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Neuromuscular Disorders : NMD Oct 2022Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is...
Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was to assess the effectiveness, prevalence of side effects and net benefit of pyridostigmine. All MG patients participating in the Dutch-Belgian myasthenia patient registry were included. A dynamic online questionnaire was developed to assess the effectiveness, side effects and net benefit of pyridostigmine. Out of 642 invited patients, 410 patients (64%) fully completed the questionnaire; 61% reported that they currently used pyridostigmine, 36% had discontinued pyridostigmine and 2% reported to never have used pyridostigmine. Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84. Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group). Most frequently reported side effects were flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. In the group of patients who discontinued pyridostigmine, side effects were the reason for discontinuation in 26%. Diarrhea, abdominal cramps and muscle twitching were the most frequently cited reasons to discontinue pyridostigmine. These results can be used to guide shared decision making prior to starting symptomatic treatment for MG.
Topics: Humans; Pyridostigmine Bromide; Cross-Sectional Studies; Myasthenia Gravis; Muscle Weakness
PubMed: 36184373
DOI: 10.1016/j.nmd.2022.09.002 -
Life Sciences Feb 2021Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces...
Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces improves in the autonomic nervous system. In the current study, we investigated the effect of physical exercise and pyridostigmine treatment on gastrointestinal and cardiovascular changes in cisplatin-treated rats. Rats were divided into groups: Saline (S), Cisplatin (Cis), Exercise (Ex), Cisplatin+Exercise (Cis+Ex), Pyridostigmine (Pyr), and Cisplatin+Pyridostigmine (Cis+Pyr). We induced gastrointestinal dysmotility by administering 3 mg kg of cisplatin once week for 5 weeks. The Ex was swimming (1 h per day/5 days per week for 5 weeks with 5% b.w.). GE was evaluated through the colorimetric method of fractional red phenol recovery 10 min after feeding. Pyr groups received 1.5 mg kg, p.o. or concomitant Cis treatment. Moreover, gastric contraction in vitro and hemodynamic parameters such as MAP, HR, and evoked baroreflex sensitivity were assessed, as well as sympathetic and parasympathetic tone and intrinsic heart rate (IHR). Cis decrease GE vs. saline (p<0.05). Cis+Ex or Cis+Pyr prevented (p<0.05) decrease in GE vs. Cis rats. Cis decreased (p<0.05) gastric responsiveness in vitro vs. saline. Cis+Ex or Cis+Pyr prevented this phenomenon. Cis treatment increase MAP and decrease in HR (p<0.05) vs saline. Cis+Ex or Cis+Pyr attenuated (p<0.05) both alterations. Cis increased sympathetic tone and decreased vagal tone and IHR (p<0.05) vs. the saline. Cis+Ex or Cis+Pyr prevented those effects vs. the Cis group. In conclusion, physical exercise and pyridostigmine treatment improves autonomic dysfunction and prevented GE delay and changes in hemodynamic parameters, baroreflex sensitivity, and cardiac autonomic control in cisplatin-treated rats.
Topics: Animals; Autonomic Nervous System; Baroreflex; Blood Pressure; Cardiovascular System; Cisplatin; Gastric Emptying; Heart; Heart Rate; Male; Myocardial Infarction; Physical Conditioning, Animal; Pyridostigmine Bromide; Rats; Rats, Wistar; Vagus Nerve
PubMed: 33383052
DOI: 10.1016/j.lfs.2020.118972 -
Transactions of the American Clinical... 2015It has been more than 20 years since the United States and coalition forces entered Kuwait and Iraq. Actual combat was of remarkably short duration: less than 1 week of... (Review)
Review
It has been more than 20 years since the United States and coalition forces entered Kuwait and Iraq. Actual combat was of remarkably short duration: less than 1 week of sustained ground activity and 6 weeks of air missions. Thus, it was surprising when approximately 200,000 returning US veterans were affected by a chronic multi-symptom illness that came to be known as Gulf War Illness (GWI). There were many challenges in investigating GWI, not least of which was that it took several years before the condition was officially taken seriously. There were multiple exposures to potentially causal agents on and off the battlefield, but these exposures were documented incompletely if at all, leaving epidemiologists to rely on self-report for information. In the past 2 years, significant controversy has arisen over the future directions of the field. Despite these challenges, several studies have implicated exposure to acetylcholinesterase inhibitors such as pyridostigmine bromide in the genesis of the condition. The story of GWI can inform research into other conditions and guide future work on veterans' health.
Topics: Chronic Disease; Gulf War; History, 20th Century; History, 21st Century; Humans; Military Medicine; Persian Gulf Syndrome; Prognosis; Risk Factors; Veterans Health
PubMed: 26330683
DOI: No ID Found -
Revista de Neurologia Aug 2021Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological...
INTRODUCTION
Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce.
AIM
This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published.
PATIENTS AND METHODS
The medical records of 13 patients with LEMS with clinical findings, compatible electromyogram and/or positive antibodies were reviewed. Follow-up was performed until associated neoplasia was ruled out or confirmed according to the recommended algorithms.
RESULTS
Four patients were diagnosed with T-LEMS, two of them with small-cell lung carcinoma. Of the nine patients with NT-LEMS, five had a DELTA-P score of 3 and 4. Nine patients presented with the classic clinical triad from the onset of the disease. All patients had electromyogram findings compatible with presynaptic neuromuscular plaque defect. Of the total, 70% improved symptomatically with pyridostigmine.
CONCLUSIONS
The clinical findings, together with compatible neurophysiological studies, are sufficient for the diagnosis of LEMS. The relationship between the DELTA-P score and the risk of small-cell lung carcinoma could not be replicated. Symptomatic treatment with pyridostigmine represents an effective therapeutic alternative.
Topics: Adolescent; Adult; Aged; Argentina; Carcinoma, Small Cell; Electromyography; Female; Humans; Immunoglobulins, Intravenous; Lambert-Eaton Myasthenic Syndrome; Lung Neoplasms; Male; Middle Aged; Neuromuscular Junction; Pyridostigmine Bromide; Retrospective Studies; Symptom Assessment; Young Adult
PubMed: 34291446
DOI: 10.33588/rn.7303.2021140 -
Current Gastroenterology Reports Sep 2023Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose... (Review)
Review
PURPOSE OF REVIEW
Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose and treat. We review the recent updates on diagnosis and management of ACPO.
RECENT FINDINGS
Recent guidelines have posited that conservative management can be tried in most cases of ACPO, but that early decompression and surgery should be considered. Use of neostigmine is still a viable option but there is also promising data on pyridostigmine as well as prucalopride. Resolution of ACPO should be followed by daily use of polyethylene glycol (PEG) to help prevent recurrence. ACPO warrants early and accurate diagnosis with exclusion of alternate causes of large bowel dilation. Conservative management can be attempted for 48-72 h in those with cecal diameters < 12 cm and without signs of peritonitis and perforation. Early escalation of management should be attempted with neostigmine followed by endoscopy and/or surgery as needed, given that longer periods of dilation are associated with worse outcomes. There is promising new evidence for use of pyridostigmine and prucalopride, but further trials are needed prior to incorporating them into regular use. Finally, studies are lacking regarding prevention of ACPO after initial resolution.
Topics: Humans; Acute Disease; Colonic Pseudo-Obstruction; Endoscopy, Gastrointestinal; Neostigmine; Polyethylene Glycols; Pyridostigmine Bromide; Cholinesterase Inhibitors; Parasympathomimetics; Treatment Outcome
PubMed: 37486594
DOI: 10.1007/s11894-023-00881-w -
ANZ Journal of Surgery Sep 2023Chronic intestinal pseudo-obstruction (CIPO) may be a primary or secondary phenomenon and is often multifactorial. Treatment is largely directed at improving colonic... (Review)
Review
BACKGROUND
Chronic intestinal pseudo-obstruction (CIPO) may be a primary or secondary phenomenon and is often multifactorial. Treatment is largely directed at improving colonic motility. The use of cholinesterase inhibitors such as pyridostigmine has been hypothesized to increase acetylcholine in the bowel, improving symptoms and transit times.
METHODS
A systematic review of the use of pyridostigmine in CIPO was conducted using scientific and commercial search engines identifying scientific studies enrolling adult human subjects, published from 2000 to 2022 in the English language.
RESULTS
Four studies were identified including two randomized controlled trials (RCT) and two observational studies. The studies had heterogenous inclusion criteria, dosing regimens and reported outcomes. Two studies were identified as being at high risk of bias. All studies reported improved patient outcomes with use of pyridostigmine, and low rates (4.3%) of mild cholinergic side effects. No major side effects were reported.
CONCLUSION
The use of pyridostigmine in management of CIPO is biologically plausible due to its ability to increase colonic motility, and early studies on its role are uniformly suggestive of benefit with low side-effect profile. Four clinical studies have been conducted to date, with small sample sizes, heterogeneity and high risk of bias. Further high-quality studies are required to enable assessment of pyridostigmine's utility as an effective management strategy in CIPO.
Topics: Adult; Humans; Pyridostigmine Bromide; Gastrointestinal Motility; Intestinal Pseudo-Obstruction; Cholinesterase Inhibitors; Chronic Disease
PubMed: 37132128
DOI: 10.1111/ans.18478 -
Annals of the New York Academy of... Sep 2019Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell... (Review)
Review
Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as first-line treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.
Topics: Antibodies, Monoclonal; Azathioprine; Cholinesterase Inhibitors; Humans; Immunosuppressive Agents; Immunotherapy; Myasthenia Gravis; Pyridostigmine Bromide; Treatment Outcome
PubMed: 31393614
DOI: 10.1111/nyas.14195 -
Indian Journal of Pharmacology 2018The management of myasthenia gravis (MG) during pregnancy requires special skills as both diseases as well as its treatment can have deleterious effects on mother and... (Review)
Review
The management of myasthenia gravis (MG) during pregnancy requires special skills as both diseases as well as its treatment can have deleterious effects on mother and fetus. MG often affects women in second and third decades of life during the childbearing age. Exacerbations of MG are likely to occur during the first trimester and postpartum period. The treatment of MG during pregnancy needs to be individualized depending on the severity of MG as well as the efficacy of various treatment modalities and their possible harmful effects on pregnancy. In addition, special attention has to be given to avoid drugs and other factors (such as urinary tract infections) which may worsen MG. The key to successful outcome during pregnancy in myasthenic women lies in multidisciplinary care involving obstetricians, neurologists, anesthetist as well as neonatologist. In this review, we discuss various therapeutic options available for the management of MG during pregnancy and provide recommendations based on the current best evidence.
Topics: Azathioprine; Cholinesterase Inhibitors; Disease Management; Female; Humans; Immunosuppressive Agents; Myasthenia Gravis; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Pyridostigmine Bromide; Severity of Illness Index
PubMed: 30783322
DOI: 10.4103/ijp.IJP_452_17 -
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