related to neuromuscular junction disorders. We will describe the research models of neuromuscular junction disorders and provide an overview of recent key findings.

New Onset of Myasthenia Gravis following COVID-19 Vaccination: A Case Report

Myasthenia gravis (MG) is a rare autoimmune disease and the most common neuromuscular junction disorder. The most common symptoms are diplopia, ptosis, and fluctuating weakness of ocular and limb muscles. Here we report a case of MG after COVID-19 vaccination. A 37-year-old Iranian lady presented with generalized weakness, diplopia, and ptosis after three days from taking the second dose of COVID-19 vaccine. Symptoms began three days after taking the second dose of Sinopharm BIBP COVID-19 vaccine (BBIBP-CorV) and worsened within a week. Her past medical history included migraine-type headaches and gastric reflux. She was consuming Rizatriptan and Nortriptyline for her migraine headache and Pantoprazole, Domperidone, and Sertraline for stomach reflux. She had a family history of Essential tremor in her father, uncle, and grandfather. Antibody against the acetylcholine receptor (AChR-Ab) was more than eight times compared to the normal range. The pattern of repetitive nerve stimulation was suggestive for MG. Treatment with corticosteroid, azathioprine, and pyridostigmin led to amelioration of symptoms. Follow-up testing revealed AChR-Ab returned to the normal range. There are some case reports in that a chronic autoimmune disorder flared up after the COVID1-9 infection or its vaccination. There are several reports of MG exacerbations, acute respiratory distress syndrome, higher ICU admission, and mortality rate and worsening neurological symptoms after COVID-19 infection. There is still debate about the association between neuromuscular disorders and COVID-19 infection and vaccination. This matter is more doubtful for myasthenia gravis.

Myasthenia gravis with achalasia secondary to thymoma: a case report and literature review

BackgroundMyasthenia gravis is an autoimmune neuromuscular junction disorder characterized by fatigable muscle weakness and autoantibodies. Frequent associations exist between myasthenia gravis and thymic abnormalities, including hyperplasia and thymoma. Several autoimmune illnesses have been identified to be associated with thymoma; however, a few case reports have linked thymoma and achalasia, and the underlying mechanism is unknown.Case reportA 43-year-old man with thymoma-associated myasthenia gravis presented with dysphagia that was refractory to conventional treatment of myasthenia gravis. This dysphagia was challenging to diagnose even after multiple gastroenterology consults and upper endoscopy. The diagnosis of achalasia type II was established after a comprehensive evaluation, including upper endoscopy, barium swallow, and high-resolution esophageal manometry. The patient underwent elective pneumatic balloon dilatation, which successfully alleviated his dysphagia.ConclusionThis case confirmed the association between myasthenia gravis secondary to thymoma and achalasia and showed how the diagnosis of achalasia was challenging. Awareness of this association is crucial for early diagnosis and treatment, improving affected patients’ quality of life.

A Case of Myasthenia Gravis Successfully Treated with Individualized Homoeopathic Treatment - A Case Report

Myasthenia gravis (MG), an autoimmune disorder affecting receptors on the postsynaptic end-plate, leads to functional disability of end organs. The treatment of MG in conventional system remains still unsatisfactory on account of its after effects on the immune system. Due to lack of advocacy on the effectiveness of homeopathic medicines, a very few cases of neurological diseases like MG opt for treatment. In this case report of refractory MG, after administration of homeopathic potentized Natrum Muriaticum, shown a marked improvement in a brief period without any adverse reaction. The MONARCH score of + 8/11 shows a positive causal relationship between Natrum Muriaticum and treatment outcome. This case report shows the efficacy of classical homeopathy in neuromuscular junction disorders like MG.

Efgartigimod: a breakthrough medicine for myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction origin that causes persistent fatigue and weakening of voluntary muscles. MG is the most prevalent neuromuscular junction disorder, with an estimated 150–200 new cases per million individuals per year. Patients with MG presently lack a specific and effective long-term therapeutic option. Patients with generalized MG who test positive for anti-acetylcholine receptor antibodies have demonstrated a positive response to Efgartigimod therapy. Thus, the clinical trial of Efgartigimod for the treatment of generalized MG is a significant step toward the availability of an internationally licensed medicine for the ailment.

Benign food-borne type B botulism presenting as unilateral internal ophthalmoplegia: a case report

BackgroundFood-borne botulism is a rare neuromuscular junction disorder due to the effect of toxins released from Clostridium botulinum ingested by eating improperly stored food. Its classic manifestation is a rapidly evolving descending symmetrical flaccid paralysis with dysautonomia.Case presentationWe have described a case of type B food-borne botulism with a benign clinical course characterized by an initially unilateral tonic mydriatic pupil. An extensive neurophysiological evaluation inclusive of pilocarpine eye drop(s) test, facial and limbs nerve stimulation and sudomotor tests, was decisively leading the diagnostic process.ConclusionsThe importance of what has been described here lies in underlining that it is always advisable to consider food-borne botulinum intoxication, even in the case of unilateral/asymmetrical internal ophthalmoplegia without generalized progressive involvement of the voluntary muscles.

Clinical picture and treatment of myasthenia gravis in the adult population

Introduction and purpose: Myasthenia gravis (MG, myasthenia gravis ) is a classic example of an autoimmune disease caused by antibodies against acetylcholine receptors ( AChR) , muscle-specific kinase (MuSK) or other AChR-related proteins in the postsynaptic muscle membrane leading to characteristic muscle weakness.&#x0D; Description of the state of knowledge: It is not fully known why the body begins to produce antibodies that act against its own acetylcholine receptors. The main role in producing these antibodies is played by the thymus gland, a gland located in the chest. The thymus gland is normally present in children, while it atrophies in adults. In about 60% of myasthenia gravis patients, however, it is present (we say they have a persistent thymus), and 15% of patients have a thymic neoplasm called a thymoma.&#x0D; Summary: Myasthenia gravis is the most common neuromuscular junction disorder. Myasthenia gravis is a rare disease that involves muscle weakness of the eyes, pharynx, larynx, respiratory muscles and limbs. Clinical manifestations vary depending on the type of autoantibody and the presence of thymoma. The diagnosis of the disease should be confirmed by electrodiagnostic and laboratory tests in addition to the typical symptoms. Myasthenia gravis can manifest at any age, both in men ( peak incidence 50-60 years of age) and women ( peak incidence 20-30 years of age). Muscle fatigue intensifies after any exercise, even small ones. The patient feels best in the morning hours, right after waking up. As time passes, the symptoms of muscle fatigue intensify and the patient becomes less and less fit. For this reason, patients should rest frequently.

Overview of biomarkers in myasthenia gravis

Myasthenia gravis (MG) is a rare auto-immune neuromuscular junction (NMJ) disorder which is caused by formation of autoantibodies and destruction of NMJ components. The MG diagnosis is based on the symptoms, autoantibodies detection and paraclinical tests. Given that MG patients have so many differential diagnosis and various medication responses, choosing an accurate diagnosis and the therapy plan in MG is challenging. According to the studies, there are the immunologic, genetic, microRNAs, gut microbiome, and other established or newly proposed biomarkers for diagnosis and prognosis of MG. More studies are needed to provide better collection of biomarkers in MG patients and evaluate their role in MG pathology.

Characteristics of Repetitive Nerve Stimulation (Rns) and Correlation with Severity and Quality of Life of Myasthenia Gravis Patients

Background: Myasthenia gravis is a rare autoimmune disease due to neuromuscular junction (NMJ) disorders. The diagnosis of myasthenia gravis is based on cardinal clinical symptoms, including fluctuating weakness, worsening with activity, and improving with rest. In addition to clinical signs and antibody tests, other tests that are also crucial for diagnosis are electrodiagnostic examination (EDX) such as repetitive nerve stimulation (RNS) and single fibre electromyography (SFEMG). Recent studies have focused on assessing patients' severity and quality of life, essential for determining the prognosis and subsequent treatment plans. Objective: To evaluate the characteristic of RNS and its correlation with rigor and quality of life of myasthenia gravis patients. Methods: Inclusion criteria: patients diagnosed with myasthenia gravis, aged 18-65 years, willing to participate in the study. Exclusion criteria include a history of neuropathy, motor neuron disease, or myopathy and dropping out of the study. Patient demographic data were collected. The results of the RNS examination were divided into two categories, normal and abnormal. MG severity was assessed by the Myasthenia gravis foundation of America (MGFA) classification, and the patient's quality of life was assessed by Myasthenia Gravis Quality of Life 15 (MG-QOL 15). Results: Of the 24 samples, 69.1% of RNS were positive. The most sensitive muscle for assessing RNS is the anconeus muscle, followed by the trapezius and nasal. There was no significant relationship between RNS features and severity and the quality of life of myasthenic Gravis patients. Conclusion: Onconeus muscle is the best location for assessing RNS. Although the number of patients with normal RNS had lower severity and better quality of life, there was no statistically significant relationship. Further studies with larger samples and longer follow-ups are needed.

I.01Congenital myasthenic syndromes

Neuromuscular junction disorders are a heterogeneous group of acquired (Myasthenia Gravis, MG) and inherited (Congenital Myasthenic Syndromes, CMS) disorders associated with distinctive clinical, electrophysiological, laboratory and ultrastructural abnormalities. The genetic defects in CMS either impair neuromuscular transmission directly or result in secondary impairments, which eventually compromise the safety margin of neuromuscular transmission. More recently, we have identified two genes (<i>DOK7, GFPT1</i>) that cause fatigable weakness of muscles in a limb-girdle distribution, but rarely affecting facial or eye muscles. Next-generation sequencing and deep phenotyping, in combination with international data sharing, reveals new genetic causes of CMS, but also unusual, overlapping clinical phenotypes, which blur the boundaries with primary myopathies and motor neuropathies. Mitochondrial dysfunction has been implicated with both myopathies and neuromuscular transmission defects. TEFM is a nuclear gene that codes for a mitochondrial transcription elongation factor – the protein responsible for prolonging activity of RNA polymerase to ensure distal transcripts of the mitochondrial genome are transcribed. We identified the first human <i>TEFM</i> variants associated with mitochondrial respiratory chain deficiency in seven patients with varying clinical presentations. While symptoms included classical features of a mitochondrial disease, some patients also presented with a treatable neuromuscular transmission defect. We will cover the significant progress made in understanding the molecular pathogenesis of CMS, which is important for both patients and clinicians in terms of reaching a definite diagnosis and selecting the most appropriate treatment.

MYASTHENIA GRAVIS PRECIPITATED BY ASYMPTOMATIC COVID-19 INFECTION, VACCINE, OR BOTH? HOW GENETIC PREDISPOSITION AND IMMUNE RESPONSES PLAY A ROLE IN THE NEUROMUSCULAR JUNCTION

MYASTHENIA GRAVIS PRECIPITATED BY ASYMPTOMATIC COVID-19 INFECTION, VACCINE, OR BOTH? HOW GENETIC PREDISPOSITION AND IMMUNE RESPONSES PLAY A ROLE IN THE NEUROMUSCULAR JUNCTION