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Frontiers in Immunology 2024Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who...
Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.
Topics: Humans; Myasthenia Gravis; Aged; Receptors, Cholinergic; Treatment Outcome; Receptor Protein-Tyrosine Kinases; Autoantibodies; Male; Female
PubMed: 38911858
DOI: 10.3389/fimmu.2024.1401972 -
Frontiers in Immunology 2024Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating... (Review)
Review
Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.
Topics: Humans; Myasthenia Gravis; Precision Medicine; Autoantibodies; Autoimmunity; Animals; Immunosuppressive Agents; Neuromuscular Junction
PubMed: 38903526
DOI: 10.3389/fimmu.2024.1404191 -
Internal Medicine (Tokyo, Japan) Jun 2024An 86-year-old woman was admitted to our hospital with cryptogenic progressive dyspnea and dysphagia following a tracheostomy procedure 4 months prior to presentation....
An 86-year-old woman was admitted to our hospital with cryptogenic progressive dyspnea and dysphagia following a tracheostomy procedure 4 months prior to presentation. She exhibited fluctuating diplopia, bilateral vocal fold paralysis, normal nerve test results, negative findings for serum anti-acetylcholine receptor and anti-muscle-specific kinase antibodies, and positive findings for anti-LDL-receptor related protein 4 (LRP4). A videofluoroscopic swallowing study (VFSS) with edrophonium revealed an improvement in bulbar paralysis. Consequently, the patient was diagnosed with double-seronegative myasthenia gravis (DSN-MG) and began immunomodulatory therapy. This case emphasizes the diagnostic challenges of bulbar-type DSN-MG and underscores the value of a VFSS with edrophonium for diagnosing this condition.
PubMed: 38897960
DOI: 10.2169/internalmedicine.3348-23 -
Frontiers in Medicine 2024Malacoplakia is a rare chronic granulomatous disease that mostly affects the gastrointestinal tract and urinary tract of immunocompromised patients; malacoplakia rarely...
Malacoplakia is a rare chronic granulomatous disease that mostly affects the gastrointestinal tract and urinary tract of immunocompromised patients; malacoplakia rarely effects the female reproductive tract. Here, we report a 56-year-old patient who underwent thymectomy for thymoma and myasthenia gravis prior to developing cervical and vaginal malacoplakia. The patient presented with recurrent vaginal bleeding. We discovered that there were alterations in the cervical cauliflower pattern during colposcopy, which is suggestive of cervical cancer. Pathological examination of the lesion tissue showed that a large number of macrophages aggregated, and M-G bodies with concentric circles and refractive properties were observed between cells. Immunostaining for CD68 and CD163 was positive, and special staining for D-PAS and PAS was positive. The discovery of in bacterial culture can aid in the diagnosis of malacoplakia. Following surgery, we performed vaginal lavage with antibiotics in addition to resection of local cervical and vaginal lesions. This study provides a fresh perspective on the management of genital malacoplakia.
PubMed: 38895183
DOI: 10.3389/fmed.2024.1409239 -
CNS Neuroscience & Therapeutics Jun 2024We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+)...
BACKGROUND
We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG).
METHODS
This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events.
RESULTS
Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues.
CONCLUSION
Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.
Topics: Humans; Antibodies, Monoclonal, Humanized; Female; Middle Aged; Male; Myasthenia Gravis; Adult; Aged; Prospective Studies; Treatment Outcome; Cohort Studies; Activities of Daily Living; Immunotherapy; Registries
PubMed: 38894580
DOI: 10.1111/cns.14793 -
Journal of Clinical Medicine Jun 2024: In the context of a comparative study of efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases (CAESAR-call AIFA_FV_2012-13-14), we...
: In the context of a comparative study of efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases (CAESAR-call AIFA_FV_2012-13-14), we assessed the use patterns of drugs indicated for myasthenia gravis (MG). : A retrospective cohort study was conducted based on administrative healthcare data. For a cohort of MG patients, prevalent and incident use of pyridostigmine (Py) and other indicated drugs in the first year after case identification was evaluated. Prevalent combined use of major therapies (azathioprine (Az), prednisone (Pr), vitamin D (Vd)) stratified by Py use was assessed, and a comparison between therapies at the time of MG identification and during the first year of follow-up was performed. : We included 2369 MG patients between 2013 and 2019. Among them, prevalent and incident Py users were 38.4% and 22.0%, respectively. In the first year of follow-up, the use of Pr was observed in 74.5% of Py prevalent users and in 82.0% of Py incident users, respectively; the use of Az was observed in 24.9% and 23.0%, respectively; and the use of Vd was observed in 53.3% and 48.2%, respectively. Among 910 Py prevalent users, 13.1% also used Az, Pr, and Vd, while 15.3% used none of these. Among 938 non-Py users, 2.7% used Az, Pr, and Vd, while 53.8% used none of these. During the first year, an increase in combined therapies was evident in incident Py users. : Our results suggest that, for some MG patients, there may be a need for treatments that combine a rapid onset of benefit with long-term and consistent disease control. These issues may be addressed by the new treatments currently being developed. To date, more studies are needed to address the heterogeneity, quality, and generalizability of the existing data and to evaluate patterns of use, efficacy, and safety of new or emerging therapies for MG.
PubMed: 38893023
DOI: 10.3390/jcm13113312 -
Journal of Clinical Medicine May 2024Robotic thoracic surgery is a prominent minimally invasive approach for the treatment of various thoracic diseases. While this technique offers numerous benefits... (Review)
Review
Robotic thoracic surgery is a prominent minimally invasive approach for the treatment of various thoracic diseases. While this technique offers numerous benefits including reduced blood loss, shorter hospital stays, and less postoperative pain, effective pain management remains crucial to enhance recovery and minimize complications. This review focuses on the application of various loco-regional anesthesia techniques in robotic thoracic surgery, particularly emphasizing their role in pain management. Techniques such as local infiltration anesthesia (LIA), thoracic epidural anesthesia (TEA), paravertebral block (PVB), intercostal nerve block (INB), and erector spinae plane block (ESPB) are explored in detail regarding their methodologies, benefits, and potential limitations. The review also discusses the imperative of integrating these anesthesia methods with robotic surgery to optimize patient outcomes. The findings suggest that while each technique has unique advantages, the choice of anesthesia should be tailored to the patient's clinical status, the complexity of the surgery, and the specific requirements of robotic thoracic procedures. The review concludes that a multimodal analgesia strategy, potentially incorporating several of these techniques, may offer the most effective approach for managing perioperative pain in robotic thoracic surgery. Future directions include refining these techniques through technological advancements like ultrasound guidance and exploring the long-term impacts of loco-regional anesthesia on patient recovery and surgical outcomes in the context of robotic thoracic surgery.
PubMed: 38892852
DOI: 10.3390/jcm13113141 -
Acta Neuropathologica Jun 2024Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to...
Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active disease requiring intensified monitoring and therapy; their identification is the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. We studied an exploration and a prospective validation cohort consisting of 114 and 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia gravis patients, respectively. For downstream analysis, we applied a machine learning approach. Protein expression levels were confirmed by ELISA and compared to other myasthenic cohorts, in addition to myositis and neuropathy patients. Anti-AChR-Ab levels were determined by a radio receptor assay. Immunohistochemistry and immunofluorescence of intercostal muscle biopsies were employed for validation in addition to interactome studies of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine learning identified ITIH3 as potential serum biomarker reflective of disease activity. Serum levels correlated with disease activity scores in the exploration and validation cohort and were confirmed by ELISA. Lack of correlation between anti-AChR-Ab levels and clinical scores underlined the need for biomarkers. In a subgroup analysis, ITIH3 was indicative of treatment responses. Immunostaining of muscle specimens from these patients demonstrated ITIH3 localization at the neuromuscular endplates in myasthenia gravis but not in controls, thus providing a structural equivalent for our serological findings. Immunoprecipitation of ITIH3 and subsequent proteomics lead to identification of its interaction partners playing crucial roles in neuromuscular transmission. This study provides data on ITIH3 as a potential pathophysiological-relevant biomarker of disease activity in myasthenia gravis. Future studies are required to facilitate translation into clinical practice.
Topics: Humans; Myasthenia Gravis; Biomarkers; Male; Female; Middle Aged; Adult; Aged; Autoantibodies; Receptors, Cholinergic; Proteomics; Cohort Studies; Young Adult; Proteinase Inhibitory Proteins, Secretory; Machine Learning
PubMed: 38888758
DOI: 10.1007/s00401-024-02754-6 -
BMC Neurology Jun 2024Mutations in the SLC5A7 gene cause congenital myasthenia, a rare genetic disorder. Mutation points in the SLC5A7 gene differ among individuals and encompass various...
BACKGROUND
Mutations in the SLC5A7 gene cause congenital myasthenia, a rare genetic disorder. Mutation points in the SLC5A7 gene differ among individuals and encompass various genetic variations; however, exon deletion variants have yet to be reported in related cases. This study aims to explore the clinical phenotype and genetic traits of a patient with congenital myasthenic syndrome due to SLC5A7 gene variation and those of their family members.
CASE PRESENTATION
We describe a case of a Chinese male with congenital myasthenic syndrome presenting fluctuating limb weakness. Genetic testing revealed a heterozygous deletion mutation spanning exons 1-9 in the SLC5A7 gene. QPCR confirmed a deletion in exon 9 of the SLC5A7 gene in the patient's mother and brother. Clinical symptoms of myasthenia improved following treatment with pyridostigmine.
CONCLUSION
Exons 1, 5, and 9 of the SLC5A7 gene encode the choline transporter's transmembrane region. Mutations in these exons can impact the stability and plasma membrane levels of the choline transporter. Thus, a heterozygous deletion in exons 1-9 of the SLC5A7 gene could be the pathogenic cause for this patient. In patients exhibiting fluctuating weakness, positive RNS, and seronegativity for myasthenia gravis antibodies, a detailed family history should be considered, and enhanced genetic testing is recommended to determine the cause.
Topics: Humans; Myasthenic Syndromes, Congenital; Male; Mutation; Pedigree; Adult; Genetic Testing; Female; Symporters
PubMed: 38886633
DOI: 10.1186/s12883-024-03716-x -
Scientific Reports Jun 2024Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile... (Comparative Study)
Comparative Study
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.
Topics: Humans; Myasthenia Gravis; Female; Male; Adult; France; Thymus Gland; Thymectomy; Adolescent; Autoantibodies; Receptors, Cholinergic; Young Adult; Child; Cohort Studies; Germinal Center
PubMed: 38886398
DOI: 10.1038/s41598-024-63162-0