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European Journal of Neurology May 2024Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants...
BACKGROUND
Generalized myasthenia gravis (MG) with antibodies against the acetylcholine receptor is a chronic disease causing muscle weakness. Access to novel treatments warrants authoritative treatment recommendations. The Nordic countries have similar, comprehensive health systems, mandatory health registers, and extensive MG research.
METHODS
MG experts and patient representatives from the five Nordic countries formed a working group to prepare treatment guidance for MG based on a systematic literature search and consensus meetings.
RESULTS
Pyridostigmine represents the first-line symptomatic treatment, while ambenonium and beta adrenergic agonists are second-line options. Early thymectomy should be undertaken if a thymoma, and in non-thymoma patients up to the age of 50-65 years if not obtaining remission on symptomatic treatment. Most patients need immunosuppressive drug treatment. Combining corticosteroids at the lowest possible dose with azathioprine is recommended, rituximab being an alternative first-line option. Mycophenolate, methotrexate, and tacrolimus represent second-line immunosuppression. Plasma exchange and intravenous immunoglobulin are used for myasthenic crises and acute exacerbations. Novel complement inhibitors and FcRn blockers are effective and fast-acting treatments with promising safety profiles. Their use depends on local availability, refunding policies, and cost-benefit analyses. Adapted physical training is recommended. Planning of pregnancies with optimal treatment, information, and awareness of neonatal MG is necessary. Social support and adaptation of work and daily life activities are recommended.
CONCLUSIONS
Successful treatment of MG rests on timely combination of different interventions. Due to spontaneous disease fluctuations, comorbidities, and changes in life conditions, regular long-term specialized follow-up is needed. Most patients do reasonably well but there is room for further improvement. Novel treatments are promising, though subject to restricted access due to costs.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Middle Aged; Aged; Myasthenia Gravis; Receptors, Cholinergic; Neuromuscular Diseases; Pyridostigmine Bromide; Immunosuppressive Agents; Thymus Neoplasms; Autoantibodies; Thymectomy
PubMed: 38321574
DOI: 10.1111/ene.16229 -
Exposure to Gulf war illness-related chemicals exacerbates alcohol- induced liver damage in rodents.Research Square Jan 2024Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war consisting of cognitive, neurological and gastrointestinal dysfunctions. Two...
Gulf War Illness (GWI) describes a series of symptoms suffered by veterans of the Gulf war consisting of cognitive, neurological and gastrointestinal dysfunctions. Two chemicals associated with GWI are the insecticide permethrin (PER) and the nerve gas prophylactic pyridostigmine-bromide (PB). In this study we assessed the effects of PER and PB exposure on pathology and subsequent alcohol (EtOH)-induced liver injury, and the influence of a macrophage depletor, PLX3397, on EtOH-induced liver damage in PER/PB- treated mice. Male C57BL/6 mice were injected daily with vehicle or PER/PB for 10 days, followed by 4 months recovery, then treatment with PLX3397 and a chronic-plus-single-binge EtOH challenge for 10 days. PER/PB exposure resulted in the protracted increase in liver transaminases in the serum and induced chronic low-level microvesicular steatosis and inflammation in GWI vs Naïve mice up to 4 months after cessation of exposure. Furthermore, prior exposure to PER/PB also resulted in exacerbated response to EtOH-induced liver injury, with enhanced steatosis, ductular reaction and fibrosis. The enhanced EtOH-induced liver damage in GWI-mice was attenuated by strategies designed to deplete macrophages in the liver. Taken together, these data suggest that exposure to GWI-related chemicals may alter the liver's response to subsequent ethanol exposure.
PubMed: 38313276
DOI: 10.21203/rs.3.rs-3838282/v1 -
Medicine Jan 2024Patients with elderly-onset myasthenia gravis can have a good prognosis with appropriate diagnosis and response, although it is difficult to differentiate between...
RATIONALE
Patients with elderly-onset myasthenia gravis can have a good prognosis with appropriate diagnosis and response, although it is difficult to differentiate between exacerbations of myasthenia gravis in elderly patients and age-related changes. Therefore, it is important for physicians to understand the clinical characteristics and safe assessment methods for patients with elderly-onset myasthenia gravis.
PATIENT CONCERNS
An 82-year-old male diagnosed with myasthenia gravis 6 months prior had no difficulty in daily living. After falling on a golf course, he was diagnosed with a right femoral neck fracture on the 1st day and underwent right total hip replacement surgery on the 12th day, being transferred to our hospital for rehabilitation therapy on the 32nd day. However, immediately after transfer, the patient showed fatigability during training and difficulty swallowing food.
DIAGNOSES
This case was diagnosed as an exacerbation of myasthenia gravis.
INTERVENTIONS
Pyridostigmine was initiated with the expectation of immediate effect on the 54th day.
OUTCOMES
His symptoms and physical functions improved immediately, and walking distance and food intake increased. From this clinical course, it was judged that immunosuppressive therapy was indicated as a transition to generalized myasthenia gravis. For this reason, he was discharged after arranging postdischarge visits to the department of neurology, accordingly.
LESSONS
A better understanding of the characteristics of elderly-onset myasthenia gravis may allow for relatively safe assessment of the condition and improve its diagnosis and treatment.
Topics: Aged, 80 and over; Humans; Male; Aftercare; Deglutition Disorders; Myasthenia Gravis; Patient Discharge; Pyridostigmine Bromide
PubMed: 38277576
DOI: 10.1097/MD.0000000000036989 -
Medicina (Kaunas, Lithuania) Dec 2023: The association between myasthenia gravis (MG) and depression is intricate and characterized by bidirectional causality. In this regard, MG can be a contributing...
: The association between myasthenia gravis (MG) and depression is intricate and characterized by bidirectional causality. In this regard, MG can be a contributing factor to depression and, conversely, depression may worsen the symptoms of MG. This study aimed to identify any differences in the progression of the disease among patients with MG who were also diagnosed with depression as compared to those without depression. Our hypothesis focused on the theory that patients with more severe MG symptoms may have a higher likelihood of suffering depression at the same time. : One hundred twenty-two male and female patients (N = 122) aged over 18 with a confirmed diagnosis of autoimmune MG who were admitted to the Neurology II department of Myasthenia Gravis, Clinical Institute Fundeni in Bucharest between January 2019 and December 2020, were included in the study. Patients were assessed at baseline and after six months. The psychiatric assessment of the patients included the Hamilton Depression Rating Scale-17 items (HAM-D), and neurological status was determined with two outcome measures: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Life (MG-ADL). The patients were divided into two distinct groups as follows: group MG w/dep, which comprised 49 MG patients diagnosed with depressive disorder who were also currently receiving antidepressant medication, and group MG w/o dep, which consisted of 73 patients who did not have depression. : In our study, 40.16% of the myasthenia gravis (MG) patients exhibited a comorbid diagnosis of depression. Among the MG patients receiving antidepressant treatment, baseline assessments revealed a mean MG-ADL score of 7.73 (SD = 5.05), an average QMG score of 18.40 (SD = 8.61), and a mean Ham-D score of 21.53 (SD = 7.49). After a six-month period, a statistically significant decrease was observed in the MG-ADL (2.92, SD = 1.82), QMG (7.15, SD = 4.46), and Ham-D scores (11.16, SD = 7.49) ( < 0.0001). These results suggest a significant correlation between MG severity and elevated HAM-D depression scores. Regarding the MG treatment in the group with depression, at baseline, the mean dose of oral corticosteroids was 45.10 mg (SD = 16.60). Regarding the treatment with pyridostigmine, patients with depression and undergoing antidepressant treatment remained with an increased need for pyridostigmine, 144.49 mg (SD = 51.84), compared to those in the group without depression, 107.67 mg (SD = 55.64, < 0.001). : Our investigation confirms that the occurrence of depressive symptoms is significantly widespread among individuals diagnosed with MG. Disease severity, along with younger age and higher doses of cortisone, is a significant factor associated with depression in patients with MG. Substantial reductions in MG-ADL and QMG scores were observed within each group after six months, highlighting the effectiveness of MG management. The findings suggest that addressing depressive symptoms in MG patients, in addition to standard MG management, can lead to improved clinical outcomes.
Topics: Humans; Female; Male; Adolescent; Adult; Pyridostigmine Bromide; Depression; Myasthenia Gravis; Antidepressive Agents; Disease Progression
PubMed: 38256317
DOI: 10.3390/medicina60010056 -
Biomedical Chromatography : BMC Mar 2024The present study focuses on the development of a simple, rapid, specific, and stability-indicating HPLC method for the simultaneous analysis of pyridostigmine bromide...
Stability indicating reversed-phase-high-performance liquid chromatography method development and validation for pyridostigmine bromide and sodium benzoate in oral solution.
The present study focuses on the development of a simple, rapid, specific, and stability-indicating HPLC method for the simultaneous analysis of pyridostigmine bromide (PGB) and sodium benzoate (SBN) in oral liquid dosage forms. Analytical techniques should enhance sensitivity and specificity for the estimation of pharmaceutical drug products. Stress studies were conducted under various International Conference on Harmonization (ICH) conditions for evaluation. The further optimized HPLC method was validated in accordance with the current ICH guidelines. Chromatographic separation was accomplished using a mobile phase consisting of a 950:50 v/v ratio of perchloric acid buffer and acetonitrile as mobile phase-A, and 100% acetonitrile as mobile phase-B. The flow rate is 1.0 mL/min, and the injection volume is 20 μL. Detection of components was carried out at 220 nm for PGB and 228 nm for SBN. The validated HPLC method demonstrated high specificity, with linearity ranging between 24 and 72 μg/mL for PGB and 5.2-15.6 μg/mL for SBN. The correlation coefficient for both drugs exceeded 0.999. The method demonstrated high accuracy, exceeding 97%. In stress studies, PGB was found to be sensitive to alkaline stress conditions. The results reveal the successful applicability of the current method for the estimation of PGB and SBN in its marketed formulation, which can be reasonably inferred to assess other formulation systems.
Topics: Sodium Benzoate; Chromatography, High Pressure Liquid; Pyridostigmine Bromide; Acetonitriles; Chromatography, Reverse-Phase; Drug Stability
PubMed: 38081595
DOI: 10.1002/bmc.5800 -
The American Journal of Case Reports Nov 2023BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is...
BACKGROUND Myasthenia gravis is a neuromuscular disorder that is strongly associated with thymoma. Although the presence of myasthenia gravis with other tumors is uncommon, approximately 50% of patients with thymoma have myasthenia gravis. Thymic Hodgkin lymphoma should be considered due to the multiple reported cases of patients with myasthenia gravis and Hodgkin lymphoma. In this report, we present the case of 24-year-old woman with myasthenia gravis who was incidentally found to have coexisting thymoma with thymic Hodgkin lymphoma. CASE REPORT A 24-year-old woman with a known case of vitiligo presented with a 2-year history of diplopia and incidental anterior mediastinal mass. Following investigations, myasthenia gravis was diagnosed and managed by pyridostigmine, prednisolone, and azathioprine. Regarding the anterior mediastinal mass, thymoma was suspected based on the presence of myasthenia gravis and radiological findings. She underwent extended transsternal thymectomy. The final histopathological report of the dissected thymus disclosed Hodgkin lymphoma pathology coexisting with thymoma. After the diagnosis of Hodgkin lymphoma nodular sclerosis type IIA was confirmed, 6 cycles of chemotherapy were administered. Four years of follow-up revealed no evidence of Hodgkin lymphoma. However, her symptoms of myasthenia gravis persisted despite Hodgkin lymphoma remission. CONCLUSIONS There is an unclear association between myasthenia gravies and Hodgkin lymphoma. Prior reports revealed regression of myasthenia gravies following Hodgkin lymphoma management, which suggests that myasthenia could be a complication of Hodgkin lymphoma. However, in our case, myasthenia gravis persisted after Hodgkin lymphoma management; therefore, further studies are needed to explore this association.
Topics: Female; Humans; Young Adult; Hodgkin Disease; Myasthenia Gravis; Pyridostigmine Bromide; Thymoma; Thymus Neoplasms
PubMed: 38006204
DOI: 10.12659/AJCR.941792 -
Brain Research Jan 2024Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting approximately 30 % of Veterans deployed to the Persian Gulf from 1990 to 91. GWI encompasses a wide...
Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting approximately 30 % of Veterans deployed to the Persian Gulf from 1990 to 91. GWI encompasses a wide spectrum of symptoms which frequently include neurological problems such as learning and memory impairments, mood disorders, and an increased incidence of neurodegenerative disorders. Combined exposure to both reversible and irreversible acetylcholinesterase (AChE) inhibitors has been identified as a likely risk factor for GWI. It is possible that the exposures affected connectivity in the brain, and it was also unknown whether this could benefit from treatment. We assessed chronic changes in dendritic architecture in granule cells of the dentate gyrus following exposure to pyridostigmine bromide (PB, 0.7 mg/kg), chlorpyrifos (CPF, 12.5 mg/kg), and N,N-diethyl-m-toluamide (DEET, 7.5 mg/kg) in male C57Bl/6J mice. We also evaluated the therapeutic effects of dietary administration for eight weeks of 1 % tert-butylhydroquinone (tBHQ), a Nrf2 activator, on long-term neuronal morphology. We found that Gulf War toxicant exposure resulted in reduced dendritic length and branching as well as overall spine density in dentate granule cells at 14 weeks post-exposure and that these effects were ameliorated by treatment with tBHQ. These findings indicate that Gulf War toxicant exposure results in chronic changes to dentate granule cell morphology and that modulation of neuroprotective transcription factors such as Nrf2 may improve long-term neuronal health in the hippocampus.
Topics: Mice; Animals; Male; NF-E2-Related Factor 2; Acetylcholinesterase; Gulf War; Persian Gulf Syndrome; Cholinesterase Inhibitors; Brain; Disease Models, Animal
PubMed: 37989436
DOI: 10.1016/j.brainres.2023.148682 -
Medicine Nov 2023Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG)...
RATIONALE
Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG) is an antibody-mediated and complement-involved acquired autoimmune disorder of the post-synaptic neuromuscular junction. There have been few reports about if there is related between the 2. In this study, we present the case of a man who was diagnosed as FOSMN with MG in continuity.
PATIENT CONCERNS
The patient chief complaints were right-side facial numbness and right-eyelid incomplete closure, followed by slurred speech and dysphagia, and the symptoms gradually progressed. The patient serum was positive for anti-AchR and anti-Titin antibodies.
DIAGNOSES
The patient was diagnosed FOSMN with MG.
INTERVENTIONS
The patient symptoms were relieved after pyridostigmine bromide and prednisolone treatment.
OUTCOMES
Symptoms have improved.
LESSONS
Facial-onset sensory and motor neuronopathy and MG have disparate clinical features. Therefore, we reported a rare case in which the 2 conditions concurrently existed. Immune dysfunction might be the pathogenesis of this association, while there is no definite evidence to support it, further studies are needed.
Topics: Male; Humans; Myasthenia Gravis; Pyridostigmine Bromide; Deglutition Disorders
PubMed: 37986404
DOI: 10.1097/MD.0000000000034215 -
PloS One 2023Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial... (Observational Study)
Observational Study
Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit-to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.
Topics: Humans; Adenosine Triphosphate; Biological Warfare Agents; DNA, Mitochondrial; Energy Metabolism; Gulf War; Leukocytes, Mononuclear; Persian Gulf Syndrome; Pesticides; Pyridostigmine Bromide; Veterans; Case-Control Studies
PubMed: 37910447
DOI: 10.1371/journal.pone.0287412 -
Acta Neurologica Taiwanica Jun 2024Myasthenia gravis (MG) is the most common autoimmune disease that affects the neuromuscular junction and can cause weakness in various muscle groups. The most commonly...
PURPOSE
Myasthenia gravis (MG) is the most common autoimmune disease that affects the neuromuscular junction and can cause weakness in various muscle groups. The most commonly affected muscles are the eye, facial, and neck flexors. Focal or dominant weakness of the triceps muscle is rare. In this case, we aimed to describe a rare form of MG consisting of selective or dominant triceps muscle weakness.
CASE REPORT
We present a 45-year-old male patient whose initial complaints were diplopia and ptosis. Acetylcholine receptor antibody was positive. After 10 years of well-being following thymectomy, bilateral triceps weakness was added to his ocular symptoms despite regular medication (pyridostigmine and prednisone). Repetitive nerve stimulation (RNS) showed decremental responses in the right triceps muscles.
CONCLUSION
It is important to recognize this type of myasthenia gravis to facilitate diagnosis and appropriate treatment and to avoid unnecessary investigations and treatments.
Topics: Male; Humans; Middle Aged; Myasthenia Gravis; Muscle Weakness; Muscle, Skeletal; Pyridostigmine Bromide; Blepharoptosis
PubMed: 37848221
DOI: No ID Found