Ocular Myasthenia Gravis Research Articles

What's in the Neuromuscular Junction Literature?

Four retrospective studies from the United States, Europe, and Asia address outcomes in juvenile myasthenia gravis. Common features include earlier onset with ocular myasthenia gravis (MG) and generally good outcomes overall. Patients who were seronegative, had equivocal acetylcholine receptor (AChR) antibodies, or had only clustered AChR antibodies had better outcomes. An article highlighting the utility of median nerve slow-repetitive stimulation is reviewed and another showing the high sensitivity of repetitive nerve stimulation in myasthenic crisis is covered. Two articles address the thymus and thymectomy in non-AChR antibody-positive autoimmune MG. Longer term data on eculizumab as well as studies of cyclophosphamide, rituximab, and tacrolimus are summarized. Other topics include the possible role of statins in MG and central nervous system autoimmune comorbidities.

Aims of the Childhood Myasthenia Gravis Study Group in Japan

AbstractA Japanese epidemiological study about the age of onset of myasthenia gravis (MG) showed the highest peak at ages <5 years, besides the peak observed in adults, which was confirmed in east Asian populations, such as Korea, China and Hong Kong, and is different from that observed in white populations. The Childhood MG Study Group in Japan held an annual workshop for 12 years (from 2006 to 2017), in which the participants debated and obtained information about the clinical problems and related basic sciences of childhood MG. This workshop featured two kinds of presentations: research and clinical experiences. For the case presentation, 42 cases were reported, of which 14 were ocular MG and 28 were generalized MG, including nine cases of latent generalized MG. Seronegative MG was reported in eight cases, muscle‐specific receptor tyrosine kinase‐positive MG in one case and congenital myasthenic syndrome in four cases. Treatment of MG patients was various; tacrolimus was used for 23 cases, cyclosporine for two, a high dose of gamma‐globulin for 13 and thymectomy for 10. For the research presentation, various points of view were reported about the pathogenetic mechanism or treatment by top neurologists and scientists in Japan. This workshop will contribute to continued efforts of clinicians to treat patients, and researchers further progressing in their studies.

SAT-108 Growth Hormone Deficiency in a Patient with Ectodermal Dysplasia

Background information:Ectodermal dysplasia (ED) is a rare heterogeneous group of genetic disorders of ectodermal derived tissues, characterized by abnormalities in skin, teeth, hair and eccrine glands. Growth failure in these children varies depending on the genetic mutation and has not been well characterized. This clinical case report presents a 11-year-old male with a heterozygous mutation in WNT 10 A, a variant of the hypohydrotic ED gene, who was found to have growth hormone (GH) deficiency and treated with GH.Case report:He was born at 35 weeks gestation by C-section with a birth weight of 5 lbs. 12 oz. to a mother who had invitro fertilization with donor eggs from the maternal aunt with ocular myasthenia gravis and sperm from the father. Pregnancy was complicated by twin gestation and polyhydraminos. He had transient myasthenia gravis and treated with pyridostigmine for 3 months for feeding problems and swallowing difficulty. He also had arthrogryposis of the distal upper extremities attributed to placental transfer of the maternal aunt’s myasthenia gravis antibodies.He was referred to the endocrine clinic for evaluation of his growth failure around the age of 8 years. His growth chart indicated that he grew along the 5thpercentile until age 5 year with a gradual decline to the 3rd percentile by age 7 year and close to 2nd percentile by age 8 year. His BMI was at 7th percentile. Mid parental height was 5’9”. There was no history of delayed adolescence in the family. His twin sister had very mild form of arthrogryposis with dental delay but steady linear growth. He also had decreased exercise tolerance. His body tended to become hot during sports activities and had to wrap his face and neck with cold soaked towels. His other problems included delayed dental development with conical incisor, thin nail, missing teeth and hearing defects that raised suspicion for ectodermal dysplasia. Genetic testing at the age of 4 years had demonstrated a heterozygous mutation in the WNT 10A gene, an important gene for tooth development. Physical examination revealed a mild facial dysmorphism with conical incisor, missing teeth and high arched palate. He had contracture of the proximal inter phalangeal joints of the hands. Investigations revealed a normal thyroid function test, IGF-1 and IGFBP-3 level, CBC, sedimentation rate, chemistry panel and celiac titer. The bone age was concordant with his chronological age of 8 years. A GH stimulation study demonstrated a peak GH level of 4.94 ng/ml. An MRI of the brain revealed a normal pituitary gland. He was started on GH therapy with 0.3 mg/kg/week at age 9 year. His height improved from 2nd percentile at age 9 year to 20th percentile by age 11 year on growth hormone therapy. His exercise capacity and stamina also improved.Conclusion:Growth failure and GH axis should be evaluated in children with ED. GH therapy improves growth velocity and exercise capacity in patients with ED.

Vision therapy may reveal symptoms of ocular myasthenia gravis

Myasthenia gravis is a severe, treatable autoimmune disorder of the neuromuscular junction, with 80–90-per cent of cases having detectable auto‐antibodies to the α subunit of the acetylcholine rece...

Histopathologic study of extraocular muscles in thyroid-associated ophthalmopathy coexisting with ocular myasthenia gravis: a case report

BackgroundCoexistence of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis (OMG) is very rare. Little is known about the orbital histopathology associated with this condition. The authors reported a case of TAO coexisting with OMG and explored the histopathologic changes in extraocular muscles.Case presentationA 32-year-old man complaint of bilateral proptosis for 2 years. The patient was documented with a history of OMG and was treated with blepharoplasty to correct ptosis 3 years prior to presentation. Physical examination revealed right upper eyelid retraction resulting from the eyelid surgery. Computed tomographic scan demonstrated bilateral enlargement of the extraocular muscles. Thyroid function test confirmed hyperthyroid status. The patient was diagnosed with TAO (clinical activity score = 2/7) coexisting with OMG. Orbital decompression surgery reduced proptosis but resulted in new onset of left upper eyelid retraction because of the increased motor impulses to sustain eyelid elevation. Extraocular muscles were sampled during surgery and subjected to histopathologic stain. The stain results were analyzed against samples from age-, gender- matched TAO and control (non-TAO non-OMG) subjects. The measurement of myofiber size and glycosaminoglycan/collagen-occupied area was repeated in 3 randomly chosen fields of each slide. The variation of myofiber size was larger in the TAO + OMG (289.9 ± 142.5 μm2) samples than the TAO (544.1 ± 160.6 μm2) and control (157.0 ± 47.7 μm2) samples. Glycosaminoglycan was more abundant in the TAO + OMG (48.8 ± 12.2%) samples than the TAO (28.4 ± 3.6%) and control (3.3 ± 0.8%) samples. Collagen fibers accumulated in the TAO (60.5 ± 6.4%) samples but not in the TAO + OMG (36.1 ± 4.3%) and control (33.9 ± 2.7%) samples. Typical OMG changes were observed in the TAO + OMG samples but not in the TAO and control samples. These changes included central nuclei, aggregation of mitochondria and fiber type grouping. The histopathologic findings of TAO + OMG were summarized as inhomogeneously enlarged muscle fibers and predominantly endomysial accumulation of glycosaminoglycan.ConclusionThis study highlights the possibility of TAO coexisting with OMG and demonstrates the histopathologic features in this rare condition.

Risk of generalization in ocular myasthenia gravis after 10 years. (4778)

Risk of generalization in ocular myasthenia gravis after 10 years. (4778)

Long-term risk of generalization in patients with pure ocular myasthenia gravis (1954)

Long-term risk of generalization in patients with pure ocular myasthenia gravis (1954)

Features of depression development in myasthenia gravis.

The relative risk of developing depression in myasthenia gravis is 2.14 times higher than in the general population. The features of depression in myasthenia patients remain poorly understood and need to be clarified. The purpose of this work was to study the features of the development of depression in patients with myasthenia gravis. From 2014 to 2017, 182 patients with myasthenia gravis were examined. 147 (80.8%) patients had a generalized form of the disease, 35 (19.2%) had an ocular form. The clinical examination included assessment of complaints, medical history, neurological examination, as well as MGFA (Myasthenia Gravis Foundation of America) disease class and subclass of the disease determination. The severity of myasthenia gravis has been quantified according to the QMG score (Quantitative Myasthenia Gravis Score). All the patients were examined for the titer of antibodies to acetylcholine receptors (AchR) and muscle-specific tyrosine kinase (MuSK) by enzyme-linked immunosorbent assay (ELISA). Patients were also tested for the presence of antibodies to titin and SOX1 by indirect immunofluorescence. To detect depression the Beck depression inventory (BDI) was used. The mean depression score in the total sample was 16.0 (10.0; 24.0), which corresponds to a moderate depression level. The mean depression score in patients with ocular form was 6.0 (3.0; 11.0) points (ie, depression is absent), whereas in patients with generalized myasthenia gravis – 19.0 (12.0; 29.0) points (corresponds to moderate depression) (p <0.001). The distribution of patients with mild depression was also uneven: significantly bigger part of the patients was recorded with myasthenia gravis of class I (ocular form) – 10 (28.6%), and with myasthenia gravis of class II – 23 (44.2%). Among the patients with myasthenia gravis of class III, only 13 (20.3%) patients were reported with mild depression and 1 (3.2%) with class IV, p<0.001. The distribution of patients with moderate depression was the opposite of others: most patients had myasthenia gravis of class II – 12 (18.8%), and there were no patients with myasthenia gravis of class I. A similar tendency is also observed in the case of severe depression: patients with myasthenia gravis of class II – 23 (35.6%) dominated, to a lesser extent - patients with myasthenia gravis of class IV – 6 (19.4%). Among patients with ocular myasthenia gravis, only 1 (2.9%) patient was found to have severe depression. Severe depression was mainly recorded in patients with myasthenia gravis of class IV – 22 (71%) patients. The number of patients with severe depression has been decreased in the class of myasthenia gravis: 13 patients (20.3%) patients with ІІІ class, 1 (1.9%) with II class, no patients with class I. The degree of depression correlates with the clinical form of myasthenia gravis (ρ= -0.52; p<0.001), class (ρ= -0.30; p<0.001) and the subclass of the disease according to MGFA (ρ= -0.36; p<0.001). A reliable correlation relationship was established between the quantitative evaluation of the severity of myasthenia gravis (according to the QMG score) and the results of the evaluation according to the BDI score in the total sample (ρ=0.73; p<0.001). The assessment indicators on the QMG score and the BDI score significantly correlated in patients with ocular (ρ=0.36; p<0.05) and generalized forms (ρ=0.67; p<0.05). In addition, the level of depression correlates with the presence (ρ=0.15; p=0.040) and the titer of antibodies to AchR (ρ=0.42; p<0.001), with the presence (ρ=0.18; p=0.016) and the titer of antibodies to MuSK-AB (ρ=0.19; p=0.011). No correlation was found between the presence of antibodies to titin and to SOX1 (ρ=0.14; p<0.05 and ρ=0.07; p<0.05, respectively). There are no relationships between the use of anticholinesterase drugs, prednisone, the combined use of prednisone with / without azathioprine with / without anticholinesterase drugs and the development of depression in patients with myasthenia gravis.

Acupuncture for ocular myasthenia gravis: A protocol for systematic review and meta-analysis.

Background:The aim of this systematic review with meta-analysis is to determine the efficacy and security of acupuncture in treatment of ocular myasthenia gravis and find out whether or not the quick short-term efficacy of acupuncture exists.Methods:The following electronic databases will be searched by 2 independent reviewers: PubMed, Cochrane Library, EMBASE, Springer, China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature Database. All randomized controlled trials on acupuncture for ocular myasthenia gravis published in electronic databases from inception to March 1, 2020, with language restricted in Chinese and English will be included in the study.Methodologic quality is assessed by 2 blinded reviewers independently screen and score the articles using the PEDro scale and the Cochrane Collaboration risk of bias tool. A meta-analysis was performed when there is sufficient clinical homogeneity in at least 2 studies. The Grading of Recommendations Assessment, Development and Evaluation approach is used to rate the body of evidence in each meta-analysis. When the quantitive evaluation is not available, a qualitative description of the results of single study is provided.Results:An evidence of variety of acupuncture treatment methods for treating ocular myasthenia gravis will be illustrated using subjective reports and objective measures of performance. The primary outcomes consisted of effective rate, MGFA PIS, QMG, and MG-composite. Secondary outcomes involve clinical absolute and relative score, titers of AchR antibodies, and the side effects. The treatment frequency and courses will be measured.Conclusion:This protocol will present the evidence of whether acupuncture is an effective and safe intervention for ocular myasthenia gravis.Trial registration number:CRD42019141325

Repetitive ocular vestibular evoked myogenic potentials in myasthenia gravis.

To validate the repetitive ocular vestibular evoked myogenic potentials (RoVEMP) test for diagnostic use in myasthenia gravis (MG) and to investigate its value in diagnostically challenging subgroups. The RoVEMP test was performed in 92 patients with MG, 22 healthy controls, 33 patients with a neuromuscular disease other than MG (neuromuscular controls), 4 patients with Lambert-Eaton myasthenic syndrome, and 2 patients with congenital myasthenic syndrome. Mean decrement was significantly higher in patients with MG (28.4% ± 32.2) than in healthy controls (3.2% ± 13.9; p < 0.001) or neuromuscular controls (3.8% ± 26.9; p < 0.001). With neuromuscular controls as reference, a cutoff of ≥14.3% resulted in a sensitivity of 67% and a specificity of 82%. The sensitivity of the RoVEMP test was 80% in ocular MG and 63% in generalized MG. The RoVEMP test was positive in 6 of 7 patients with seronegative MG (SNMG) with isolated ocular weakness. Of 10 patients with SNMG with negative repetitive nerve stimulation (RNS) results, 73% had an abnormal RoVEMP test. The magnitude of decrement was correlated with the time since the last intake of pyridostigmine (B = 5.40; p = 0.019). The RoVEMP test is a new neurophysiologic test that, in contrast to RNS and single-fiber EMG, is able to measure neuromuscular transmission of extraocular muscles, which are the most affected muscles in MG. Especially in diagnostically challenging patients with negative antibody tests, negative RNS results, and isolated ocular muscle weakness, the RoVEMP test has a clear added value in supporting the diagnosis of MG. This study provides Class III evidence that RoVEMP distinguishes MG from other neuromuscular diseases.

Autophagy-deficiency in bone marrow mononuclear cells from patients with myasthenia gravis: a possible mechanism of pathogenesis

Myasthenia gravis (MG) is a chronic autoimmune disorder resulting from autoantibodies against neuromuscular junction components. Research shows that this disease might be a primary bone marrow (BM) stem cell disorder. Autophagy protects the dynamics and homeostasis of the host cells by removing damaged mitochondria, protein aggregates and other intercellular materials. Dysfunctional autophagy is associated with autoimmune diseases. However, the autophagy activity and mechanisms in BM stem cell from MG patients remain largely uncharacterized. We evaluated the autophagy activity in bone marrow mononuclear cells (BM-MNCs) and the effects of autophagy on cell survival from patients with MG and healthy controls. Our results revealed that autophagy was significantly decreased in patients with MG before immunomodulation treatment compared with that in age-/sex-matched controls, and was lower in generalized MG (GMG) patients than in ocular MG (OMG) patients. Immunomodulatory treatment partially increased autophagy activity of BM-MNCs in MG patients and improved the symptoms. Furthermore, defective BM-MNCs differentiation, proliferation and apoptosis were observed due to dysfunctional autophagy. These findings suggest for the first time that BM-MNCs autophagy is impaired in patients with MG before immunomodulation therapy, and that autophagy is indispensable for the survival of BM-MNCs, implicating autophagy might be a potential pathogenic mechanism of MG and a novel therapeutic strategy for MG treatment.

Circulating miRNAs as Potential Biomarkers in Myasthenia Gravis: Tools for Personalized Medicine.

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies which attack receptors at the neuromuscular junction. One of the main difficulties in predicting the clinical course of MG is the heterogeneity of the disease, where disease progression differs greatly depending on the subgroup that the patient is classified into. MG subgroups are classified according to: age of onset [early-onset MG (EOMG; onset ≤ 50 years) versus late-onset MG (LOMG; onset > 50 years]; the presence of a thymoma (thymoma-associated MG); antibody subtype [acetylcholine receptor antibody seropositive (AChR+) and muscle-specific tyrosine kinase antibody seropositive (MuSK+)]; as well as clinical subtypes (ocular versus generalized MG). The diagnostic tests for MG, such as antibody titers, neurophysiological tests, and objective clinical fatigue score, do not necessarily reflect disease progression. Hence, there is a great need for reliable objective biomarkers in MG to follow the disease course as well as the individualized response to therapy toward personalized medicine. In this regard, circulating microRNAs (miRNAs) have emerged as promising potential biomarkers due to their accessibility in body fluids and unique profiles in different diseases, including autoimmune disorders. Several studies on circulating miRNAs in MG subtypes have revealed specific miRNA profiles in patients’ sera. In generalized AChR+ EOMG, miR-150-5p and miR-21-5p are the most elevated miRNAs, with lower levels observed upon treatment with immunosuppression and thymectomy. In AChR+ generalized LOMG, the miR-150-5p, miR-21-5p, and miR-30e-5p levels are elevated and decrease in accordance with the clinical response after immunosuppression. In ocular MG, higher levels of miR-30e-5p discriminate patients who will later generalize from those remaining ocular. In contrast, in MuSK+ MG, the levels of the let-7 miRNA family members are elevated. Studies of circulating miRNA profiles in Lrp4 or agrin antibody-seropositive MG are still lacking. This review summarizes the present knowledge of circulating miRNAs in different subgroups of MG.

Prognostic predictors of remission in ocular myasthenia after thymectomy.

BackgroundIdentifying prognostic predictors can assist in making clinical decisions. This study aimed to identify the potential predictors of remission in patients with ocular myasthenia gravis (OMG) after thymectomy.MethodsOMG patients who had thymectomy between 2011 and 2017 were reviewed retrospectively. Clinical outcomes were assessed according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS). Kaplan-Meier analysis was used to estimate the cumulative probability of complete stable remission (CSR). Univariate and multivariable analyses with Cox proportional hazards regression were used to identify predictors of CSR.ResultsFifty-one patients (23 male, 28 female) with a median age at OMG onset of 40 (range, 5–79) years were eligible for inclusion. Patients with thymomatous OMG (n=9) had a statistically older median age at disease onset [61 (range, 32–78) vs. 33.5 (range, 5–79) years, P=0.001], shorter duration from disease onset to thymectomy [3 (range, 2–24) vs. 10 (range, 1–132) months, P=0.004], and a higher rate of postoperative complication (44.4% vs. 9.5%, P=0.025), compared with non-thymomatous OMG (n=42). The estimated cumulative probability of CSR in the whole cohort was 41.8% (95% CI, 28.6–58.2%) 5 years after surgery. Age at onset of 40 years or younger (P=0.00016), female sex (P=0.069), and thymic hyperplasia (P=0.0061) were potential predictors under univariate analysis. However, only age at onset of 40 years or younger (HR: 4.117, 95% CI, 1.177–14.399, P=0.027) remained significant after multivariable analysis.ConclusionsCSR could be achieved in about 40% of OMG patients 5 years after thymectomy and is likely to be predicted by age at onset of 40 years or younger.

Outcomes After Transcervical Thymectomy for Ocular Myasthenia Gravis: A Retrospective Cohort Study With Inverse Probability Weighting.

The benefit of thymectomy in reducing requirement for corticosteroids, symptom severity, need for immunosuppression, and hospitalization rates in patients with seropositive generalized myasthenia has recently been established. It is unclear whether this benefit applies to patients with myasthenia and purely ocular manifestations (ocular myasthenia gravis [OMG]). We conducted a retrospective single-center cohort study of patients with OMG. Patients were included if their diagnosis was confirmed by acetylcholine receptor or muscle-specific kinase antibodies, abnormal electrophysiology, or a positive edrophonium test and at least 1 year of clinical follow-up. At each visit, the presence and severity of ocular and generalized symptoms was ascertained using a 4-point scale. Prednisone dose, steroid-sparing agent use, and need for intravenous immunoglobulin or plasmapheresis were recorded. The effect of thymectomy on time-weighted prednisone dose and symptom severity score was assessed using linear regression models. To adjust for nonrandomization of thymectomy, we used inverse probability weighting using a propensity score model derived from the prethymectomy observation period for thymectomy patients and a 6-month lead-in period for nonthymectomy patients that incorporated age, sex, acetylcholine receptor antibody seropositivity, disease severity (as defined by both symptom severity and treatment requirement), and treating physician preferences. Eighty-two patients (30 with thymectomy and 52 nonthymectomy) were included. In unadjusted analyses, time-weighted daily prednisone dose was 2.9 mg higher with thymectomy compared with nonthymectomy (95% CI: 0.2-5.7), but after inverse probability weighting, this was no longer statistically significant (difference = 1.7 mg, 95% CI: -0.8 to 4.2). There was no statistically significant difference in symptom severity score (adjusted difference = 0.35, 95% CI: -0.02 to 0.72) or risk of generalization (P = 0.22). In this retrospective study that used statistical techniques to account for nonrandomization, no significant differences in prednisone dose or symptom severity after thymectomy in ocular myasthenia were demonstrated.

Ophthalmic adverse effects of lithium.

Lithium is the current mainstay treatment for both acute and maintenance management of bipolar disorders. However, its narrow therapeutic index and array of side effects, although well-documented, can be challenging to manage. Comparatively, the side effects of lithium that involve the ophthalmic structures are not as well established in the literature and only partially appreciated, which can potentially lead to noncompliance. In this article, an extensive literature review of lithium and its ophthalmic adverse effects were performed and comprehensively summarized. Based on the search, documented ophthalmic adverse effects of lithium include: exophthalmos; abnormal eye movements; ocular myasthenia gravis; papilledema; photophobia; and abnormal tear film, contributing to dry eye disease. Additional studies are anticipated to be helpful in expanding the current understanding of lithium and its adverse ophthalmic side effects and certainly warranted to fill the knowledge gap. Close interprofessional management between psychiatrists and ophthalmologists is expected to be beneficial in patient care.

Clinical and therapeutic features of myasthenia gravis in adults based on age at onset.

To describe the characteristics of patients with very-late-onset myasthenia gravis (MG). This observational cross-sectional multicenter study was based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases. Patients were classified into 3 age subgroups: early-onset MG (age at onset <50 years), late-onset MG (onset ≥50 and <65 years), and very-late-onset MG (onset ≥65 years). Demographic, immunologic, clinical, and therapeutic data were reviewed. A total of 939 patients from 15 hospitals were included: 288 (30.7%) had early-onset MG, 227 (24.2%) late-onset MG, and 424 (45.2%) very-late-onset MG. The mean follow-up was 9.1 years (SD 4.3). Patients with late onset and very late onset were more frequently men (p < 0.0001). Compared to the early-onset and late-onset groups, in the very-late-onset group, the presence of anti-acetylcholine receptor (anti-AChR) antibodies (p < 0.0001) was higher and fewer patients had thymoma (p < 0.0001). Late-onset MG and very-late-onset MG groups more frequently had ocular MG, both at onset (<0.0001) and at maximal worsening (p = 0.001). Although the very-late-onset group presented more life-threatening events (Myasthenia Gravis Foundation of America IVB and V) at onset (p = 0.002), they required fewer drugs (p < 0.0001) and were less frequently drug-refractory (p < 0.0001). Patients with MG are primarily ≥65 years of age with anti-AChR antibodies and no thymoma. Although patients with very-late-onset MG may present life-threatening events at onset, they achieve a good outcome with fewer immunosuppressants when diagnosed and treated properly.

Ocular myasthenia gravis: updates on an elusive target.

Ocular myasthenia gravis (OMG) is a complex condition with heterogenous phenotypes and ill-defined diagnostic criteria. Understanding concomitant risk factors and autoimmune serology can help inform prognosis for generalization and guide treatment. Although antibodies to acetylcholine receptors or muscle-specific kinase likely increase risk of generalization, they are less frequent in OMG. Patients without either antibody tend to have a milder disease process and often have variable antibodies to other end-plate proteins such as LRP4, agrin, or cortactin. The treatment of OMG begins with pyridostigmine and is supplemented by oral prednisone if treatment-resistant or high risk for generalization. Variable oral prednisone regimens have been used with success and further immunosuppression may be best achieved with mycophenolate mofetil and azathioprine. Checkpoint inhibitor-induced myasthenia gravis is increasingly recognized and likely has high rates of mortality associated with myocarditis. Our understanding of OMG and its variable phenotypes continues to evolve. Autoantibody testing increasingly provides valuable diagnostic and prognostic information. Despite these improvements, a lack of quality treatment trials creates significant challenges for evidence-based management guidelines.

Comparison of peripheral blood B cell subset ratios and B cell-related cytokine levels between ocular and generalized myasthenia gravis

BackgroundThe pathogenesis of myasthenia gravis (MG) depends upon T and B cells, as well as complement and cytokines. The activation of functional subpopulations of T and B cells is the basis of the immune response. However, the activation levels of T and B cell subsets remain unclear in the pathogenesis of MG. Here, we evaluated the proportions of T and B cell subsets and related cytokines in ocular MG (oMG) patients and generalized MG (gMG) patients, and analyzed the potential roles of T and B cell subsets in the pathogenesis of oMG. MethodsIn total, 16 patients with oMG, 31 patients with gMG, and 20 healthy controls (HCs) were included in this study. Peripheral blood mononuclear cells (PBMCs) were separated from venous blood via density centrifugation. The percentages of CD3+CD4+ T cells, CD3+CD8+ T cells, CD4+CD25+CD127- regulatory T cells (Tregs), CD19+CD27+CD38- memory B cells, CD19+CD24hiCD27+ regulatory B cells (Bregs), CD19+CD38+CD138+ plasma cells, and CD19+CD40+ B cells in PBMCs were detected by flow cytometry. The levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, and interferon (IFN)-γ in serum were detected by enzyme linked immunosorbent assay (ELISA). Differences in T and B cell subsets and related cytokines were compared among the three groups of participants. ResultsThe proportions of CD19+CD27+CD38- memory B cells were significantly higher in the oMG and gMG groups than in the HC group (P = 0.004; P < 0.001), whereas the proportion of CD19+CD27+CD38- memory B cells was significantly lower in the oMG group than in the gMG group (P < 0.001). Moreover, the proportion of CD19+CD24hiCD27+ Bregs was significantly higher in the oMG group than in the gMG and HC groups (P = 0.001). The proportion of CD4+CD25+CD127- Tregs was significantly lower in the gMG group than in the oMG and HC groups (P < 0.001). Finally, the level of serum IL-10 was significantly higher in the oMG group than in the gMG and HC groups (P < 0.05). Compared with the HC group, serum IL-2 levels were significantly increased in the oMG and gMG groups (P = 0.016; P = 0.002). DiscussionThe reduced ratios of Tregs and Bregs may contribute to the progression of oMG to gMG, and the increased proportion of memory B cells may be closely related to the progression of oMG. IL-2 and IL-10 are important in the development of oMG.

Ocular myasthenia gravis: A case series

Aim: To report the clinical profile of patients with myasthenia gravis (MG) at a tertiary eye care center in Tamil Nadu. Material and Methods: This is a retrospective case series of patients in a single center between February 2019 and March 2020. Result: We present a series of five cases of ocular myasthenia in the pediatric age group (0–16 years), comprising three males and two females. The patients had varied presentations on the initial examination. Conclusion: It is important to differentiate MG from other diagnostic mimics such as neurological causes such as cranial nerve palsy, myopathies, ocular pathologies, and neuromuscular junction pathologies such as botulism and brainstem tumors. Diagnosis and treatment of myasthenia is done as a team effort of ophthalmologist and neurologist. This study is to reinforce a vigilant lookout for this great masquerader.

Juvenile Ocular Myasthenia Gravis: A Case Report

Myasthenia gravis is a chronic autoimmune disease of neuromuscular blockade, characterized by rapid fatigability of striated muscle. Estimated incidence has been reported at 1/200,000 to 1/1,000,000 worldwide, but its incidence in Indonesia is not clearly recorded. We report a rare case of juvenile ocular myasthenia gravis which is considered rare in child population. The objective of this case report is to describe the proper assessment of its clinical presentation. Patient is an eleven years old boy who had ptosis and opthalmoplegia on both sides for three weeks duration. Its complaint was exaggerated with sustained gaze on daily activities. Ptosis was triggered quickly after being induced by fixated upgaze without blinking and improved after ice pack was put on his eyelids for five minutes. However, his vision was preserved and no slurred speech, dysphagia or limb weakness on physical examination. Neostigmine test showed positive result and rapid nerve stimulation test also revealed withsignificant decrement on the affected eyelid muscles. No thymoma was seen on chest CT scan and thyroid function test was also normal. Hence the diagnosis was made and pyridostigmine was started for its medication. This report present a rare case of juvenile ocular myasthenia gravis. Early recognizing by some diagnostic modalities confirms its diagnosis so that treatment could be started to control the muscle weariness and improving patient's quality of life.