Acetylcholine Receptor Antibodies Research Articles

Tekrarlayan başarısız weaning ve uzamış apne ile tanı konulan yaşlı myastenia gravis hastası

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder caused by the development of antibodies to nicotinic acetylcholine receptors. The disease characterized by variable muscle weakness worsening with exercise. Although most patients have neurological signs and symptoms, respiratory symptoms occur in the late stages of the disease. However, rarely, respiratory failure may be the first symptom in some undiagnosed patients. We report the case of an elderly patient who was admitted with respiratory failure and intubated and transferred to the internal medicine intensive care unit. Two days after intubation, when she was awake and met the extubation criteria, endotracheal tube was successfully removed. At this time, her vital signs were normal. However, next day, her arterial blood gas CO2 rose and he became drowsy, requiring re-intubation. This situation repeated on the fifth and 16th days of her hospitalization and prolonged apnea was observed after intubation with rocuronium. All other causes of failed extubation, such as sepsis and pneumonia, were ruled out. During follow-up, ptosis was detected in the right eye and acetylcholine receptor antibody was positive. On the 30th day of the follow-up, methylprednisolone 1mg/kg and pyridostigmine 240 mg/day was initiated. The patient, whose spontaneous respiration was sufficient, was extubated and taken to the neurology clinic for further examination and treatment.

Advancements in Targeted Therapies for Generalized Acetylcholine Receptor Antibody Positive Myasthenia Gravis: Beginnings of a Paradigm Shift.

In recent years, a new era of biologic therapeutics has emerged for the treatment of generalized myasthenia gravis (gMG). Compared to traditional immune modulatory therapies (steroids, non-steroidal immunosuppressive agents), these agents have more specific target engagement via inhibition of complement activation (eculizumab, ravulizumab, zilucoplan) or blockade of IgG recycling via the neonatal Fc receptor (FcRn; efgartigimod, rozanolixizumab). Phase 3 trials with each of these agents have shown rapid clinical improvement and good safety and tolerability. B-cell targeting with rituximab was safe and well-tolerated but with less impressive efficacy in two phase 2 studies. As a result, four new therapies are now approved for use (eculizumab, ravulizumab, efgartigimod, rozanolixizumab), another (zilucoplan) is in regulatory approval process and several others are in pivotal trials. A paradigm shift is afoot. The challenge is figuring out where these therapies may fit in gMG treatment algorithms.

Clinical presentation, evaluation, and management of patients with myasthenia gravis at a tertiary care center in Pakistan

Note: The editors of PJNS are aware that this article contains old data. However, we have decided to publish this article because a) the data is still important as there is paucity of data in this regard from Pakistan, and b) the authors have written the article well and have mentioned this limitation of their manuscript.
 Background and objectives:
 Little is known about the clinical profile and outcome of myasthenia gravis in Pakistan. The objective of this study is to review the clinical characteristics of patients with myasthenia gravis in Pakistan, and the outcome of investigations and treatment.
 Methods: 
 The study comprised a retrospective review of charts of patients diagnosed with myasthenia gravis at Aga Khan University Hospital in Karachi, Pakistan, over a period of 16 years from 1987 to 2003. The following features were reviewed: (i) clinical presentation, (ii) investigations especially nerve conduction studies, acetylcholine receptor antibodies, and imaging studies of the thorax, (iii) treatments administered (including thymectomy). Data analysis was done using Excel sheets.
 Results: 
 Of the 83 patients, 51(61.4%) were males, whereas 32 (38.6%) were females. The age range was from 12 to 81 years, mean age of 43.7 years (SD± 18.2). In the 60 years plus group, there were three times as many males as compared to females. Limb weakness was noted in 58 (69.9%), ocular symptoms in 57(68.7%), and oropharyngeal symptoms in 54(65.1%) patients. Three (3.6%) presented in a state of myasthenic crisis. Tensilon test was performed in 34 patients and was positive in 31(91.2%), repetitive nerve conduction studies (RNS) were performed in 37 patients and was positive in 26(70.3%), acetylcholine receptor antibodies were done in 60 patients, and were positive in 55(91.7%). Thymic enlargement was seen in 28 out of 43 patients who underwent CT-Scan/MRI studies of the thorax. Besides pyridostigmine, most patients received immunosuppressive therapy with either steroids or azathioprine or both. The thymectomy was performed in 44 patients. 
 Conclusion: 
 The general disease pattern of MG, as noted in our series, appears to follow a similar pattern as noted worldwide. However, this retrospective and hospital-based study has its limitations, and more prospective and epidemiological studies are needed.

Suspected Fluoroquinolone-Induced Exacerbation of Myasthenia Gravis in Dogs.

Acquired myasthenia gravis (MG) in dogs can present with focal or generalized weakness and is diagnosed by the presence of circulating antibodies to the acetylcholine receptor. Megaesophagus is the most common focal form of MG. Although exacerbation of MG has been associated with the use of fluoroquinolones in humans, it has not been previously described in dogs. The medical records of 46 dogs diagnosed with MG based on acetylcholine receptor antibody testing from 1997 to 2021 were retrospectively evaluated to identify any dogs who demonstrated exacerbation of MG after the administration of a fluoroquinolone. Exacerbation of MG, from focal to generalized, occurred in a median of 4.5 days after initiation of fluoroquinolone therapy in six dogs. In addition, one dog with generalized MG and megaesophagus developed pyridostigmine resistance subsequent to fluoroquinolone therapy. Marked improvement in generalized weakness was reported 36 hr after discontinuation of fluoroquinolone therapy alone in one dog and in combination with pyridostigmine in two dogs. Fluoroquinolone therapy was never stopped in three dogs who were euthanized because of severe weakness and one dog who died of respiratory arrest.

Effect of thymectomy on the frequencies of peripheral regulatory B and T lymphocytes in patients with Myasthenia gravis-a pilot study

Aim We aimed to investigate the relationship between the peripheral lymphocyte subset frequency and thymectomy in patients with myasthenia gravis (MG). Materials and Methods The frequencies of regulatory B (Breg) and regulatory T (Treg) cells in peripheral blood samples obtained from 69 patients with MG and 10 healthy controls were analyzed using flow cytometry. Serum acetylcholine receptor antibodies (AchR-Ab) were measured. Patients with MG were subdivided into pre-thymectomy, post-thymectomy, and normal thymus control group. Results The percentage of Breg cells was significantly decreased in both the pre-thymectomy (7.92 ± 1.30%) and post-thymectomy (8.14 ± 1.34%) groups compared to healthy controls (16.02 ± 2.78%) and reduced in the exacerbation and relapse phase compared to the stable maintenance stage. The proportion of cluster of differentiation (CD) 4 + CD25 + T cells and CD4 + CD25 + CD127low/- Treg cells in MG patients were not significantly different than healthy controls. AchR-Ab titers in aggravating or recurrence patients after thymectomy were significantly higher than that of the stable remission patients (11.13 ± 0.70 and 6.03 ± 0.85 nmol/L, respectively; p < 0.001). Conclusion The frequency of Breg cells may serve as a potential indicator of MG prognosis, while Treg cell frequency did not demonstrate the same prognostic ability. The concentration of AchR-Ab can be used as a dynamic monitoring index of disease severity in patients with MG.

Complement inhibition in Myasthenia – from basics to RCT data

Myasthenia gravis (MG) is the prototypic autoimmune neurological disorder causing fatiguable muscle weakness either limited to the ocular muscles or becoming generalised involving the limb and bulbar muscles. Nine out of 10 generalised MG patients have IgG1 or IgG3 antibodies against the acetylcholine receptor (AChR). AChR antibodies cause neuromuscular weakness by internalisation of AChR, receptor blockade and by activating the complement pathway. Complement activation causes formation of the membrane attack complex (MAC) leading to degradation of the neuromuscular junction (NMJ). Several animal models have confirmed the role of complement in the pathogenesis of MG, with the experimental models (EAMG) often needing complement inhibitory therapies to prevent or reverse the disease. Various molecules that target the complement system have now been developed to treat myasthenia gravis. The vast majority of the currently studied molecules target the C5 protein, thereby preventing the formation of MAC and subsequent NMJ destruction. The currently studied anti-complement therapies for MG include Eculizumab, Zilucoplan, Ravulizumab, Pozelimab, Cemdisiran, Gefurilimab, Danicopan and few others in the pipeline. Eculizumab has been shown in clinical trials to be effective in the treatment of refractory MG, but further sub-group analysis and real-life experience have shown that this can be beneficial in various patients including those receiving regular IVIG, plasma exchange or Rituximab. It was approved for use by FDA in Oct 2017. Ravulizumab is a long-acting monoclonal antibody which has similar mechanism of action to Eculizumab and was approved for use in MG by FDA in April 2022. Zilucoplan is a macrocyclic peptide which binds to C5 and C5b thus preventing terminal complement activation, which can be given subcutaneously (FDA new drug application accepted in Nov 2022). Many of these have also been shown to have long term benefit in different sub-groups of patients with MG. Patients would need to be vaccinated against Neisseria meningitidis because of the risk of Gram-negative septicaemia, although no major safety signatures have been noted in the studies so far. Future studies may be able to identify specific biomarkers which might aid in selecting the most appropriate patients who might respond to these therapies.

Myasthenia research over the last 50 years – a personal perspective

Myasthenia gravis (MG) research has, in many respects, been a trail blazer for the growing number of autoantibody-mediated disorders that affect the nervous system. The breakthroughs in MG understanding were made in the 1970s and even 50 years later, MG still remains a topic which scientists, clinicians and, most recently Pharma, return to as the most common and well-studied disorder. Here, some of the main discoveries will be reviewed very briefly focusing on how the knowledge of the disease evolved during the first decades after the discovery of acetylcholine receptor antibodies. It should be noted that this is a personal perspective and not a systematic or fully referenced review.

Clinical characteristics and treatment outcomes in patients with double-seronegative myasthenia gravis.

Double-seronegative myasthenia gravis (dSNMG) is defined as myasthenia gravis (MG) without detectable or low affinity antibodies to acetylcholine receptor (AChR) and muscle-specific kinase (MuSK). There are limited data on detailed clinical features and outcomes after treatment in dSNMG patients. The aim was to describe the clinical characteristics and outcomes in dSNMG patients based on MG scales. A retrospective study was performed of patients diagnosed with MG who had negative AChR or MuSK antibodies and they were compared with an AChR-positive MG cohort. Correlations were made with data from the first and last clinic visits, between demographics, clinical characteristics, treatment and disease severity, based on the Myasthenia Gravis Foundation of America category, Myasthenia Gravis Impairment Index (MGII), Patient Acceptable Symptom State and simple single question (SSQ). Eighty patients met the inclusion criteria for dSNMG. The baseline MGII and SSQ scores in the dSNMG cohort showed no significant differences from the AChR group (p = 0.94 and p = 0.46). The dSNMG cohort MGII and SSQ scores improved significantly at the last clinical evaluation (p = 0.001 and p = 0.047). The MGII improvement in the AChR cohort was significantly better (p = 0.003). The initial severity of dSNMG based on clinical scores is similar to antibody-positive MG patients. There is significant clinical improvement in dSNMG patients after therapy, measured in the last clinical evaluation. This supports an immune pathophysiology of many dSNMG patients.

IgG1-3 MuSK Antibodies Inhibit AChR Cluster Formation, Restored by SHP2 Inhibitor, Despite Normal MuSK, DOK7, or AChR Subunit Phosphorylation.

Up to 50% of patients with myasthenia gravis (MG) without acetylcholine receptor antibodies (AChR-Abs) have antibodies to muscle-specific kinase (MuSK). Most MuSK antibodies (MuSK-Abs) are IgG4 and inhibit agrin-induced MuSK phosphorylation, leading to impaired clustering of AChRs at the developing or mature neuromuscular junction. However, IgG1-3 MuSK-Abs also exist in MuSK-MG patients, and their potential mechanisms have not been explored fully. C2C12 myotubes were exposed to MuSK-MG plasma IgG1-3 or IgG4, with or without purified agrin. MuSK, Downstream of Kinase 7 (DOK7), and βAChR were immunoprecipitated and their phosphorylation levels identified by immunoblotting. Agrin and agrin-independent AChR clusters were measured by immunofluorescence and AChR numbers by binding of 125I-α-bungarotoxin. Transcriptomic analysis was performed on treated myotubes. IgG1-3 MuSK-Abs impaired AChR clustering without inhibiting agrin-induced MuSK phosphorylation. Moreover, the well-established pathway initiated by MuSK through DOK7, resulting in βAChR phosphorylation, was not impaired by MuSK-IgG1-3 and was agrin-independent. Nevertheless, the AChR clusters did not form, and both the number of AChR microclusters that precede full cluster formation and the myotube surface AChRs were reduced. Transcriptomic analysis did not throw light on the pathways involved. However, the SHP2 inhibitor, NSC-87877, increased the number of microclusters and led to fully formed AChR clusters. MuSK-IgG1-3 is pathogenic but seems to act through a noncanonical pathway. Further studies should throw light on the mechanisms involved at the neuromuscular junction.

Rituximab therapy in anti-musk positive juvenile myasthenia gravis; A case report

Juvenile myasthenia gravis is a rare acquired disease of childhood. It is difficult to differentiate it from congenital myasthenic syndrome due to the negativity of the Acetylcholine receptor antibody.

Childhood myasthenia gravis in Japan: Pathophysiology and treatment options

AbstractMyasthenia gravis (MG) is a disease that causes muscle weakness and fatigue due to an abnormality in the neuromuscular junction, which prevents the transmission of information. In the 1970s, it became clear that MG was caused by an autoimmune mechanism, and treatments began to be developed. Most studies on the pathophysiology and treatment of MG have been conducted in adults. However, even in terms of acetylcholine receptor antibodies, which are related to MG pathophysiology, adults and children differ significantly. Moreover, epidemiological studies around the world have revealed significant differences in the prevalence of MG between East Asia, Europe, and the United States. Treatment methods also differ slightly across countries, depending on the differences in pathophysiology and medical practices that have been developed in each region of the world. Japanese pediatric neurologists have revealed a pathophysiology unique to children and differences in treatment methods for childhood MG. However, few studies have systematically reported these findings. Therefore, this article reviews the current basic concepts related to the pathophysiology and treatment of childhood MG in Japan.

Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study

BackgroundApproximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients.MethodsThis retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded.ResultsThe recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent.ConclusionsThe independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

The impact of thymectomy in subgroups of Myasthenia gravis patients: a single center longitudinal observation

BackgroundMyasthenia gravis (MG) is a rare neuromuscular disorder. Symptoms can range from ptosis only to life threatening myasthenic crisis. Thymectomy is recommended for anti-acetylcholine receptor-antibody positive patients with early-onset MG. Here, we investigated prognostic factors shaping therapeutic outcomes of thymectomy to improve patient stratification.MethodsWe retrospectively collected single-center data from a specialized center for MG from all consecutive adult patients that underwent thymectomy from 01/2012 to 12/2020. We selected patients with thymoma-associated and non-thymomatous MG for further investigations. We analyzed the patient collective regarding perioperative parameters in relation to the surgical approach. Furthermore, we investigated the dynamics of the anti-acetylcholine receptor-antibody titers and concurrent immunosuppressive therapies, as well as the therapeutic outcomes in dependence of clinical classifications.ResultsOf 137 patients 94 were included for further analysis. We used a minimally invasive approach in 73 patients, whereas 21 patients underwent sternotomy. A total of 45 patients were classified as early-onset MG (EOMG), 28 as late-onset MG (LOMG) and 21 as thymoma-associated MG (TAMG). The groups differed in terms of age at diagnosis (EOMG: 31.1 ± 12.2 years; LOMG: 59.8 ± 13.7 years; TAMG: 58.6 ± 16.7 years; p < 0.001). Patients with EOMG and TAMG were more often female than patients in the LOMG group (EOMG: 75.6%; LOMG: 42.9%; TAMG: 61.9%; p = 0.018). There were no significant differences in outcome scores (quantitative MG; MG activities of daily living; MG Quality of Live) with a median follow-up of 46 months. However, Complete Stable Remission was achieved significantly more frequently in the EOMG group than in the other two groups (p = 0.031). At the same time, symptoms seem to improve similarly in all three groups (p = 0.25).ConclusionOur study confirms the benefit of thymectomy in the therapy of MG. Both, the concentration of acetylcholine receptor antibodies and the necessary dosage of cortisone therapy show a continuous regression after thymectomy in the overall cohort. Beyond EOMG, groups of LOMG and thymomatous MG responded to thymectomy as well, but therapy success was less pronounced and delayed compared to the EOMG subgroup. Thymectomy is a mainstay of MG therapy to be considered in all subgroups of MG patients investigated.

Autoantibodies, clinical phenotypes and quality of life in Lebanese patients with myasthenia gravis.

Myasthenia gravis (MG) is a rare autoimmune disease that affects the neuromuscular junction. It is characterized by the production of heterogeneous autoantibodies that bind to the neuromuscular junction and alter neural transmission. Recently, more attention was given to MG-related antibodies and their clinical influence. In Lebanon, studies about MG are very rare. To date, there is still no research on the different autoantibodies developed by Lebanese MG patients. We conducted a study aimed at detecting the prevalence of different antibodies in a group of seventeen Lebanese patients with MG, and exploring their associations with clinical phenotypes and quality of life (QOL). MG antibody test in Lebanon is restricted only to two antibodies: acetylcholine receptor (anti-AChR) and muscle-specific kinase (anti-MUSK) antibodies. Results showed that 70.6% of patients were anti-AChR positive and all of them were anti-MUSK negative. Association between MG serological profiles, clinical outcomes and QOL was not significant. Together, current findings suggest that anti-MUSK antibody is not common and difference in antibody profile may not change the clinical phenotypes and QOL of MG Lebanese patients. In the future, it is recommended to check also for autoantibodies other than anti-AChR and anti-MUSK, which may reveal new antibody profiles and possible associations with clinical outcomes.

An observational study on the safety of COVID-19 vaccination in patients with myasthenia gravis

ObjectiveThere is concern that the coronavirus disease (COVID-19) vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of COVID-19 vaccination on symptom severity in patients with myasthenia gravis (MG).MethodsA total of 106 enrolled patients with MG who were vaccinated against COVID-19 were followed up, and a questionnaire was used to document in detail the exacerbation of muscle weakness after vaccination and all other uncomfortable reactions after vaccination. Demographic, clinical characteristics, medication, and vaccination data were collected by follow-up interview. The main observation outcome was whether the MG symptoms of patients were exacerbated. The definition of exacerbation is according to the subjective feeling of the patient or a 2-point increase in daily life myasthenia gravis activity score relative to before vaccination, within 30 days after vaccination.ResultsOf 106 enrolled patients [median age (SD) 41.0 years, 38 (35.8%) men, 53 (50.0%) with generalized MG, 74 (69.8%) positive for acetylcholine receptor antibody, and 21 (19.8%) with accompanying thymoma], muscle weakness symptoms were stable in 102 (96.2%) patients before vaccine inoculation. Muscle weakness worsened in 10 (9.4%) people after vaccination, of which 8 patients reported slight symptom worsening that resolved quickly (within a few days). Two (1.9%) of patients showed serious symptom aggravation that required hospitalization.ConclusionOur results suggest that inactivated virus vaccines against COVID-19 may be safe for patients with MG whose condition is stable. Patients with generalized MG may be more likely to develop increased muscle weakness after vaccination.

THYMECTOMY IN SEVERE (MGFA CLASS IV-V) GENERALIZED MYASTHENIA GRAVIS: IS THE GAME REALLY WORTH THE CANDLE?

Total thymectomy in addition to medical treatment is an accepted standard therapy for myasthenia gravis. Patients with severe generalized myasthenia gravis present life-threatening events, poor prognosis and higher risk of postoperative myasthenic crisis. Aim of our study is to investigate neurological and surgical results in patients with MGFA class IV and V MG following thymectomy. Data on 76 myasthenia gravis patients with preoperative MGFA class IV and V who underwent thymectomy were retrospectively collected. Primary end-points included short-term surgical outcomes and long-term neurological results including the achievement of complete stable remission and any improvement as defined by MGFA postintervention status criteria. There were 27(35.5%) males and 49(64.5%) females; 53(69.7%) were classified as MGFA class IV and 23(30.3%) as class V. Thymectomy was performed through sternotomy in 25(32.9%) patients, by VATS in 5(6.6%) and RATS in 46(60.5%). Median operative time was 120(IQR 95; 148) min. In-hospital mortality was observed in 1(1.3%) patient, postoperative complications in 14 (18.4%). Median postoperative hospital stay was 4(IQR 3; 6) days. Pathological examination revealed 31(40.8%) thymic hyperplasia/other benign and 45(59.2%) thymomas. Cumulative complete stable remission and improvement probabilities were 20.6% and 83.7% at 5-year, and 66.9% and 97.6% at 10-year, respectively. A significant improvement rate was found in patients with age at time of thymectomy of ≤ 50 years(p = 0.0236), MGFA class V(p = 0.0154), and AchR-antibodies positivity(p = 0.0152). Thymectomy in patients with severe myasthenia gravis yields good perioperative outcomes and satisfactory long-term neurological improvement, especially for patients younger than 50 years, with MGFA class V and anti-AChR+ myasthenia gravis.

Acquired Rippling Muscle Disease with Acetylcholine Receptor Antibodies (P1-8.008)

<h3>Objective:</h3> To report a case series of acquired rippling muscle disease (RMD) with acetylcholine receptor (AChR) antibodies. <h3>Background:</h3> Previous studies have demonstrated association of acquired RMD with autoimmune disorders, or less commonly with cancer. AChR antibodies are often observed in RMD in parallel with the presumed immune-mediated etiology of acquired RMD. Despite having AChR antibodies, acquired RMD patients may exhibit minimal or no manifestations of myasthenia gravis (MG). Treatment selection in these RMD patients may prove challenging. <h3>Design/Methods:</h3> All cases of acquired RMD seen at our institution since 2010 were identified by search of the electronic medical record. <h3>Results:</h3> Three patients with acquired RMD were identified. These were men with classic RMD symptoms beginning in the fourth to sixth decade. Two developed ocular MG after onset of RMD, while the third had no MG symptoms. None had other autoimmune disorders or malignancy. AChR-binding antibodies were detected in all three patients, and two had positive striational antibodies. None had thymoma. Creatine kinase was mildly elevated, and caveolin-3 genetic testing was negative in all three patients. Concentric needle electromyography showed electrical silence during spontaneous muscle contractions in 2 of 3 patients. The third patient exhibited decreased caveolin-3 and dystrophin sarcolemmal immunoreactivity on muscle biopsy. All patients received at least one immunosuppressive (IS) therapy. While MG symptoms responded to IS treatment, RMD symptoms were more refractory. Only one individual who received intravenous immunoglobulin (IVIg) experienced significant improvement in RMD symptoms. Symptomatic treatment for RMD yielded only minimal benefit. <h3>Conclusions:</h3> Acquired RMD is a rare disorder of muscular hyperexcitability, presumably related to an underlying immune-mediated phenomenon. Most cases of RMD/MG were heralded by RMD and may only exhibit minimal or no manifestations of MG despite AChR antibody positivity. IS therapies appear to be ineffective for RMD symptoms, although one patient had significant symptomatic benefit with IVIg. <b>Disclosure:</b> Dr. Wannarong has nothing to disclose. Dr. Gable has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape, Web MD. Dr. Gable has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pharmacy Times. Dr. Gable has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cowen. Dr. Gable has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Gable has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ultragenx. Dr. Gable has received personal compensation in the range of $5,000-$9,999 for serving as a Lecture series with Medscape. Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Juel 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. Juel has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accordant Health Services. The institution of Dr. Juel has received research support from argenx. The institution of Dr. Juel has received research support from Alexion. The institution of Dr. Juel has received research support from Janssen. The institution of Dr. Juel has received research support from NIH Rare Diseases Network.

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.

Immune Checkpoint Inhibitors Related New Onset Myasthenia Gravis: Case Series (P4-5.028)

<h3>Objective:</h3> Immune checkpoint inhibitors (ICI), such as cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are treatment for several malignancies. Myasthenia gravis (MG) is a rare but life-threatening adverse event of ICI. <h3>Background:</h3> With ICI single agent use, 42 cases of new-onset MG are reported in literature, among those, 14 patients developed severe respiratory failure and required intubation whereas 10 patients died. Combination ICI-induced MG was reported in 7 cases, with at least 2 cases complicated by respiratory failure and 1 death. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms). <h3>Design/Methods:</h3> Case series and literature review <h3>Results:</h3> <h3>Case 1:</h3> 87-year-old woman with stage IV adenocarcinoma of colon received pembrolizumab. Ten days after second dose she presented with worsening new onset bilateral ptosis (left&gt;right) and dysphagia, seropositive with acetylcholine receptor antibodies. There was no significant improvement after a course of IVIG in combination with high dose steroids. A trial of pyridostigmine could not be completed due to symptomatic bradycardia and hospice care was started thirty-eight days after first dose of pembrolizumab. <h3>Case 2:</h3> 73-year-old man with metastatic melanoma, received 2 doses of combined ipilimumab and nivolumab. Fifteen days after second dose, he presented with worsening dysphagia, dysarthria, fatigable generalized weakness and shortness of breath, seronegative for MG antibodies. Symptoms improved dramatically with IVIG. His course was complicated by rostral brainstem ischemic stroke and discharged to hospice ninety-four days after the first dose of combined ipilimumab and nivolumab <h3>Conclusions:</h3> Evidence is limited and data from a large cohort of patients is needed to recognize and manage this fatal complication. <b>Disclosure:</b> Dr. Habib has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Al-Awwad has nothing to disclose. Sarah Sung, MD has nothing to disclose.

Efgartigimod for Pembrolizumab-induced Myasthenia Gravis Refractory to Standard Therapy (P1-8.006)

<h3>Objective:</h3> NA <h3>Background:</h3> Checkpoint inhibitor-induced myasthenia gravis is a life-threatening complication with mortality near 60%.¹ Two patients with pembrolizumab-induced myasthenia gravis responded favorably to efgartigimod. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 68-year-old female with metastatic gallbladder cancer developed ptosis, ophthalmoparesis, and weakness one month after receiving pembrolizumab. She has acetylcholine receptor (binding, blocking) and striated muscle antibodies without thymoma. Her ptosis improved with prednisone 20mg daily. She developed dysphagia, hoarseness, and gait instability which resolved with increased prednisone 60mg. Prednisone was tapered; proximal limb weakness and ptosis returned at 30mg. Efgartigimod improved symptoms after second infusion. Three weeks after cycle one while alternating prednisone 25mg–20mg, she developed exertional dyspnea, hoarseness, and worsening ptosis. Increased prednisone to 25mg. Her symptoms persisted; five weeks after cycle one, the second cycle of efgartigimod started and her symptoms nearly resolved, with intermittent ptosis. She is stable on prednisone 25mg with slow taper. A 78-year-old female with metastatic urothelial carcinoma status post two doses of pembrolizumab presented with dyspnea, leg weakness, and myalgias. She developed ptosis, ophthalmoparesis, and dysphagia. Acetylcholine receptor and MuSK antibodies were negative. Intravenous immunoglobulin was ineffective to prevent worsening. After the second dose, she developed respiratory failure requiring intubation. Prednisone 40mg BID and plasmapheresis (PLEX) were initiated. Her strength improved enough for extubation; subsequently aspirated and required reintubation. Rituximab was infused for long-term immunosuppression while another PLEX cycle was started. She developed thrombocytopenia and gastrointestinal bleeding; PLEX was discontinued after 3 doses. Efgartigimod initiation two days after the final PLEX infusion led to improved strength, ophthalmoparesis, and thrombocytopenia within one week. She died from urosepsis two days after the second dose. <h3>Conclusions:</h3> Current treatments for pembrolizumab-induced myasthenia gravis are corticosteroids, IVIG, and plasmapheresis. Rituximab is effective in refractory cases, although onset of action can take more than 6 weeks.² Efgartigimod rapidly improved myasthenia gravis symptoms in both patients. <b>Disclosure:</b> Miss Campbell has nothing to disclose. Dr. Rodriguez-Hernandez has nothing to disclose. Dr. Rizvi has nothing to disclose. Dr. Swerdloff has nothing to disclose. The institution of Dr. Zakin has received research support from American Board of Psychiatry and Neurology. Dr. Faktorovich has a non-compensated relationship as a Board of Directors with Brother’s Brother Foundation that is relevant to AAN interests or activities.