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Journal of Clinical Medicine Mar 2023To examine associations between the pyridostigmine bromide (PB) pill and/or pesticide exposure during the 1990-1991 Gulf War (GW) and eye findings years after...
To examine associations between the pyridostigmine bromide (PB) pill and/or pesticide exposure during the 1990-1991 Gulf War (GW) and eye findings years after deployment. A cross-sectional study of South Florida veterans who were deployed on active duty during the GW Era (GWE). Information on GW exposures and ocular surface symptoms were collected via standardized questionnaires and an ocular surface examination was performed. Participants underwent spectral domain-ocular coherence tomography (SD-OCT) imaging that included retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and macular maps. We examined for differences in eye findings between individuals exposed versus not exposed to PB pills or pesticides during service. A total of 40.7% (n = 44) of individuals reported exposure to PB pills and 41.7% (n = 45) to pesticides; additionally, 24 reported exposure to both in the GW arena. Demographics were comparable across groups. Individuals exposed to PB pills reported higher dry eye (DE) symptoms scores (the 5-Item Dry Eye Questionnaire, DEQ-5: 9.3 ± 5.3 vs. 7.3 ± 4.7, = 0.04) and more intense ocular pain (average over the last week: 2.4 ± 2.6 vs. 1.5 ± 1.8, = 0.03; Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E): 18.2 ± 20.0 vs. 10.8 ± 13.8, = 0.03) compared to their non-exposed counterparts. DE signs were comparable between the groups. Individuals exposed to PB pills also had thicker OCT measurements, with the largest difference in the outer temporal segment of the macula (268.5 ± 22.2 μm vs. 260.6 ± 14.5 μm, = 0.03) compared to non-exposed individuals. These differences remained significant when examined in multivariable models that included demographics and deployment history. Individuals exposed to pesticides had higher neuropathic ocular pain scores (NPSI-E: 17.1 ± 21.1 vs. 11.6 ± 12.9, = 0.049), but this difference did not remain significant in a multivariable model. Individuals exposed to PB pills during the GWE reported more severe ocular surface symptoms and had thicker OCT measures years after deployment compared to their non-exposed counterparts.
PubMed: 36983407
DOI: 10.3390/jcm12062407 -
International Journal of Environmental... Feb 2023(1) Background: Early thymectomy is suggested in all clinically indicated myasthenia gravis (MG) patients. However, short-term clinical response after thymectomy in MG...
(1) Background: Early thymectomy is suggested in all clinically indicated myasthenia gravis (MG) patients. However, short-term clinical response after thymectomy in MG patients has been limitedly described in the literature. This study aimed to compare the 5-year post-thymectomy outcomes between thymoma (Th) and non-thymoma (non-Th) MG patients. (2) Methods: MG patients aged ≥18 years who underwent transsternal thymectomy and had tissue histopathology reports in Songklanagarind Hospital between 2002 and 2020 were enrolled in a retrospective review. The differences in the baseline demographics and clinical characteristics between ThMG and non-Th MG patients were studied. We compared the time-weighted averages (TWAs) of daily required dosages of pyridostigmine, prednisolone or azathioprine to efficiently maintain daily living activities and earnings between the MG patient groups during 5 consecutive years following thymectomy. Post-thymectomy clinical status, exacerbations or crises were followed. Descriptive statistics were used for analysis with statistical significance set at < 0.05. (3) Results: ThMG patients had significantly older ages of onset and shorter times from the MG diagnosis to thymectomy. Male gender was the only significant factor associated with ThMG. TWAs of the daily MG treatment drug dosages required showed no differences between the groups. Additionally, the rates of exacerbations and crises were not different, but decremental trends were shown in both groups after the thymectomies. (4) Conclusions: The daily dosage requirements of MG treatment drugs were not different. There was a trend of decreasing adverse event rates despite no statistically significant differences during the first 5 years after thymectomy in ThMG and non-ThMG patients.
Topics: Humans; Male; Adolescent; Adult; Thymectomy; Thymus Neoplasms; Myasthenia Gravis; Pyridostigmine Bromide; Retrospective Studies; Treatment Outcome
PubMed: 36833734
DOI: 10.3390/ijerph20043039 -
Journal of Cellular and Molecular... Apr 2023Gulf War Illness (GWI) has been reported in 25%-35% of veterans returned from the Gulf war. Symptoms of GWI are varied and include both neurological and gastrointestinal... (Review)
Review
Gulf War Illness (GWI) has been reported in 25%-35% of veterans returned from the Gulf war. Symptoms of GWI are varied and include both neurological and gastrointestinal symptoms as well as chronic fatigue. Development of GWI has been associated with chemical exposure particularly with exposure to pyridostigmine bromide (PB) and permethrin. Recent studies have found that the pathology of GWI is connected to changes in the gut microbiota, that is the gut dysbiosis. In studies using animal models, the exposure to PB and permethrin resulted in similar changes in the gut microbiome as these found in GW veterans with GWI. Studies using animal models have also shown that phytochemicals like curcumin are beneficial in reducing the symptoms and that the extracellular vesicles (EV) released from gut bacteria and from the intestinal epithelium can both promote diseases and suppress diseases through the intercellular communication mechanisms. The intestinal epithelium cells produce EVs and these EVs of intestinal epithelium origin are found to suppress inflammatory bowel disease severity, suggesting the benefits of utilizing EV in treatments. On the contrary, EV from the plasma of septic mice enhanced the level of proinflammatory cytokines in vitro and neutrophils and macrophages in vivo, suggesting differences in the EV depending on the types of cells they were originated and/or influences of environmental changes. These studies suggest that targeting the EV that specifically have positive influences may become a new therapeutic strategy in the treatment of veterans with GWI.
Topics: Mice; Animals; Permethrin; Gastrointestinal Microbiome; Dysbiosis; Gulf War; Persian Gulf Syndrome; Pyridostigmine Bromide; Disease Models, Animal
PubMed: 36716094
DOI: 10.1111/jcmm.17631 -
Acta Neurologica Belgica Apr 2023As new treatments are becoming available for patients with myasthenia gravis (MG), it is worth reflecting on the actual status of MG treatment to determine which... (Review)
Review
INTRODUCTION
As new treatments are becoming available for patients with myasthenia gravis (MG), it is worth reflecting on the actual status of MG treatment to determine which patients would most likely benefit from the new treatments.
METHODS
We reviewed the clinical files of all MG patients seen at the Department of Neurology of the Antwerp University Hospital during the years 2019, 2020 and 2021.
RESULTS
163 patients were included. Age at diagnosis varied from the first to the eighth decades, with a peak of incidence from 60 to 70 years for both genders, and an additional peak from 20 to 30 years in women. Diplopia and ptosis were by far the most common onset symptom. At maximum disease severity, 24% of the patients still had purely ocular symptoms and 4% needed mechanical ventilation. 97% of the patients received a treatment with pyridostigmine and 68% with corticosteroids, often in combination with immunosuppressants. More than half reported side effects. At the latest visit, 50% of the patients were symptom-free. Also, half of the symptomatic patients were fulltime at work or retired with no or mild limitations in daily living. The remaining patients were working part-time, on sick leave, or retired with severe limitations.
DISCUSSION AND CONCLUSION
The majority of MG patients are doing well with currently available treatments, but often at the cost of side effects in the short and in the long term. A significant group is in need of better treatments.
Topics: Humans; Female; Male; Belgium; Myasthenia Gravis; Pyridostigmine Bromide; Blepharoptosis; Diplopia
PubMed: 36658451
DOI: 10.1007/s13760-023-02187-0 -
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 -
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 -
Computational and Structural... 2022Gulf War Illness (GWI) is a chronic illness that affects upward of 32% of deployed Veterans to the 1991 Gulf War (GW). The symptoms are medically unexplained, ranging...
Gulf War Illness (GWI) is a chronic illness that affects upward of 32% of deployed Veterans to the 1991 Gulf War (GW). The symptoms are medically unexplained, ranging across cognitive deficits, fatigue, gastrointestinal problems, and musculoskeletal pain. Research indicates that chemical warfare agents play a key role in the onset and progression of GWI. The Khamisiyah ammunition storage that housed chemical warfare agents such as sarin, an acetylcholinesterase (AChE) inhibitor, was demolished during the GW, releasing toxicants into the atmosphere affecting deployed troops. Exposure to other chemical agents such as pyridostigmine bromide, N,N-diethyl-m-toluamide, permethrin and chlorpyrifos, were also prevalent during the war. These additional chemical agents have also been shown to inhibit AChE. AChE inhibition induces an acetylcholine build-up, disrupting signals between nerves and muscles, which in high doses leads to asphyxiation. Little is known about low dose exposure. As bioactive compounds tend to interact with multiple proteins with various physiological effect, we aimed to identify other potential shared targets to understand the extent in which these chemicals could lead to GWI. We followed a reverse screening approach where each chemical is computationally docked to a library of protein targets. The programs PharmMapper and TargetNet were used for this purpose, and further analyses were conducted to mark significant changes in participants with GWI. Previously published work on DNA methylation status in GWI was reanalyzed focusing specifically on the predicted shared targets indicating significant changes in DNA methylation of the associated genes. Our findings thus suggest that exposure to GWI-related agents may converge on similar targets with roles in inflammation, neurotransmitter and lipid metabolism, and detoxification which may have impacts on neurodegenerative-like disease and oxidative stress in Veterans with GWI.
PubMed: 36420170
DOI: 10.1016/j.csbj.2022.11.006 -
Brain, Behavior, & Immunity - Health Dec 2022Chemical overexposures and war-related stress during the 1990-1991 Gulf War (GW) are implicated in the persisting pathological symptoms that many GW veterans continue to...
Chemical overexposures and war-related stress during the 1990-1991 Gulf War (GW) are implicated in the persisting pathological symptoms that many GW veterans continue to endure. These symptoms culminate into a disease known as Gulf War Illness (GWI) and affect about a third of the GW veteran population. Currently, comprehensive effective GWI treatment options are unavailable. Here, an established GWI mouse model was utilized to explore the (1) long-term behavioral and neuroinflammatory effects of deployment-related GWI chemicals exposure and (2) ability of the immunotherapeutic lacto-N-fucopentaose III (LNFPIII) to improve deficits when given months after the end of exposure. Male C57BL6/J mice (8-9 weeks old) were administered pyridostigmine bromide (PB) and DEET for 14 days along with corticosterone (CORT; latter 7 days) to emulate wartime stress. On day 15, a single injection of the nerve agent surrogate diisopropylfluorophosphate (DFP) was given. LNFPIII treatment began 7 months post GWI chemicals exposure and continued until study completion. A battery of behavioral tests for assessment of cognition/memory, mood, and motor function in rodents was performed beginning 8 months after exposure termination and was then followed by immunohistochemcal evaluation of neuroinflammation and neurogenesis. Within tests of motor function, prior GWI chemical exposure led to hyperactivity, impaired sensorimotor function, and altered gait. LNFPIII attenuated these motor-related deficits and improved overall grip strength. GWI mice also exhibited more anxiety-like behavior that was reduced by LNFPIII; this was test-specific. Short-term, but not long-term memory, was impaired by prior GWI exposure; LNFPIII improved this measure. In the brains of GWI mice, but not in mice treated with LNFPIII, glial activation was increased. Overall, it appears that months after exposure to GWI chemicals, behavioral deficits and neuroinflammation are present. Many of these deficits were attenuated by LNFPIII when treatment began long after GWI chemical exposure termination, highlighting its therapeutic potential for veterans with GWI.
PubMed: 36405424
DOI: 10.1016/j.bbih.2022.100553 -
BMC Neurology Nov 2022Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive hereditary neuromuscular disorder caused by the expanded trinucleotide repeat in the androgen...
BACKGROUND
Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive hereditary neuromuscular disorder caused by the expanded trinucleotide repeat in the androgen receptors gene. The major clinical manifestations of SBMA consist of weakness in the bulbar and limb muscles, fasciculations, tremors, cramps, sensory impairment, and gynecomastia. However, atypical SBMA cases may lead to misdiagnosis. Muscular fatigue and decremental responses to repetitive nerve stimulation (RNS), despite being observed in some SBMA patients, are usually occurred in MG patients, and patient with the symptom of mastication fatigue was rarely reported. In addition, cardiological investigations have been performed in SBMA patients and several ECG alterations were identified. Here we report an SBMA patient presenting with a rare onset symptom of mastication fatigue, who has been detected with a positive titin antibody in the serum and showed a WPW pattern electrocardiogram.
CASE PRESENTATION
The patient showed mildly progressive fatigue in the muscles of mastication over 3 years. Neurological examination showed facial muscle weakness and a wasting tongue with fasciculations, but the weakness, wasting, or fasciculations were not obvious in the limbs. 3-Hz RNS showed a decremental response in bilateral orbicularis oculi. The test of titin antibody was positive in the serum, and the electrocardiogram showed a WPW pattern ECG. Genetic analysis revealed an increased number (39 repeats) of tandem CAG repeats in the AR gene, which confirmed the diagnosis of SBMA. The fatigue symptom was significantly improved after oral pyridostigmine bromide treatment.
CONCLUSION
This case calls for more attention to muscular fatigue as the onset symptoms of Kennedy's disease. ECG screening is of importance in SBMA patients and further studies are needed to investigate the titin antibody in SBMA patients as well as other neurogenic disorders.
Topics: Humans; Male; Bulbo-Spinal Atrophy, X-Linked; Connectin; Mastication; Fasciculation; Muscular Atrophy, Spinal; Fatigue
PubMed: 36376797
DOI: 10.1186/s12883-022-02971-0