Anti-acetylcholine Receptor Antibodies Research Articles

Risk Factors for the Exacerbation of Myasthenic Symptoms After Surgical Therapy for Myasthenia Gravis and Thymoma

Extended thymectomy is employed for patients with myasthenia gravis (MG) and/or thymoma with elevated serum antiacetylcholine receptor antibody (AchR) titers. However, MG symptoms occasionally worsen in post-thymectomy patients. We explored the risk factors for exacerbation of MG symptoms after surgical therapy for patients with MG and/or thymoma with an elevated AchR titer. We retrospectively analyzed 90 patients suffering from MG and/or thymoma with an elevated AchR titer who underwent thymectomy in our institute. Patients were classified into Improved, Unchanged, and Exacerbated groups by assessing their postoperative myasthenic symptoms, amount of medication, and incidence of myasthenic crisis. Risk factors for postoperative exacerbation of myasthenic symptoms were assessed by comparing the Exacerbated with the Improved and Unchanged groups. Of the 90 patients, 29 were classified into the Improved group, 47 into the Unchanged group, and 14 into the Exacerbated group. The presence of thymoma and Masaoka stage were significantly different between the Exacerbated and Improved/Unchanged groups. Although preoperative AchR titers did not significantly differ among the groups, the perioperative AchR titers in the Exacerbated group were significantly higher than those in the other groups (P = 0.003). A multiple logistic regression analysis with stepwise forward selection showed that advanced-stage thymoma was a risk factor for postoperative exacerbation of myasthenic symptoms (P = 0.007). Patients with advanced-stage thymoma have a relative risk for exacerbation of myasthenic symptoms after surgical therapy.

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Do Myelin Oligodendrocyte Glycoprotein Antibodies Represent a Distinct Syndrome?

Frequency and features of myasthenia gravis developing after thymectomy.

Thymectomy is an effective treatment for myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies. We rarely encounter patients who develop MG after surgery for thymic tumors. This study aimed to investigate the characteristics and frequency of post-thymectomy onset (PostTx) MG. We reviewed the clinical information of thymoma-associated MG in 158 patients. Of these, 18 (11%) patients with PostTx MG were identified. The presence of anti-AChR antibodies (82%) and electrophysiological abnormalities (50%) was confirmed before thymectomy in patients with PostTx MG. The clinical characteristics of PostTx MG were similar to those of pre-thymectomy onset (PreTx) MG. In PostTx MG, the duration between thymectomy and MG onset were distributed as<6months (early-onset PostTx MG) and≥6months (late-onset PostTx MG). Notably, some patients with late-onset PostTx MG were associated with thymoma relapse. Our results suggest that approximately 11% of patients with thymoma-associated MG were PostTx MG and pre-surgical assessment of anti-AChR antibody titer or electrophysiological testing may predict PostTx MG development. However, no difference in clinical manifestation and prognosis was observed between PreTx MG and PostTx MG.

Study of Rare Cases of Congenital Myasthenic Syndrome in Bangladesh

Congenital myasthenic syndromes (CMS) comprise a heterogeneous group of rare inherited diseases in which the neuromuscular transmission in the motor plate is compromised by one or more genetic pathophysiological specific mechanisms are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. The diagnosis of CMS is based on clinical findings, a decremental EMG response of the compound muscle action potential (CMAP) on low-frequency (2- 3 Hz) stimulation, absence of anti-acetylcholine receptor (AChR) and anti-MuSK antibodies in the serum, a positive response to acetylcholinesterase (AchE) inhibitors and lack of improvement of clinical symptoms with immunosuppressive therapy. Pathogenic variants in one of multiple genes encoding proteins expressed at the neuromuscular junction are currently known to be associated with subtypes of CMS. The most commonly associated genes include: CHAT, CHRNE, COLQ, DOK7, GFPT1 and RAPSN. We studied on a sibling presented with progressive fatigability and fluctuating ptosis with frequent exacerbations of muscle weakness during infections since infancy. On both cases CT scan of chest were negative for thymoma, antibodies against the acetylcholine receptor (AChR) and the muscle specific kinase (MuSK) were negative and decremental response on electrophysiological study of Repetitive nerve stimulation (RNS) and EMG were consistent with disease of neuromuscular junction (post synaptic) and they were only on pyridostigmine for long time with marked improvement of symptoms and signs. Considering all scenario both of our cases mostly fits with the autosomal recessive, post synaptic CMS associated with Rapsyn deficiency.&#x0D; Objective : As in Bangladesh, there is inadequate data on the epidemiological profile of CMS, our aim is to describe these cases for their rarity and the difficulty encountered in diagnosis as they are easily confused with Juvenile Myasthenia Gravis (JMG) and familial myopathies. As both the cases are very rare, it should be an original article.&#x0D; Bangladesh Journal of Neuroscience 2019; Vol. 35 (2): 95-103

Editors' note: Pearls &amp; Oy-sters: Pembrolizumab-induced myasthenia gravis

In the article “Pearls & Oy-sters: Pembrolizumab-induced myasthenia gravis,” Algaeed et al. presented a 73-year-old man who was diagnosed with myasthenia gravis (MG) after receiving pembrolizumab for recurrent melanoma and had positive anti–acetylcholine receptor antibodies (AChRAbs). In response, Robbins et al. note that antibodies like AChRAbs may be less specific for MG after immune checkpoint inhibitor (ICI) therapy and may be a marker for general autoimmunity. They note that AChRAb-positive patients receiving ICI therapy are more likely to develop myositis and that this can clinically resemble MG. In this regard, they note that some reports of ICI-associated MG had normal repetitive nerve stimulation and single-fiber EMG despite severe weakness. Using an illustrative case, they note that the distinction between myositis and MG has important implications for clinical management. In response, Algaeed et al. acknowledge these observations, but note that their patient had unequivocal fatigable ptosis strongly supporting (not pathognomonic in the editor's opinion) the diagnosis of MG. The authors also argue that further understanding of ICI-related autoimmune pathogenesis is needed before concluding that AChRAbs can just be a marker of general autoimmunity. In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study

BackgroundMyasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis.MethodsPatients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic.ResultsA total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161).ConclusionsJuvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

Refractory myasthenia gravis: Characteristics of a portuguese cohort.

Some myasthenia gravis (MG) patients are refractory to conventional treatments. To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019.

Results of Robotic Thymectomy Performed in Myasthenia Gravis Patients Older Than 60 Years at Onset

Data are limited on the safety and efficacy of robotic thymectomy in patients with myasthenia gravis (MG) older than 60 years at onset. Patients older than 60 years at MG onset who underwent robotic thymectomy in Charite Universitaetsmedizin Berlin between 2003 and 2017 were potentially eligible for inclusion. The main outcomes were perioperative complications and clinical outcome according to the Myasthenia Gravis Foundation of America Post-Intervention Status. Sixty-eight (25 women, 43 men) of 580 patients with MG who underwent robotic thymectomy were eligible for perioperative analyses (median age at MG onset 67 years, range: 61 to 85 years). The perioperative morbidity rate was 13.2%, and the only perioperative death was due to aortic dissection. Fifty-one patients were available for further analysis with a median follow-up time of 60 months (range: 12 to 263 months). The complete stable remission rate was 7.8%, the improvement rate was 68.6%, and the overall mortality rate was 11.8%. Compared with preoperative use, the mean daily dose of corticosteroid agents was significantly reduced at the last follow-up (17.6 ± 23.6 mg versus 2.6 ± 6.1 mg, p= 0.0001) without increased use of azathioprine (35.9 ± 61.9 mg versus 42.7 ± 59 mg, p= 0.427). After excluding 2 patients seronegative for the anti-acetylcholine receptor antibody, 10 of 49 seropositive patients achieved "good outcome" (including four complete stable remissions, three pharmacologic remissions, and three minimal manifestations 0) which was predicted by being free of concomitant disease (odds ratio 7.307, 95% confidence interval: 1.188 to 44.937, p= 0.032) and Myasthenia Gravis Foundation of America classification I before thymectomy (odds ratio 6.696, 95% confidence interval: 1.259 to 35.620, p= 0.026). Robotic thymectomy seems to be safe and effective in patients with MG older than 60 years at onset with a statistically significant steroid-sparing effect.

Effectiveness and safety of tacrolimus therapy for myasthenia gravis: A single arm meta-analysis

To evaluate the effectiveness and safety of tacrolimus in myasthenia gravis (MG) patients, a systematic review and meta-analysis was performed. Researches published between January 1, 2000 and December 31, 2017 in English language were searched in Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov databases. We extracted the outcome measures regarding the dose of glucocorticoids (GC), Myasthenia Gravis Foundation of America (MGFA) quantitative myasthenia gravis score (QMGS), MG activities of daily living (MG-ADL) and serum anti-acetylcholine receptor (AChR) antibody titer in each included study. Among 25 studies involving 633 patients, we observed a mean reduction in GC dose by 1.21 (95% CI, 0.44–1.98), QMGS by 2.02 (95% CI, 0.86–3.18), MG-ADL by 1.21 (95% CI, 0.81–1.62) and serum anti-AChR antibody titer by 0.61 (95% CI, 0.43–0.80), which all reached a statistical significance (p < 0.01). Interestingly, a significant correlation was acquired between the disease duration and the reduction of QMGS (p = 0.033; 95% CI, −0.64 to −0.033). Adverse events (AEs) were recorded in 258 of 633 patients (40.8%) with tacrolimus therapy while most were mild. Our meta-analysis demonstrates that tacrolimus may be a beneficial drug option to treat MG.

Analyzing clinical characteristics of patients with myasthenia gravis through repetitive nerve stimulation testing

AbstractBackgroundThe diagnosis of Myasthenia gravis (MG) is confirmed by clinical features with the presence of MG‐specific antibodies or the effect of intravenous edrophonium (Tensilon) administration. Diagnosis of MG is difficult in cases with negative serologic and Tensilon testing. Electrophysiological tests can support the diagnosis in such cases. Repetitive nerve stimulation testing (RNST) is one such electrophysiological test, and it is usually performed on several muscles.AimThe probability of RNST‐positivity varies between muscles, so we aimed to elucidate the relationship between muscle‐specific RNST‐positivity and patients’ clinical characteristics.MethodsWe included 46 patients and examined RNST results for the abductor digiti minimi (ADM), trapezius, and frontalis muscles. We classified muscles as RNST‐positive or RNST‐negative and compared RNST‐positive and RNST‐negative muscles for various clinical characteristics.ResultsWe observed RNST‐positivity in 11 out of 40 (27.5%) ADM muscles, 20 out of 35 (57.1%) trapezius muscles, and 14 out of 29 (48.3%) frontalis muscles. The trapezius muscle's RNST‐positivity rate was the highest in the 21 patients who underwent RNST for all 3 muscles and was significantly higher than the ADM's RNST‐positivity rate. RNST‐positivity in any muscle was significantly associated with higher serum antiacetylcholine receptor antibody (AChR‐Ab) titers. Frontalis muscle RNST‐positivity was significantly associated with higher Quantitative Myasthenia Gravis scores.ConclusionWhen diagnosing MG, physicians should recognize that the trapezius has the highest RNST‐positivity rate and that patients with low AChR‐Ab titers may exhibit negative RNST results. Furthermore, patients with frontalis muscle RNST‐positivity may present severe symptoms.

Cell-Based Versus Enzyme-Linked Immunosorbent Assay for the Detection of Acetylcholine Receptor Antibodies in Chinese Juvenile Myasthenia Gravis

BackgroundPatients in China with juvenile-onset myasthenia gravis present early, with a high prevalence of purely ocular symptoms, spontaneous remission rates, and low antibody seropositivity. Antibody detection using a cell-based assay has been reported to increase the diagnostic sensitivity in adult-onset myasthenia gravis. However, this method in patients with juvenile-onset myasthenia gravis has not been investigated. MethodsPatients with juvenile-onset myasthenia gravis who had not received prednisone or immunosuppressive therapy were recruited between June 2015 and April 2018 at the Huashan Hospital. Clinical information was collected. Serum anti-acetylcholine receptor antibodies were detected via cell-based assay with HEK293T cells expressing acetylcholine receptor subunits and rapsyn. Additionally, the IgG antibody subclass was identified. ResultsEighty-two patients with juvenile-onset myasthenia gravis were enrolled in the current study. Among them, 48 patients were anti-acetylcholine receptor positive (58.5%) and 34 were seronegative (41.5%), as assessed via enzyme-linked immunosorbent assay. Cell-based assay yielded 63 positive subjects (76.8%) and 19 seronegative subjects (23.2%). All the enzyme-linked immunosorbent assay-positive samples showed robust immunofluorescence in the cell-based assay, whereas 15 of 34 enzyme-linked immunosorbent assay-negative patients (44.1%) were found to have low-affinity acetylcholine receptor antibodies. Among all the cell-based assay-positive patients, 41 were positive for both adult and fetal acetylcholine receptor antibodies (50.0%), 18 were found positive for only adult acetylcholine receptor antibodies (21.9%), and four were found to possess only fetal acetylcholine receptor antibodies (4.9%). Fifteen antibody-positive samples underwent subclassification and were confirmed to be IgG1 subclass predominant (n = 15, including eight adult and fetal acetylcholine receptor antibody positive, five only adult acetylcholine receptor antibody positive, and two only fetal acetylcholine receptor antibody positive). There were no significant differences in clinical features among patients with different antibody profiles. ConclusionsThe cell-based assay showed increased sensitivity in acetylcholine receptor antibody detection in Chinese patients with juvenile-onset myasthenia gravis, and most cases of Chinese juvenile-onset myasthenia gravis are still acetylcholine receptor autoantibody mediated. Furthermore, the antibodies detected are predominately of the IgG1 subclass.

A prospective, double-blind, randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis

ObjectiveTo investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG). MethodsAn influenza vaccination or placebo was administered to 47 AChR MG patients. Before and 4 weeks after administration blood samples and clinical outcome scores were obtained. Antibodies to the vaccine strains A/California/7/2009 (H1N1)pdm09, A/Hong Kong/4801/14 (H3N2) and B/Brisbane/060/08 were measured using the hemagglutination-inhibition (HI) assay and disease-specific AChR antibody titers were measured with a radio-immunoprecipitation assay. Forty-seven healthy controls (HC) were vaccinated with the same influenza vaccine to compare antibody titers. ResultsA post-vaccination, seroprotective titer (HI ≥ 1:40) was achieved in 89.4% of MG patients vs. 93.6% in healthy controls for the H3N2 strain, 95.7% vs 97.9% for the H1N1 strain and 46.8 vs 51% for the B-strain. A seroprotective titer for all three strains of the seasonal influenza vaccine was reached in 40.4% (19/47) of the MG group and in 51% (24/47) of the HC group. Immunosuppressive medication did not significantly influence post geomean titers (GMT). The titers of disease-specific AChR antibodies were unchanged 4 weeks after vaccination. The clinical outcome scores showed no exacerbation of MG symptoms. ConclusionThe antibody response to an influenza vaccination in patients with AChR MG was not different from that in healthy subjects, even in AChR MG patients using immunosuppressive medication. Influenza vaccination does not induce an immunological or clinical exacerbation of AChR MG. Clinical trial registryThe influenza trial is listed on clinicaltrialsregister.eu under 2016-003138-26.

Serious Myasthenia at the Department of Internal Medicine of Point G University Teaching Hospital: A Clinical Case

Introduction: Myasthenia is a rare and disabling autoimmune disease. Few studies were devoted to this pathology. We report a clinical case of myasthenia in the Department of Internal Medicine at the Point G University Teaching Hospital. Observation: This is a 41-year-old patient of Malian origin, a trader with a history of hemorrhoidectomy in 2011 and familial hypertension, was admitted on August 19, 2014, for muscle weakness, dysphonia, and dysphagia. The disease started 1 year before admission at the department with progressive muscle weakness of the upper limbs aggravated by repetitive movements and spreading to the head “drooping head” and inferior limbs, associated with general fatigue, dysphonia and selective dysphagia for solid foods. The diagnosis of myasthenia was maintained based on the clinical signs such as ptosis, bilateral diplopia, and weakness with lower limbs muscle strength rated at 3/5, and confirmed with confirmatory exams; a positive anti-acetylcholine receptor antibody (RIA), the post-synaptic neuromuscular conduction block at ENMG and the positive neostigmine pharmacological test. The patient received Neostigmine (prostagmine) 0.5 mg one ampoule in IM/day and Prednisone at a dosage of 1 mg/kg/day. The evolution was marked by a moderate improvement of the symptomatology afterward the patient was evacuated to Tunisia on family request where he received a course of immunoglobulin 2 g/kg in 2 days. The evolution in Tunisia was favorable. The patient returned in Mali and death occurred after 2 months in a context of respiratory distress. Conclusion: Myasthenia is a rare but serious disease requiring careful management and monitoring to reduce respiratory complications.

Predictive score for oral corticosteroid-induced initial worsening of seropositive generalized myasthenia gravis

BackgroundInitial worsening of symptoms after the start of corticosteroid administration is a major concern in the treatment of myasthenia gravis (MG). However, the risk factors or specific patient backgrounds related to this issue have not been fully understood. We aimed to determine the risk factors and developed a scoring system for predicting initial worsening in generalized MG. MethodsWe enrolled 62 generalized MG patients with anti-acetylcholine receptor antibody. Initial worsening was defined as an increment of three points in the Quantitative MG score within 2 weeks after the start of steroid treatment. A multivariate logistic regression model was used to determine the risk factors, and predictive scores were assigned. Bootstrap resampling was applied to evaluate the risk score model's internal validity. ResultsSteroid-induced initial worsening occurred in 26% of MG patients and was correlated with thymoma-associated or early-onset MG (p = 0.018), initial prednisolone doses ≥40 mg/day (p = 0.029), and upper limb weakness (p = 0.039). Stepwise multivariate logistic regression identified these three clinical factors for predicting initial worsening in MG. A predictive score of 0–3 points had a bootstrapping area under the curve of 0.770 (0.625–0.878). ConclusionsOur scoring system based on three clinical characteristics can predict the likelihood of steroid-induced initial worsening in MG.

P3.CR-31 A Case of Thymoma with Autoimmune Hepatitis Following Preoperative Chemotherapy

We encountered a case of thymoma with autoimmune hepatitis. A 63-year-old woman was found to have an abnormal finding on chest radiography during a medical checkup, but did not seek further care. She was referred to our hospital one year later when a bilateral hilar abnormality was again found during a checkup. Chest computed tomography (CT) showed a 4.6 × 3.0 × 5.6 cm mass with calcifications in the anterior mediastinum. The tumor invaded the right lung and middle lobe, in association with a 2.0-cm daughter nodule in the head of the main tumor, with multiple pleural seeding lesions in the right thoracic cavity. Although she was asymptomatic, the anti-acetylcholine receptor antibody level was elevated to 33 nmol/L and the soluble IL-2 receptor antibody was elevated to 1,700 U/mL. The mass was diagnosed with CT-guided biopsy as a type-B2 thymic tumor (cT3N0M1a, c-Stage IV). She underwent induction chemotherapy (ADOC, 2 courses). After chemotherapy, abnormal liver enzyme levels (aspartate aminotransferase: 451 U/L, alanine aminotransferase: 529 U/L) were noted on preoperative examination. She was diagnosed with autoimmune hepatitis based on liver biopsy findings and treated with oral prednisolone 30 mg. Surgery was performed after prednisolone dose was gradually decreased to 20 mg. Extended thymectomy and pulmonary wedge resection using median sternotomy were performed. Pleural dissemination was resected using video-assisted thoracoscopic surgery. The pathological findings showed type-B3 thymic carcinoma (pT3N0M1a, p-Stage IV, Masaoka classification IVa). She was placed under observation without any additional treatment. Prednisolone dose has been gradually decreased to 15 mg without exacerbation of liver function. The anti-acetylcholine receptor antibody level decreased after surgery. Autoimmune diseases in association with thymoma are well known, but reports of autoimmune hepatitis are very rare. Autoimmune hepatitis must be considered when acute liver damage is observed.

West Nile virus induces a post-infectious pro-inflammatory state that explains transformation of stable ocular myasthenia gravis to myasthenic crises

West Nile virus (WNV) infection has been reported to promote myasthenia gravis (MG) and various other diseases that have a presumed autoimmune pathogenesis. Molecular mimicry between WNV proteins and host proteins has been postulated as the major mechanism for WNV-triggered breaking of immunological self-tolerance. We present a patient with stable ocular MG and positive anti-acetylcholine receptor antibodies who progressed to myasthenic crisis after WNV neuroinvasive disease. In this case of stable autoimmune disease with proven auto-antibodies, transformation to generalized disease cannot be attributed to molecular mimicry, which requires that an immune response first be generated against an infectious agent. Rather, the evidence supports the concept of a post-infectious pro-inflammatory state that may contribute to the amplification and promotion of autoimmune disease in some WNV survivors.

CIDP, myasthenia gravis, and membranous glomerulonephritis \u2013 three autoimmune disorders in one patient: a case report

BackgroundWe present a patient fulfilling the electrophysiological criteria for definite chronic inflammatory demyelinating polyneuropathy (CIDP), antibody-positive myasthenia gravis (MG), and membranous glomerulonephritis (MGN) confirmed by biopsy. To our knowledge, this is the first case of the concomitant appearance of these three autoimmune diseases in a single patient.Case representationA 42-year-old Caucasian male presented with rapidly progressive gait disturbance, distal weakness of the lower extremities, ascending hypoesthesia, impaired fine motor skills, and beginning cranial nerve palsy showing dysarthrophonia, facial paralysis, and eye movement abnormalities and was diagnosed as rapid onset (atypical) CIDP. After 3 months, the patient complained of increasing physical exhaustion, reduction of his walking distance, worsening of the residual dysphagia, and dysarthria with an inability to swallow. AChR antibodies (17.0 nmol/L, RF < 0.4) and titin antibodies were positive and repetitive nerve stimulation showed an abnormal decrement matching the criteria of myasthenia gravis. Over time the patient developed severe acute-on-chronic renal failure with high-grade proteinuria resulting in generalized edema followed by secondary hyperparathyroidism and dialysis-dependent renal failure. Renal biopsy confirmed beginning anti-phospholipase A2 receptor antibody membranous nephropathy.ConclusionAll three diseases are of autoimmune origin with distinctive immunopathogenetic mechanisms. The present case of CIDP, MG, and MGN occurring in one patient indicates a common underlying immune mechanism in these distinct conditions, including the involvement of autoantibodies and T cells.

Immune checkpoint inhibitor-related myositis and myocarditis in patients with cancer.

To report the clinicopathologic features and outcome of myositis in patients treated with immune checkpoint inhibitors (ICIs) (irMyositis). We retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015 to July 2017. The main outcomes were clinical manifestations and muscle histology, which included major histocompatibility complex class I (MHC-I), C5b-9, CD3, CD4, CD8, CD20, CD68, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L) 1, and programmed cell death 1 ligand 2 (PD-L2). Ten patients with metastatic cancer were included; median age was 73 (range 56-87) years. Median follow-up duration was 48 (range 16-88) weeks. Six patients developed myositis during nivolumab therapy, 1 patient during pembrolizumab, 1 patient during durvalumab, and 2 patients during combined nivolumab and ipilimumab. Median delay between ICI initiation and myositis onset was 25 (range 5-87) days. Clinical manifestations were dominated by acute or subacute myalgia (8 patients) and limb-girdle (7), axial (7), and oculomotor (7) weakness. Four patients had evidence of myocarditis. In all patients, creatine kinase levels were elevated (median 2,668, range 1,059-16,620 U/L), while anti-acetylcholine receptor and myositis-associated antibodies were negative. Electrodiagnostic studies showed myopathic process without decrement in all patients. Muscle biopsy constantly showed multifocal necrotic myofibers, sarcolemmal MHC-I, and endomysial inflammation, consisting mainly of CD68+ cells expressing PD-L1 and CD8+ cells expressing PD-1. ICI treatment was withdrawn in all patients; 9 patients received immunosuppressive therapy, which consistently led to marked clinical improvement. irMyositis presents with remarkably homogeneous and unique clinicopathologic features, expanding the nosologic spectrum of inflammatory myopathies in patients with cancer. ICI withdrawal and treatment with corticosteroids improve outcome.

Blepharospasm with elevated anti-acetylcholine receptor antibody titer.

To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.

Repetitive nerve stimulation: Relative muscles sensitivity in generalized myasthenia gravis

Objectives The diagnosis of myasthenia gravis (MG) is established through the medical history and examination and confirmed by the clinical response to anti-cholinesterase medication, the detection of anti-acetylcholine receptor antibodies (AchR) and especially electrodiagnostic testing using repetitive nerve stimulation (RNS) [3] . However, the sensitivity of RNS depends on the distribution of clinically affected muscles and its severity [2] . We aimed to investigate the decrement of RNS of various muscles in patients with generalized MG in order to test the nerve-muscle sensitivity. Methods We performed a retrospective study of patients with clinical diagnosis of MG, who attended our neurology department [2011–2018] (n:33) and we included those with generalized MG to investigate their neurophysiological outcomes. All patients had a neurological examination. Patients who have not a detailed neurophysiological study including RNS within these 3 spots (facial-nerve, accessory-nerve, upper limbs nerves) were excluded. Results Among the 33 patients with MG, we selected 27 patients (M/F:8/19) who had generalized MG with fluctuating motor weakness and oculo-bulbar involvement. Their age ranged from 14 to 77 years (mean, 47.77 years) and the average age at onset was 44.18 years. Forty-four percent had thymus abnormality and 83.33% had positive antibody testing to AchR. RNS studies showed at least one abnormal muscle response (significant decrement > 10% in low frequencies) in 96.29%. Decrement was most detected in the facial nerve (77.77%). An abnormal trapezius response was observed in 55.55%. However, hand muscles abnormalities tested using the ulnar, medial and radial nerves stimulation were detected respectively in 48.14%, 37.03% and 14.81%. The facial nerve was significantly more sensitive than any other nerve (P Conclusion RNS is a commonly used technique to evaluate patients with MG, through multiple nerve-muscle testing [1] . Therefore, the facial nerve seems to be the most sensitive one.