Ocular Myasthenia Gravis Research Articles

Ocular myasthenia gravis: Side effect of urografin

Ocular myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Diplopia and ptosis are common symptoms at the onset of ocular myasthenia gravis. It may occur due to the antibodies developed against various drugs. We are reporting a case of ocular myasthenia gravis which was developed in a patient post angiography which may be due to antibody developed against the dye used in angiography.

Quantitative motor assessment of muscular weakness in myasthenia gravis: a pilot study.

BackgroundMuscular weakness in myasthenia gravis (MG) is commonly assessed using Quantitative Myasthenia Gravis Score (QMG). More objective and quantitative measures may complement the use of clinical scales and might detect subclinical affection of muscles. We hypothesized that muscular weakness in patients with MG can be quantified with the non-invasive Quantitative Motor (Q-Motor) test for Grip Force Assessment (QGFA) and Involuntary Movement Assessment (QIMA) and that pathological findings correlate with disease severity as measured by QMG.MethodsThis was a cross-sectional pilot study investigating patients with confirmed diagnosis of MG. Data was compared to healthy controls (HC). Subjects were asked to lift a device (250 and 500 g) equipped with electromagnetic sensors that measured grip force (GF) and three-dimensional changes in position and orientation. These were used to calculate the position index (PI) and orientation index (OI) as measures for involuntary movements due to muscular weakness.ResultsOverall, 40 MG patients and 23 HC were included. PI and OI were significantly higher in MG patients for both weights in the dominant and non-dominant hand. Subgroup analysis revealed that patients with clinically ocular myasthenia gravis (OMG) also showed significantly higher values for PI and OI in both hands and for both weights. Disease severity correlates with QIMA performance in the non-dominant hand.ConclusionQ-Motor tests and particularly QIMA may be useful objective tools for measuring motor impairment in MG and seem to detect subclinical generalized motor signs in patients with OMG. Q-Motor parameters might serve as sensitive endpoints for clinical trials in MG.

Association of HLA class II (DRB1, DQA1, DQB1) alleles and haplotypes with myasthenia gravis and its subgroups in the Iranian population

Heterogenic pattern of HLA associations with myasthenia gravis (MG) among different ethnicities and also among different MG subgroups has been the subject of debate in large series of many studies. One hundred and sixty Iranian MG patients were investigated for HLA class II (DRB1, DQA1, DQB1) associations compared to two hundred healthy controls from the same ethnic population. DRB1*11 DQA1*0501 DQB1*0301 haplotype was found to be protective for total (ocular plus generalized) MG (Pc=0.005, OR=0.49) and generalized MG (Pc=0.008, OR=0.49). DRB1*04 DQA1*0301 DQB1*0302 haplotype (Pc=0.03, OR=2.25) was predisposing for anti-acetylcholine receptor (AChR) antibody-positive MG, while DRB1*16 DQA1*0102 DQB1*05 (Pc=0.013, OR=4.28) was predisposing for anti-muscle specific tyrosine kinase (MuSK) antibody-positive MG. There was also a trend of positive association for DRB1*14 DQA1*0104 DQB1*05 haplotype with MuSK-positive MG (Pc=0.054, OR=3.97). Among other MG subgroups and with less significance, DRB1*0101 DQA1*0101 DQB1*05 haplotype (P=0.016, OR=3.68) had positive association with pure ocular MG, and DRB1*03 DQA1*0501 DQB1*0201 haplotype (P=0.024) had negative association with thymomatous MG. This study highlights the importance of appropriate MG subgrouping according to clinical and paraclinical characteristics in HLA studies among MG patients.

Myasthenia gravis with thymic epithelial tumour: a retrospective analysis of a Japanese database.

Myasthenia gravis (MG) has been reported to correlate with earlier stage and Type B thymomas by the World Health Organization classification. We analysed a large database of clinical characteristics of patients with MG and thymic epithelial tumours to elucidate whether the severity of MG affected postoperative survival of those with thymic epithelial neoplasms. We conducted a multi-institutional study on the patients who had undergone surgical treatment for thymic epithelial tumours between 1991 and 2010. We examined Masaoka stage, pathological type, serum titre of antiacetylcholine receptor antigen, severity of MG and postoperative prognosis of the patients with or without MG. Of the 2835 registered patients at 32 institutes belonging to the Japanese Association for Research on the Thymus, 2638 were eligible for the study. MG was present in 598 patients (23%). Patients with MG had thymic epithelial tumours with significantly earlier stage (P = 0.0082) and significantly smaller tumours (P = 0.000) than those without. Type A, Type AB thymomas and thymic carcinomas were less frequently observed in patients with MG. Three of 304 patients (1%) with thymic carcinomas had MG preoperatively. Serum titres of antiacetylcholine receptor antibodies were positive in 98% of patients with MG, and 23% of those without. Patients with generalized MG had significantly higher titres of antiacetylcholine receptor antibodies than those with ocular MG (P = 0.000). The postoperative 30-day mortality rate was 0.3%. Postoperative 5- and 10-year survival rates of thymoma patients with MG and those without MG were 94 and 96, and 89 and 89%, respectively. We found no statistical difference in the postoperative survival rate or recurrence-free rate between the two groups. We found no significant statistical differences of these rates by MGFA classification or surgical approach. We conclude that earlier stage, smaller size or Type B thymomas are more frequently associated with MG, and MG may have no impact on the overall survival of patients with thymoma. We suggest that postoperative survival time of the patients with MG and thymic epithelial tumours may be mainly affected by the tumours, not by MG.

Single-fiber Electromyography in the Extensor Digitorum Communis for the Predictive Prognosis of Ocular Myasthenia Gravis: A Retrospective Study of 102 Cases.

Background:Single-fiber electromyography (SFEMG) abnormality in the extensor digitorum communis (EDC) was reported in ocular myasthenia gravis (OMG), which indicated subclinical involvement beyond extraocular muscles in OMG patients. The relationship between the abnormal findings of SFEMG in EDC and the probability for OMG to develop generalized myasthenia gravis (GMG) is unknown. This retrospective study aimed to determine the predictive value of abnormality of SFEMG in EDC of OMG patients.Methods:One-hundred and two OMG patients underwent standard clinical diagnosis process and SFEMG test in EDC muscle when diagnosed and were clinically followed up for 5 years. The SFEMG data were compared between different clinical groups according to thymus status, onset age, and different outcome of OMG developing. Chances of progressing to GMG were compared between two different groups according to SFEMG and repetitive nerve stimulation (RNS) results, acetylcholine receptor antibody (AchRAb) titer, thymus status, and onset age.Results:Abnormal SFEMG results were observed in 84 (82.4%) patients. The mean jitter, percentage of jitter >55 μs (%), and blocking were higher in OMG patients than in healthy volunteers. There were no statistical differences in jitter analysis between thymoma group and non-thymoma group (P = 0.65), or between the later OMG group and the later GMG group (P = 0.31), including mean jitter, percentage of jitter >55 μs (%), and blocking. Elderly group (≥45 years old) had a higher mean jitter than younger group (t = 2.235, P = 0.028). Total 55 OMG developed GMG, including 47 in abnormal SFEMG group while 8 in normal SFEMG group. There was no statistical difference in the conversion rates between the two groups (χ2 = 0.790, P = 0.140). RNS abnormality, AchRab titer, or onset age had no correlation with OMG prognosis (P = 0.150, 0.070, 0.120, respectively) while thymoma did (χ2 = 0.510, P = 0.020).Conclusion:SFEMG test in the EDC showed high abnormality in OMG, suggesting subclinical involvement other than extraocular muscles. Nevertheless, the abnormal jitter analysis did not predict the prognosis of OMG according to clinical follow-up.

Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit immunization in HLA DR3 transgenic mice

Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR). To investigate the significance of the ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic mice showed significantly higher clinical ocular and generalized MG severity scores and lower grip strength values than HLA-DQ8 mice. H-AChR ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did not show clinical and immunopathological features of ocular and generalized EAMG. Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. coli extract-immunized and CFA-immunized transgenic mice. Our results indicate that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. Diversity of the autoimmune responses displayed by mice expressing different HLA class II molecules suggests that the interplay between HLA class II alleles and AChR subunits might have a profound impact on the clinical course of MG.

Clinical Features and Prognosis of Ocular Myasthenia Gravis Patients with Different Phenotypes.

Clinical Features and Prognosis of Ocular Myasthenia Gravis Patients with Different Phenotypes.

Clinical Utility of Acetylcholine Receptor Antibody Testing in Ocular Myasthenia Gravis.

The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the largest cohort of patients with OMG available to date. Older age, male sex, and progression to generalized myasthenia gravis were significantly associated with a positive antibody test result. In addition, to our knowledge, this is the first report of an association between high AChR antibody levels and progression from OMG to generalized disease.

Sensitivity of Acetylcholine Receptor Antibody in the Diagnosis of Ocular Myasthenia Gravis

Acetylcholine receptor (AChR) binding antibodies are present in approximately 80% of patients with generalized myasthenia gravis (MG), but in only 55%

Retroperitoneal teratoma causing ptosis: A case report.

The present study reports the case of a patient who had undergone unsuccessful hormone therapy for ocular myasthenia gravis 14-years prior to the current presentation. The diagnosis of ocular myasthenia gravis was once again confirmed by a neostigmine test and repeat nerve stimulation study. Computed tomography scans in an external institution revealed a retroperitoneal cystic tumor with calcification above the left adrenal gland. The tumor was removed via a transperitoneal laparoscopic resection and was diagnosed as a mature cystic teratoma upon pathological examination. A teratoma is a common form of germ cell tumor, but primary teratomas of the retroperitoneum are quite rare in the adult population. Post-operative observation of the patient showed resolution of the ptosis and improved movement of the eyeballs. The potential mechanism was unclear, but the patient's teratoma was mature and may have contained myoid cells with antigenicity for anti-acetylcholine receptor (anti-AchR), as has been established in the thymus. Therefore, the anti-AchR antibody may have been involved.

A case of multiple tuberculomas of brain presenting as ocular myasthenia gravis

A six and a half year old child presented with four months history of bilateral ptosis which was initially diagnosed as ocular myasthenia gravis after a positive edrophonium test and being treated accordingly. Over the course of time he developed headache with occasional vomiting, so referred to us for evaluation. Neurological examination revealed presence of mild bilateral ptosis with mid-dilated pupils sluggishly reacting to light and gait ataxia. There was complete sparing of other extra ocular muscles. Ophthalmoscopy showed bilateral papilloedema. CT scan and later on MRI of brain pointed out multiple tuberculomas both at cortical and subcortical (including midbrain and cerebellum) level with obstructive hydrocephalus. Conservative therapy to decrease intracranial pressure was initiated soon along with antitubercular drugs, and response was found to be dramatic. Isolated bilateral ptosis as the initial presenting feature of multiple intracranial tuberculoma is very rare. Moreover tuberculoma of brain masquerading as ocular myasthenia with false positive edrophonium test is unique and hence reportable.

The Effect of Acupuncture on Blepharoptosis and Diplopia in Ocular Myasthenia Gravis: A Report of Three Cases

Introduction: The aim of this study was to evaluate the efficacy of acupuncture therapy on relieving ocular symptoms in resistant Ocular Myasthenia Gravis (OMG). Case: In this pilot study, three patients with OMG were offered ten sessions of acupuncture therapy, twice weekly, while they received their routine medical treatment. Their symptoms included ptosis and diplopia. Subjective impression of changes was assessed based on Ocular-quantitative Myasthenia Gravis (QMG) scoring before and after treatment sessions. Conclusion:All three patients enrolled in this study showed resolution of diplopia. Their subjective impression of symptoms was improved. However, the score of ptosis did not improve considerably. Acupuncture is another choice for reducing ocular symptoms besides conventional treatment in resistant Ocular Myasthenia Gravis (OMG). However, future randomized controlled trial studies are needed to approve this issue.

Geographical Distribution of Myasthenia Gravis in Northern Europe - Results from a Population-Based Study from Two Countries

Objectives: To compare the prevalence of myasthenia gravis (MG) subgroups based on immunological markers and clinical presentation in two geographically complete MG populations in northern Europe. Methods: This cross-sectional study included all living MG patients in Norway and a regional cohort from the Netherlands. Patients were identified using their hospital registration codes. Medical charts of subjects >16 years were reviewed. Inclusion criteria were clinical MG, a positive antibody test for acetylcholine receptor (AChR MG) or muscle-specific kinase (MuSK MG), or if seronegative MG, confirmed by an electrophysiological test. Results: 1,205 MG patients (534 Norwegians and 671 Dutch) fulfilled the criteria, giving a higher point prevalence in the Netherlands (167/million, 95% CI 155-180) than in Norway (138/million, 95% CI 126-150). In particular, rates of AChR MG (143 vs. 111/million), MuSK MG (6.5 vs. 0.5/million), and ocular phenotype (62 vs. 24/million) were higher in the Netherlands. Conclusion: Novel findings are an AChR MG geographical north-south gradient and a 2.6-fold more ocular MG patients in the Netherlands than in Norway. The MuSK MG latitudinal gradient supports the notion of a north-south gradient in Europe, with a higher prevalence in the south. The variation is probably explained by genetic differences between the populations, in addition to environmental interactions.

Clinical Features and Diagnostic Usefulness of Antibodies to Clustered Acetylcholine Receptors in the Diagnosis of Seronegative Myasthenia Gravis.

Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). Herein, we asked whether these assays were able to help determine the diagnosis in patients studied in routine clinical practice. To determine the diagnostic usefulness of CBAs in the diagnosis of MG and to compare the clinical features of patients with antibodies only to clustered AChRs with those of patients with seronegative MG (SNMG). All patients with clinical suspicion of MG who were seen within the Division of Clinical Neurology at the John Radcliffe Hospital in Oxford, England, between November 1, 2009, and November 30, 2013. Their serum antibodies and clinical features were studied. Radioimmunoprecipitation assay (RIPA) and CBA were used to test for standard AChR antibodies and antibodies to clustered AChRs in 138 patients. All available samples from patients with SNMG were retrospectively tested for lipoprotein receptor-related protein 4 (LRP4) antibodies. Demographic, clinical, neurophysiological, and laboratory data. In total, 138 patients were tested for antibodies to clustered AChRs, and 42 had a final diagnosis of MG. The clustered AChR CBA detected antibodies in 38.1% (16 of 42) of RIPA-negative patients with MG with 100% specificity. All patients with SNMG who were tested for LRP4 antibodies (21 of 26) were negative by CBA. Compared with patients with SNMG, patients with antibodies only to clustered AChRs had frequent prepubertal onset (62.5% [median age, 6 years; age range, 1-52 years] vs 11.5% [median age, 38 years; age range, 2-72 years], P ≤ .05), high prevalence of ocular MG (62.5% vs 42.3%), milder disease severity with less bulbar involvement (25.0% vs 46.2%), and absence of respiratory symptoms (0% vs 23.1%). Response to treatment and prognosis was good, with a reduced need for thymectomy (6.3% vs 19.2%) and a high proportion of patients going into remission (50.0% vs 8.3%, P ≤ .05). These observations also apply to the classic AChR MG phenotype seen in large series. Cell-based assay is a useful procedure in the routine diagnosis of RIPA-negative MG, particularly in children. Patients with antibodies only to clustered AChRs appear to be younger and have milder disease than other patients with MG. These observations will have implications in planning treatment.

The HLA-B*4601-DRB1*0901 haplotype is positively correlated with juvenile ocular myasthenia gravis in a southern Chinese Han population.

Myasthenia gravis (MG) is a sporadic disorder that has been increasingly linked to inherited genetic factors. Previous studies have demonstrated that human leukocyte antigen (HLA) plays an important role in the pathogenesis of MG. We determined the genotypes of the HLA-A, B, and DRB1 alleles in 257 southern Chinese Han MG patients using polymerase chain reaction sequence-based typing (PCR-SBT). The allele frequencies in the MG patients were compared to 292 healthy controls using the case-control method. HLA-A*0207, HLA-B*4601, HLA-DRB1*0403, HLA-DRB1*0901, and HLA-DRB1*1602 were more frequent in juvenile ocular MG patients than controls. HLA-DRB1*0701 was significantly reduced in the juvenile ocular MG group compared with controls. HLA-A*0207-B*4601, HLA-B*4601-DRB1*0403, HLA-B*4601-DRB1*0901, and HLA-B*4601-DRB1*1602 were found to be in strong linkage disequilibrium in juvenile ocular MG patients. Within the MG patients, there was a strong positive association between HLA-B*4601-DRB1*0901 and juvenile ocular MG patients, and the value of odds ratios (OR) decreased as the disease became more severe and the age of onset increased. We believe this could be the main heredity phenotype in juvenile ocular MG patients from southern China and may be a clinical marker to predict the severity of the disease.

Prognosis of Ocular Myasthenia Gravis: Retrospective Multicenter Analysis

To calculate the rate and timing of conversion from ocular myasthenia gravis to generalized myasthenia gravis. Retrospective multicenter analysis. Patients included in the study were diagnosed with ocular myasthenia gravis without the presence of generalized disease at onset. We conducted a retrospective multicenter analysis. We reviewed charts of 158 patients who met diagnostic criteria for ocular myasthenia gravis. Patients were divided into 2 subgroups: an immunosuppressant treatment group and a nonimmunosuppressant treatment group. Timing of conversion to generalized disease and duration of follow-up also was evaluated. Additional data such as clinical symptoms at presentation, laboratory test results, and chest imaging results also were recorded. Conversion rates to generalized myasthenia at 2 years, effect of immunosuppression on conversion, and timing of conversion. The 158-patient cohort included 76 patients who received immunosuppressant therapy; the remaining 82 patients did not. The overall conversion rate to generalized disease was 20.9%. At 2 years, generalized myasthenia developed in 8 of 76 patients in the treated group and in 15 of 82 patients in the nonimmunotherapy group (odds ratio, 0.52; 95% confidence interval, 0.20-1.32). Median time for conversion to generalized disease was 20 months in the nonimmunosuppressant group and 24 months in the immunosuppressant group. Conversion occurred after 2 years of symptom onset in 30% of patients. Conversion rates from ocular to generalized myasthenia gravis may be lower than previously reported both in immunosuppressed and nonimmunosuppressed patients. A subset of patients may continue to convert to generalized disease beyond 2 years from onset of symptoms, and close monitoring should be continued.

Ocular LEMS or MG and LEMS Overlap Syndrome? (P7.078)

Ocular LEMS or MG and LEMS Overlap Syndrome? (P7.078)

Clinical characteristics and therapeutic evaluation of childhood myasthenia gravis.

This study aimed to analyze the clinical characteristics, classification and treatment of childhood myasthenia gravis (MG) and address the prognosis through follow-up. The clinical data of 135 children with MG were grouped according to clinical type and therapeutic drugs, retrospectively analyzed and prospectively monitored. Of the 135 MG patients, 85.2% had type I (ocular type), with only 4.2% progressing to systemic MG; 13.4% had type II (general type); and 1.5% had type III (fulminating type). Relapse occurred in 46.1% of the 102 patients that were followed up. The positive rate for the primary acetylcholine receptor antibody was 40.19%, without significant differences among clinical subtypes. The positive rate of the repetitive nerve stimulation frequency test by electromyography was 37.97%. Decreased expression of CD4+, CD8+, or CD3+ was present in 71% of the patients. Thymic hyperplasia was present in 5.93% of the patients, while 1.48% had thymoma. Steroid treatment was effective in the majority of the patients. Ocular type MG was common in this cohort of patients. The incidence and mortality of myasthenia crisis were low, the presence of concurrent thymoma was rare and only a limited number of children developed neurological sequelae.

A clinical approach to ocular myasthenia gravis

Myasthenia gravis is a common disorder of the neuromuscular junction characterized clinically by muscle weakness and fatigability. Ocular myasthenia is often misdiagnosed in the initial stages due to the fluctuating nature of ptosis and diplopia. Here, we describe the clinical characteristics of ocular myasthenia gravis along with the diagnostic difficulties in a tertiary eye care center in Nepal. We retrospectively reviewed the charts of the patients diagnosed as ocular myasthenia gravis in Neuro-ophthalmology clinic, BPKLCOS, from 2010 to 2013. The diagnosis of ocular myasthenia was based on the association of typical history and signs together with at least one of these features: unequivocal improvement of ocular signs after injection of neostigmine, positive response to electrophysiological tests and detection of serum antibodies to acetylcholine receptors. There were 24 cases of diagnosed ocular myasthenia gravis during the 3 years. Among them 11 cases (45.8%) were males and 13 cases (54.1%) were females. The mean age was 32.04±19.56 years with the age range from 9 years to68 years. The most common symptoms among patients were drooping of the lids (45.8%, n=11), followed by both double vision and drooping of the lids (37.5%, n=9) and only intermittent double vision in16.6% (n=4). In two patients (9.09%) CT-scan findings were suggestive of thymoma. The symptoms were resolved with anticholinesterases alone in 66.6% (n=16) and anticholinesterases were supplemented with immunosuppressive drugs in 33.3% (n=8) patients. Ocular myasthenia is often misdiagnosed in the initial stages due to its fluctuating nature. With a high index of clinical suspicion simple clinical tests accompanied by pharmacological tests can be useful in diagnosing the condition.DOI: http://dx.doi.org/10.3126/jcmc.v4i3.11931Journal of Chitwan Medical College 2014; 4(3): 5-8

Blepharoptosis surgery in patients with myasthenia gravis

Background/aimsTo review our approach of cautious surgical correction of blepharoptosis in patients with myasthenia gravis (MG) to minimise risk of exposure complications.MethodsRetrospective case note review of 30 patients with symptomatic...