-
Therapeutic Advances in Neurological... 2024Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating muscle weakness. Severe patients may develop life-threatening respiratory failure and...
Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating muscle weakness. Severe patients may develop life-threatening respiratory failure and experience crisis. Plasma exchange or intravenous immunoglobulin (IVIg) is the first-line treatment option for myasthenia crisis, but some patients still poorly respond to them. Here, we first reported a generalized MG patient from China who was in a state of impending myasthenic crisis and did not respond effectively to IVIg but was successfully rescued by add-on efgartigimod. Especially, we also detected meaningful changes in T-cell and B-cell subsets after efgartigimod, promoting a potential role of efgartigimod in re-establishing immune homeostasis.
PubMed: 38813520
DOI: 10.1177/17562864241254895 -
Pediatric Neurology Jul 2024This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG).
BACKGROUND
This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG).
METHODS
Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded.
RESULTS
Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab.
CONCLUSIONS
Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.
Topics: Humans; Adolescent; Antibodies, Monoclonal, Humanized; Myasthenia Gravis; Male; Female; Child; Complement Inactivating Agents; Treatment Outcome; Quality of Life; Outcome Assessment, Health Care
PubMed: 38810600
DOI: 10.1016/j.pediatrneurol.2024.04.020 -
World Journal of Clinical Cases May 2024Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction. The primary pathology in MG involves the presence of autoantibodies to...
Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junction. The primary pathology in MG involves the presence of autoantibodies to acetylcholine receptors (AChRs), which results in qualitative and quantitative reductions in the availability of functional AChRs. Cardiac muscles are also affected, resulting in various perioperative cardiac complications. Antistriational antibodies are commonly reported in MG cases with cardiac involvement. In the presence of thymoma, the prevalence of cardiac manifestations in patients with MG increases to approximately 10%-15%. Cardiac involvement in MG may range from asymptomatic electrocardiogram changes to ventricular tachycardia, myocarditis, conduction disorders, heart failure, and sudden death. Increased incidence of atrial fibrillation, ventricular and supraventricular extra systoles, and prolonged QTc have also been reported in patients with MG. Clinicians should consider the evaluation of autonomic dysfunction and risk of cardiovascular disease in patients with MG.
PubMed: 38808348
DOI: 10.12998/wjcc.v12.i13.2147 -
Cureus Apr 2024Myasthenia gravis (MG) is an autoimmune illness characterized by autoantibodies against the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and an... (Review)
Review
Myasthenia gravis (MG) is an autoimmune illness characterized by autoantibodies against the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and an increasing number of extra postsynaptic proteins. Pathogenic autoantibodies reduce the number of functional AChRs in the neuromuscular junction's (NMJ) muscle end plate. The cause of the autoimmune response is unknown, but thymic abnormalities and immune regulatory deficiencies are significant. The disease's incidence is likely influenced by genetic predisposition, with sex hormones and exercise playing a role. MG can affect any age, race, or gender and can be caused by any stressor, with infections being the most frequent cause. Treatment focuses on airway support and the triggering incident. MG is a rare autoimmune disease causing fatigue-inducing weakness in the axial, respiratory, leg, and bulbar muscles. Initially affecting the eyes, most MG patients experience at least one worsening symptom during their illness. The disease is mainly caused by antibodies against the AChR, dependence on the immune system within cells, and engagement of the complement system. The complement system plays a significant role in MG, and complement inhibition can both prevent the onset and slow its development. Ocular MG affects around 15% of people, with most patients having blocking antibodies against the cholinergic receptor. There may be correlations between thymoma and other autoimmune conditions, especially thyroid illness. Treatment and management for MG involve removing autoantibodies from circulation or blocking effector mechanisms using techniques such as complement inhibition, plasmapheresis, and B-cell elimination.
PubMed: 38803727
DOI: 10.7759/cureus.59104 -
Experimental and Therapeutic Medicine Jul 2024The coexistence of Parkinson's disease (PD) and myasthenia gravis (MG) is rare. When similar symptoms of both diseases overlap, it is challenging to make a concomitant...
The coexistence of Parkinson's disease (PD) and myasthenia gravis (MG) is rare. When similar symptoms of both diseases overlap, it is challenging to make a concomitant diagnosis of PD and MG. The present study describes the case of a patient with concomitant PD and MG. In addition, a systematic literature review was conducted by searching PubMed and Embase for reports on all patients with concomitant PD and MG, which were then grouped and compared according to different preexisting diseases. Finally, a total of 47 cases of concomitant PD and MG (35 men; 12 women), including the present case, were analyzed. The median age of the patients at first diagnosis was 66.59±9.91 years. The interval between the two diseases varied from 2 months to 22 years. Based on the sequential occurrence of these two diseases, the patients were categorized into three groups: The prePD-MG (30 cases), preMG-PD (12 cases), and coPD-MG (5 cases) groups. In the prePD-MG group, the onset age of MG was older and head drop was more common. In the preMG-PD group, the patients were more likely to have comorbid immune diseases.
PubMed: 38800046
DOI: 10.3892/etm.2024.12570 -
Frontiers in Immunology 2024There is always a lack of effective treatment for highly active refractory generalized myasthenia gravis (GMG). Recently, telitacicept combined with efgartigimod...
There is always a lack of effective treatment for highly active refractory generalized myasthenia gravis (GMG). Recently, telitacicept combined with efgartigimod significantly reduces circulating B cells, plasma cells, and immunoglobulin G, which brings promising therapeutic strategies. We report a case of a 37-year-old female patient with refractory GMG, whose condition got significant improvement and control with this latest treatment after multiple unsuccessful therapies of immunosuppressants. The new combination deserves further attention in the therapeutic application of myasthenia gravis.
Topics: Humans; Myasthenia Gravis; Female; Adult; Drug Therapy, Combination; Treatment Outcome; Immunosuppressive Agents
PubMed: 38799457
DOI: 10.3389/fimmu.2024.1400459 -
Pharmaceutics May 2024Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against the postsynaptic membrane receptors present at the... (Review)
Review
Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against the postsynaptic membrane receptors present at the neuromuscular junction. This condition is characterized by fatigue and muscle weakness, including diplopia, ptosis, and systemic impairment. Emerging evidence suggests that in addition to immune dysregulation, the pathogenesis of MG may involve mitochondrial damage and ferroptosis. Mitochondria are the primary site of energy production, and the reactive oxygen species (ROS) generated due to mitochondrial dysfunction can induce ferroptosis. Nanomedicines have been extensively employed to treat various disorders due to their modifiability and good biocompatibility, but their application in MG management has been rather limited. Nevertheless, nanodrug delivery systems that carry immunomodulatory agents, anti-oxidants, or ferroptosis inhibitors could be effective for the treatment of MG. Therefore, this review focuses on various nanoplatforms aimed at attenuating immune dysregulation, restoring mitochondrial function, and inhibiting ferroptosis that could potentially serve as promising agents for targeted MG therapy.
PubMed: 38794313
DOI: 10.3390/pharmaceutics16050651 -
Children (Basel, Switzerland) May 2024Juvenile myasthenia gravis (MG) is a rare autoimmune neuromuscular disease, often treated with anticholinesterases, corticosteroids, and immunosuppressants. However,...
Juvenile myasthenia gravis (MG) is a rare autoimmune neuromuscular disease, often treated with anticholinesterases, corticosteroids, and immunosuppressants. However, optimal treatment durations remain unclear. This study investigated the clinical characteristics and treatment of juvenile MG, including medication duration. The administration period for all drugs, immunosuppressants, and prednisolone at doses greater than 0.35 mg/kg daily was extracted retrospectively from medical records. Nineteen participants (8 boys, 11 girls) aged 8 months to 14 years (median, 2.5 years) at onset were identified. Fourteen patients (73.7%) had ocular MG and five (26.3%) had generalized MG. Drug treatment was conducted in 18 cases; however, 7 patients did not complete the treatment. Among the patients who completed drug treatment, the duration of treatment ranged from 11 to 100 months (median, 47 months). In the six patients treated with continuous administration of prednisolone or immunosuppressants, the treatment duration ranged from 33 to 99 months (median, 56 months). No severe adverse effects requiring hospitalization were reported. The patients treated with prednisolone or immunosuppressants required at least 33 months of treatment. These results will help develop protocols for juvenile MG treatment.
PubMed: 38790567
DOI: 10.3390/children11050572 -
Molecular Medicine Reports Jul 2024Astragaloside IV (AS‑IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms....
Astragaloside IV (AS‑IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms. However, the potential mechanism underlying the effects of AS‑IV on MG remains to be elucidated. The present study aimed to investigate whether AS‑IV has a therapeutic effect on MG and its potential mechanism of action. By subcutaneously immunizing rats with R97‑116 peptide, an experimental autoimmune (EA) MG rat model was established. AS‑IV (40 or 80 mg/kg/day) treatment was then applied for 28 days after modeling. The results demonstrated that AS‑IV significantly ameliorated the weight loss, Lennon score and pathological changes in the gastrocnemius muscle of EAMG rats compared with the model group. Additionally, the levels of acetylcholine receptor antibody (AChR‑Ab) were significantly decreased, whereas mitochondrial function [ATPase and cytochrome c (Cyt‑C) oxidase activities] and ultrastructure were improved in the AS‑IV treated rats. Moreover, the mRNA and protein expression levels of phosphatase and tensin homolog‑induced putative kinase 1, Parkin, LC3II and Bcl‑2, key signaling molecules for mitophagy and apoptosis, were upregulated, whereas the mRNA and protein expression levels of p62, Cyt‑C, Bax, caspase 3 and caspase 9 were downregulated following AS‑IV intervention. In conclusion, AS‑IV may protect against EAMG in a rat model by modulating mitophagy and apoptosis. These findings indicated the potential mechanism underlying the effects of AS‑IV on MG and provided novel insights into treatment strategies for MG.
Topics: Animals; Saponins; Apoptosis; Triterpenes; Mitophagy; Rats; Myasthenia Gravis, Autoimmune, Experimental; Female; Disease Models, Animal; Mitochondria; Muscle, Skeletal; Receptors, Cholinergic; Rats, Sprague-Dawley; Protective Agents
PubMed: 38785143
DOI: 10.3892/mmr.2024.13253 -
Cureus Apr 2024The current pharmaceutical management of myasthenia gravis (MG) is widely accepted to be pyridostigmine and prednisone, both known to cause adverse effects and incur...
The current pharmaceutical management of myasthenia gravis (MG) is widely accepted to be pyridostigmine and prednisone, both known to cause adverse effects and incur significant costs. This treatment may be particularly burdensome for patients primarily complaining of localized ocular MG, and little is known about the management of MG ptosis with topical medications. Oxymetazoline hydrochloride 0.1% ophthalmic solution has recently been approved by the FDA for the treatment of ptosis, but there have been limited studies in MG ptosis and no report to date of symptomatic improvement with the intranasal formulation. This case report discusses a 71-year-old female whose newly diagnosed MG ptosis resolved after three days of intranasal oxymetazoline hydrochloride 0.05%, followed by three days of intranasal flunisolide. Our patient's rapid resolution of symptoms, along with the favorable side effect profile and over-the-counter availability, highlights the promising indication for the use of intranasal oxymetazoline and flunisolide as potential alternatives or adjuncts in MG management. Further research in larger cohorts is necessary to confirm the efficacy of these nasal sprays in treating MG ptosis.
PubMed: 38784340
DOI: 10.7759/cureus.58812