Anti-acetylcholine Receptor Antibody Titer Research Articles

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

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

Relationship between Low and High Anti-acetylcholine Receptor Antibody Titers and Clinical Severity in Myasthenia Gravis.

To determine the frequency of low and high anti-AChR (acetylcholine receptor) antibody titers and to evaluate their relationship with clinical severity in myasthenia gravis. Cross-sectional, observational study. Department of Neurology, King Edward Medical University/Mayo Hospital, Lahore from April 2017 to March 2018. Fifty-six seropositive patients, aged between 18-75 years, were included. A blood sample was obtained from each patient to assess for the anti-AChR antibody titers by enzyme-linked immunosorbent assay (ELISA) technique and classified as low (0.4-<50 nmol/L) and high AChR antibody titers (>50 nmol/L). Clinical severity was graded according to the Osserman's classification. Out of 56 patients, 51.79% (n=29) were males and 48.21% (n=27) were females, and mean age was 32.73 +8.48 years. Mean anti-AChR antibody titer was found 40.45 + 13.54; 60.71% (n=34) had low and 39.29% (n=22) had high titers. Upon grading the severity, 1.79% (n=1) had grade I, 25% (n=14) had grade IIa, 26.79% (n=15) had grade IIb, 37.5% (n=21) had grade III, and 8.93% (n=5) had grade IV. These grades were significantly associated with high/low titers of anti-AChR antibody (p<0.001) but no significant association was found with age and gender (p=0.39 and 0.19 respectively). Serum concentration of anti-AChR antibodies has significant association with the clinical severity in myasthenia gravis. Key Words: Anti-acetylcholine receptor antibody, Myasthenia gravis, Neuromuscular junction diseases.

Risk factors for developing post-thymectomy myasthenia gravis in patients with thymoma.

Thymectomy is required for the treatment of thymoma-associated myasthenia gravis (MG). However, MG may develop only after thymectomy, a condition known as post-thymectomy MG. This study aimed to investigate the risk factors for post-thymectomy MG in patients with thymoma. We retrospectively identified 235 patients with thymoma who underwent thymectomy at a single hospital from January 2008 to December 2017: 44 with preoperatively diagnosed MG were excluded, leaving 191 patients in the final analysis. Univariable survival analyses using Cox proportional hazards regression model and Kaplan-Meier estimate were conducted to identify risk factors for post-thymectomy MG. Post-thymectomy MG developed in 4.2% (8/191) of the patients with thymoma between 18 days and 108 mo after surgery. Hazard ratios (HRs) of pre- and postoperative anti-acetylcholine receptor antibody (AChR-Ab) titers were 2.267 (P = .002) and 1.506 (P < .001), respectively. Patients with extended thymectomy had a low chance of post-thymectomy MG (HR 0.035, P = .007). Larger thymoma (HR, 1.359; P = .005) and type A or AB thymoma according to World Health Organization histological classification (HR, 11.92; P = .021) were associated with higher chances of post-thymectomy MG. Within the subgroup of preoperatively AChR-Ab seropositive patients, post-thymectomy MG developed in 22.2% (6/27). Pre- and postoperative AChR-Ab levels should be measured in patients with thymoma. A large thymoma and partial thymectomy appear to be associated with a higher probability of post-thymectomy MG.

Severe worsening of myasthenic symptoms after the eculizumab discontinuation

Myasthenia gravis (MG) is an autoantibody-mediated disease of the neuromuscular junction. The neuromuscular junction damage associated with MG is caused by anti-acetylcholine receptor (AChR) antibody and complements. Recently, eculizumab (an anti-C5 monoclonal antibody) was approved for patients with anti-AChR antibody-positive generalized refractory MG. Here, we report a Japanese man with MG who well responded to eculizumab, but experienced acute severe worsening of myasthenic symptoms 2months after its discontinuation. Plasmapheresis did not improve his symptoms; hence, eculizumab was re-administered, resulting in a dramatic response within a week. This is an informative case because eculizumab discontinuation in patients with MG has been very rarely reported. If eculizumab treatment is clinically well effective and AChR antibody titer does not decrease, clinicians should be aware that acute and critical deterioration of MG may occur after the eculizumab discontinuation.

Serum level of soluble urokinase plasminogen activator receptor (suPAR) as a disease severity marker of myasthenia gravis: a pilot study.

Myasthenia gravis (MG) is an autoantibody-mediated inflammatory disease of the neuromuscular junction. Biomarkers indicating disease activity in MG are warranted. Recently, the soluble urokinase plasminogen activator receptor (suPAR) has been reported to be associated with inflammation, tissue damage, disease activity and prognosis in various diseases, including autoimmune diseases. In this study, serum suPAR levels were measured in 40patients with anti-acetylcholine receptor antibody-positive MG and 30controls, and their correlations with clinical variables and severity scale scores were investigated. We identified that serum suPAR levels significantly correlated with MG activities of daily living scale (Spearman's ρ=0·45; P=0·004) and MG Foundation of America classification (Spearman's ρ=0·37; P=0·02) at serum sampling, but not with anti-acetylcholine receptor antibody titers. In conclusion, serum suPAR levels can be a candidate for a novel biomarker of disease activity in anti-acetylcholine receptor antibody-positive MG.

Subxiphoid completion thymectomy for refractory non-thymomatous myasthenia gravis.

BackgroundCompletion thymectomy may be performed in patients with non-thymomatous refractory myasthenia gravis (MG) to allow a complete and definitive clearance from residual thymic tissue located in the mediastinum or in lower neck. Hereby we present our short- and long-term results of completion thymectomy using subxiphoid video-assisted thoracoscopy.MethodsBetween July 2010 and December 2017, 15 consecutive patients with refractory non-thymomatous myasthenia, 8 women and 7 men with a median age of 44 [interquartile range (IQR) 38.5–53.5] years, underwent video-thoracoscopic completion thymectomy through a subxiphoid approach.ResultsPositron emission tomography (PET) showed mildly avid areas [standardized uptake value (SUV) more than or equal to 1.8] in 11 instances. Median operative time was 106 (IQR, 77–141) minutes. No operative deaths nor major morbidity occurred. Mean 1-day postoperative Visual Analogue Scale value was 2.53±0.63. Median hospital stay was 2 (IQR, 1–3.5) days. A significant decrease of the anti-acetylcholine receptor antibodies was observed after 1 month [median percentage changes −67% (IQR, −39% to −83%)]. Median follow-up was 45 (IQR, 21–58) months. At the most recent follow-up complete stable remission was achieved in 5 patients. Another 9 patients had significant improvement in bulbar and limb function, requiring lower doses of corticosteroids and anticholinesterase drugs. Only one patient remained clinically stable albeit drug doses were reduced. One-month postoperative drop of anti-acetylcholine receptor antibodies was significantly correlated with complete stable remission (P=0.002).ConclusionsThis initial experience confirms that removal of ectopic and residual thymus through a subxiphoid approach can reduce anti-acetylcholine receptor antibody titer correlating to good outcome of refractory MG.

C3, C5a and anti-acetylcholine receptor antibody as severity biomarkers in myasthenia gravis.

Background:Although the pathogenesis of myasthenia gravis (MG) is well known, prognostic markers are not yet available. We assessed the utility of anti-acetylcholine receptor (AChR) antibody (AChR-ab) titer and concentration of C3, C4, and C5a as potential severity biomarkers in MG.Methods:Levels of C3, C4, C5a, and AChR-ab were measured in 60 AChR-ab-positive patients with MG. Their relationship with clinical severity was analyzed using the activities of daily living (ADL) and MG composite (MGC) scales.Results:AChR-ab titer correlated with severity of MG according to ADL (p = 0.002) and MGC scales (p = 0.001). When patients were classified according to disease duration, a statistically significant correlation between AChR-ab titer and clinical severity was only found in the subgroup of patients with fewer than 5 years from symptoms onset. C5a levels showed a positive correlation with MG severity according to the ADL scale (p = 0.041; τb = 0.18), although C5a levels were not different from the control group.Discussion:AChR-ab titers and C5a levels could potentially be considered markers of severity in patients with MG.

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.

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.

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.

Time-series analysis: variation of anti-acetylcholine receptor antibody titer in myasthenia gravis is related to incidence of Mycoplasma pneumoniae and influenza virus infections

ObjectivesThe exacerbating factors of myasthenia gravis (MG) are unknown. However, it has been speculated that infections may play a role in disease progression.MethodsWe calculated the adjusted anti-acetylcholine receptor antibody (Adj-AChR-Ab) titers (range, 0–1) in 58 MG patients between 2006 and 2012. We determined the relationship between Adj-AChR-Ab titer and infection incidence.ResultsA cross-correlation function (CCF) analysis of Adj-AChR-Ab titer and incidence of Mycoplasma pneumoniae (M. pneumoniae) (r = 0.449, P < 0.0001) and influenza virus (r = 0.411, P < 0.001) infections indicated significant correlations. MG with thymoma was highly correlated with M. pneumoniae infection (r = 0.798, P < 0.0001). The relative risk for Adj-AChR-Ab titer was 1.407 for M. pneumoniae (95% CI, 1.193–1.661 for an increase in one infected patient per monitoring point) and 1.158 for influenza (95% CI, 1.071–1.253 for 100 infected patients).ConclusionVariation of Adj-AChR-Ab titer is significantly influenced by the presence of M. pneumoniae and influenza virus infections.

The time trends of anti-acetylcholine receptor antibody titer variation in myasthenia gravis is related to the incidence of mycoplasma and influenza infections

The time trends of anti-acetylcholine receptor antibody titer variation in myasthenia gravis is related to the incidence of mycoplasma and influenza infections

Tacrolimus Improves Symptoms of Children With Myasthenia Gravis Refractory to Prednisone

BackgroundMyasthenia gravis tends to affect children in China. Oral pyridostigmine and prednisone could effectively improve the symptoms, but multiple side effects become a major concern after long-term oral prednisone. To avoid the long-term complications of prednisone therapy and to obtain more satisfactory improvement, we tested the efficacy and safety of tacrolimus in children with myasthenia gravis. MethodsChildren with myasthenia gravis who had not achieved satisfactory improvement or who experienced severe side effects after prednisone therapy were recruited between January 2015 and December 2016 at Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily and the dose was adjusted on the basis of the clinical response and the serum concentration. The dosage of prednisone, the severity of symptoms, blood samples, the serum concentration of tacrolimus, and titers of antiacetylcholine receptor antibodies were evaluated every four weeks. ResultsFourteen children were enrolled. One child withdrew two weeks after the enrollment. Thirteen children have completed the therapy for one year. At the end point, the dosage of prednisone was significantly decreased (P < 0.05), the symptoms were evaluated by the quantitative myasthenia gravis score, and myasthenia gravis-specific manual muscle testing and myasthenia gravis-activities of daily living scores were significantly improved (P < 0.05, P < 0.05, and P < 0.01, respectively). More importantly, ten (76.9%) patients had completely discontinued prednisone, and the major side effects were nearly reversed. The mean titer of antiacetylcholine receptor antibodies significantly dropped from 1.96±2.62 nmol/L to 0.70±1.04 nmol/L (P < 0.05). No severe adverse events were reported. ConclusionsOur results suggest that tacrolimus is a promising agent for children with refractory myasthenia gravis. Randomized clinical trials are needed to confirm the observation.

Clinical and pathological aspects of microscopic thymoma with myasthenia gravis and review of published reports.

Microscopic thymomas, defined as epithelial proliferations smaller than 1 mm in diameter, characteristically occur in patients with myasthenia gravis without macroscopic thymic epithelial tumors. However, some clinical and pathological aspects of this entity are still unclear. This retrospective study includes five consecutive patients who had undergone extended thymectomy for myasthenia gravis at our institution from April 2007 to March 2016 and in whom microscopic thymomas were diagnosed by histopathological examination of the resected specimens. During the same period, we performed 32 extended transsternal thymothymectomies/thymectomies in patients with myasthenia gravis, including the above five cases. We here review 18 cases of microscopic thymoma, including our five cases and 13 previously reported cases. The incidence of previously undiagnosed microscopic thymoma in patients undergoing thymectomy for myasthenia gravis in our institution is 15.2%. Serum preoperative anti-acetylcholine receptor antibody (anti-AchR Ab) titers were abnormally high in all of our five cases h (74.4±53.3 nmol/L) and decreased significantly after surgery (11.7±13.5 nmol/L, P=0.037). We divided our cases into the following three groups: microscopic thymoma group (Group M), thymoma group (Group T) and non-thymic tumor group (Group N). The mean preoperative anti-AchR Ab titers of these groups were 74.4, 26.5, and 368 nmol/L, respectively. All these values decreased postoperatively. The mean anti-AchR Ab titer was significantly higher in Group M than in Group T (P=0.034). All five cases in Group M were found by post-operative pathological examination to have multifocal type A thymomas. Microscopic thymomas tend to be multifocal type A thymomas. Anti-AchR Ab titers decreased significantly in all groups. It is very important to both perform complete extended thymectomies in patients with myasthenia gravis and pathological examination of thin slices of thymic tissue to maximize detection of microscopic thymomas.

Adequate tacrolimus concentration for myasthenia gravis treatment.

A single, oral dose of 3 mg/day tacrolimus, approved for myasthenia gravis (MG) treatment in Japan, was shown to reduce steroid dose and anti-acetylcholine receptor (AChR) antibody titers as well as to improve MG symptoms. However, no studies have investigated the association between tacrolimus concentration and its clinical efficacy in MG. In this study, we aimed to determine the optimal tacrolimus concentration for MG treatment. The trough tacrolimus concentration in 51 patients with MG (positive for anti-AChR antibody, n = 48; negative for anti-AChR and anti-muscle-specific tyrosine kinase antibodies, n = 3) who received 3 mg/day tacrolimus for more than 1 year was measured using a chemiluminescent enzyme immunoassay. The clinical characteristics of patients with MG as well as the dose of prednisolone used before and after tacrolimus treatment were evaluated retrospectively. The median trough tacrolimus concentration was 5.4 (range, 2.9-7.6) ng/mL, which was correlated with 'minimal manifestation or better status' (P = 0.0190, r = 0.3273) and the reduction in anti-AChR antibody 1 year after tacrolimus initiation (P = 0.0170, r = 0.3465). When the cut-off value for tacrolimus was defined as 4.8 ng/mL using a receiver operating characteristic curve, patients with adequate tacrolimus concentration (≥4.8 ng/mL) showed more reduction in anti-AChR antibody titers and more improvement in MG-related activities in daily life scores. More patients with adequate tacrolimus concentration achieved 'minimal manifestation or better status' compared with those with low tacrolimus concentration. An adequate tacrolimus concentration is required for better MG prognosis.

B-cell-activating factor is elevated in serum of patients with myasthenia gravis.

Myasthenia gravis (MG) is a B-cell-mediated autoimmune disease. B-cell-activating factor (BAFF) is a major factor in B-cell development and activation. In this study we investigated serum BAFF levels in MG patients. We compared the serum BAFF levels of 20 MG patients with gender-matched healthy controls. We assayed serum concentrations of BAFF and anti-acetylcholine receptor antibody (AChR) titers. Serum BAFF levels of MG patients with AChR antibodies were significantly higher than those of healthy controls. A significant positive correlation was observed between serum BAFF levels and anti-AChR antibody titers. BAFF values did not correlate with disease severity. BAFF may play a major role in the pathogenesis of MG, and it may provide a potential target for therapy in patients with MG. Muscle Nerve 54: 1030-1033, 2016.

Two-year outcome of thymectomy in non-thymomatous late-onset myasthenia gravis.

Thymectomy is an effective treatment for myasthenia gravis (MG). However, there is limited data on its effectiveness in non-thymomatous late-onset MG (LOMG). The aim of this study was to analyze the effects of thymectomy in LOMG. We retrospectively reviewed the 2-year post-thymectomy prognosis in 39 consecutive patients with non-thymomatous, anti-acetylcholine receptor antibody positive, and generalized LOMG (age at onset ≥ 50 years). The MG foundation of America (MGFA) classification, MGFA post-intervention status, dosage of prednisolone and pyridostigmine, and anti-acetylcholine receptor antibody titers were evaluated. Among the 39 LOMG patients, thymic hyperplasia was seen in 5 (12.8%). MGFA classification and prednisolone dosage before thymectomy were similar between the LOMG with thymic hyperplasia group (n = 5) and the LOMG with involuted thymus group (n = 34). Two years after thymectomy, the LOMG patients with thymic hyperplasia showed higher proportion of remission (60 vs. 26%) and received lower prednisolone dosage compared to patients with involuted thymus (0.8 vs. 4.0 mg/day). Notably, the proportion of patients with minimal manifestation or better status with receiving ≤ 5 mg/day prednisolone was much higher in the thymic hyperplasia group than in the involuted thymus group (100 vs. 62%). In conclusion, thymectomy could have beneficial effects in generalized LOMG, particularly in patients with thymic hyperplasia.

Predictive factors of myasthenic crisis after extended thymectomy for patients with myasthenia gravis.

Postoperative myasthenic crisis (POMC) is one of the serious complications after extended thymectomy for patients with myasthenia gravis (MG). This study aims to clarify the risk factors of POMC occurrence. The clinical data of 55 MG patients (25 male, 30 female; median age, 51 years) who underwent extended thymectomy at Kyoto University from 2000 to 2013 were retrospectively reviewed. Surgical outcomes and pre- and perioperative predictive factors of POMC were analysed. The preoperative Myasthenia Gravis Foundation of America stage was I, II, III and IV in 24, 22, 8 and 1 patients, respectively. Ten patients (18.2%) developed POMC; 6 required prolonged intubation over 24 h and 4 required reventilatory support. All patients were weaned after 5.6 (2-26) days of ventilator support, and were discharged. Univariate analysis revealed a correlation with a high preoperative anti-acetylcholine receptor antibody titre (P = 0.009), history of myasthenic crisis (MC) (P = 0.0004) and unstable MG after preoperative medical therapy (P = 0.003). Multivariate logistic regression analysis showed history of MC (odds ratio, 11.84; 95% confidential interval, 1.05-372; P = 0.045) and unstable MG (odds ratio, 29.45; 95% confidential interval, 2.00-1063; P = 0.013) independently predicted POMC. The surgical response rate was not significantly different between the two groups (66.7% with POMC, 85.4% without POMC; P = 0.334). POMC occurred more frequently in unstable MG before surgery or in patients with a history of MC. Adequate preoperative medical therapy and perioperative care should be provided to these patients.

An Increase in Circulating B Cell–Activating Factor in Childhood-Onset Ocular Myasthenia Gravis

BackgroundMyasthenia gravis is a B cell–mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell–activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. MethodsBlood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell–activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. ResultsSerum B cell–activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell–activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell–activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. ConclusionsCirculating B cell–activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis.