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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 -
Journal of Neuro-ophthalmology : the... Mar 2022Myasthenia gravis (MG) is an autoimmune disorder involving neuromuscular junctions and more than half of MG patients manifested with extraocular muscle weakness...
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disorder involving neuromuscular junctions and more than half of MG patients manifested with extraocular muscle weakness initially. In the remained patients, ocular weakness may occur later in the course of the disease. However, little data are available about ocular involvement in such patients. Therefore, the study aims to investigate ocular weakness in MG patients with nonocular onset and evaluate the associated factors influencing it.
METHODS
In our monocentric retrospective study, 54 adult-onset patients with MG with nonocular onset were included and were followed up for at least 2 years from the onset. The primary outcome was the occurrence of ptosis, diplopia, or both. Kaplan-Meier analysis was performed to estimate the time to the ocular weakness, and log-rank tests were used to analyze the association between clinical characteristics and ocular weakness. Multivariate Cox proportional hazards regression models were used to identify factors associated with ocular involvement.
RESULTS
A total of 47 (87.0%) patients developed ocular weakness during the study period. The median time to ocular weakness was 6.0 months. Time to the ocular involvement was earlier in patients with bulbar onset (P = 0.007), whereas patients receiving pyridostigmine monotherapy and immunomodulatory therapy had a longer median time of ocular weakness (P < 0.0001). No significant difference was noted between ocular weakness and age of onset, gender, and thymoma. The Cox analysis showed that bulbar onset was a risk factor of ocular weakness (adjusted hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.41-4.99), whereas pyridostigmine monotherapy (adjusted HR 0.28, 95% CI 0.13-0.60) and immunotherapy (adjusted HR 0.09, 95% CI 0.04-0.22) were protective factors.
CONCLUSIONS
Eighty-seven percent of patients with MG with nonocular onset developed ocular weakness. Bulbar onset was an independent risk factor for ocular involvement, whereas pyridostigmine and immunotherapy were protective factors.
Topics: Adult; Blepharoptosis; Humans; Muscles; Myasthenia Gravis; Pyridostigmine Bromide; Retrospective Studies
PubMed: 34369469
DOI: 10.1097/WNO.0000000000001325 -
Dysphagia Feb 2022Weak or absent peristalsis of the esophageal musculature is a common finding in ambulatory patients suffering from dysphagia and frequently associated with...
Weak or absent peristalsis of the esophageal musculature is a common finding in ambulatory patients suffering from dysphagia and frequently associated with gastroesophageal reflux. There is currently no pharmacologic intervention that reliably improves esophageal contractility in patients suffering from various esophageal motility disorders. Our objective was to evaluate the acute effects of pyridostigmine on high-resolution manometry parameters in patients suffering from dysphagia with evidence of esophageal dysmotility. Pyridostigmine is an acetylcholinesterase inhibitor which increases effective concentrations of acetylcholine at the neuromuscular junction of both striated and smooth muscle cells. We conducted a prospective crossover study of five patients with dysphagia and proven esophageal dysmotility. Three patients had baseline ineffective esophageal motility and two had achalasia. Patients underwent pharyngeal and esophageal manometry before and after pyridostigmine administration. The median distal contractile integral (DCI), a marker of esophageal contractile vigor, was significantly higher post pyridostigmine administration 3001 (1950.3-3703.2) mmHg × s × cm compared to pre-pyridostigmine DCI of 1229.9 (956.2-2100) mmHg × s × cm; P < 0.001. Pre-pyridostigmine 18/25 (72%) of the patient's swallows was peristaltic compared to 25/25 (100%) post-pyridostigmine; P < 0.005. No other pharyngeal or esophageal high-resolution manometry parameter differed significantly after pyridostigmine administration. The results of this pilot study demonstrate that pyridostigmine acutely improves esophageal contractile vigor in patients suffering from dysphagia with esophageal dysmotility. Further investigation with larger sample size, longer follow-up, side effect profile, and patient-reported outcome measures is still needed to determine the clinical usefulness of pyridostigmine in specific disorders of esophageal motility.
Topics: Acetylcholinesterase; Cross-Over Studies; Esophageal Motility Disorders; Humans; Manometry; Peristalsis; Pilot Projects; Prospective Studies; Pyridostigmine Bromide
PubMed: 33452552
DOI: 10.1007/s00455-020-10243-7 -
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 -
Life Sciences Jan 2022To characterize neuroinflammatory and gut dysbiosis signatures that accompany exaggerated exercise fatigue and cognitive/mood deficits in a mouse model of Gulf War...
Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment.
AIMS
To characterize neuroinflammatory and gut dysbiosis signatures that accompany exaggerated exercise fatigue and cognitive/mood deficits in a mouse model of Gulf War Illness (GWI).
METHODS
Adult male C57Bl/6N mice were exposed for 28 d (5 d/wk) to pyridostigmine bromide (P.O.) at 6.5 mg/kg/d, b.i.d. (GW1) or 8.7 mg/kg/d, q.d. (GW2); topical permethrin (1.3 mg/kg), topical N,N-diethyl-meta-toluamide (33%) and restraint stress (5 min). Animals were phenotypically evaluated as described in an accompanying article [124] and sacrificed at 6.6 months post-treatment (PT) to allow measurement of brain neuroinflammation/neuropathic pain gene expression, hippocampal glial fibrillary acidic protein, brain Interleukin-6, gut dysbiosis and serum endotoxin.
KEY FINDINGS
Compared to GW1, GW2 showed a more intense neuroinflammatory transcriptional signature relative to sham stress controls. Interleukin-6 was elevated in GW2 and astrogliosis in hippocampal CA1 was seen in both GW groups. Beta-diversity PCoA using weighted Unifrac revealed that gut microbial communities changed after exposure to GW2 at PT188. Both GW1 and GW2 displayed systemic endotoxemia, suggesting a gut-brain mechanism underlies the neuropathological signatures. Using germ-free mice, probiotic supplementation with Lactobacillus reuteri produced less gut permeability than microbiota transplantation using GW2 feces.
SIGNIFICANCE
Our findings demonstrate that GW agents dose-dependently induce differential neuropathology and gut dysbiosis associated with cognitive, exercise fatigue and mood GWI phenotypes. Establishment of a comprehensive animal model that recapitulates multiple GWI symptom domains and neuroinflammation has significant implications for uncovering pathophysiology, improving diagnosis and treatment for GWI.
Topics: Animals; Biomarkers; Cholinesterase Inhibitors; Cognitive Dysfunction; Disease Models, Animal; Dose-Response Relationship, Drug; Dysbiosis; Endotoxemia; Fatigue; Gastrointestinal Microbiome; Gene Expression Profiling; Gene Expression Regulation; Gliosis; Male; Mice; Mice, Inbred C57BL; Neuralgia; Neuroinflammatory Diseases; Persian Gulf Syndrome; Physical Conditioning, Animal; Pyridostigmine Bromide
PubMed: 34801513
DOI: 10.1016/j.lfs.2021.120153 -
Minerva Ginecologica Feb 2020Myasthaenia gravis (MG) is the most common disease of the neuromuscular junction; clinical presentation of the disease includes a variety of symptoms, the most frequent...
INTRODUCTION
Myasthaenia gravis (MG) is the most common disease of the neuromuscular junction; clinical presentation of the disease includes a variety of symptoms, the most frequent beign the only ocular muscles involvement, to the generalized myasthenic crisis with diaphragmatic impairment and respiratory insufficiency. It is most common in women between 20 ad 40 years.
EVIDENCE ACQUISITION
We performed a comprehensive search of relevant studies from January1990 to Dicember 2019 to ensure all possible studies were captured. A systematic search of Pubmed databases was conducted.
EVIDENCE SYNTHESIS
Pregnancy has an unpredictable and variable effect on the clinical course of MG; however, a stable disease before is likely not to relapse during pregnancy. exacerbations can still occur more often during the first trimester and the post partum period. The transplacental passage of antibodies results in a neonatal transient disease, whereas the major concern is related to foetal malformations such as fetal arthrogryposis and polyhydramnios. The overall neonatal outcome described in literature is variable, perinatal mortality in women with MG is generally the same as non affected patients, although in one study the risk of premature rupture of the membranes was higher. Treatment of MG in pregnangncy includes pyridostigmine and corticosteroids, although the latter have been associated with higher risk of cleft palate, premature rupture of the membranes and preterm delivery. These drugs appear also to be safe in breastfeeding. In MG patients spontaneous vaginal delivery should be encouraged, for surgery could cause acute worsening of myasthenic symptoms; also an accurate anesthesiological evaluation must be performed prior to both general and local anesthesia due to increased risk of complications.
CONCLUSIONS
Most of the myasthenic women could have uneventful pregnancy with good obstetrical outcomes, both for mother and neonate. However, a careful planning of pregnancy and multidisciplinary team approach, composed by neurologists, obstetricians, neonatologists and anesthesiologists, is required to manage these pregnancies.
Topics: Adrenal Cortex Hormones; Arthrogryposis; Breast Feeding; Cholinesterase Inhibitors; Cleft Palate; Congenital Abnormalities; Delivery, Obstetric; Disease Progression; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Myasthenia Gravis; Patient Care Team; Perinatal Mortality; Polyhydramnios; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pyridostigmine Bromide; Recurrence
PubMed: 32153161
DOI: 10.23736/S0026-4784.20.04505-0 -
Neurotoxicology Sep 2020Shortly after the Gulf War in 1990-1991, service men and women began reporting multiple symptoms ranging from persistent headaches, widespread pain, chronic fatigue,... (Review)
Review
Shortly after the Gulf War in 1990-1991, service men and women began reporting multiple symptoms ranging from persistent headaches, widespread pain, chronic fatigue, cognitive dysfunction, mood dysregulation, gastrointestinal issues, skin abnormalities, and respiratory problems. This prompted the Centers for Disease Control and Prevention (CDC) to initially classify the disorder as chronic multi-symptom illness (CMI), where it later became known as Gulf War Illness (GWI). Researchers and healthcare professionals since the early 1990s have been working extensively on alleviating the symptoms expressed in GWI as well as attempting to understand the mechanisms behind this illness. Scientific literature as well as reports from GWI veterans indicate that the toxic exposures during deployment may be responsible for the symptoms. These toxic exposures potentially include nerve agents, pyridostigmine bromide pills, pesticides, munitions with depleted uranium, and burning oil well fires. GWI currently affects 25-32 % of the 697,000 American troops who were stationed overseas during the short conflict. The purpose of this paper is to review the literature on neurotoxic exposures in Gulf War Illness, to explain how these exposures may lead to glutamate excitotoxicity, which has been implicated in the majority of the symptoms characterizing the illness, and to propose a novel treatment option for GWI.
Topics: Animals; Brain; Glutamic Acid; Humans; Neurotoxicity Syndromes; Oxidative Stress; Persian Gulf Syndrome; Risk Factors; Up-Regulation; Veterans Health
PubMed: 32585289
DOI: 10.1016/j.neuro.2020.06.008 -
Medicine Jun 2021To investigate clinical features and diagnosis process of ocular myasthenia gravis (OMG) in ophthalmology department.A total of 36 patients with ptosis or diplopia who... (Observational Study)
Observational Study
To investigate clinical features and diagnosis process of ocular myasthenia gravis (OMG) in ophthalmology department.A total of 36 patients with ptosis or diplopia who had follow-up for at least 3 months between March 2016 and December 2019 were included in this study. Clinical symptoms of patients and the test results were analyzed. According to the positivity of serologic test, these patients were divided into 2 groups (confirmed OMG and possible OMG with relief of symptoms after antimyasthenic treatment) for comparison.Ptosis was present in 12 (33.33%) patients, diplopia was present in 14 (38.89%) patients, and both ptosis and diplopia were present in 10 (27.78%) patients. Acetylcholine receptor auto-antibody (AchR Ab) was positive in 14 (38.89%) of 36 patients and ice test was positive in 15 (71.43%) of 21 patients with ptosis. Unequivocal response to pyridostigmine was observed in 31 (86.11%) patients. For seropositive cases, AchR Ab titer was significantly higher in the group with 2 clinical symptoms than that in the 1 clinical symptom (P = .011).This study presents the usefulness and diagnostic validity of antimyasthenic treatment for OMG, especially seronegative OMG, with detailed symptom analysis.
Topics: Adult; Aged; Autoantibodies; Blepharoptosis; Cholinesterase Inhibitors; Diagnosis, Differential; Diplopia; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myasthenia Gravis; Oculomotor Muscles; Pyridostigmine Bromide; Receptors, Cholinergic; Treatment Outcome; Young Adult
PubMed: 34160444
DOI: 10.1097/MD.0000000000026457 -
Clinical Neurophysiology : Official... Oct 2023To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the electrophysiological basis of pyridostigmine enhancement of endurance performance documented earlier in patients with spinal muscular atrophy (SMA).
METHODS
We recorded surface electromyography (sEMG) in four upper extremity muscles of 31 patients with SMA types 2 and 3 performing endurance shuttle tests (EST) and maximal voluntary contraction (MVC) measurements during a randomized, double blind, cross-over, phase II trial. Linear mixed effect models (LMM) were used to assess the effect of pyridostigmine on (i) time courses of median frequencies and of root mean square (RMS) amplitudes of sEMG signals and (ii) maximal RMS amplitudes during MVC measurements. These sEMG changes over time indicate levels of peripheral muscle fatigue and recruitment of new motor units, respectively.
RESULTS
In comparison to a placebo, patients with SMA using pyridostigmine had fourfold smaller decreases in frequency and twofold smaller increases in amplitudes of sEMG signals in some muscles, recorded during ESTs (p < 0.05). We found no effect of pyridostigmine on MVC RMS amplitudes.
CONCLUSIONS
sEMG parameters indicate enhanced low-threshold (LT) motor unit (MU) function in upper-extremity muscles of patients with SMA treated with pyridostigmine. This may underlie their improved endurance.
SIGNIFICANCE
Our results suggest that enhancing LT MU function may constitute a therapeutic strategy to reduce fatigability in patients with SMA.
Topics: Humans; Pyridostigmine Bromide; Muscular Atrophy, Spinal; Electromyography; Muscles; Muscle Fatigue; Muscle, Skeletal
PubMed: 37595479
DOI: 10.1016/j.clinph.2023.06.024