Ocular Myasthenia Gravis Research Articles

Clinical features of double seronegative ocular myasthenia gravis.

To clarify the clinical features of patients with Double seronegative (DS) ocular myasthenia gravis (OMG). Sixty-one patients diagnosed with DS OMG at the Department of Ophthalmology, Hyogo Medical University Hospital over a 5-year period from 2017 were included. Patients were classified into three groups based on the initial examination findings: group P (ptosis alone), group M (ocular motility disorder alone), and group PM (combination of both). We retrospectively reviewed the patients and clarified their clinical features. There were 32 males and 29 females, with a mean age of 49.8 ± 20.9:1-82years. Twenty-one patients (34.4%) were in group P, 23 (37.7%) in group M, and 17 (27.8%) in group PM. The proportion of males (73.9%) was significantly higher in group M compared with the other two groups. The diagnosis was proven by detection of neuromuscular junction (NMJ) disorder in 73.8%, oral pyridostigmine trial test in 13.1%, and eight patients (13.1%) in group M were diagnosed after surgical treatment. The clinical symptoms were resolved by oral pyridostigmine treatment in 54.1% of cases. About 30% of patients with DS OMG had no obvious NMJ disorder, and an oral pyridostigmine trial test was necessary to diagnose these patients. Although DS OMG is often considered as the mildest form of MG, its prognosis is not optimistic and it requires aggressive therapeutic intervention. Trial registration number: 202104-750, "2016/4/18," retrospectively registered.

GOOD OUTCOMES OF OCULAR MYASTHENIA GRAVIS IN A YOUNG ADULT MALE: A CASE REPORT

Abstract
 Introduction : Myasthenia gravis (MG) is characterized by fluctuating weakening and fatigability of skeletal muscles. Ocular MG (OMG) occurs when the symptoms of MG are limited to the ocular muscles.
 Case Illustration : A 21-year-old male presents with a two-month history of drooping both eyelids. The drooping eyelids improved in the morning or after a nap, and got worse in the evening. Ocular examination revealed limitation towards all gazes with bilateral ptosis. Visual acuity, anterior segment, visual fields, slit lamp, and fundus examinations were unremarkable. The ice pack and rest test resulted in a significant improvement after two minutes of ice pack application and 30-minute rest, raising suspicion for the diagnosis of MG. Acetylcholine receptor antibody (AChR) test was positive for AChR binding antibody. Treatment for OMG is initiated with an oral acetylcholinesterase inhibitor, pyridostigmine, and corticosteroid. The ptosis and ophthalmoplegia improved after one week follow- up and recovered completely after eight weeks of follow-up.
 Discussion : The hallmarks of MG are fluctuating fatigable muscle weakness that worsen with activity and improve on rest. Neurological exam and clinical neurological history are essential to establish the diagnosis. Bedsite tests, electrophysiologic test, and the antibody test all support the clinical diagnosis of MG.
 Conclusion : OMG progresses to its generalized form 90% of the time during the first two years of the onset of ocular symptoms. Early detection and prompt treatment are the key which may help to prevent or minimize the occurrence of myasthenia crisis.

Exploring Factors That Prolong the Diagnosis of Myasthenia Gravis.

Myasthenia gravis (MG) is a condition with significant phenotypic variability, posing a diagnostic challenge to many clinicians worldwide. Prolonged diagnosis can lead to reduced remission rates and morbidity. This study aimed to identify factors leading to a longer time to diagnosis in MG that could be addressed in future to optimize diagnosis time. One hundred and ten patients from 3 institutions in Melbourne, Australia, were included in this retrospective cohort study. Demographic and clinical data were collected for these patients over the first 5 years from diagnosis and at 10 years. Nonparametric statistical analysis was used to identify factors contributing to a longer diagnosis time. The median time for MG diagnosis was 102 (345) days. 90% of patients were diagnosed before 1 year. Female patients took longer than male patients to be diagnosed (p = 0.013). The time taken for first presentation after symptom onset contributed most to diagnosis time (median 17 [141] days), with female patients and not working as contributory factors. Neurology referral took longer if patients had diplopia (p = 0.022), respiratory (p = 0.026) symptoms, or saw an ophthalmologist first (p < 0.001). Outpatient management compared with inpatient was associated with a longer time to be seen by a neurologist from referral (p < 0.001), for the first diagnostic result to return (p = 0.001), and for the result to be reviewed (p < 0.001). Ocular MG had a median greater time to neurologist review than generalized MG (median 5 [25] days vs 1 [13] days, p = 0.035). Electrophysiology tests took longer for outpatients than inpatients (median 21 [35] days vs 2 [8] days, p < 0.001). Outpatients were also started on treatment later than inpatients (p < 0.001). There was no association of MG severity, ethnicity, age, medical and ocular comorbidities, and public or private health service on diagnosis time. There was also no impact of time to diagnosis on Myasthenia Gravis Foundation of America outcomes, number of follow-ups or hospitalizations, or prevalence of treatments used. This study is limited by low patient numbers and its retrospective nature. This study identified several factors that can contribute to a prolonged diagnosis time of MG. Patient and clinician education about MG and outpatient diagnostic efficiency needs emphasis. Further studies are also needed to explore the delayed presentation time of women and nonworking patients in MG.

A controlled clinical study on efficacy and safety of periocular triamcinolone acetonide injection for treating ocular myasthenia gravis

ObjectiveTo evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy.MethodsA total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients.ResultsAfter 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P < 0.001) after treatment. The achievement rates of minimal manifestations status (MMS)for ptosis and ophthalmoplegia after 4 week-treatment were 86.3% and 75%, respectively, while they were 50% and 30% in patients with traditional oral administration. There was statistically significant difference only in MMS (rather than symptom relief rate and generalization conversion rate) between two groups. No serious complications (except for intraorbital hematoma) were found in OMG patients during the treatment period.ConclusionRepeated peribulbar injection of triamcinolone acetonide can effectively alleviate the initial symptoms of OMG patients. However, the evaluation of its long-term efficacy is still needed.Clinical Trial RegistryThis study has been clinically registered by Chinese Clinical Trial Registry (ChiCTR), first trial registration date:05/07/2019, registration number: ChiCTR1900024285.

Comparative effectiveness and safety of intravenous methylprednisolone and tacrolimus monotherapy in ocular myasthenia gravis with unsatisfactory prednisone responses: a retrospective study

BackgroundOral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy.MethodsWe retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded.ResultsBoth IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066–2.975; p = 0.028). All the adverse events were transient and tolerable.ConclusionOur findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

Pediatric Ocular Myasthenia Gravis: Single-Center Experience

BackgroundCurrently, there is no universally accepted standard treatment for ocular myasthenia gravis (OMG) in children. We aimed to investigate the possible proper regimens and timing of treatment for pediatric OMG cases based on the clinical manifestations: OMG with ptosis only and OMG with other features. MethodsOne hundred and forty two OMG cases attended at the Department of Pediatrics, Xiangya Hospital, Central South University, from 2010 to 2019 were included, and information from medical records was reviewed and recorded. Comparisons of clinical characteristics between patients with OMG with ptosis only and patients with OMG with other features as well as between patients treated with glucocorticoid (GC) within or after six months from disease onset were performed. ResultsOMG with other features constituted about 54.9% of the cases, and 66.2% of the patients achieved optimal outcome. Patients with OMG with ptosis only responded to pyridostigmine alone more than patients with OMG with other features who required several therapies (P < 0.001). Patients with OMG with ptosis only had a larger proportion of optimal outcome than the patients with OMG with other features (P = 0.002), and the difference remained significant even when the individual outcome groups were compared (P < 0.001). Patients who received GC within six months had a greater proportion of optimal outcome than those who received it after six months (P < 0.001). ConclusionsAlthough OMG with other features is a more common subtype of OMG, it is also more severe than OMG with ptosis only. An earlier addition of GC leads to optimal outcome.

Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients.

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. Invitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. Invitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients.

Investigation of the differential susceptibility of extraocular muscles in patients diagnosed with ocular myasthenia gravis based on the computerized diplopia test and the Ocular Motor Nerve Palsy Scale.

The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern. A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles. Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%. The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.

Clinical Characteristics and Outcomes of Generalized Myasthenia Gravis in Malaysia: A Single-Center Experience.

Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. Medical records of MG patients from 1976 to 2023 were reviewed retrospectively. Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21-30 years) whereas male patients peaked at a higher age (61-70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17-18.64, p=0.029) analyses. Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.

Ocular myasthenia gravis

Myasthenia gravis is an autoimmune disease characterized by muscle weakness and pathological fatigue due to autoaggressive phenomena with the formation of antibodies directed against various structures of the neuromuscular synapse. In most patients, the disease begins with the involvement of extraocular muscles, presenting with symptoms such as intermittent ptosis of the upper eyelid and/or binocular diplopia. In 15% of cases, clinical manifestations are limited to impairment of the levator palpebrae superioris and extraocular muscles, characteristic of the ocular form of myasthenia gravis. Specialists often encounter challenges in diagnosing this form, as serological and electrophysiological studies may be uninformative, necessitating diagnosis based on patient history and clinical picture. This literature review outlines the key aspects of the pathogenesis, clinical manifestations, methods of diagnosis and treatment of ocular myasthenia gravis.

Macrophage migration inhibitory factor: A noval biomarker upregulates in myasthenia gravis and correlates with disease severity and relapse

ObjectiveTo explore the relationship between macrophage migration inhibitory factor (MIF) and disease severity and relapse in patients with myasthenia gravis (MG). Methods145 MG patients including 79 new-onset patients, 30 remission patients and 36 relapse patients were enrolled in this study. The detailed characteristics of all enrolled MG patients were routinely recorded, including gender, age, type, MGFA classification, antibody, thymic status, clinical score, treatment, MGFA-PIS and B cell subsets (memory B cells, plasmablast cells and plasma cells) detected by flow cytometry. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. The correlation of MIF levels with clinical subtypes, disease severity and B cell subsets were investigated. Moreover, logistic regression analysis was applied to assess the factors affecting relapse of generalized MG (GMG). ResultsSerum MIF levels were higher in new-onset MG patients than those in controls and were positively associated with QMG score, MGFA classification and memory B cells. Subgroup analysis revealed that MIF levels were increased in GMG patients than in ocular MG (OMG), as well as elevated in MGFA III/IV compared with MGFA I/II. With the remission of the disease, the expression of serum MIF decreased. The multivariate logistic regression models indicated that high MIF and thymoma was a risk factor for relapse of GMG, and rituximab could prevent disease relapse. ConclusionsMIF can be used as a novel biomarker to reflect disease severity and predict disease relapse in MG patients.

Effectiveness of early glucocorticoids in myasthenia gravis: a retrospective cohort study.

This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase. A retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group. Kaplan-Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05). Early intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.

Altered serum levels of cytokines in patients with myasthenia gravis

BackgroundMyasthenia gravis (MG) is an autoimmune disease characterized by generalized skeletal muscle contraction weakness due to autoantibodies targeting neural-muscular junctions. Here, we investigated the relationship between key cytokines and MG type, disease course, antibodies, and comorbidities. MethodCytokine levels in serum samples collected from MG (n = 45) and healthy control (HC, n = 38) patients from January 2020 to June 2022 were quantified via flow cytometry. ResultsLevels of IL-6 were higher in the MG group versus healthy individuals (p = 0.026) and in patients with generalized versus ocular MG (p = 0.019). IL-6 levels were positively correlated with QMG score. In patients with MG with both AChR and Titin antibodies, serum levels of sFas and granulysin were higher than in those with AChR alone (p = 0.036, and p = 0.028, respectively). LOMG had a reduction in serum levels of IL-2 compared to EOMG (p = 0.036). LOMG patients with diabetes had lower serum levels of IL-2, IL-4, and IFN-γ (p = 0.044, p = 0.038, and p = 0.047, respectively) versus those without diabetes. sFas in the MG with Abnormal thymus were reduced compared to those in MG with Normal thymus (p = 0.008). ConclusionsThis study revealed a positive correlation between IL-6 level and MG status. Serum cytokine levels of the AChR + Titin MG group differed from those of the AChR group. LOMG had a lower IL-2 level. Comorbidities affect some cytokines in peripheral blood in MG serum.

Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis

Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specific diagnostic biomarker for various MG serotypes with quantitative proteomics. Serum proteomes of 18 individuals (MG patients, healthy controls (HC), Rheumatoid Arthritis (RA) were quantified in a pilot study and occurrence of high residual fibrinogen was validated by immunoblotting and further investigated by targeted mass spectrometry on the sera of 79 individuals (31 MG of various serotypes, 30 HC, 18 RA). Initial proteomic analysis identified high residual fibrinogen in MG patient sera which was then validated by antibody-based testing. Subsequently, a blinded study of independent samples showed 100% differentiation of MG patients from controls. A final serological quantification of 14 surrogate peptides derived from α-, β-, and γ-subunits of fibrinogen in 79 individuals revealed fibrinogen to be highly specific and 100% sensitive for MG (p < 0.00001), with a remarkable average higher abundance of > 1000-fold over control groups. Our unanticipated discovery of high levels of residual serum fibrinogen in all MG patients can secure rapid bedside diagnosis of MG.

The Role of Thymoma and Thymic Hyperplasia as Prognostic Risk Factors for Secondary Generalisation in Adults with Ocular Myasthenia Gravis: A Systematic Narrative Review.

The conversion of ocular myasthenia gravis (OMG) to generalised myasthenia gravis (GMG) is reported to differ depending on the presence of generalisation risk factors (Mazzoli et al. 2018). Thymic pathology has been recognised as a potential risk factor for generalisation in the literature (Teo et al. 2017). Thymoma and thymic hyperplasia have yet to be examined as a risk factor for generalisation of OMG independently of other risk factors in the literature. Thus, the purpose of this review is to examine the literature to identify whether thymoma and thymic hyperplasia do increase the risk of OMG progressing to GMG. A literature search was carried out which employed a systematic approach. The search was undertaken using the following academic libraries: MEDLINE, Embase and Starplus. The search was limited to publications between the years 2001 to 2021. The search yielded 82 studies, which after the screening of titles and abstracts, left 62 studies for further analysis against the inclusion and exclusion criteria. The review found thymoma to be associated with an increased risk of GMG development. However, there was a scarce amount of literature which investigated thymic hyperplasia. Therefore, a firm conclusion could not be made with regards to thymic hyperplasia and the risk of GMG development. This review provides evidence for the consideration of thymectomy early after thymomatous OMG diagnosis to prevent GMG conversion. As the review did not collect enough evidence to support the influence of thymic hyperplasia on OMG conversion, further research is required.

Ocular myasthenia gravis and blepharospasm: similarities and differences

The ocular myasthenia gravis and blepharospasm are two diseases that can involve the periocular area in the pathological process. In both diseases, patients complain of closing their eyes. In both cases may be observed frequent blinking, worsening of symptoms in bright light. Blepharospasm associated with a violent contraction of the circular muscle of the eye, and myasthenia gravis related pathology of the neuromuscular synapse of the extraocular muscles. The article presents the clinical features of both diseases and diagnostic maneuvers that help in determining the diagnosis of the ocular myasthenia gravis and blepharospasm in clinically difficult cases.

Study of serum exosome miRNA as a biomarker for early onset adult ouclar myastthenia gravis

BackgroundBy extracting and sequencing miRNAs from serum exosomes of patients with early-onset ocular myasthenia gravis (OMG), generalized myasthenia gravis (GMG) and healthy controls, we screened differentially expressed miRNAs and explored the possibility as potential biomarkers for early-onset OMG. MethodsPeripheral blood samples were collected from patients with early-onset OMG, early-onset GMG, and age-matched healthy subjects, with 6 samples in each group. All these patients were diagnosed as MG for the first time and did not undergo any treatment. Exosomes miRNAs were extracted from the serum and performed deep sequencing; the differentially expressed miRNAs were compared and analyzed between OMG, GMG, and healthy control groups using edgeR. The differential expression standard was set to | log2FC |>1, p < 0.05. Target prediction of mRNAs were performed using miRTarBase, TargetScan, and miRDB databases, and a protein–protein interaction (PPI) network was constructed subsequently. The miRNAs with a significant difference were validated using RT-qPCR (10 early-onset OMG patients, 10 early-onset GMG patients and 10 age-sex-matched healthy subjects), and the value of the area under the ROC curve (AUC) was used to assess the diagnostic accuracy and evaluate clinical prognostic value. ResultsIn total, one upregulated (miR-130a-3p) miRNA was obtained through the upregulated intersection between control vs OMG and OMG vs GMG; four downregulated (miR-4712-3p; miR-6752-5p; miR-320d; miR-3614-3p) miRNAs were obtained through the downregulated intersection between control vs OMG and OMG vs GMG. A total of 408 target genes were predicted for the five differentially expressed miRNAs. The mTOR signaling pathway and Rap1 signaling pathway were significantly enriched based on the enrichment results. RT-qPCR findings revealed that for the OMG, the expression of miR-320d, miR-4712-3p and miR-3614-3p was markedly up-/down-regulated as compared to GMG and healthy control group. The AUC for the three miRNAs between OMG and healthy control groups were 0.78, 0.79 and 0.79 respectively; the AUC between OMG and GMG was 0.84. ConclusionsThe present study identified three novel miRNAs as candidate biomarkers for early-onset OMG patients and it was expected to provide a possibility and a new orientation for serum exosomal miRNAs as OMG diagnostic biomarkers.

Clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis: a retrospective analysis

To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

Ophthalmologic Manifestations of Ocular Myasthenia Gravis

Purpose: We investigated the ophthalmic manifestations observed in patients diagnosed with ocular myasthenia gravis.Methods: In total, 58 patients diagnosed with ocular myasthenia gravis visited the ophthalmology and neurology departments between January 2011 and August 2022. Patients were followed for &gt; 6 months; their ophthalmic manifestations were analyzed retrospectively.Results: The study included 29 males and 29 females with a mean age of 55.52 ± 15.60 years. Among the patients, 31 tested positive for anti-acetylcholine receptor antibodies, resulting in a positive rate of 53.45%. Abnormalities in repeated nerve stimulation tests were observed in 33.33% of the patients. The antibody-positive group exhibited a higher frequency of progression to generalized myasthenia gravis (p = 0.011) and a higher incidence of chest abnormalities (p &lt; 0.001) compared to the antibody-negative group. Horizontal and vertical diplopia were commonly observed in a complex group of patients with diplopia and blepharoptosis (p &lt; 0.001); there was a difference in the pattern of strabismus between the diplopia single group with esotropia and the complex group with exotropia (p = 0.029). In addition, the combination group demonstrated a higher antibody titer (p = 0.034), a higher frequency of abnormalities in repeated nerve stimulation tests (p = 0.022), and a higher incidence of chest abnormalities (p = 0.022).Conclusions: The anti-acetylcholine receptor antibody-positive group had a higher incidence of progression to generalized myasthenia gravis; moreover, the complex group of patients with diplopia and ptosis exhibited elevated levels of anti-acetylcholine receptor antibodies and frequently accompanied both horizontal and vertical strabismus.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. To investigate the association between specific environmental factors and the generalization of OMG. The cohort study was conducted in China based on a nationwide multicenter database. Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.