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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 -
Cureus Apr 2024Eculizumab is a biologic medication used for the treatment of complement-related disorders including anti-acetylcholine receptor antibody-positive generalized myasthenia...
Eculizumab is a biologic medication used for the treatment of complement-related disorders including anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. It targets C5 complement, preventing its cleavage into active terminal components. Thus, vaccination against encapsulated organisms is advised before starting this treatment. C5 also has a critical role against infection. Here, we present a case of a 34-year-old man with a history of myasthenia gravis who was treated with prednisone and azathioprine in addition to eculizumab that was added to his regimen about a year ago, and who came to the hospital with headache, and was found to have Cryptococcus meningitis with disseminated cryptococcosis. The patient was negative for human immunodeficiency virus. He was treated with antifungal medications, and his condition improved. Although rarely reported, it is important to have a low threshold for diagnosis of cryptococcosis in patients on eculizumab given its complement inhibition mechanism of action.
PubMed: 38784297
DOI: 10.7759/cureus.58852 -
BMC Neurology May 2024Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG).
BACKGROUND
Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG).
CASE PRESENTATION
We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies.
CONCLUSIONS
Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention.
Topics: Humans; Female; Myasthenia Gravis; Middle Aged; Thymoma; Thymus Neoplasms; Choristoma
PubMed: 38783232
DOI: 10.1186/s12883-024-03656-6 -
F1000Research 2022Pulmonary alveolar proteinosis is a very rare diffuse lung disease characterized by the accumulation of amorphous and periodic acid Schiff-positive lipoproteinaceous...
Pulmonary alveolar proteinosis is a very rare diffuse lung disease characterized by the accumulation of amorphous and periodic acid Schiff-positive lipoproteinaceous material in the alveolar spaces due to impaired surfactant clearance by alveolar macrophages. Three main types were identified: Autoimmune, secondary and congenital. Pulmonary alveolar proteinosis has been previously reported to be associated with several systemic auto-immune diseases. Accordingly, we present the first case report of pulmonary alveolar proteinosis associated with myasthenia gravis. A 27-year-old female patient, ex-smoker, developed a dyspnea on exertion in 2020. The chest X-ray detected diffuse symmetric alveolar opacities. Pulmonary infection was ruled out, particularly COVID-19 infection. The chest scan revealed the "crazy paving" pattern. The bronchoalveolar lavage showed a rosy liquid with granular acellular eosinophilic material Periodic acid-Schiff positive. According to the lung biopsy results, she was diagnosed with pulmonary alveolar proteinosis. The granulocyte macrophage colony-stimulating factor autoantibodies were negative. Nine months later, she was diagnosed with bulbar seronegative myasthenia gravis, confirmed with the electroneuromyography with repetitive nerve stimulation showing significant amplitude decrement of the trapezius and spinal muscles. She was treated with pyridostigmine, oral corticosteroids and azathioprine. Given the worsening respiratory condition of the patient, a bilateral whole lung lavage was performed with a partial resolution of symptoms. Thus, this previously unreported association was treated successfully with rituximab, including improvement of dyspnea, diplopia and muscle fatigability at six months of follow-up. This case emphasizes on the possible association of auto-immune disease to PAP, which could worsen the disease course, as the specific treatment does not exist yet. Hence, further studies are needed to establish clear-cut guidelines for PAP management, particularly when associated to auto-immune diseases.
Topics: Humans; Pulmonary Alveolar Proteinosis; Female; Adult; Myasthenia Gravis
PubMed: 38779463
DOI: 10.12688/f1000research.127299.2 -
Neuromuscular Disorders : NMD Jul 2024Patients with myasthenia gravis (MG) can present with respiratory dysfunction, ranging from exercise intolerance to overt respiratory failure, increased fatigue, or...
Patients with myasthenia gravis (MG) can present with respiratory dysfunction, ranging from exercise intolerance to overt respiratory failure, increased fatigue, or sleep-disordered breathing. To investigate the value of multiple respiratory tests in MG, we performed clinical and respiratory assessments in patients with mild to moderate generalized disease. One-hundred and thirty-six patients completed the myasthenia gravis quality-of-life score(MG-QOL-15), myasthenia gravis impairment index(MGII), Epworth sleepiness scale(ESS), University of California-San Diego Shortness of Breath Questionnaire(UCSD-SOB), Modified Medical Research Council Dyspnea Scales(MRC-DS), supine and upright forced vital capacity(FVC), maximal inspiratory pressures(MIPs) and sniff nasal inspiratory pressures(SNIP). Seventy-three (54 %) had respiratory and/or bulbar symptoms and 45 (33 %) had baseline abnormal FVC, with no significant postural changes (p = 0.89); 55 (40.4 %) had abnormal MIPs and 50 (37 %) had abnormal SNIPs. Overall, there were low scores on respiratory and disability scales. Females had increased odds of presenting with abnormal FVC (OR 2.89, p = 0.01) and MIPs (OR 2.48, p = 0.022). There were significant correlations between MIPs, FVC and SNIPs; between MGII/MG-QOL15 and UCSD-SOB/MRC-DS and between ESS and respiratory scales in the whole group. Our data suggests that office-based respiratory measurements are a useful screening method for stable MG patients, even when presenting with minimal respiratory symptoms and no significant disability.
Topics: Humans; Myasthenia Gravis; Female; Male; Middle Aged; Adult; Aged; Quality of Life; Respiratory Function Tests; Vital Capacity; Surveys and Questionnaires
PubMed: 38776756
DOI: 10.1016/j.nmd.2024.05.005 -
Frontiers in Immunology 2024To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs),...
BACKGROUND
To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk.
METHODS
By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results.
RESULTS
Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility.
CONCLUSION
In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments and , are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.
Topics: Humans; Parkinson Disease; Mendelian Randomization Analysis; Autoimmune Diseases; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38774879
DOI: 10.3389/fimmu.2024.1370831 -
Ecotoxicology and Environmental Safety Jul 2024Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B...
Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.
Topics: Animals; Female; Pregnancy; NLR Family, Pyrin Domain-Containing 3 Protein; Placenta; Mice; Inflammasomes; Mice, Inbred C57BL; Inflammation; Apoptosis; NF-kappa B; Fluorocarbons; Signal Transduction
PubMed: 38772139
DOI: 10.1016/j.ecoenv.2024.116453 -
Frontiers in Neurology 2024This study investigated the impact of COVID-19 pandemic on the incidence and severity of myasthenia gravis (MG) using the National Health Insurance Service (NHIS)...
BACKGROUND
This study investigated the impact of COVID-19 pandemic on the incidence and severity of myasthenia gravis (MG) using the National Health Insurance Service (NHIS) database in Korea.
METHODS
We analyzed data from patients with MG in the NHIS registry from 2015 to 2021. MG was defined as (1) patients aged ≥18 years with the G70.0 code, and (2) patients who visited tertiary hospitals regarldless of department in Korea (outpatient clinics at least twice or hospitalization at least once), and (3) patients who were prescribed pyridostigmine as MG medications at least once. We designated pre-COVID-19 as 2019 and post-COVID-19 as 2021 and analyzed the MG incidence and prevalence in 2019 and 2021. We compared the clinical data of patients with MG between the two years. MG exacerbation was defined as the administration of intravenous immunoglobulin or plasma exchange. Analysis of COVID-19 cases was conducted using an integrated database from the Korea Disease Control and Prevention Agency and NHIS. Patients with MG were divided into two groups according to COVID-19 status to compare their clinical characteristics.
RESULTS
A total of 6,888 and 7,439 MG cases were identified in 2019 and 2021, respectively. The standardized incidence was 1.56/100,000 in 2019, decreasing to 1.21/100,000 in 2021. Although the frequency of MG exacerbations was higher in 2019, there were no differences in the number and duration of hospitalizations, duration of ICU stays, hostalization expense, and mortality between 2019 and 2021. Patients with MG and COVID-19 had a higher frequency of MG exacerbations than patients without COVID-19, but there were no differences in the number and duration of hospitalizations, hospitalization expense, and mortality.
CONCLUSION
This study was the first nationwide population-based epidemiological study of MG during COVID-19 pandemic in Korea. The incidence of MG decreased during COVID-19 pandemic, and the severity of MG was not affected by COVID-19.
PubMed: 38770524
DOI: 10.3389/fneur.2024.1374370 -
Cureus Apr 2024An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then...
An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then switched to nivolumab and ipilimumab in view of sorafenib intolerance and disease progression. Subsequently, he developed dysphagia and generalized dyspnea culminating in hypercapnic respiratory failure requiring intubation. After an extensive workup, the etiology of his fluctuating respiratory issues was narrowed down to a likely neuromuscular process. Although antibodies to acetylcholine receptors (anti-AChR Ab) were negative, he was treated with high-dose steroids due to clinical concern for Immune Checkpoint Inhibitor (ICI) neurotoxicity. His recovery post immune suppression and absence of recurrence after ICI cessation suggested the possibility of this being an ICI neurotoxicity manifesting with myasthenic symptoms. Incidentally, he also had evidence of aseptic meningitis on cerebrospinal fluid analysis further strengthening this diagnosis. This case illustrates the importance of early recognition of ICI toxicity which will in turn lead to initiating treatments sooner and also decreasing the length of illness.
PubMed: 38770481
DOI: 10.7759/cureus.58651 -
Veterinary Research Forum : An... 2024A 2-year-old intact male Asian Shepherd dog was referred with a history of chronic regurgitation along with normal appetite and diagnosis of megaesophagus on plain...
A 2-year-old intact male Asian Shepherd dog was referred with a history of chronic regurgitation along with normal appetite and diagnosis of megaesophagus on plain radiography. Clinical examination revealed normothermia, normocardia, normopnea, low body condition score and poor hair coat. The most important laboratory findings include anemia, azotemia, hyperlipidemia, increased thyroid stimulating hormone, decreased thyroxine and hypocortisolemia, as well as a marked increase in acetylcholine receptor antibody concentration. Based on the results, in addition to primary hypothyroidism and primary hypoadrenocorticism, myasthenia gravis was also diagnosed as an underlying cause of megaesophagus. Following nursing care and preferred treatment of each disease, the megaesophagus was resolved in the next visit. This clinical report describes for the first time, to the authors' knowledge, a dog with a rare type of autoimmune polyglandular syndrome (APS) known in human medicine as a Schmidt's syndrome. We want to emphasize the importance of clinicians' awareness regarding the possibility of APS to identify different diseases caused by it in order to achieve successful treatment.
PubMed: 38770199
DOI: 10.30466/vrf.2024.2011964.4014