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Journal of Korean Medical Science May 2024During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness...
BACKGROUND
During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea.
METHODS
This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients.
RESULTS
Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized ( < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients ( = 0.019 and = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients ( = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients.
CONCLUSION
This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
Topics: Humans; COVID-19; Myasthenia Gravis; Retrospective Studies; Male; Female; Middle Aged; Republic of Korea; Aged; SARS-CoV-2; Adult; COVID-19 Vaccines; Hospitalization; Vaccination; Prognosis; Intensive Care Units; Respiration, Artificial
PubMed: 38742290
DOI: 10.3346/jkms.2024.39.e150 -
CNS Neuroscience & Therapeutics May 2024This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab.
BACKGROUND
This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab.
METHODS
We retrospectively reviewed 108 patients who received rituximab of 600 mg every 6 months in Huashan Hospital and Tangdu Hospital. Of them, 76 patients from Huashan Hospital were included in the derivation cohort to develop the predictive nomogram, which was externally validated using 32 patients from Tangdu Hospital. The clinical response is defined as a ≥ 3 points decrease in QMG score within 6 months. Both clinical and genetic characteristics were included to screen predictors via multivariate logistic regression. Discrimination and calibration were measured by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively.
RESULTS
Disease duration (OR = 0.987, p = 0.032), positive anti-muscle-specific tyrosine kinase antibodies (OR = 19.8, p = 0.007), and genotypes in FCGR2A rs1801274 (AG: OR = 0.131, p = 0.024;GG:OR = 0.037, p = 0.010) were independently associated with clinical response of post-rituximab patients. The nomogram identified MG patients with clinical response with an AUC-ROC (95% CI) of 0.875 (0.798-0.952) in the derivation cohort and 0.741(0.501-0.982) in the validation cohort. Hosmer-Lemeshow test showed a good calibration (derivation: Chi-square = 3.181, p = 0.923; validation: Chi-square = 8.098, p = 0.424).
CONCLUSIONS
The nomogram achieved an optimal prediction of short-term outcomes in patients treated with low-dose rituximab.
Topics: Humans; Rituximab; Myasthenia Gravis; Male; Female; Middle Aged; Nomograms; Adult; Retrospective Studies; Immunologic Factors; Treatment Outcome; Aged; Young Adult; Receptors, IgG
PubMed: 38739094
DOI: 10.1111/cns.14761 -
Journal of Neuroinflammation May 2024Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T...
Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.
Topics: Myasthenia Gravis; Thymoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; T-Lymphocytes, Regulatory; Th17 Cells; Thymus Gland; Male; Female; Thymus Neoplasms; Adult; Middle Aged; Aged
PubMed: 38734662
DOI: 10.1186/s12974-024-03095-7 -
Neurology(R) Neuroimmunology &... Jul 2024To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.
OBJECTIVES
To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.
METHODS
We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of and were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population.
RESULTS
We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups.
DISCUSSION
Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Female; Adult; Male; Incidence; Young Adult; Retrospective Studies; Adolescent; California; Hispanic or Latino; Health Status Disparities; White People; Black or African American; Ovarian Neoplasms; Teratoma; Middle Aged; Ethnicity
PubMed: 38728608
DOI: 10.1212/NXI.0000000000200255 -
Medicine May 2024Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of... (Review)
Review
RATIONALE
Paraneoplastic neurological syndrome with anti-Hu antibody (Hu-PNS) is a neurological disorder that occur in patients with malignancy. The syndrome has a wide range of presentations and can present before diagnosis of primary malignancy. Familiarity with these paraneoplastic neurological syndromes can help early recognition and take appropriate regimens.
PATIENTS CONCERNS
Diagnosis and treatment of Hu-PNS.
DIAGNOSES
This is retrospective study that analyzed the clinical data of this case. Through retrospective analysis and targeted antibody screening, serum anti-Hu antibody was detected. Subsequent spinal imaging revealed a mass in the paraspinal region, which was confirmed as ganglioneuroblastoma by pathologic examination.
INTERVENTIONS
The child was treated with a course of intravenous immunoglobulin and radical surgical operation without chemotherapy.
OUTCOMES
The neurological symptoms were gradually improved and no signs indicate disease progression or tumor recurrence.
LESSONS
Hu-PNS has rarely been reported in children with ganglioneuroblastomas. They can mimic non-neoplastic processes, making detection and diagnosis difficult. Serum and/or cerebrospinal fluid onconeural antibody can strongly indicate occult cancers. Early detection of paraneoplastic neurological syndromes can help take appropriate regimens and improve prognosis.
Topics: Humans; Ganglioneuroblastoma; Paraneoplastic Syndromes, Nervous System; Male; ELAV Proteins; Autoantibodies; Child, Preschool; Retrospective Studies
PubMed: 38728479
DOI: 10.1097/MD.0000000000038148 -
Saudi Journal of Kidney Diseases and... Nov 2023Tumor-induced osteomalacia (TIO) is a disorder in which the clinical signs and symptoms of osteomalacia and the biochemical abnormalities of hypophosphatemia,...
Tumor-induced osteomalacia (TIO) is a disorder in which the clinical signs and symptoms of osteomalacia and the biochemical abnormalities of hypophosphatemia, phosphaturia, and low serum levels of 1,25(OH)2 Vitamin D3 are secondary to a neoplasm. A 33-year-old woman presented with musculoskeletal pain and proximal myopathy with a duration of 2.5 years which was treated with Vitamin D supplements. On the basis of the biochemical tests and histopathology, she was reevaluated and found to have TIO secondary to a phosphaturic mesenchymal tumor. The tumor was resected (limb salvage with endoprosthesis), and she had no pain or weakness at followup. The case reminds the readers to consider the possibility of TIO when evaluating patients with isolated hypophosphatemia, which may lead to long-term disability and prolonged morbidity if untreated. Early recognition and diagnosis of TIO is crucial since resection of the tumor usually reverses its manifestations.
Topics: Humans; Female; Adult; Osteomalacia; Paraneoplastic Syndromes; Hypophosphatemia; Muscular Diseases; Mesenchymoma; Treatment Outcome; Limb Salvage; Biopsy; Neoplasms, Connective Tissue
PubMed: 38725216
DOI: 10.4103/sjkdt.sjkdt_250_23 -
Autoimmunity Apr 2024Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some...
Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some patients with thymoma develop MG and others do not. In this study, we conducted a comparative phenotype analysis of thymocytes in type B thymomas in patients with MG (MG (+) thymomas) and without MG (MG (-) thymomas) fluorescence-activated cell sorting (FACS). Our results show that the developmental stages defined by the expression of CD3, CD4, and CD8 were largely maintained in both MG (+) and MG (-) thymomas, with CD4CD8 cells constituting the majority of thymocytes in type B thymoma, and no significant difference between this cell population was observed in MG (+) and MG (-) thymomas.We discovered that CD4CD8 thymocytes in MG (+) thymomas expressed low levels of αβ TCR and high levels of IL-7 receptor α (IL-7Rα), whereas in MG (-) thymomas, CD4CD8 thymocytes exhibited the opposite pattern of αβ TCR and IL-7Rα expression. These results suggest that the positive and negative selection processes of CD4CD8 thymocytes might differ between MG (+) thymomas and MG (-) thymomas. The expression of the Helios transcription factor is induced during negative selection and marks a group of T cells that have undergone negative selection and are likely to be deleted due to strong TCR binding with self-peptides/MHC ligands. We observed that the percentage of Helios-positive CD4SP T cells was greater in MG (-) than in MG (+) thymomas. Thus, the differentially regulated selection process of CD4CD8 thymocytes, which involves TCR and IL-7/IL-7Rα signaling, is associated with the presence of MG in type B thymomas.
Topics: Humans; Thymoma; Myasthenia Gravis; Receptors, Antigen, T-Cell, alpha-beta; Male; Thymocytes; Female; Middle Aged; Receptors, Interleukin-7; Adult; Aged; Thymus Neoplasms; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Immunophenotyping
PubMed: 38723105
DOI: 10.1080/08916934.2024.2347379 -
WMJ : Official Publication of the State... May 2024Hypokalemia is a common disorder in clinical practice. The underlying pathophysiology can be attributed to 3 main mechanisms: insufficient potassium intake, excessive...
Hypokalemia is a common disorder in clinical practice. The underlying pathophysiology can be attributed to 3 main mechanisms: insufficient potassium intake, excessive urinary or gastrointestinal losses, and transcellular shift. Renal loss is the most common cause of hypokalemia. Renal loss of potassium can occur due to diuretics, mineralocorticoid excess or hypercortisolism (Cushing syndrome). Among patients with Cushing syndrome, ectopic adrenocorticotropic hormone (ACTH) is the most frequent cause. We present a case of hypokalemia and hypertension due to ectopic ACTH production leading to Cushing syndrome.
Topics: Humans; Hypokalemia; Cushing Syndrome; ACTH Syndrome, Ectopic; Female; Male; Adrenocorticotropic Hormone; Middle Aged; Diagnosis, Differential
PubMed: 38718244
DOI: No ID Found -
Frontiers in Immunology 2024Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of...
INTRODUCTION
Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied.
METHODS
We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17-79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2-82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20-68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry.
RESULTS
We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission.
DISCUSSION
We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.
Topics: Humans; Myasthenia Gravis; Male; Middle Aged; Female; Adult; Aged; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Immunoglobulin G; Retrospective Studies; Young Adult; Adolescent; Autoantibodies; Aged, 80 and over; Immunosuppression Therapy; Immunosuppressive Agents; Severity of Illness Index; Child
PubMed: 38715598
DOI: 10.3389/fimmu.2024.1325171 -
Frontiers in Immunology 2024Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and...
Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear. Thus, in this study, we aimed to elucidate the pathogenic mechanism of seronegative MG using scRNA-seq analysis and plasma proteome analysis; in particular, we investigated the relationship between immune dysregulation status and disease severity in refractory seronegative MG. Employing single-cell RNA-sequencing and plasma proteome analyses, we analyzed peripheral blood samples from 30 women divided into three groups: 10 healthy controls, 10 early-onset AChR-positive MG, and 10 refractory early-onset seronegative MG patients, both before and after intravenous immunoglobulin treatment. The disease severity was evaluated using the MG-Activities of Daily Living (ADL), MG composite (MGC), and revised 15-item MG-Quality of Life (QOL) scales. We observed numerical abnormalities in multiple immune cells, particularly B cells, in patients with refractory seronegative MG, correlating with disease activity. Notably, severe MG cases had fewer regulatory T cells without functional abnormalities. Memory B cells were found to be enriched in peripheral blood cells compared with naïve B cells. Moreover, plasma proteome analysis indicated significantly lower plasma protein levels of soluble CD22, expressed in the lineage of B-cell maturation (including mature B cells and memory B cells), in refractory seronegative MG patients than in healthy donors or patients with AChR-positive MG. Soluble CD22 levels were correlated with disease severity, B-cell frequency, and RNA expression levels of CD22. In summary, this study elucidates the immunopathology of refractory seronegative MG, highlighting immune disorders centered on B cells and diminished soluble CD22 levels. These insights pave the way for novel MG treatment strategies focused on B-cell biology.
Topics: Humans; Myasthenia Gravis; Female; Adult; B-Lymphocytes; Sialic Acid Binding Ig-like Lectin 2; Middle Aged; Autoantibodies; Immunoglobulins, Intravenous; Receptors, Cholinergic; Severity of Illness Index; Young Adult; Proteome
PubMed: 38711503
DOI: 10.3389/fimmu.2024.1382320