Ocular Myasthenia Gravis Research Articles

Positive ice test in a patient with a lymphomatous infiltration of the levator palpebrae superioris

The ice test is known to be specific for the diagnosis of ocular myasthenia gravis in patients with ptosis, with reported specificities of 97%-100%. We report a patient with diffuse large B-cell lymphoma who showed a positive result to the ice test. A 53-year-old woman presented with left eyelid ptosis of 3weeks' duration. She had finished chemotherapy and radiotherapy for diffuse large B-cell lymphoma a year previously. On ophthalmological examination, her best-corrected visual acuity was 20/20 in each eye. Marginal reflex distances were +4 in the right eye and -1 in the left eye. Levator palpebrae superioris functions were 11mm in the right eye and 8mm in the left eye. Ptosis improved after 5minutes' application of ice to both eyelids, after which marginal reflex distances were +4 in the right eye and +1 in the left eye. Thyroid function tests, anti-acetylcholine receptor antibody test, and the repetitive nerve stimulation test were all negative. Magnetic resonance imaging showed fusiform masslike enlargement of the left superior rectus muscle and left levator palpebrae superioris muscles, with enhancement suggesting metastatic infiltration.

Clinical features of ocular myasthenia gravis in japan

Clinical features of ocular myasthenia gravis in japan

Necessary number of records for the diagnosis of ocular myasthenia gravis during single fiber electromyography

Background: Single fiber electromyography (SFEMG) is the most sensitive diagnostic tool for diagnosis of myasthenia gravis.

P.424 - Tacrolimus treatment in patients with long-standing ocular myasthenia gravis

P.424 - Tacrolimus treatment in patients with long-standing ocular myasthenia gravis

Validity of Forced Eyelid Closure Test: A Novel Clinical Screening Test for Ocular Myasthenia Gravis

Forced eyelid closure test (FECT) is a clinical screening test developed from the original Cogan lid twitch (CLT) sign to assist in the diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and specificity of FECT compared with CLT and benchmarked to standard diagnostic tests. This study was a retrospective chart review of 48 patients using electronic medical records of those that presented with ptosis and/or diplopia at Doheny Eye Institute, University of California, Los Angeles between February 2015 and April 2016. Patients without FECT testing were excluded. FECT and CLT results, and final diagnosis were recorded. To perform FECT, the patient was asked to squeeze his or her eyelids shut for 5-10 seconds then open quickly and fixate in primary position. The excessive upward overshoot of eyelids movement indicated a positive FECT. The test was performed by a neuro-ophthalmologist before establishing the diagnosis. Patients who had equivocal test results and/or inconclusive final diagnosis were excluded. Of the 48 patients studied, 18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG (83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48 patients, 35 patients also had a documented CLT result (72.9%). CLT was positive in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24 patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity of FECT were 94% and 91% (joint 95% confidence region: sensitivity × specificity = [0.70, 1] × [0.75, 1]). The relative true-positive fraction (rTPF) between FECT and CLT was 1.15; the relative false-positive fraction was 1.31. FECT is a simple clinical screening test with good sensitivity and specificity for OMG.

Recording Fewer Than 20 Potential Pairs With SFEMG May Suffice for the Diagnosis of Myasthenia Gravis.

Our aim in the current study was to determine the minimum number of SFEMG potential pairs required to confirm neuromuscular junction impairment and relate this number to disease severity. Ninety-four patients with myasthenia gravis (MG) attending the neuromuscular clinic from February 2013 to November 2015 were included. The SFEMG sensitivity was determined for each number of recorded pairs up to 20. In addition, we compared clinical and electrophysiologic characteristics between patients with abnormality within the first 3, 4 to 7, and ≥8 recorded pairs to determine whether this number is associated with disease severity. Ninety-eight percent of patients had abnormal SFEMG, within 17 pairs in ocular MG, and within 15 pairs in generalized MG. All patients with generalized MG had at least one abnormal pair in the first five recorded pairs. Patients with three abnormal pairs apparent earlier during the test had more frequent bulbar, respiratory, and limb muscle weakness, and had higher mean jitter values and decrement values. In most cases, an abnormal SFEMG examination can be demonstrated in the first 15 recorded potential pairs in patients with generalized MG, and in the first 17 pairs in patients with ocular MG, thus shortening the test time and decreasing patient discomfort while preserving test sensitivity.

Low-Density Lipoprotein Receptor-Related Protein 4-Positive Myasthenia Gravis in a Double-Seronegative, Electromyography-Negative Patient

We describe a patient with ocular myasthenia gravis, where single-fiber electromyography and testing for acetylcholine receptor and muscle-specific kinase antibodies were negative. However, antibodies to low-density lipoprotein receptor-related protein 4 (LRP4) were positive, and this prompted appropriate management. We recommend that testing for LRP4 antibodies be considered when the clinical suspicion for myasthenia gravis is high despite negative conventional diagnostic tests.

Diagnostic Utility of Repetitive Nerve Stimulation in a Large Cohort of Patients With Myasthenia Gravis.

Optimizing the diagnostic utility of repetitive nerve stimulation in myasthenia gravis (MG) may include tailoring the examination to clinical phenotype. Therefore, we analyzed all available repetitive nerve stimulation parameters in a large cohort of patients with confirmed MG diagnosis. All repetitive nerve stimulation examinations at the Uppsala University Hospital rendering an MG diagnosis during 1996 to 2014 were analyzed. The deltoid, trapezius, anconeus, nasalis, abductor digiti quinti, and frontalis muscles were examined. Two hundred one patients with MG were diagnosed. Abnormal amplitude decrement was found in 54% of patients with ocular MG, 77% of patients with predominantly bulbar fatigue, and in 83% of patients with predominantly limb fatigue. The deltoid muscle had the highest sensitivity in all MG subtypes, with a mean of 77% sensitivity in all clinical subtypes, and the most pronounced decrement for amplitude (P = 0.0002) and area (P < 0.0001). Technical issues were rare. These data contribute to further optimization of repetitive nerve stimulation strategies regarding muscle selection and technical performance in the electrodiagnostic workup of MG.

Effect of Jianpiyiqi granule on ocular myasthenia gravis in children prepared with a formula from Traditional Chinese Medicine

ObjectiveTo investigate the effect of Jianpiyiqi granule, prepared according to a Traditional Chinese Medicine (TCM) formula, on the ocular type of myasthenia gravis (MG) caused by a defect in synaptic transmission at the neuromuscular junction. MethodsA total of 155 children with ocular MG were recruited from January 2008 to January 2015. All individuals received ineffective glucocorticoid treatment prior to admission, and were given Jianpiyiqi granules (two doses per day) for 12 months. Plasma levels of acetylcholine receptor autoantibodies (AChR-Ab), cytokines, immune parameters and clinical score were analyzed. ResultsAfter intervention with Jianpiyiqi granule for 12 months, the levels of cytokines [including interleukin (IL)-6, IL-12, IL-17], immune parameters [including immunoglobulin G (IgG), IgM, free triiodothyronine, free thyroxine] and AChR-Ab were significantly decreased (P = 0.042, P = 0.049, P = 0.011, P = 0.02, P = 0.04, P = 0.03, P = 0.01; F = 21.60, P = 0.000). In contrast, IL-4 levels were significantly increased (P = 0.049). The absolute clinical score after treatment declined significantly compared with before treatment (F = 33.24, P = 0.000). The effective cure rate and the total effective rate gradually increased to a maximum of 149 (96.2%) and 151 (97.4%) in MG patients after 12 months of treatment, respectively. ConclusionThe Jianpiyiqi granule treatment lowered AChR-Ab levels and improved cytokine and other immune parameter levels, which suggests that the granule could be an ancillary treatment for ocular MG in children caused by a defect in synaptic transmission at the neuromuscular junction.

Myasthenia Gravis with Thymoma Recurrence 20 Years after Thymectomy: What Is the Optimal Follow-up Duration?

Thymoma occurs in about 20% of patients with myasthenia gravis (MG), but the recurrence of thymoma has rarely been reported. A 68-year-old man presented with ptosis and weakness of the neck muscles. He had undergone thymectomy for ocular MG with invasive thymoma 20 years previously. Chest computed tomography revealed recurrence of the thymoma. This 20-year period is, to our knowledge, the longest reported interval for recurrence of an MG-associated thymoma. The literature on the optimal follow-up duration after thymectomy is reviewed. Key Words: Myasthenia gravis, Thymoma, Recurrence

Outcomes of Preoperative and Postoperative Corticosteroid Therapies in Myasthenia Gravis

Aims: To compare the long-term outcomes of non-thymomatous myasthenia gravis (MG) patients receiving pre-thymectomy (Pre-CS) or post-thymectomy corticosteroid (Post-CS) therapy. Methods: In a retrospective cohort study, 41 patients with MG were treated with Pre-CS therapy, and 110 were treated with Post-CS therapy. Results: In the MG cohorts, 9 of 40 patients (22.5%) in the Pre-CS group vs. 28 of 105 patients (26.7%) in the Post-CS group achieved a complete remission (CR) at 1 year, 29.7% (11/37) vs. 38.6% (32/83) at 2 years and 36.4% (8/22) in the Pre-CS group vs. 50.0% (28/56) in the Post-CS group achieved a CR at 5 years. For the entire population, Post-CS therapy (hazard rate [HR] 3.042, p = 0.020) was a positive predictor for remission, and a long preoperative interval (HR 0.936, p = 0.030) was a negative predictor. In 98 original ocular MG patients, Post-CS therapy (HR 2.663, p = 0.014) and an age at onset ≥15 years (HR 4.865, p = 0.001) were positive predictors for remission. Discussion: Post-CS therapy with a shorter preoperative interval increases the likelihood of CR in postpubertal and adult patients.

Irrelevance of anti‑nAChR cytoplasmic loop antibody in the degree of myasthenia gravis.

Anti‑nicotinic acetylcholine receptor(nAChR) antibody in myasthenia gravis(MG) usually refers to that against the extracellular domain(ECD) of nAChR. However, growing evidence has indicated that there also exists the nAChR antibody against the nAChR cytoplasmic loop(CL) in patients with MG. Some studies have demonstrated that the anti‑CL antibody may play a protective role in animal models of experimental autoimmune MG. However, to date, limited or no information is available as to whether anti‑CL antibody plays a beneficial role in patients with MG. In this, we examined the levels of anti‑CL and anti‑ECD antibodies in the sera of 76patients with MG from the MG sample bank of our department, including 29generalized MG(gMG) and 47ocularMG(OMG) cases, as well as 40healthy controls by radioimmunoassay. We also analyzed the correlation between anti‑CL antibody levels and the degree of severity in patients with MG. Our results revealed that among the 76patients with MG, 61serumsamples(80.3%) were positive for anti‑ECD nAChR antibody, among which 38(38/61, 62.3%) were positive for anti‑CL antibody. The levels of anti‑ECD antibodies in gMG were higher than those in OMG; however, the levels of anti‑CL antibodies in gMG were comparable with those in OMG. No clear correlation was observed between the anti‑ECD antibody levels and those of anti‑CL antibody. Taken together, our findings provide the first clinical evidence of the possibly different role of anti‑CL antibody in patients with MG compared to its role in animal models of MG. Anti‑CL antibody may not exert a beneficial effect in patients with MG, but may play an as yet udetermined role in the development of MG.

Factors affecting outcome in ocular myasthenia gravis

ABSTRACTAim of the study: 50%–60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables.Materials and methods: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients.Results: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL.Conclusions: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.

Thymectomy is a beneficial therapy for patients with non-thymomatous ocular myasthenia gravis: a systematic review and meta-analysis.

Ocular myasthenia gravis, an autoimmune disease, is characterized by extraocular muscle weakness. Myasthenia gravis is closely associated with the functional status of the thymus gland. The efficacy of thymectomy for non-thymomatous ocular myasthenia gravis remains controversial. Here, we present the first systematic review and meta-analysis of studies assessing the outcome of thymectomy in patients with non-thymomatous ocular myasthenia gravis and found that the pooled rate of complete stable remission was 0.5074 with considerable heterogeneity. Furthermore, subgroup analysis showed that the efficacy of thymectomy differed according to geographical location. Furthermore, thymectomy outcomes are better in children than they are in adults. Thymectomy clearly represents an effective treatment for patients with non-thymomatous ocular myasthenia gravis. However, more multicenter, randomized, controlled clinical trials are now required to confirm these conclusions.

Asociere miastenia gravis – leucemie eritroblastică acută

Myasthenia Gravis is a chronic autoimmune neuromuscular disorder that is characterized by fluctuating weakness of the voluntary muscle groups. It occurs in all races, at any age (especially under 40 or over 60), both genders, with a prevalence of 20/100,000 population in the United States. About 15 percent of patients with myasthenia gravis have thymomas, much rarely another solid tumor, thyroid dysfunction and more often another autoimmune condition, such as rheumatoid arthritis, lupus, Biermer anaemia. We present a 72 year-old male patient with ocular myasthenia gravis treated with cholinesterase inhibitors, that, after many laboratory exams, was diagnosed with acute erythroblastic leukemia, a very rare clinical association.

Ocular vestibular evoked myogenic potential in patients with myasthenia gravis: A prospective clinical study

ObjectiveMyasthenia gravis (MG) is an archetypic disorder of neuromuscular junctions (NMJs) and autoantibody-mediated disease causing fatigable weakness of skeletal muscles with an ocular onset in up to 85%. The aim of this study was to detect extra ocular muscles (EOMs) abnormalities in MG patients using ocular vestibular evoked myogenic potential (oVEMP) n10 response. MethodsThe oVEMP was performed on 40 myasthenia gravis patients that were divided into three groups: newly diagnosed (10 patients), uncontrolled on treatment (15 patients) and controlled on treatment (15 patients) groups in addition to a control group of 10 subjects. Also a comparison of oVEMP response was held between patients with generalized and ocular MG. ResultsThe oVEMP n10 showed significant difference between the 3 study groups and the control. The n10 showed no significant difference between the newly diagnosed group and the other 2 groups. There was also significant difference between uncontrolled and controlled on treatment group and between generalized and ocular types of myasthenic patients. ConclusionThe oVEMP can be usefully used in diagnosis of new MG patients as regard n10 amplitude, threshold and AR except n10 latency with no therapeutic or monitoring value of oVEMP in MG.

Incidence of Autoimmune Myasthenia Gravis in a Health Maintenance Organization in Buenos Aires, Argentina

Background: Different epidemiological studies, especially in Europe, have estimated the incidence density of myasthenia gravis (MG) to range between 1.7 and 21.3/1,000,000/person-year; however, data from regions such as Latin America are scarce. This study is aimed at estimating the incidence and prevalence of acquired MG in Buenos Aires, Argentina. Methods: The study population comprised of affiliates of the Italian Hospital Medical Care Program, a prepaid health maintenance organization located in Buenos Aires. The evaluation method for case detection included a retrospective search from January 1, 2006, through December 31, 2012. Results: Of the 60 cases identified, 36 (60%) were females. The median age at diagnosis was 69 years (IQR 51.5-79). The mean age at diagnosis was 63.3 years (SD ±20). A total of 28 patients (46.7%) had generalized MG and 32 had ocular MG (53.3%). Thirty five patients (58.3%) had acetylcholine receptor antibodies and 2 (3.3%) had muscle-specific receptor tyrosine kinase antibodies. The crude incidence density (ID) of MG was 61.33 per 1,000,000 person-years (95% CI 47.62-79.99). The adjusted ID for the Argentinean population was 38.8 per 1,000,000 person-years (95% CI 27.09-50.51) and for the Buenos Aires population was 47.49 (95% CI 34.73-60.25). Conclusions: The results obtained are similar to those published for other geographical areas.

Single-fiber electromyography in the orbicularis oculi muscle in patients with ocular myasthenia gravis symptoms: does abnormal jitter predict response to treatment?

BackgroundSeronegative ocular myasthenia gravis (OMG) is diagnosed by ocular symptoms with supporting SFEMG, typically of frontalis or extensor digitorum muscles. We aimed to determine the sensitivity and specificity of orbicularis oculi SFEMG to diagnose and exclude myasthenia gravis and predict response to therapy.MethodsOrbicularis oculi SFEMG studies were conducted in 142 consecutive patients with symptoms and/or findings of OMG and negative AChR antibody during the period of 5 years. Retrospective chart review was conducted 2 years after the SFEMG to determine whether treatments were given and responses to treatment.ResultsOrbicularis oculi SFEMG was abnormal in 31 patients and normal in 111 patients. Twenty-nine patients with abnormal SFEMG were treated, and 25 had a good response. Twenty-four patients with normal SFEMG received treatment; none responded to treatment or developed generalized myasthenia.ConclusionAn abnormal orbicularis oculi SFEMG in patients with seronegative OMG has a high predictive value for response to therapy. Our study findings may affect the treatment decisions in practice and aid better management of myasthenic patients.

Epidemiological and clinical study of juvenile myasthenia gravis in Dakar, Senegal

Objective: Autoimmune Myasthenia Gravis (MG) is uncommon in childhood. The purpose of this study was to describe epidemiological, clinical, electrophysiological and biological features of autoimmune MG and to assess short-term evolution in a cohort of Senegalese children. Method: The medical records of 20 patients diagnosed with autoimmune MG at the Neurological Department of Fann National Teaching Hospital and the National Children's Hospital Albert Royer were reviewed from July 2003 to July 2013. Results: Twenty patients (6 males and 14 females) were enrolled with ages ranging from 17 months to 17 years. Sixteen (16/20) patients had ocular myasthenia and others (4/20) had generalized myasthenia. Decrement responses on low-frequency repetitive nerve stimulation (RNS) between 10% and 37 % was found in all (20/20) the patients. Serum level tests of acetylcholine receptors antibodies were positive in 60% (12/20) of patients with a mean level of 54.57 nmol/l. Chest tomodensitometry found thymoma in 2 patients. All the patients received cholinesterase inhibitors as treatment. Complete symptom remission was found in 20% (4/20) of patients and there was significant improvement in 70% (14/20) others. Two patients died of respiratory failure during MG acute exacerbation. Conclusion: Many similarities exist between Senegalese MG patients and those of other populations, mainly those with ocular MG predominance. Multicentric studies with standardized protocols and thorough follow-up are necessary to better understand autoimmune MG in African context.

Diagnostic value of repeated ice tests in the evaluation of ptosis in myasthenia gravis.

Twenty-six patients with ptosis related to Myasthenia gravis (MG) and 38 controls with ptosis other than MG were included. All patients were tested with the ice test 2 times on separate days in the afternoon. The margin reflex distance (MRD) was measured before and immediately after 2-minute application of ice on the eyelids. The ice test was judged positive if there was an improvement of at least 2.0 mm of MRD after the ice test. Among the patients with negative test results, 'equivocal’ was defined by improvement of MRD from at least 1.0 mm to less than 2.0 mm after the ice test. Repeated ice test results showed an agreement of 61.5% in MG, and 97.4% in nonmyasthenic ptosis. Repeated ice tests increased the sensitivity by 34.6% compared to a single test. Among the patients with repeatedly negative test results, 63.6% of those who showed equivocal results at least once turned out to be MG. Of those with repeated non-equivocal negative results, nobody turned out to be MG. There was no significant difference of the ice test results between ocular MG and generalized MG (p = 0.562).