Acetylcholine Receptor Autoantibodies Research Articles

Post-hoc analyses from the ADAPT clinical study demonstrate aggregate sustained benefit of Efgartigimod in generalized myasthenia gravis

ObjectivesThis post-hoc analysis evaluates the long-term efficacy of efgartigimod versus placebo in adult patients with generalized myasthenia gravis (gMG) with acetylcholine-receptor autoantibodies (AChR-Ab+), based on data from the ADAPT RCT and its open-label extension ADAPT+. MethodsChanges from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores were assessed by treatment group over the ADAPT (up to 20 weeks) and ADAPT+ time horizon (extended to 64 weeks for efgartigimod group patients). Response to treatment was defined as (Meriggioli, 2009 [3])5-point reduction in QMG or (Meriggioli, 2009 [3])3-point reduction in MG-ADL vs. baseline values. ResultsAChR-Ab+ patients treated with efgartigimod spent a substantially greater percentage of time in response in ADAPT based on at least a 5-point change in QMG compared to the placebo group (44 % versus 13 % respectively, p = 0.0034). Analyses based on a 3-point change in MG-ADL in ADAPT showed the percentage of time in response was nearly double for efgartigimod versus placebo (59 % versus 30 % respectively, p = 0.010). These trends were also maintained using different response definitions, as well as in patients with and without prior immune therapy exposure and by time from diagnosis (<7 years versus ≥7 years). ConclusionsThe clinical benefit of efgartigimod was sustained over repeat treatment cycles and maintained over the long term. Response to treatment was consistent regardless of response definition and was repeated in different patient subgroups. Overall, the results of this analysis indicate that efgartigimod is an effective therapeutic option, demonstrating a robust benefit among AChR-Ab+ patients with gMG.

Myasthenia gravis in pregnancy: Successful outcome with multidisciplinary management

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by nicotinic acetylcholine receptor autoantibodies, affecting the neuromuscular transmission leading to progressive weakness. MG during pregnancy is a high-risk condition that may affect both the mother and the fetus leading to adverse perinatal outcomes. We are presenting clinical course of two pregnant women, one of them was already diagnosed case of MG and second was diagnosed during postpartum period while waiting for discharge of baby. Literature review of the previously published cases and their management is also presented.

Comparison of juvenile and adult myasthenia gravis in a French cohort with focus on thymic histology

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR+ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

IL-6 receptor antibody treatment improves muscle weakness in experimental autoimmune myasthenia gravis mouse model.

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG.

B-cell immune dysregulation with low soluble CD22 levels in refractory seronegative myasthenia gravis.

Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear. Thus, in this study, we aimed to elucidate the pathogenic mechanism of seronegative MG using scRNA-seq analysis and plasma proteome analysis; in particular, we investigated the relationship between immune dysregulation status and disease severity in refractory seronegative MG. Employing single-cell RNA-sequencing and plasma proteome analyses, we analyzed peripheral blood samples from 30 women divided into three groups: 10 healthy controls, 10 early-onset AChR-positive MG, and 10 refractory early-onset seronegative MG patients, both before and after intravenous immunoglobulin treatment. The disease severity was evaluated using the MG-Activities of Daily Living (ADL), MG composite (MGC), and revised 15-item MG-Quality of Life (QOL) scales. We observed numerical abnormalities in multiple immune cells, particularly B cells, in patients with refractory seronegative MG, correlating with disease activity. Notably, severe MG cases had fewer regulatory T cells without functional abnormalities. Memory B cells were found to be enriched in peripheral blood cells compared with naïve B cells. Moreover, plasma proteome analysis indicated significantly lower plasma protein levels of soluble CD22, expressed in the lineage of B-cell maturation (including mature B cells and memory B cells), in refractory seronegative MG patients than in healthy donors or patients with AChR-positive MG. Soluble CD22 levels were correlated with disease severity, B-cell frequency, and RNA expression levels of CD22. In summary, this study elucidates the immunopathology of refractory seronegative MG, highlighting immune disorders centered on B cells and diminished soluble CD22 levels. These insights pave the way for novel MG treatment strategies focused on B-cell biology.

Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.

Efficacy and safety of rozanolixizumab in patients with muscle-specific tyrosine kinase autoantibody-positive generalised myasthenia gravis: a subgroup analysis of the randomised, double-blind, placebo-controlled, adaptive phase III MycarinG study.

Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG. To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study. A randomised, double-blind, placebo-controlled phase III study. Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-‍ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed. Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg (n = 5), 10 mg/kg (n = 8) or placebo (n = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7.28 (1.94); 10 mg/kg, -4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9.56 (97.5% confidence interval: -15.25, -3.87); 10 mg/kg, -6.45 (-11.03, -1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred. This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies. ClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrials‌register.eu/ctr-search/trial/2019-000968-18/GB).

Assay Development and Measurement of Autoantibody-Mediated Complement Activity in Myasthenia Gravis

Autoantibodies against the acetylcholine receptor (AChR) play a critical role in myasthenia gravis, where autoantibody-mediated complement activation has been implicated in neuromuscular junction damage. However, the exact pathogenic role of the autoantibodies in complement activation remains unclear. We developed a cell-based assay that measures AChR autoantibody–mediated complement membrane attack complex (MAC) formation. A modified HEK293T cell line using CRISPR/Cas9 genome editing to disrupt expression of the complement regulator genes (CD46, CD55, and CD59)—was used to measure AChR autoantibody–mediated membrane attack complex (MAC) formation through flow cytometry. We observed a modest correlation between autoantibody-mediated complement mediated activity and disease burden suggesting heterogeneity in autoantibody-mediated activation of complement system.

No evidence of increased anti-M3 muscarinic acetylcholine receptor autoantibodies in SSA-positive connective tissue disease patients.

Anti-muscarinic type 3 receptor autoantibodies (M3R) and anti-SSA antibodies are both related to salivary secretion. The presence of M3R antibodies in Sjögren's syndrome is previously demonstrated; nevertheless, the relationship between the anti-SSA antibodies and M3R fragment antibodies, namely the N terminal, first, second, and third extracellular loops, remains to be elucidated. In this study, we analyzed the antibodies against the M3R epitopes in healthy controls and anti-SSA antibody-positive connective tissue disease patients through ELISA method. Antibodies against the first, second, and third extracellular loop (M3R211-230 ) were not increased in anti-SSA positive patients compared to healthy controls. Indeed, antibodies against the N terminal (M3R1-33 ) were found to be high in healthy controls. High levels of M3R1-33 in healthy controls are a novel original finding; further research is needed for the clinical significance. There is no significant difference between SSA-positive patients and healthy controls in terms of autoantibodies against the remainder of the linear M3R fragments.

CD20-mediated B cell depletion in acetylcholine receptor autoantibody-positive myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness and fatigue, mediated in the majority of cases by IgG1 autoantibodies targeting the acetylcholine receptor (AChR). As AChR autoantibodies have been shown to be pathogenic, therapies targeting B cells have been applied in patients with AChR MG for more than a decade. Recently, a phase 2 trial of the CD20-targeting agent, rituximab, in AChR MG unfortunately failed to meet its primary endpoint. Converging data however from non-randomized clinical series, some of which with more participants than the phase 2 trial, support efficacy of rituximab in AChR MG, especially early onset disease. In this opinion article, we summarize both clinical data and mechanistic principles on the use of CD20 depletion therapy in AChR MG, which we believe lend support to the argument that CD20 depletion can still be a useful therapeutic strategy for patients with AChR MG.

Subgroup outcomes from RAISE: A randomized, Phase 3 trial of zilucoplan in generalized myasthenia gravis (P1-5.006)

Subgroup outcomes from RAISE: A randomized, Phase 3 trial of zilucoplan in generalized myasthenia gravis (P1-5.006)

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study

Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18-74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II-IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871). Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change -4·39 [95% CI -5·28 to -3·50] vs -2·30 [-3·17 to -1·43]; least squares mean difference -2·09 [-3·24 to -0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug. Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. UCB Pharma.

Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study

Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might provide a novel therapeutic option for myasthenia gravis. We aimed to assess the safety and efficacy of rozanolixizumab for generalised myasthenia gravis. MycarinG is a randomised, double-blind, placebo-controlled, adaptive phase 3 study done at 81 outpatient centres and hospitals in Asia, Europe, and North America. We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America class II-IVa), a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 3 (non-ocular symptoms), and a quantitative myasthenia gravis score of at least 11. Patients were randomly assigned (1:1:1) to receive subcutaneous infusions once a week for 6 weeks of either rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg, or placebo. Randomisation was stratified by AChR and MuSK autoantibody status. Investigators, patients, and people assessing outcomes were masked to random assignments. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. Treatment-emergent adverse events (TEAEs) were assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03971422) and EudraCT (2019-000968-18); an open-label extension study has been completed (NCT04124965; EudraCT 2019-000969-21) and another is underway (NCT04650854; EudraCT 2020-003230-20). Between June 3, 2019, and June 30, 2021, 300 patients were assessed for eligibility, of whom 200 were enrolled. 66 (33%) were randomly assigned to rozanolixizumab 7 mg/kg, 67 (34%) to rozanolixizumab 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change -3·37 [SE 0·49]) and in the rozanolixizumab 10 mg/kg group (-3·40 [0·49]) than with placebo (-0·78 [0·49]; for 7 mg/kg, least-squares mean difference -2·59 [95% CI -4·09 to -1·25], p<0·0001; for 10 mg/kg, -2·62 [-3·99 to -1·16], p<0·0001). TEAEs were experienced by 52 (81%) of 64 patients treated with rozanolixizumab 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent TEAEs were headache (29 [45%] patients in the rozanolixizumab 7 mg/kg group, 26 [38%] in the rozanolixizumab 10 mg/kg group, and 13 [19%] in the placebo group), diarrhoea (16 [25%], 11 [16%], and nine [13%]), and pyrexia (eight [13%], 14 [20%], and one [1%]). Five (8%) patients in the rozanolixizumab 7 mg/kg group, seven (10%) in the rozanolixizumab 10 mg/kg group, and six (9%) in the placebo group had a serious TEAE. No deaths occurred. Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis. Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis. UCB Pharma.

The diagnostic and prognostic utility of repetitive nerve stimulation in patients with myasthenia gravis

Repetitive nerve stimulation (RNS) is a standard test for the diagnosis of myasthenia gravis (MG), where decrement of compound muscle action potentials (CMAP) corresponds to clinical muscle fatigability. Our aim was to ascertain the diagnostic and prognostic utility of RNS in MG patients. This study included MG patients treated between 01/2000 and 12/2016, with an observational period of at least one year and a minimum of two neurological examinations. Clinical and electrophysiological data were retrospectively gathered from patient records, and CMAP decrement was correlated with autoantibody titers and clinical disease severity at different time points. Ninety-four patients were included, with 88.3% of the cohort testing positive for acetylcholine receptor autoantibodies (AChR-Abs). RNS sensitivity was higher in patients with generalized disease (71.6%) than in purely ocular MG (38.5%). CMAP decrement did not significantly correlate with AChR-Ab titers, nor with clinical symptom severity at the time of testing or last follow up. However, there was a significant correlation between CMAP decrement and the worst recorded clinical status on a group level. RNS testing is more sensitive in generalized disease and AChR-Ab positive patients, but our data do not support RNS as a tool for long-term outcome prediction. Future studies with a prospective study design could help to overcome a number of limiting factors discussed in our study.

Vibrance-mg: Clinical Trial of Nipocalimab in Pediatric Myasthenia Gravis

Objective We describe an open-label study of nipocalimab to determine the effect of nipocalimab in pediatric participants with gMG. Background Nipocalimab is a high affinity, fully human, aglycosylated, effectorless IgG1 anti FcRn monoclonal antibody that targets the neonatal Fc receptor (FcRn) with high affinity, thereby lowering IgG pathogenic antibodies in autoimmune disease. Data from Vivacity-MG, a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of nipocalimab demonstrated safety, tolerability, and efficacy of nipocalimab in adult generalized myasthenia gravis (gMG) (clinicaltrials.gov NCT03772587). Design/Methods This global study will enroll at least 12 participants, aged 2 to &lt;18, with a diagnosis of gMG and an insufficient clinical response to ongoing, stable standard-of-care therapy, as reflected by a Myasthenia Gravis Foundation of America (MGFA) Class of IIa/b through IVa at screening. Participants must have a positive serologic test for either acetylcholine receptor or Muscle Specific Tyrosine Kinase pathogenic autoantibody. The study will consist of a screening period of up to 4 weeks, a 24-week open-label Active Treatment Phase where participants will receive nipocalimab intravenously every two weeks, and a Long-term Extension phase; after last dose, a safety follow-up assessment will be conducted at 8 weeks. The primary outcome is the effect of nipocalimab on total serum IgG, safety and tolerability, and PK in pediatric participants with gMG. Results Study enrollment will begin in 2022. Conclusions The vibrance-mg study will assess the PK/PD, safety and activity of Nipocalimab in pediatric gMG.

Autoimmune Encephalitis With Ganglionic a3-AChR Antibodies

Objective To describe a case of autoimmune encephalitis presented as new onset refractory nonconvulsive status epilepticus and autonomic failure caused by alpha-3 ganglionic acetylcholine receptor autoantibodies (a3-AChR Ab). Background Autoimmune autonomic ganglionopathy (AAG) is rare acquired dysautonomia in adults due to a3-AChR Ab. A patient typically presents with subacute autonomic dysfunction, and encephalitis has not been reported yet. Design/Methods NA. Results A 60 years old female presented with progressive worsening of mental status for two weeks. Vital signs were normal. The patient was somnolent, nonverbal, with tonic non-reactive pupils on the exam. CT head showed multiple subcortical hypodensities. MRI brain demonstrated T2-FLAIR hyperintense lesions in bifrontal lobes sparing the U-fibers, with abnormal leptomeningeal/pial perivenular type enhancement. MRI C/T spine, CT chest/Abd/pelvis were negative. Although serum and CSF testing showed inflammatory markers, meningoencephalitis and autoimmune encephalitis panel were negative, except for the serum Paraneoplastic panel was positive with high titer a3-AChR Abs. EEG showed nonconvulsive status epilepticus, which required management with three antiseizure medications. Initially, the patient had little response to empirical pulse methylprednisolone therapy. Later showed good clinical response with plasmapheresis. Later on she presented with nonobstructive small bowel obstruction, resolved with another pulse steroid therapy, discharged on dexamethasone taper. On a three-month follow-up, the patient was in near clinical remission, supported with resolved lesions on a repeat MRI. She never relapsed after two years of follow-up. Conclusions Studies have shown that a3-AChR Abs can result in diverse neurological manifestations, mainly dysautonomia. Our patient presented with encephalitis, dysautonomia, and refractory nonconvulsive status epilepticus. Scans suggested diffuse leukoencephalopathy, patient was found to have high 3-ACHR antibody seropositivity. Initially, the patient was steroid-resistant but showed clinical improvement with plasmapheresis. We have described an interesting case of encephalitis likely associated with a3-AChR Ab that has not been previously described. More studies are required to confirm this association.

Granulomatous myopathy: Sarcoidosis and beyond.

Non-necrotizing granulomatous inflammation is a rare but easily recognized histopathological finding in skeletal muscle biopsy. A limited number of diseases are known to be associated with non-necrotizing granulomatous myopathy. Once identified, a careful evaluation for evidence of extramuscular granulomatosis and other signs suggestive of sarcoidosis is warranted as about half of the patients have sarcoid myopathy. In addition, the presence of granulomatous myopathy should trigger a search for clinical and pathological clues of inclusion body myositis (IBM), which accounts for most of the remaining patients and can coexist with sarcoidosis. Recognizing the features of IBM in patients with granulomatous myopathy can potentially spare the patients from unnecessary exposure to immunosuppressive therapies. In patients whose granulomatous myopathy remain unexplained, further investigations should aim at identifying myasthenia gravis and other autoimmune disorders, especially those known to cause granulomatous inflammation in other organs. Laboratory investigations should include acetylcholine receptor, antimitochondrial, antineutrophil cytoplasmic, thyroglobulin, and thyroid peroxidase autoantibodies. In the appropriate clinical context, exposure to immune checkpoint inhibitors and chronic graft-vs-host disease can be causes of granulomatous myopathy. In cases of unexplained granulomatous myopathy, natural killer/T-cell lymphoma should be considered and careful histopathological examination for atypical cells and appropriate immunostaining is crucial. Identifying the etiology of granulomatous myopathy in each patient can guide appropriate treatment.

PLASMAPHERESIS, A USEFUL TOOL FOR BETTER OUTCOME OF PATIENTS UNDERGOING THYMECTOMY FOR MYASTHENIA GRAVIS

Background: Thymectomy for widespread Myasthenia gravis may be associated with a turbulent postoperative course especially if preoperative circulating acetylcholine receptor autoantibody levels are towering. Plasmapheresis remove these antibodies. The aim of this study was to explore the results of preoperative Plamapheresis on postoperative course after thymectomy. Material And Method This is a retrospective study at tertiary care center where 13 patients of myasthenia gravis were operated in 3 year duration (2017-2020). All patients had undergone 2 cycles of plasmapheresis before surgery. Result was evaluated postoperatively in ICU, at the time of discharge, and at follow up after 7 days, 1 month and 6 month in terms of weaning from ventilator, ICU stay, level of autoantibodies and length of hospital stay, improvement in symptoms, and mortality. Results Out of 13 patients 5 (38.46%) were male and 8 (61.54%) were female in the age range of 20 to 60 years. 6 (46.15%) were in stage IIA and 7 (53.85%) in stage IIB. Preoperative autoantibody levels were in the range of 30-50 nmol/ml. Almost total thymectomy was done in all patients. Patients were extubated with in 4-6 hrs after surgery and there was no mortality. Patients were discharged at postoperative day 4-7. Conclusion The study shows that preoperative use of plasmapheresis to reduce the autoantibody level is associated with an early extubation, early discharge and less complication after thymectomy.

WEST NILE-INDUCED MYASTHENIA GRAVIS CRISIS: AN UNEXPECTED CASE OF RESPIRATORY FAILURE

WEST NILE-INDUCED MYASTHENIA GRAVIS CRISIS: AN UNEXPECTED CASE OF RESPIRATORY FAILURE

Abdeg technology for the treatment of myasthenia gravis: efgartigimod drug experience

ABSTRACT Introduction Myasthenia gravis is characterized by fluctuating muscle weakness that improves with rest and worsens with effort or throughout the day. Areas Covered Efgartigimod is a human IgG1–derived Fc fragment modified at five residues to increase its affinity for the neonatal Fc receptor by Abdeg technology. Thus, efgartigimod binds to the neonatal Fc receptor and decreases the levels of IgG, including autoantibodies of this isotype. For acetylcholine receptor (AChR) antibody-positive patients, efgartigimod had a higher proportion of MG-ADL responders than placebo in the first treatment cycle. The mean changes of multiple outcomes from baseline were better for efgartigimod than placebo from weeks 1 to 7 in the first treatment cycle. The decrease of IgG and AChR autoantibodies was 61.3% and 57.6% one week after the first treatment cycle ends, respectively. The most common adverse events were headache, nasopharyngitis, nausea, and diarrhea, which occurred in the same proportion in the efgartigimod and placebo groups. Urinary and upper respiratory tract infections were twice as frequent in efgartigimod-treated patients. Expert Opinion Efgartigimod was efficacious and safe for generalized myasthenia patients with AChR antibody-positive patients. These findings need to be confirmed in AChR antibody-negative patients, and long-term safety studies are currently ongoing.