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Muscle & Nerve Oct 2022We studied the progression of myasthenia gravis (MG) disease burden and medication adjustment among MG Patient Registry participants.
INTRODUCTION/AIMS
We studied the progression of myasthenia gravis (MG) disease burden and medication adjustment among MG Patient Registry participants.
METHODS
Participants diagnosed with MG (age ≥18 years), registered between July 1, 2013 and July 31, 2018 and completing both 6- and 12-month follow-up surveys, were included in this investigation. Participants were grouped into high-burden (Myasthenia Gravis Activity of Daily Living scale [MG-ADL] score ≥6) and low-burden (MG-ADL <6) groups based on MG-ADL scores at enrollment. Demographics and disease history were compared between groups. MG-ADL score change and medication changes (escalation, no change, de-escalation) between enrollment and 12-month follow-up were compared between groups. Minimal symptom expression (MSE, MG-ADL <2) at 12 months was compared between groups. Logistic regression analysis was performed to study factors associated with MSE at 12 months.
RESULTS
In total, 520 participants (56% female) were included in high-burden (n = 248) and low-burden (n = 272) groups. Those in the high-burden group were more likely to be younger, female, and have shorter disease duration. At 12 months, MSE was achieved in 6% of the high-burden group and newly achieved (42 of 201, 21%) or maintained (52 of 71, 73%) in the low-burden group. In the multivariable analysis, being in the high-burden group and use of pyridostigmine were associated with less likelihood of MSE, whereas MG-ADL score improvement (>2 or >20%) at 6 months significantly increased the likelihood of achieving MSE at 12 months (P = .0004).
DISCUSSION
In both groups, but more so in the high-burden group, patients infrequently achieved MSE after 1 year of MG treatment. Baseline low disease burden, improvement at 6 months and no pyridostigmine use were associated with a higher likelihood of MSE at 12 months.
Topics: Activities of Daily Living; Adolescent; Cost of Illness; Female; Follow-Up Studies; Humans; Male; Myasthenia Gravis; Pyridostigmine Bromide; Registries
PubMed: 35673964
DOI: 10.1002/mus.27659 -
The British Journal of Ophthalmology Oct 2005The optimal treatment of ocular myasthenia gravis (OMG) remains unknown. The authors evaluated the efficacy of prednisone and pyridostigmine in reducing diplopia, ocular...
AIM
The optimal treatment of ocular myasthenia gravis (OMG) remains unknown. The authors evaluated the efficacy of prednisone and pyridostigmine in reducing diplopia, ocular motor dysfunction, and ptosis in patients with OMG.
METHODS
Review of records from a clinical database from one neuro-ophthalmology service of patients presenting with OMG between 1990 and 2002, excluding those who developed generalised MG within the first month after diagnosis. Institutional review board approval was obtained for this study.
PARTICIPANTS/INTERVENTIONS
Non-randomised, unmasked, therapy was given. 55 patients with diplopia in primary or downward gaze and clinically demonstrable extraocular muscle dysfunction received prednisone. 34 patients who had contraindications to steroids or who refused treatment with prednisone received pyridostigmine only. Over 5 days the daily prednisone dose was increased to 50-60 mg and then gradually reduced to 10 mg, followed by further reduction as tolerated. The pyridostigmine dose was begun at 180 mg daily and increased as tolerated.
MAIN OUTCOME MEASURES
Follow up evaluations, performed at 1, 3-6, 12, and 24 months, detailed the frequency of ptosis and diplopia and the amount of ocular motor deviation in primary and downward gaze.
RESULTS
The prednisone and pyridostigmine groups were similar for age, sex, acetylcholine receptor antibody level, prism cover test results for primary and downward gaze, diplopia in primary and downward gaze, and unilateral ptosis. Bilateral ptosis was present in 32.4% of the pyridostigmine group and 10.9% of the prednisone group (p = 0.02). The prednisone group showed resolution in primary gaze diplopia, downgaze diplopia, unilateral ptosis, and bilateral ptosis in 73.5%, 75.5%, 85.7%, and 98%, respectively at 1 month. The benefit persisted at 3-6, 12, and 24 months except for the bilateral ptosis. The pyridostigmine group showed resolution in primary gaze diplopia, downgaze diplopia, unilateral ptosis, and bilateral ptosis in 6.9%, 17.2%, 50%, and 76.7% of patients after 1 month of treatment. The prism cover results improved (p = 0.003) in the prednisone group only. In the prednisone group, four patients had no response to therapy. Among the 51 prednisone responsive patients, there were 33 recurrences in 26 patients. 12 patients, all prednisone treated, had remissions. Except for three patients who developed diabetes, no patient developed a clinically significant systemic corticosteroid complication.
CONCLUSION
These results suggest that 50-60 mg daily prednisone followed by lower doses (10 mg or less) has the benefit of resolving ptosis and diplopia that lasts for at least 2 years in approximately 70% of patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blepharoptosis; Child; Child, Preschool; Cholinesterase Inhibitors; Diplopia; Drug Administration Schedule; Drug Evaluation; Female; Glucocorticoids; Humans; Male; Middle Aged; Myasthenia Gravis; Ocular Motility Disorders; Prednisone; Pyridostigmine Bromide; Secondary Prevention; Treatment Outcome
PubMed: 16170126
DOI: 10.1136/bjo.2004.063404 -
Proceedings of the Royal Society of... Dec 1976
Topics: Child; Child, Preschool; Eye Diseases; Humans; Infant; Male; Myasthenia Gravis; Neostigmine; Pyridostigmine Bromide
PubMed: 1013123
DOI: No ID Found -
Journal of Cancer Research and... Aug 2015The objective of this study is to investigate the risk factors for developing postthymectomy myasthenic crisis in thymoma patients.
OBJECTIVE
The objective of this study is to investigate the risk factors for developing postthymectomy myasthenic crisis in thymoma patients.
PATIENTS AND METHODS
Patients with thymoma received thymectomy from January 2001 to December 2014 were reviewed and included in this retrospective study in Lishui People's Hospital. Seventy-seven patients were included in this study. For the 77 cases, 66 patients not developing postthymectomy myasthenic crisis were considered as a control group, and other 11 subjects developing postthymectomy myasthenic were considered as the case group. The potential risk factors such age, gender, Osseman stage, Masaoka, pyridostigmine bromide, and et al. were compared between case and control group firstly by Chi-square test or Student's t-test and then by logistic regression test.
RESULTS
Eleven patients developed postthymectomy myasthenic with the incidence of 14.3%; logistic regression analysis indicates that pyridostigmine bromide >360 mg/day administration (OR = 21.2, P < 0.05), postsurgery pulmonary infection (OR = 8.3, P < 0.05) and myasthenic crisis prior surgery (OR = 3.2, P < 0.05) were the independent risk factors for developing postthymectomy myasthenic crisis in thymoma patients.
CONCLUSION
Thymoma patients with a large dosage of pyridostigmine bromide administration, postsurgery pulmonary infection and myasthenic crisis prior surgery were easy to have postthymectomy myasthenic crisis.
Topics: Adult; Case-Control Studies; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Postoperative Complications; Retrospective Studies; Risk Factors; Thymectomy; Thymoma
PubMed: 26323908
DOI: 10.4103/0973-1482.163863 -
Brain, Behavior, and Immunity Mar 2018Diminished cognitive and mood function are among the most conspicuous symptoms of Gulf War Illness (GWI). Our previous studies in a rat model of GWI have demonstrated...
Curcumin treatment leads to better cognitive and mood function in a model of Gulf War Illness with enhanced neurogenesis, and alleviation of inflammation and mitochondrial dysfunction in the hippocampus.
Diminished cognitive and mood function are among the most conspicuous symptoms of Gulf War Illness (GWI). Our previous studies in a rat model of GWI have demonstrated that persistent cognitive and mood impairments are associated with substantially declined neurogenesis, chronic low-grade inflammation, increased oxidative stress and mitochondrial dysfunction in the hippocampus. We tested the efficacy of curcumin (CUR) to maintain better cognitive and mood function in a rat model of GWI because of its neurogenic, antiinflammatory, antioxidant, and memory and mood enhancing properties. Male rats were exposed daily to low doses of GWI-related chemicals, pyridostigmine bromide, N,N-diethyl-m-toluamide (DEET) and permethrin, and 5-minutes of restraint stress for 28 days. Animals were next randomly assigned to two groups, which received daily CUR or vehicle treatment for 30 days. Animals also received 5'-bromodeoxyuridine during the last seven days of treatment for analysis of neurogenesis. Behavioral studies through object location, novel object recognition and novelty suppressed feeding tests performed sixty days after treatment revealed better cognitive and mood function in CUR treated GWI rats. These rats also displayed enhanced neurogenesis and diminished inflammation typified by reduced astrocyte hypertrophy and activated microglia in the hippocampus. Additional studies showed that CUR treatment to GWI rats enhanced the expression of antioxidant genes and normalized the expression of multiple genes related to mitochondrial respiration. Thus, CUR therapy is efficacious for maintaining better memory and mood function in a model of GWI. Enhanced neurogenesis, restrained inflammation and oxidative stress with normalized mitochondrial respiration may underlie better memory and mood function mediated by CUR treatment.
Topics: Affect; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cognition; Curcumin; DEET; Disease Models, Animal; Hippocampus; Inflammation; Male; Mitochondria; Neurogenesis; Oxidative Stress; Permethrin; Persian Gulf Syndrome; Rats
PubMed: 29454881
DOI: 10.1016/j.bbi.2018.01.009 -
Thorax Oct 1995Pyridostigmine, an acetylcholinesterase antagonist, is useful in improving respiratory function in patients with myasthenia gravis. More recently, plasma exchange has... (Comparative Study)
Comparative Study
BACKGROUND
Pyridostigmine, an acetylcholinesterase antagonist, is useful in improving respiratory function in patients with myasthenia gravis. More recently, plasma exchange has been employed in myasthenia gravis because it acts presumably by removal of circulating antibodies against acetylcholine receptors. Surprisingly, comparative data on the effects of pyridostigmine and plasma exchange on lung volumes, respiratory muscle strength, and ventilatory control system in patients with myasthenia gravis are lacking.
METHODS
Nine consecutive patients with grade IIb myasthenia gravis were studied under control conditions and after a therapeutic dose of pyridostigmine. In a second study the patients were re-evaluated a few days after a cycle of plasma exchange, before taking pyridostigmine. In each subject pulmonary volumes, inspiratory (MIP) and expiratory (MEP) muscle force, and respiratory muscle strength, calculated as average MIP and MEP as percentages of their predicted values, were measured. The ventilatory control system was evaluated in terms of volume (tidal volume, VT) and time (inspiratory time, TI, and total time, TTOT) components of the respiratory cycle. Mean inspiratory flow (VT/TI)--that is, the "driving"--and TI/TTOT: that is, the "timing"--components of ventilation were also measured.
RESULTS
In each patient treatment relieved weakness and tiredness, and dyspnoea grade was reduced with plasma exchange. Following treatment, vital capacity (VC) increased on average by 9.7% with pyridostigmine and by 14% with plasma exchange, and MIP increased by 18% and 26%, respectively. In addition, with plasma exchange but not with pyridostigmine forced expiratory volume in one second (FEV1) increased by 16% and MEP increased by 24.5%, while functional residual capacity (FRC) decreased a little (6.8%). The change in respiratory muscle strength was related to change in VC (r2 = 0.48). With plasma exchange, VT increased by 18.6% and VT/TI increased by 13.5%, while neither TI nor TI/TTOT changed.
CONCLUSIONS
Plasma exchange can be used in patients with myasthenia gravis when symptoms are not adequately controlled by anticholinesterase agents. Plasma exchange increases respiratory muscle force and tidal volume due to changes in "driving" but not "timing" of the respiratory cycle.
Topics: Adult; Aged; Cholinesterase Inhibitors; Female; Humans; Male; Middle Aged; Myasthenia Gravis; Plasma Exchange; Pyridostigmine Bromide; Respiration; Respiratory Function Tests; Respiratory Muscles; Tidal Volume
PubMed: 7491557
DOI: 10.1136/thx.50.10.1080 -
Neurology Jul 2013To identify patients with GFPT1-related limb-girdle myasthenia and analyze phenotypic consequences of the mutations.
OBJECTIVE
To identify patients with GFPT1-related limb-girdle myasthenia and analyze phenotypic consequences of the mutations.
METHODS
We performed genetic analysis, histochemical, immunoblot, and ultrastructural studies and in vitro electrophysiologic analysis of neuromuscular transmission.
RESULTS
We identified 16 recessive mutations in GFPT1 in 11 patients, of which 12 are novel. Ten patients had slowly progressive limb-girdle weakness responsive to cholinergic agonists with onset between infancy and age 19 years. One patient (no. 6) harbored a nonsense mutation and a second mutation that disrupts the muscle-specific GFPT1 exon. This patient never moved in utero, was apneic and arthrogrypotic at birth, and was bedfast, tube-fed, and barely responded to therapy at age 6 years. Histochemical studies in 9 of 11 patients showed tubular aggregates in 6 and rimmed vacuoles in 3. Microelectrode studies of intercostal muscle endplates in 5 patients indicated reduced synaptic response to acetylcholine in 3 and severely reduced quantal release in patient 6. Endplate acetylcholine receptor content was moderately reduced in only one patient. The synaptic contacts were small and single or grape-like, and quantitative electron microscopy revealed hypoplastic endplate regions. Numerous muscle fibers of patient 6 contained myriad dilated and degenerate vesicular profiles, autophagic vacuoles, and bizarre apoptotic nuclei. Glycoprotein expression in muscle was absent in patient 6 and reduced in 5 others.
CONCLUSIONS
GFPT1-myasthenia is more heterogeneous than previously reported. Different parameters of neuromuscular transmission are variably affected. When disruption of muscle-specific isoform determines the phenotype, this has devastating clinical, pathologic, and biochemical consequences.
Topics: Acetylcholine; Acetylcholinesterase; Action Potentials; Adolescent; Child; Child, Preschool; DNA Mutational Analysis; Female; Genotype; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); Humans; In Vitro Techniques; Infant; Male; Microscopy, Electron, Transmission; Muscle, Skeletal; Mutation; Myasthenia Gravis; Neuromuscular Junction; Pyridostigmine Bromide; Receptors, Cholinergic; Sarcoplasmic Reticulum; Young Adult
PubMed: 23794683
DOI: 10.1212/WNL.0b013e31829c5e9c -
Frontiers in Psychiatry 2020Gulf War Illness is a chronic multisystem disorder affecting approximately a third of the Veterans of the Gulf War, manifesting with physical and mental health symptoms... (Review)
Review
Gulf War Illness is a chronic multisystem disorder affecting approximately a third of the Veterans of the Gulf War, manifesting with physical and mental health symptoms such as cognitive impairment, neurological abnormalities, and dysregulation of mood. Among the leading theories into the etiology of this multisystem disorder is environmental exposure to the various neurotoxins encountered in the Gulf Theatre, including organophosphates, nerve agents, pyridostigmine bromide, smoke from oil well fires, and depleted uranium. The relationship of toxin exposure and the pathogenesis of Gulf War Illness converges on the innate immune system: a nonspecific form of immunity ubiquitous in nature that acts to respond to both exogenous and endogenous insults. Activation of the innate immune system results in inflammation mediated by the release of cytokines. Cytokine mediated neuroinflammation has been demonstrated in a number of psychiatric conditions and may help explain the larger than expected population of Gulf War Veterans afflicted with a mood disorder. Several of the environmental toxins encountered by soldiers during the first Gulf War have been shown to cause upregulation of inflammatory mediators after chronic exposure, even at low levels. This act of inflammatory priming, by which repeated exposure to chronic subthreshold insults elicits robust responses, even after an extended period of latency, is integral in the connection of Gulf War Illness and comorbid mood disorders. Further developing the understanding of the relationship between environmental toxin exposure, innate immune activation, and pathogenesis of disease in the Gulf War Veterans population, may yield novel therapeutic targets, and a greater understanding of disease pathology and subsequently prevention.
PubMed: 32848904
DOI: 10.3389/fpsyt.2020.00704 -
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