Positive Acetylcholine Receptor Antibody Research Articles

Seeing Double: a Case of a Massive Type B2 Thymoma Presenting with Pseudo-Internuclear Ophthalmoplegia (P9-13.004)

<h3>Objective:</h3> NA <h3>Background:</h3> Thymomas are rare, malignant epithelial cell tumors usually diagnosed in the 5th decade. Median tumor size is approximately 5 cm. An estimated 20 – 25% present as paraneoplastic myasthenia gravis (MG) with positive acetylcholine receptor antibodies (AChR Ab). A rarely described presentation of MG is pseudo-internuclear ophthalmoplegia (p-INO). This presents a diagnostic conundrum as INO is discretely localizable to the brainstem and more commonly associated with cerebrovascular disease or demyelination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 27-year-old man presented with a three-month history of binocular horizontal diplopia, night sweats, weight loss and generalized weakness. The rapid progression of weakness occurred almost immediately following the COVID-19 vaccine. Examination demonstrated bilateral INO, worrisome for central nervous system inflammatory demyelination. An MRI of brain and cervical spine showed no evidence of demyelination, but the thoracic MRI showed a large soft tissue mass in the right hemithorax. A chest CT demonstrated a massive multilobulated mass encompassing almost the entirety of the right thoracic cavity. Given the mass in conjunction with the neurological symptoms, AchR Ab was obtained demonstrating positivity (51.2 nmol/L) for MG. Biopsy revealed thymoma type B2 and positron emission tomography showed metastatic disease, stage IVa. The patient was treated with four cycles of cisplatin, cyclophosphamide, and doxorubicin with prednisone, as well as a thymus gland resection. He was additionally started on pyridostigmine 60mg every 4 hours which improved his p-INO and generalized weakness. <h3>Conclusions:</h3> This case represents a rare presentation of myasthenia gravis in a young patient with p-INO. The incidental finding of a large thymoma (measuring ~30cm) discovered on thoracic spine imaging for work-up of demyelinating disease prompts alternative diagnostic consideration when presented with MRI-negative INO. It also evokes the question, should there be more emphasis on expediting CT chest imaging to evaluate for thymoma in patients with antibody positive MG. <b>Disclosure:</b> Dr. Hart has nothing to disclose. Maja Ostojic has nothing to disclose. Dr. Farrell has nothing to disclose. Dr. Esch has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.

E015 A case of ocular myasthenia gravis seen by rheumatology as suspected mononeuritis multiplex in an adult male shortly after Pfizer-BioNTech SARS-CoV-2 vaccination

Abstract Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of new-onset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARS-COV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link. Disclosure A. Storrie: None. R.M. Hum: None. J. Lilleker: None. P. Ho: None.

Chronic mimics of myasthenia gravis: a retrospective case series

Myasthenia gravis often presents a diagnostic challenge and may be misdiagnosed, particularly in seronegative disease with active symptoms. We retrospectively evaluated 61 patients following the introduction of single fibre electromyography at our service, and identified 8 mimics which had been inappropriately diagnosed and treated as refractory myasthenia gravis. 6 of these were seronegative, but two had positive acetylcholine receptor (AChR) antibodies. The final diagnoses included one case each of chronic progressive external ophthalmoplegia, chronic ptosis, oculopharyngeal muscular dystrophy, and an undifferentiated disorder suspicious for either a mitochondrial cytopathy or low-grade myositis. Four were diagnosed with functional neurological disorder, one of which had a superimposed thyroid myopathy and orbitopathy. We found the average duration of misdiagnosis was 9 years (SD±5.2, median 11 years), and patients were often exposed to years of unnecessary treatment. All patients had received anticholinesterase therapy, three had immunotherapy, and three surgical interventions were performed including two thymectomies. We found myasthenic mimics should be suspected in disease that is static and treatment refractory, and functional mimics in disease with frequent flares. Thorough neurophysiologic assessment is important, particularly when making a diagnosis of seronegative myasthenia gravis.

Unusual Association of Non-paraneoplastic Variant of Lambert-Eaton Myasthenic Syndrome with Predominant B-cell Inflammatory Myopathy

Introduction: Myasthenia gravis disease (MGD) and inflammatory myopathy (IM) are commonly reported in the literature and usually appear with thymic pathology. Lambert-Eton myasthenic syndrome (LEMS) associated with IM is extremely rare. Case Presentation: We report a 42-year-old female patient who presented with proximal muscle weakness of the upper and lower limbs, normal creatinine kinase (CK) level, and positive acetylcholine and voltage-gated calcium channel receptor antibodies. There were no oculobulbar symptoms and no history of thymoma, and the electrophysiological tests were unremarkable. Muscle biopsy revealed focal perimysial and perivascular inflammation, predominantly B-cell lymphocytes, in a non-necrotizing muscle. Conclusions: LEMS associated with IM, particularly B-cell inflammation, has never been reported in the absence of cancer history. Clinical investigations and myopathological features can help establish the diagnosis.

Outcome of thymectomy in myasthenia gravis patients at Neurological Institute of Thailand

Background &amp; Objective: Myasthenia gravis is the most common neuromuscular junction disorders and is caused by autoantibodies against acetylcholine receptors at the postsynaptic muscle endplate. Although thymectomy is current standard treatment but the benefit in long-term outcomes and in non- thymomatous generalized MG patients with negative AChR antibody are still unclear. The objective is to determine the treatment outcomes of thymectomy in non-thymomatous generalized MG patients with or without AChR antibody and identify features related to remission. Methods: Retrospective chart review of the patients diagnosed with non-thymomatous generalized MG from January 1st, 2014 to December 31th, 2018. Patients were classified into two groups: patients with thymectomy (thymectomy group) and patients with no thymectomy (medication group). Results: Seventy-six patients were included. All baseline clinical features, investigations and treatment response were compared. At 6 and 12 months follow up, most patients in both groups had a good response to treatment. At 24 months follow up, ratio of patients in thymectomy group with complete stable remission is higher than in medication group (25% vs. 7.5%) and all patients in this group had positive acetylcholine receptor antibody. The patients in thymectomy group required lower dosage of prednisone, azathioprine and cholinesterase inhibitors than in medication group. Conclusion: Thymectomy was associated with a high probability of achieving remission, reduced cholinesterase inhibitors and immunosuppressive drugs when compared to medication group. Therefore, thymectomy should be strongly considered for non-thymomatous generalized MG patient with positive AChR antibody; and may be considered in non-thymomatous generalized MG patients with negative AChR antibody.

Robotic-assisted minimally invasive thymectomy for myasthenia gravis with thymoma.

Robotic-assisted minimally invasive thymectomy for myasthenia gravis with thymoma.

Positive acetylcholine receptor antibody in nonmyasthenic patients.

In this study we aimed to determine the frequency of acetylcholine receptor (AChR) binding antibody positivity via neuroautoimmunity panel testing, and describe its occurrence in a group of nonmyasthenic disorders. This is a retrospective analysis of patients who underwent neuroautoimmunity antibody panel testing from 2010 to 2018 at the Cleveland Clinic. A total of 10 855 patients received neuroautoimmunity antibody panel testing, and 224 (2.1%) patients were positive for AChR binding antibody. Fifty-eight patients with a known myasthenia gravis (MG) diagnosis and 11 patients with incomplete follow-up were excluded. Among the remaining 155 patients, 30 had newly diagnosed MG and 125 were nonmyasthenic. In 35 patients, MG was within the initial differential diagnosis based on the clinical presentation. In contrast to nonmyasthenic patients, myasthenic patients were more likely to have an initial clinical presentation raising suspicion for MG (73.3% vs 10.4%, P < .001), higher mean AChR binding antibody titer (8.2 ± 15.6 vs 0.4 ± 1.6nmol/L, P=.011), and higher frequency of abnormal AChR modulating antibody (89.3% vs 23.9%, P < .001). A combination of AChR binding antibody of >0.5nmol/L and modulating antibody of over 20% in patients with clinical suspicion of MG is virtually diagnostic of MG. A total of 31 (24.8%) nonmyasthenic patients carried coexisting autoimmune conditions. Elevated titers of AChR binding antibody can sometimes be found in nonmyasthenic patients. Combined analysis of clinical presentation, AChR binding antibody titer, and AChR-modulating antibody results can be helpful in confirming an MG diagnosis.

AB019. Extended subxiphoid thymectomy for a large B3/B2 thymoma with positive acetylcholine receptor antibodies but without myasthenia

AB019. Extended subxiphoid thymectomy for a large B3/B2 thymoma with positive acetylcholine receptor antibodies but without myasthenia

Characteristics of low frequency repetitive nerve stimulation in patients with myasthenia gravis and its correlation with clinical features

Objective: To investigate the characteristics of low frequency repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) and analyze the correlation between RNS results and clinical characteristics. Methods: The clinical and electrophysiological data of 107 MG patients who were admitted to Guangdong Provincial People's Hospital and underwent electromyography (EMG) between September 2015 to September 2020 were retrospectively reviewed. The characteristics of low frequency RNS in ocular MG and generalized MG patients were analyzed. Patients were divided into RNS-negative group and RNS-positive group according to the RNS results. The clinical features, serological and thymic CT findings, thymic pathology were collected and compared. Binary logistic regression analysis was used to analyze the related factors of low frequency RNS. Results: Generalized MG (73.0%, 46/63) showed a lower positive rate of low frequency RNS compared to ocular MG (34.1%, 15/44) (P<0.001). In generalized MG, the positive rate of low frequency RNS in accessory nerve (68.3%, 43 cases) and facial nerve (52.4%, 33 cases) was higher than that in ulnar nerve (14.3%, 9 cases) (P<0.001). The decrease rate of compound muscle action potential (CMAP) in facial nerve (32%±11%) was higher than that in ocular muscle type (22%±7%) in RNS-positive group (P=0.011). Patients with positive facial nerve RNS were more likely to involve the throat muscles than those with negative result [22 cases (52.4%) compared with 17 cases (26.2%), P=0.006]. RNS-positive group showed a significantly higher quantitative myasthenia gravis (QMG) score than that of negative group (P<0.001). In ocular MG, patients with positive RNS showed a later onset (P=0.021), higher acetylcholine receptor (AChR) antibody-positive rate (P=0.03) and QMG score (P<0.001). Additionally, In generalized MG, patients with positive RNS showed a significantly higher AChR antibody-positive rate (P=0.023) and QMG score (P<0.001). The logistic regression analysis showed that QMG score [OR(95%CI)=1.66(1.36-2.03), P<0.001] and positive AChR antibody [OR(95%CI)=5.45(1.28-23.14), P=0.022] were independently related to abnormal RNS. Conclusions: Low frequency RNS is more sensitive in generalized MG. The stimulation of facial and accessory nerves increases the positive rate of RNS in MG patients. Abnormal results of low frequency RNS tend to be combined with positive AChR antibody and higher QMG score, reflecting the severity of muscle weakness. Therefore, serological examination and early intervention are required for those with abnormal RNS.

Rituximab in Refractory Myasthenia Gravis: Experience in a Single Healthcare Center in Mexico.

Background: Ten to fifteen percent of patients with myasthenia gravis (MG) have treatment-refractory disease. In short series and case reports, rituximab has proven to be effective in refractory MG.Methods: A retrospective, longitudinal study was conducted. Recruitment was performed in an MG cohort from a single third-level healthcare center in Mexico. The selection included refractory MG patients that were treated with rituximab. Response after rituximab therapy was assessed with MG composite score (MGCS) and prednisone dose reduction at 6, 12, and 18 months after initiation. Wilcoxon signed-rank test was used to evaluate differences between related groups for non-continual variables. P<0.05 was considered statistically significant.Results: Ten patients (7%) fulfilled criteria for refractory MG, and eight of them were treated with rituximab. The mean age at MG diagnosis was 25.5 (±2) years, with a female predominance (75%). All our patients (100%) had positive acetylcholine receptor (AchR) antibodies. The median MG duration was six years (interquartile range [IQR] 4.2-6) before rituximab initiation. All patients were previously treated with azathioprine and 50% additionally with cyclophosphamide. The median prednisone doses before rituximab treatment and 18-month follow-up were 50 mg (IQR 30-50 mg) and 10 mg (IQR 0-20 mg), respectively (p=0.011). The median baseline MGCS and at 18-month follow-up were 19.5 (IQR 11-31) and 6 (IQR0-16), respectively (p = 0.012).Conclusion: Rituximab appears to be associated with clinical improvement and prednisone dose reduction in Latin-American patients diagnosed with anti-AchR MG. Our findings need to be interpreted in light of the limitations mentioned.

Increased serum IL-27 concentrations and IL-27-producing cells in MG patients with positive AChR-Ab

ObjectiveThis study aims to explore the serum levels of IL-27 and the percentages of IL-27-producing cells in MG patients with positive acetylcholine receptor antibody (AChR-MG). MethodsA total of 17 AChR-MG patients and 22 sex- and age- matched healthy controls (HCs) were recruited. Serum IL-27 levels were determined by enzyme linked immunosorbent assay. The percentages of IL-27+ cells, IL-27-producing T (CD3+IL-27+) cells, and IL-27-producing B (CD19+IL-27+) cells were measured by flow cytometry. ResultsSerum IL-27 levels in AChR-MG were significantly higher than those in HCs (13.44 ± 0.89 vs 7.14 ± 0.75 pg/mL, P < 0.0001), and were decreased after intravenous immunoglobulin (IVIG) treatment (P = 0.004). Moreover, the frequencies of IL-27+ lymphocytes were significantly elevated in AChR-MG patients than those in HCs (P = 0.011), and were decreased after IVIG treatment (P = 0.014). Furthermore, the frequencies of IL-27-producing T cells (P = 0.017) and IL-27-producing B cells (P = 0.015) were significantly elevated in AChR-MG patients as compared to those in HCs. Meanwhile, we observed positive correlations between the frequencies of IL-27+ lymphocytes and MG-ADL score (P = 0.030, r = 0.527). By contrast, no significant correlation was found between IL and 27 serum levels and MG-ADL score (P = 0.099, r = −0.414). ConclusionIL-27 may play an important role in the pathological process in AChR-MG patients, and the frequencies of IL-27-producing (CD3+IL-27+) T cells may be a potential biomarker for predicting the severity of AChR-MG.

A case of chronic postural tachycardia syndrome with positive anti-ganglionic acetylcholine receptor (gAChR) antibody

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance characterized by symptoms such as lightheadedness, fainting, and brain fog that occur with a rapid elevation in heart rate when standing up from a reclining position. The etiology of POTS has yet to be established. However, a growing body of evidence suggests that POTS may be an autoimmune disorder such as autoimmune autonomic ganglionopathy, an acquired, immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (gAChRs) in the autonomic ganglia. Herein, we describe a 39-year-old female patient with an eight-year history of orthostatic intolerance. POTS was diagnosed based on the findings of a head-up tilt test, in which a rapid increase in the patient's heart rate from 58 bpm in the lying position to 117 bpm in the upright position without orthostatic hypotension was observed. The POTS symptoms were refractory to various medications except for pyridostigmine bromide, which resulted in a partial resolution of her symptoms. Her serum was found to be strongly positive for anti-gAChR (β4 subunit) autoantibody (2.162 A.I., normal range: below 1.0). Based on these findings, a limited form of autoimmune POTS was diagnosed. After obtaining written informed consent, she was treated with intravenous immunoglobulin (IVIg) 400 mg/kg/day for five days, which led to clinical improvement by reducing her heart rate increase in the upright position. She was able to return to work with IVIg treatment at regular intervals. Our case provides further evidence of a potential autoimmune pathogenesis for POTS. Aggressive immunotherapy may be effective for POTS even in chronic cases.

2638 Intestinal Pseudo-Obstruction Associated With Seropositive Myasthenia Gravis, Thymoma, and Positive CV-2 Antibodies

INTRODUCTION: Intestinal pseudo-obstruction (IPO) is a rare condition characterized by signs and symptoms of bowel obstruction without an identifiable mechanical cause. Antibody-mediated paraneoplastic syndromes and autoimmune diseases have been reported as two potential etiologies. We report a unique case of IPO presenting with thymoma, myasthenia gravis (MG), and positive CV-2 antibodies. CASE DESCRIPTION/METHODS: A 43 year old previously healthy female presented to the ED with abdominal pain, nausea and vomiting. This was her third visit to the ED in the past week for similar symptoms. On admission, laboratory studies were normal. A CT of the abdomen revealed marked gastric and small bowel distention, fecal impaction, and a mediastinal soft tissue density (Figure 1). She was initially managed medically with restriction of oral intake, intravenous fluids, and a nasogastric tube. Since she did not improve after several days, she was taken to the operating room for a diagnostic laparoscopy, which did not show evidence of mechanical obstruction. A CT chest with contrast done to investigate the mediastinal soft tissue density revealed an anterior mediastinal mass.A chest MRI had changes suggestive of a thymoma. This was subsequently confirmed by biopsy. Given the suspicion for a paraneoplastic process, multiple serologic markers were ordered. Acetylcholine receptor (AChR) antibodies and CV-2 antibodies were positive (Table 1). She was diagnosed with paraneoplastic intestinal pseudo-obstruction. The patient was treated with IV methylprednisolone and pyridostigmine with marked improvement in symptoms. DISCUSSION: The association of IPO as a paraneoplastic syndrome of thymoma and myasthenia gravis has been reported in only a few cases. The pathophysiology involves AChR antibodies targeting the neuronal nicotinic acetylcholine receptors present on autonomic ganglia. Our patient had positive AChR antibodies. She had no other symptoms of MG, indicating isolated autonomic dysfunction. IPO has also been associated with malignancies such as small cell lung cancer, which may be mediated by a variety of autoantibodies. Anti-Hu antibody has been most commonly implicated but was negative in this case. Anti-CV2 antibody was positive, which was reported in only one previously published case. In summary, patients with thymomas or MG should have testing for paraneoplastic antibodies; they tend to respond to treatment with immunosuppression and acetylcholinesterase inhibitors.

Factors Affecting Generalization of Ocular Myasthenia Gravis in Patients With Positive Acetylcholine Receptor Antibody

To evaluate the associated factors of conversion of ocular myasthenia gravis (OMG) to generalized myasthenia gravis (GMG) among patients with seropositive acetylcholine receptor antibody (AchR Ab). Retrospective cohort study. Setting: Retrospective chart review. Seventy-one OMG patients with seropositive AchR Ab presented during July 2009 and December 2016. The exclusion criteria were patients who (1) first presented with GMG, (2) were unable to identify the time of onset of OMG or GMG, (3) were unable to provide information about previous treatments before the onset of GMG, and (4) had incomplete or lost medical records. We collected demographic and clinical characteristics, including onset of OMG and GMG, presence of other autoimmune disorders, history of smoking, presence of thymic abnormalities, and medications received. Conversion to GMG and time to conversion. Thirty-six patients experienced conversion to GMG. Overall incidence of GMG was 14 (95% confidence interval [CI] 10.09-19.4) per 100 patient-years. Probability of conversion at 2 years was .37 (95% CI .27-.49). Overall median conversion time was 4.97 years. Cox proportional hazard model showed that risk factors were female sex (HR 2.52, 95% CI 1.04-6.10), history of smoking (HR 3.42, 95% CI 1.40-8.45), and thymic abnormalities (HR 1.82, 95% CI 0.91-3.67). Protective factors against conversion to GMG were receiving immunosuppressive agents (HR 0.42, 95% CI 0.19-0.97) and pyridostigmine (HR 0.37, 95% CI 0.14-0.93). OMG patients with seropositive AchR Ab should be informed that taking pyridostigmine and/or immunosuppressive agents as well as smoking cessation might prevent conversion to GMG.

Myasthenia gravis as a prognostic marker in patients with thymoma.

Thymoma is the most common mediastinal tumor, representing <1% of all cancers. It is usually associated with paraneoplastic disorders, mainly myasthenia gravis (MG). The aim of the present study was to describe patients with thymoma and the differences between those with MG and those without it. A retrospective 10-year database of the patients with thymoma treated at a single cancer referral hospital (National Institute of Cancer, Mexico City), was analyzed. Sixty-four files from patients with thymoma were analyzed, 18 of them had MG. The symptoms that occurred most frequently in patients with MG were ptosis, diplopia, appendicular weakness, dysphonia and dysphagia. The most frequent Myasthenia Gravis Foundation of America (MGFA) stage was IIIb followed by stage I. Almost all the patients with MG had positive Acetylcholine Receptor antibodies (P<0.001), with not specified antibodies in four patients. The median overall survival showed a trend to be higher among the patients with MG, but there were no significant differences. In patients with thymoma MG manifests with different clinical and autoimmune traits, but not survival differences. A larger multi-centric study should be encouraged to evaluate the prognostic implications of having MG in patients with thymoma.

False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature

ABSTRACTMethods: We present a rare case with atypical presenting features of unilateral CPEO with a false positive Acetylcholine Receptor Antibody (AchRA) test resulting in diagnostic delay. We illustrate the unilateral nature of this case and demonstrate the caveats of performing myogenic ptosis correction in such patients. We also discuss the differential diagnosis of false positive AchRA, a test commonly performed in the investigation of ptosis.Results: A 34-year old female presented with a more than 3-year history of slowly-progressive, unilateral, right-sided restriction in eye movements and ptosis. Clinical examination showed EOM were grossly restricted in the right eye with a ptosis and normal in the left eye. Serum AchRA was positive on serum enzyme-linked immunosorbent assay (ELISA) however, following two months of oral pyridostigmine therapy there were no signs of clinical improvement. The initial serum sample sent was retested for AchRA by radio-immunoassay (RIA) which came back negative. Subsequently a muscle biopsy was requested which showed the presence of ragged red fibres.Conclusion: Unilateral ptosis and ophthalmoplegia is an unusual presentation for CPEO which characteristically produces bilateral symmetrical motility defects. In addition to Myasthenia Gravis elevated AchRA levels have been reported in other autoimmune conditions such as Primary biliary cirrhosis, Eaton Lambert syndrome and Graves’s ophthalmopathy. We also highlight the superiority of RIA versus ELISA in the detection of AchRA and illustrate the diagnostic challenge of investigating and managing myogenic ptosis in this complex cohort of patients.

Low conversion rate of ocular to generalized myasthenia gravis in Singapore.

Ocular myasthenia gravis (OMG) is a common condition of the neuromuscular junction that may convert to generalized myasthenia gravis (GMG). Our aim in this study was to determine the conversion rate and predictive factors for generalization in OMG, in an Asian population. The investigation consisted of a retrospective study of OMG patients with a minimum 2 years of follow-up. Among 191 patients with OMG, 155 had the minimum 2-year follow-up. The conversion rate at median follow-up (40.8 months) was 10.6% (95% confidence interval 7.9%-13.3%), and at the 2-year follow-up it was 7.7% (95% confidence interval 5.6%-9.8%). At baseline, the predictive factors for generalization were positive acetylcholine receptor antibodies (hazard ratio 3.71, P = 0.024), positive repetitive nerve stimulation (RNS) studies (hazard ratio 4.42, P = 0.003), and presence of radiologically presumed or pathologically confirmed thymoma (hazard ratio 3.10, P = 0.013). The conversion rate of OMG to GMG in Asian patients is low, as predicted by presence of acetylcholine receptor antibodies, presence of thymoma, and positive RNS studies. Muscle Nerve 57: 756-760, 2018.

Clinical features and evolution of juvenile myasthenia gravis in a French cohort.

In this study we determined the clinical, paraclinical, and treatment-related features of juvenile myasthenia gravis (JMG) as well as the clinical course in a cohort of French children. We conducted a retrospective study of 40 patients with JMG at 2 French pediatric neurology departments from April 2004 to April 2014. Among the patients, 70% had generalized JMG, 52% had positive acetylcholine receptor antibodies, 8% had muscle-specific kinase antibodies, and 40% were seronegative. Treatment with acetylcholinesterase inhibitors was effective and sufficient in 47% of patients. The 6 patients with generalized JMG treated with rituximab and/or immunoadsorption showed improvement. Thirty percent of the patients required hospitalization in an intensive care unit during follow-up (mean 4.7 years). Remission without treatment occurred in 18% of patients. As with adults, JMG has high morbidity, particularly among children with generalized symptoms, and rituximab should be considered early in the course of the disease as a second-line treatment. Muscle Nerve 57: 603-609, 2018.

TNFAIP3 gene rs7749323 polymorphism is associated with late onset myasthenia gravis.

In this study, we intended to genotype 2 single nucleotide polymorphisms (SNPs) of tumor necrosis factor α-induced protein 3 (TNFAIP3) genes and explore an association of TNFAIP3 genetic polymorphism with the patients of myasthenia gravis (MG) at clinical level. In brief, 215 of adult MG patients were divided into subgroups according to their clinical features, age of onset, thymic pathology, and autoantibodies. Two hundred thirty-five of healthy controls were also divided into subgroups with gender- and age-matched. The allele and genotype frequencies of subgrouped patients were found to be higher than those of healthy controls. The distribution of TNFAIP3 gene rs7749323∗A allele of late onset MG (LOMG, with positive acetylcholine receptor antibody and without thymoma) subgrouped patients was also significantly higher than that of gender- and age-matched healthy controls (7.4% vs 2.4%, odds ratio [OR] = 3.27, 95% confidence interval [CI] 1.01–10.6, P = .04). Furthermore, analysis to the genotype frequencies indicates that the carriers of rs7749323∗A allele of LOMG group became more frequent than that of age-matched healthy controls (14.9% vs 4.8%, OR = 3.47, 95% CI 1.04–11.6, dominant model: P = .03). It is interesting to notice that there is no significant association between the rs7749323 and susceptibility of other MG subgroups. Therefore, it is suggested that the SNPs in the 3′ flanking region (rs7749323) of TNFAIP3 gene and the genetic variations of TNFAIP3 gene may take an important role in the susceptibility of LOMG.

Predictors of extubation outcomes following myasthenic crisis.

ObjectiveMyasthenic crisis (MC) is considered the most severe adverse event in patients with myasthenia gravis. The present retrospective study was performed to evaluate the predictors of clinical outcomes in patients with MC.MethodsThe medical charts of 33 patients (19 women, 14 men) with 76 MC attacks from 2002 to 2014 were retrospectively reviewed. Early extubation (≤7 days) and prolonged ventilation (>15 days) during the MC were used to assess patient outcomes.ResultsAmong the 33 patients, 24 (72.7%) had positive acetylcholine receptor antibody test results and 20 (60.6%) experienced recurrent MC attacks (≥2 episodes) during follow-up (median 83.6 months, range 1.5–177 months). Plasma exchange during an MC was significantly associated with early extubation. Male sex, older age (>50 years), atelectasis, and ventilator-associated pneumonia significantly contributed to prolonged ventilation. In 22 patients who underwent thymectomy, both the duration between MC attacks and the mean number of MC attacks were significantly reduced after surgery.ConclusionsPlasma exchange during MC attacks was found to be important for early extubation; older patients and those with atelectasis or ventilator-associated pneumonia were more vulnerable to prolonged ventilation. Thymectomy may be useful to prevent recurrence of MC.