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Medicina (Kaunas, Lithuania) Apr 2022: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to...
: As the use of sugammadex for reversing neuromuscular blockade during general anesthesia increases, additional effects of sugammadex have been reported compared to cholinesterase inhibitors. Here, we compare the incidence of postoperative catheter-related bladder discomfort (CRBD) between sugammadex and pyridostigmine/glycopyrrolate treatments for reversing neuromuscular blockade. : We retrospectively analyzed patients aged ≥ 18 years who underwent surgery under general anesthesia, received sugammadex or pyridostigmine with glycopyrrolate to reverse neuromuscular blockade, and had a urinary catheter in the post-anesthesia care unit between March 2019 and February 2021. After applying the exclusion criteria, 1179 patients were included in the final analysis. The incidence and severity of CRBD were collected from post-anesthesia recovery records. : The incidence was 13.7% in the sugammadex group ( = 211) and 24.7% in the pyridostigmine group ( = 968). Following propensity score matching, 211 patients each were included in the pyridostigmine and sugammadex matched group (absolute standardized difference (ASD), 0.01-0.05). Compared to the pyridostigmine group, the odds ratio for CRBD occurring in the sugammadex group was 0.568 (95% confidential interval, 0.316-1.021, = 0.059). : Sugammadex has a similar effect on the occurrence of postoperative CRBD compared with pyridostigmine.
Topics: Glycopyrrolate; Humans; Pyridostigmine Bromide; Retrospective Studies; Sugammadex; Urinary Bladder; Urinary Catheters
PubMed: 35630007
DOI: 10.3390/medicina58050590 -
Neurobiology of Stress May 2022Gulf War Illness (GWI) is a multi-symptom illness that continues to affect over 250,000 American Gulf War veterans. The causes of GWI remain equivocal; however,...
Gulf War Illness (GWI) is a multi-symptom illness that continues to affect over 250,000 American Gulf War veterans. The causes of GWI remain equivocal; however, prophylactic use of the acetylcholinesterase inhibitor pyridostigmine bromide (PB), and the stress of combat have been identified as two potential causative factors. Both PB and stress alter acetylcholine (ACh), which mediates both cognition and anti-inflammatory responses. As inflammation has been proposed to contribute to the cognitive deficits and immune dysregulation in GWI, the goal of this study was to determine the long-term effects of PB and stress on the cholinergic anti-inflammatory pathway in the central nervous system and periphery. We used our previously established rat model of GWI and microdialysis to assess cholinergic neurochemistry in the prefrontal cortex (PFC) and hippocampus following a mild immune challenge (lipopolysaccharide; LPS). We then examined LPS-induced changes in inflammatory markers in PFC and hippocampal homogenates. We found that PB treatment produces a long-lasting potentiation of the cholinergic response to LPS in both the PFC and hippocampus. Interestingly, this prolonged effect of PB treatment enhancing cholinergic responses to LPS was accompanied by paradoxical increases in the release of pro-inflammatory cytokines in these brain regions. Collectively, these findings provide evidence that neuroinflammation resulting from dysregulation of the cholinergic anti-inflammatory pathway is a mechanistic mediator in the progression of the neurochemical and neurocognitive deficits in GWI and more broadly suggest that dysregulation of this pathway may contribute to neuroinflammatory processes in stress-related neurological disorders.
PubMed: 35573808
DOI: 10.1016/j.ynstr.2022.100446 -
Chest Nov 2022Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its... (Randomized Controlled Trial)
Randomized Controlled Trial
Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.
BACKGROUND
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS.
RESEARCH QUESTION
Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity?
STUDY DESIGN AND METHODS
Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (Vo). Secondary end points included exercise pulmonary and systemic hemodynamics and gas exchange.
RESULTS
Twenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak Vo increased after pyridostigmine but decreased after placebo (13.3 ± 13.4 mL/min vs -40.2 ± 21.3 mL/min; P < .05). The treatment effect of pyridostigmine was 53.6 mL/min (95% CI, -105.2 to -2.0). Peak vs rest Vo (25.9 ± 15.3 mL/min vs -60.8 ± 25.6 mL/min; P < .01), cardiac output (-0.2 ± 0.6 L/min vs -1.9 ± 0.6 L/min; P < .05), and right atrial pressure (1.0 ± 0.5 mm Hg vs -0.6 ± 0.5 mm Hg; P < .05) were greater in the pyridostigmine group compared with placebo.
INTERPRETATION
Pyridostigmine improves peak Vo in ME/CFS by increasing cardiac output and right ventricular filling pressures. Worsening peak exercise Vo, cardiac output, and right atrial pressure following placebo may signal the onset of postexertional malaise. We suggest that treatable neurovascular dysregulation underlies acute exercise intolerance in ME/CFS.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov; No.: NCT03674541; URL: www.
CLINICALTRIALS
gov.
Topics: Humans; Fatigue Syndrome, Chronic; Pyridostigmine Bromide; Exercise; Exercise Test
PubMed: 35526605
DOI: 10.1016/j.chest.2022.04.146 -
Neurotoxicology May 2022Gulf War illness (GWI) is a chronic, multi-symptom disorder that has impacted approximately one third of Gulf War veterans. GWI and its symptoms have been linked to the...
Gulf War illness (GWI) is a chronic, multi-symptom disorder that has impacted approximately one third of Gulf War veterans. GWI and its symptoms have been linked to the exposure to neurological chemicals, including the anti-nerve gas drug pyridostigmine bromide (PB) and the insecticide permethrin (PER), among others. Mouse models utilizing these chemicals have reported symptomology analogous to human GWI. These changes include behavioral and cognitive impairment, neuroinflammation and hippocampal pathogenesis. Disease modifying interventions that target these pathological components are desperately needed. Vagus nerve stimulation (VNS) is FDA approved for drug-resistant epilepsy and depression. VNS has also been used off-label to target a myriad of symptoms, some of which are encompassed within the Kansas and CDC definitions of clinical GWI symptomology. A GWI animal model in which mice are exposed to a daily injection of PB and PER for 10 consecutive days has been shown to exhibit cognitive impairment and hippocampal pathology. The purpose of this study was to determine if 2-4 weeks of continuous vagus nerve stimulation initiated at 32 weeks after exposure to PB and PER would improve cognitive performance and hippocampal pathology. The results of the study revealed that exposure to PB and PER produces long-term cognitive deficits and reduced hippocampal neurogenesis. The results also showed that the VNS treatment was anxiolytic, improved some aspects of pattern separation deficits, and mitigated the reduced hippocampal neurogenesis. Thus, VNS improves outcomes in a mouse model of GWI and should be examined as a potential therapeutic strategy for mitigating some symptomology associated with GWI.
Topics: Animals; Disease Models, Animal; Gulf War; Mice; Neurogenesis; Permethrin; Persian Gulf Syndrome; Pyridostigmine Bromide; Vagus Nerve Stimulation
PubMed: 35421512
DOI: 10.1016/j.neuro.2022.04.001 -
Current Journal of Neurology Apr 2022Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD)...
Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD) is one of the most common complications after stroke. Despite a variety of behavioral, compensatory, and rehabilitative methods, many stroke patients still suffer from swallowing disorders that adversely affect their quality of life (QOL). The aim of this study was to evaluate the effect of pyridostigmine on patients with post-stroke dysphagia. A randomized, double-blind, placebo-controlled clinical trial was carried out on 40 patients suffering from post-stroke dysphagia. Patients were assigned randomly into two groups: intervention and control groups (20 in each group). The intervention group was treated with pyridostigmine (60 mg, three times a day, 30 minutes before each meal for three weeks), and the control group received placebo treatment in the same way. All patients (intervention and control) were evaluated according to National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Functional Communication Measures (FCM)American Speech-Language-Hearing Association (ASHA) criteria at baseline and after three weeks of intervention. Values of P < 0.05 were considered statistically significant. In the intervention group, the mean values of NIHSS, mRS, and ASHA/FCM were significantly reduced following three weeks of treatment with pyridostigmine (P = 0.002, P = 0.003, and P < 0.001, respectively), but no significant differences were found in the mean NIHSS, mRS, and ASHA/FCM in the placebo group. Although pyridogestamine is somewhat effective in post-stroke dysphagia, it has not been shown to be more important in preventing aspiration pneumonia and length of hospital stay.
PubMed: 38011458
DOI: 10.18502/cjn.v21i2.10493 -
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 -
American Journal of Ophthalmology Case... Jun 2022Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage. The aim of this study is to...
PURPOSE
Cerebrospinal fluid hypovolemia syndrome (CHS) is a rare clinical entity that can be caused by spontaneous cerebrospinal fluid (CSF) leakage. The aim of this study is to report a rare case of CHS after a traffic accident in a patient who presented with diplopia and ptosis with fluctuation and was initially diagnosed with ocular myasthenia gravis.
OBSERVEATIONS
A 29-year-old man exhibited fluctuating left ptosis and diplopia after a traffic accident. Although he was suspected of having myasthenia gravis and was treated using oral pyridostigmine bromide, his symptoms did not improve. He also had orthostatic headaches and malaise after the accident. His symptoms were suspected to be associated with traumatic cerebrospinal fluid hypovolemia. After 1000-mL fluid replacement, his diplopia and ptosis improved, and orbital T2-weghted MRI detected a high-signal zone around the optic nerve. We diagnosed him with oculomotor nerve paresis associated with cerebrospinal fluid hypovolemia. The symptoms, including ptosis, diplopia, orthostatic headaches, and malaise, disappeared after epidural blood patch therapy.
CONCLUSIONS AND IMPORTANCE
When treating patients with fluctuating ocular symptoms, such as diplopia and ptosis, who have a history of trauma and orthostatic headaches, the possibility of CHS should be considered in the differential diagnosis.
PubMed: 35313471
DOI: 10.1016/j.ajoc.2022.101478 -
Neurologia Mar 2023Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle...
INTRODUCTION
Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population.
OBJECTIVE
We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing.
MATERIAL AND METHODS
Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307 651, of whom 96 544 (31.4%) were aged ≥ 65 years.
RESULTS
We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases.
CONCLUSION
The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.
Topics: Humans; Spain; Retrospective Studies; Myasthenia Gravis; Prevalence; Incidence
PubMed: 35249845
DOI: 10.1016/j.nrleng.2020.06.013 -
BMC Neurology Mar 2022To investigate the clinical characteristics, treatments and outcomes of patients with myasthenia gravis with antibodies to muscle-specific tyrosine kinase (MuSK-MG).
BACKGROUND
To investigate the clinical characteristics, treatments and outcomes of patients with myasthenia gravis with antibodies to muscle-specific tyrosine kinase (MuSK-MG).
METHODS
We retrospectively reviewed the cases of 21 patients with confirmed MuSK-MG between January 2012 and January 2020 in our centre. Detailed clinical data and long-term follow-up information were summarized.
RESULTS
Females (17/21, 81%) predominated among these MuSK-MG patients, and the mean age of onset in this group was 51.86 ± 16.16 years. MuSK-MG patients were divided into three subgroups according to the symptoms of muscle weakness at onset: ocular myasthenia gravis (OMG, 47.6%), bulbar myasthenia gravis (BMG, 42.9%), and generalized myasthenia gravis (GMG, 9.5%). The mean progression time from symptom onset to other muscle group involvement in OMG patients was 4.38 ± 2.54 months. Pyridostigmine bromide was adopted in 81.0% of patients, and 90.5% of patients received corticosteroids. Compared to usage in hospitals, the median daily dose of corticosteroids decreased significantly at the last follow-up. A total of 85.7% of patients received a long-term follow-up, with an average time of 1202.17 ± 976.73 days. At the end of the follow-up period, 4.8% of patients had achieved complete stable remission, 42.9% of patients had minimal manifestations, 19.0% had improved, the condition of 4.8% of patients remained unchanged, and 9.5% of patients died.
CONCLUSION
Female patients were more prevalent in this study, and MuSK-MG patients rapidly progressed to a generalized state. Although approximately 50% of MuSK-MG patients can achieve a favourable outcome with conventional immunosuppressants, complete stable remission is rare, and approximately 15% respond poorly. More effective medications should be explored in these patients.
Topics: Adult; Aged; Autoantibodies; Fatty Acids, Monounsaturated; Female; Humans; Middle Aged; Myasthenia Gravis; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic; Retrospective Studies; Treatment Outcome
PubMed: 35246057
DOI: 10.1186/s12883-022-02593-6 -
Medicine Feb 2022Patients with myasthenia gravis may also have comorbid autoimmune diseases. Since both myasthenia gravis and neuromyelitis optica spectrum disease are mediated by...
RATIONALE
Patients with myasthenia gravis may also have comorbid autoimmune diseases. Since both myasthenia gravis and neuromyelitis optica spectrum disease are mediated by antibodies, they are likely to occur together. However, since multiple sclerosis is an autoimmune disease that is not mediated by a specific antibody, it has fewer immune mechanisms in common with myasthenia gravis than neuromyelitis optica spectrum disease. We encountered a case of newly developed multiple sclerosis in a patient with myasthenia gravis.
PATIENT CONCERNS
A 46-year-old man was diagnosed with ocular myasthenia gravis 6 years ago and had been taking pyridostigmine to control his symptoms.
DIAGNOSIS
The patient developed right optic neuritis, and multiple sclerosis was suspected based on the brain magnetic resonance imaging findings. However, the required diagnostic criteria were not met.
INTERVENTIONS
Disease-modifying therapy was not initiated, and clinical progression of the disease was monitored.
OUTCOMES
One year after the onset of optic neuritis, the patient developed myelitis and was diagnosed with multiple sclerosis, prompting treatment with disease-modifying therapy.
LESSONS
When optic neuritis occurs in patients with myasthenia gravis, careful evaluation is necessary while considering the possibility that it may be the first symptom of a demyelinating central nervous system disease. Therefore, it is important to conduct shorter-interval monitoring and symptom screening for patients with neurological autoimmune diseases, such as myasthenia gravis, even if multiple sclerosis is not initially suspected, to achieve early detection of multiple sclerosis.
Topics: Antibodies; Brain; Cholinesterase Inhibitors; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis; Myasthenia Gravis; Myelitis; Neuromyelitis Optica; Optic Neuritis; Pyridostigmine Bromide
PubMed: 35212290
DOI: 10.1097/MD.0000000000028887