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Brain Sciences Feb 2022Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of...
Association of Gulf War Illness-Related Symptoms with Military Exposures among 1990-1991 Gulf War Veterans Evaluated at the War-Related Illness and Injury Study Center (WRIISC).
Veterans with difficult-to-diagnose conditions who receive care in the Department of Veterans Affairs (VA) healthcare system can be referred for evaluation at one of three specialty VA War-Related Illness and Injury Study Centers (WRIISC). Veterans of the 1990−1991 Gulf War have long experienced excess rates of chronic symptoms associated with the condition known as Gulf War Illness (GWI), with hundreds evaluated at the WRIISC. Here we provide the first report from a cohort of 608 Gulf War Veterans seen at the WRIISC who completed questionnaires on chronic symptoms (>6 months) consistent with GWI as well as prominent exposures during Gulf War deployment. These included veterans’ reports of hearing chemical alarms/donning Military-Ordered Protective Posture Level 4 (MOPP4) gear, pesticide use, and use of pyridostigmine bromide (PB) pills as prophylaxis against the effects of nerve agents. Overall, veterans in the cohort were highly symptomatic and reported a high degree of exposures. In multivariable models, these exposures were significantly associated with moderate-to-severe chronic symptoms in neurocognitive/mood, fatigue/sleep, and pain domains. Specifically, exposure to pesticides was associated with problems with concentration and memory, problems sleeping, unrefreshing sleep, and joint pain. Use of MOPP4 was associated with light sensitivity and unrefreshing sleep and use of PB was associated with depression. We also evaluated the association of exposures with symptom summary scores based on veterans’ severity of symptoms in four domains and overall. In multivariable modeling, the pain symptom severity score was significantly associated with pesticide use (Odds ratio (OR): 4.13, 95% confidence intervals (CI): 1.78−9.57) and taking PB pills (OR: 2.28, 95% CI: 1.02−5.09), and overall symptom severity was significantly associated with use of PB pills (OR: 2.41, 95% CI: 1.01−5.75). Conclusion: Decades after deployment, Gulf War veterans referred to a VA tertiary evaluation center report a high burden of chronic symptoms, many of which were associated with reported neurotoxicant exposures during the war.
PubMed: 35326276
DOI: 10.3390/brainsci12030321 -
Thoracic Cancer Feb 2023To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period.
OBJECTIVE
To study the influencing factors of myasthenic crisis in patients with myasthenia gravis during perioperative period.
METHODS
A total of 564 myasthenia gravis (MG) patients who underwent standard expanded resection of thymoma/thymoma in the Department of Thoracic Surgery of Beijing Hospital from January 2011 to March 2022 were retrospectively included in the study. Clinical indicators such as gender, age, thymoma, American Society of Anesthesiologists (ASA) score, operation time, intraoperative blood loss, and some others were recorded.
RESULTS
Osserman-stages IIB + III + IV (odds ratio [OR] 16.091, 95% confidence interval [CI] 5.170-50.076, p value < 0.001), the dosage of pyridostigmine bromide more than 240 mg (OR 6.462, 95% CI 3.110-13.427, p value < 0.001), ASA score 2 and 3 (OR 3.203, 95% CI 1.461-7.020, p value = 0.004), low diffusion lung capacity for carbon monoxide (DLCO%) (OR 0.981, 95% CI 0.963-1.000 p value = 0.049), and blood loss greater than 1000 ml (OR 16.590, 95% CI 1.911-144.011, p value = 0.011) were independent risk factors for myasthenic crisis.
CONCLUSIONS
Patients with poor Osserman stages, higher preoperative dosage of pyridostigmine bromide, higher ASA score, poor pulmonary function (low DLCO%), and more intraoperative bleeding should be highly vigilant for the occurrence of postoperative myasthenic crisis.
Topics: Humans; Thymoma; Pyridostigmine Bromide; Retrospective Studies; Thymectomy; Postoperative Complications; Myasthenia Gravis; Thymus Neoplasms
PubMed: 36594520
DOI: 10.1111/1759-7714.14774 -
Journal of Medical Case Reports Oct 2021Autoimmune diseases refers to a class of diseases involving abnormal immune response of human body and tissue damage caused by the dysregulation of autoimmune balance or...
BACKGROUND
Autoimmune diseases refers to a class of diseases involving abnormal immune response of human body and tissue damage caused by the dysregulation of autoimmune balance or destruction of immune tolerance. Recent research has revealed that the occurrence of autoimmune diseases is influenced by genetic, hormonal, immunological, and environmental factors. As sex hormone levels change obviously during pregnancy and postpartum, the morbidity and recurrence rate of autoimmune diseases increase during this period.
CASE PRESENTATION
A 31-year-old Asian woman was admitted to our hospital for myasthenia gravis and treated with methylprednisolone and pyridostigmine bromide 3 months postpartum. Physical examination and laboratory inspection after admission suggested that the patient had primary biliary cirrhosis. Subsequently, azathioprine was added to the treatment, and the symptoms of both diseases were successfully controlled.
CONCLUSIONS
This case exhibits a rare condition of myasthenia gravis combined with primary biliary cirrhosis postpartum. Given the fluctuation of the immune status during the postpartum period, combined autoimmune diseases need to be taken into account when patients develop clinical symptoms of an autoimmune disease. Therefore, detailed physical and laboratory examination can help to prevent the missed diagnosis of these diseases.
Topics: Adult; Female; Humans; Liver Cirrhosis, Biliary; Myasthenia Gravis; Neoplasm Recurrence, Local; Postpartum Period; Pregnancy; Pyridostigmine Bromide
PubMed: 34627357
DOI: 10.1186/s13256-021-03092-x -
Neurotoxicology May 2023Gulf War Illness (GWI) is an unrelenting multi-symptom illness with chronic central nervous system and peripheral pathology affecting veterans from the 1991 Gulf War and...
Gulf War Illness (GWI) is an unrelenting multi-symptom illness with chronic central nervous system and peripheral pathology affecting veterans from the 1991 Gulf War and for which effective treatment is lacking. An increasing number of studies indicate that persistent neuroinflammation is likely the underlying cause of cognitive and mood dysfunction that affects veterans with GWI. We have previously reported that fingolimod, a drug approved for the treatment of relapsing-remitting multiple sclerosis, decreases neuroinflammation and improves cognition in a mouse model of Alzheimer's disease. In this study, we investigated the effect of fingolimod treatment on cognition and neuroinflammation in a mouse model of GWI. We exposed C57BL/6 J male mice to GWI-related chemicals pyridostigmine bromide, DEET, and permethrin, and to mild restraint stress for 28 days (GWI mice). Control mice were exposed to the chemicals' vehicle only. Starting 3 months post-exposure, half of the GWI mice and control mice were orally treated with fingolimod (1 mg/kg/day) for 1 month, and the other half were left untreated. Decreased memory on the Morris water maze test was detected in GWI mice compared to control mice and was reversed by fingolimod treatment. Immunohistochemical analysis of brain sections with antibodies to Iba1 and GFAP revealed that GWI mice had increased microglia activation in the hippocampal dentate gyrus, but no difference in reactive astrocytes was detected. The increased activation of microglia in GWI mice was decreased to the level in control mice by treatment with fingolimod. No effect of fingolimod treatment on gliosis in control mice was detected. To explore the signaling pathways by which decreased memory and increased neuroinflammation in GWI may be protected by fingolimod, we investigated the involvement of the inflammatory signaling pathways of protein kinase R (PKR) in the cerebral cortex of these mice. We found increased phosphorylation of PKR in the brain of GWI mice compared to controls, as well as increased phosphorylation of its most recognized downstream effectors: the α subunit of eukaryotic initiation factor 2 (eIF2α), IκB kinase (IKK), and the p65 subunit of nuclear factor-κB (NFκB-p65). Furthermore, we found that the increased phosphorylation level of these three proteins were suppressed in GWI mice treated with fingolimod. These results suggest that activation of PKR and NFκB signaling may be important for the regulation of cognition and neuroinflammation in the GWI condition and that fingolimod, a drug already approved for human use, may be a potential candidate for the treatment of GWI.
Topics: Animals; Male; Mice; Amnesia; Disease Models, Animal; Fingolimod Hydrochloride; Gulf War; Memory Disorders; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases; NF-kappa B; Persian Gulf Syndrome; Protein Kinases; Pyridostigmine Bromide
PubMed: 37160207
DOI: 10.1016/j.neuro.2023.05.006 -
Scientific Reports Nov 2021We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators...
We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.
Topics: Animals; Catechin; Dietary Supplements; Disease Models, Animal; Fatigue; Humans; Male; Metabolome; Muscle Development; Muscle, Skeletal; Muscular Atrophy; Persian Gulf Syndrome; Rats; Rats, Wistar
PubMed: 34750405
DOI: 10.1038/s41598-021-01093-w -
Journal of Cardiothoracic Surgery Jan 2023To study the influencing factors of myasthenic crisis in non-thymoma myasthenia gravis (MG) patients during perioperative period.
OBJECTIVE
To study the influencing factors of myasthenic crisis in non-thymoma myasthenia gravis (MG) patients during perioperative period.
METHODS
We retrospectively analyzed a total of 387 non-thymoma MG patients who underwent extended thymoma resection in the Department of Thoracic Surgery of Beijing Hospital from February 2011 to December 2021, recorded ASA score, Osserman classification, preoperative course, pyridostigmine dosage, operation method, operation time, and intraoperative blood loss, then analyzed the factors associated with postoperative myasthenic crisis by univariate and multivariate logistic regression.
RESULTS
Osserman classification IIB + III + IV (P < 0.001), history of myasthenic crisis (P = 0.013), pyridostigmine dosage greater than 240 (P < 0.001), ASA score 2 and 3 (P = 0.001) are independent risk factors for myasthenic crisis.
CONCLUSION
Patients with poor Osserman classification, history of myasthenic crisis before surgery, larger preoperative dosage of pyridostigmine, and higher ASA scores should be highly alert to the occurrence of postoperative myasthenic crisis.
Topics: Humans; Pyridostigmine Bromide; Retrospective Studies; Thymectomy; Postoperative Complications; Myasthenia Gravis; Thymoma; Thymus Neoplasms
PubMed: 36635776
DOI: 10.1186/s13019-023-02136-1 -
Toxicological Sciences : An Official... Aug 2019Acute intoxication with organophosphates (OPs) can trigger status epilepticus followed by persistent cognitive impairment and/or electroencephalographic abnormalities....
Acute intoxication with organophosphates (OPs) can trigger status epilepticus followed by persistent cognitive impairment and/or electroencephalographic abnormalities. Neuroinflammation is widely posited to influence these persistent neurological consequences. However, testing this hypothesis has been challenging, in part because traditional biometrics preclude longitudinal measures of neuroinflammation within the same animal. Therefore, we evaluated the performance of noninvasive positron emission tomography (PET), using the translocator protein (TSPO) radioligand [18F]PBR111 against classic histopathologic measures of neuroinflammation in a preclinical model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im) and 2-pralidoxime (25 mg/kg, im) exhibited moderate-to-severe seizure behavior. TSPO PET performed prior to DFP exposure and at 3, 7, 14, 21, and 28 days postexposure revealed distinct lesions, as defined by increased standardized uptake values (SUV). Increased SUV showed high spatial correspondence to immunohistochemical evidence of neuroinflammation, which was corroborated by cytokine gene and protein expression. Regional SUV metrics varied spatiotemporally with days postexposure and correlated with the degree of neuroinflammation detected immunohistochemically. Furthermore, SUV metrics were highly correlated with seizure severity, suggesting that early termination of OP-induced seizures may be critical for attenuating subsequent neuroinflammatory responses. Normalization of SUV values to a cerebellar reference region improved correlations to all outcome measures and seizure severity. Collectively, these results establish TSPO PET using [18F]PBR111 as a robust, noninvasive tool for longitudinal monitoring of neuroinflammation following acute OP intoxication.
Topics: Animals; Carrier Proteins; Chemokines; Cytokines; Fluorine Radioisotopes; Inflammation; Isoflurophate; Male; Neurotoxicity Syndromes; Positron-Emission Tomography; Rats; Rats, Sprague-Dawley; Receptors, GABA-A
PubMed: 31087103
DOI: 10.1093/toxsci/kfz096 -
Frontiers in Immunology 2024Though it has been over 30 years since the 1990-1991 Gulf War (GW), the pathophysiology of Gulf War Illness (GWI), the complex, progressive illness affecting... (Review)
Review
Though it has been over 30 years since the 1990-1991 Gulf War (GW), the pathophysiology of Gulf War Illness (GWI), the complex, progressive illness affecting approximately 30% of GW Veterans, has not been fully characterized. While the symptomology of GWI is broad, many symptoms can be attributed to immune and endocrine dysfunction as these critical responses appear to be dysregulated in many GWI patients. Since such dysregulation emerges in response to immune threats or stressful situations, it is unsurprising that clinical studies suggest that GWI may present with a latent phenotype. This is most often observed in studies that include an exercise challenge during which many GWI patients experience an exacerbation of symptoms. Unfortunately, very few preclinical studies include such physiological stressors when assessing their experimental models of GWI, which creates variable results that hinder the elucidation of the mechanisms mediating GWI. Thus, the purpose of this review is to highlight the clinical and preclinical findings that investigate the inflammatory component of GWI and support the concept that GWI may be characterized as having a latent phenotype. We will mainly focus on studies assessing the progressive cognitive impairments associated with GWI and emphasize the need for physiological stressors in future work to create a more unified hypothesis that can identify potential therapeutics for this patient population.
Topics: Humans; Persian Gulf Syndrome; Cognitive Dysfunction; Phenotype; Animals
PubMed: 38919622
DOI: 10.3389/fimmu.2024.1403574 -
BMJ Case Reports May 2021An 88-year-old male patient presented with left ptosis, diplopia, muscle weakness of the lower limbs, dysphagia for solids, dysphonia and constipation. On investigation,...
An 88-year-old male patient presented with left ptosis, diplopia, muscle weakness of the lower limbs, dysphagia for solids, dysphonia and constipation. On investigation, he was found to have myasthenia gravis (MG). Further evaluation for the possible cause of MG, with CT scan, revealed that the patient had concomitant prostatic cancer. The patient was given steroids and pyridostigmine, with consequent resolution of his neurological symptoms. This is a rare case of MG associated with prostatic cancer.
Topics: Aged, 80 and over; Blepharoptosis; Diplopia; Humans; Male; Myasthenia Gravis; Prostatic Neoplasms; Pyridostigmine Bromide
PubMed: 34020991
DOI: 10.1136/bcr-2021-242416 -
Journal of Cardiothoracic Surgery Sep 2020Despite the burgeoning literature describing preoperative and postoperative risks of a myasthenic crisis after thymectomy (MCAT) in patients with myasthenia gravis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the burgeoning literature describing preoperative and postoperative risks of a myasthenic crisis after thymectomy (MCAT) in patients with myasthenia gravis, substantial differences exist in the risk factors identified by previous studies. We conducted a meta-analysis to assess the reported risk factors and MCAT risk.
METHODS
We collected relevant studies on the risk factors for MCAT by searching the PubMed, Embase, The Cochrane Library, China Biology Medicine (CBM), WanFang Data, VIP and CNKI databases. The search period ranged from the establishment of the database to November 2019.
RESULTS
Twenty-five of the 458 identified studies were eligible for the meta-analysis. Seven retrospective cohort studies and 18 case-control studies were included, and 14 risk factors for MCAT were extracted. Meta-analyses of the association between MCAT and risk factors related to the patient's preoperative condition included a preoperative history of MC, preoperative bulbar symptoms, IIa + IIb + III + VI, IIb + III + VI, VI + V, dosage of pyridostigmine bromide prior to the operation, a preoperative AchR-Ab level > 100 (nm/L), preoperative pulmonary function, preoperative complications, and preoperative disease course. Meta-analyses of the association between MCAT and surgery-related risk factors included intraoperative blood loss > 1000 mL and the mode of operation. Meta-analyses of the association between MCAT and postoperative risk factors included postoperative lung infection, thymoma and the WHO classification. The operation time was not an independent risk factor for MCAT.
CONCLUSIONS
The independent risk factors for MCAT were a preoperative history of MC, preoperative bulbar symptoms, preoperative MG Osserman stage, preoperative dosage of pyridostigmine bromide, preoperative serum AchR-Ab level, lung function, major postoperative complications, disease duration before thymectomy, blood loss, thoracotomy, postoperative lung infection, thymoma, and WHO classification.
Topics: Blood Loss, Surgical; Databases, Factual; Female; Humans; Male; Myasthenia Gravis; Operative Time; Postoperative Complications; Risk Factors; Thymectomy
PubMed: 32993739
DOI: 10.1186/s13019-020-01320-x