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Medicine Nov 2023Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG)...
RATIONALE
Facial-onset sensory and motor neuronopathy (FOSMN) is a greatly rare disease, so far, autopsy evidence that is associated with neurodegenerative. Myasthenia gravis (MG) is an antibody-mediated and complement-involved acquired autoimmune disorder of the post-synaptic neuromuscular junction. There have been few reports about if there is related between the 2. In this study, we present the case of a man who was diagnosed as FOSMN with MG in continuity.
PATIENT CONCERNS
The patient chief complaints were right-side facial numbness and right-eyelid incomplete closure, followed by slurred speech and dysphagia, and the symptoms gradually progressed. The patient serum was positive for anti-AchR and anti-Titin antibodies.
DIAGNOSES
The patient was diagnosed FOSMN with MG.
INTERVENTIONS
The patient symptoms were relieved after pyridostigmine bromide and prednisolone treatment.
OUTCOMES
Symptoms have improved.
LESSONS
Facial-onset sensory and motor neuronopathy and MG have disparate clinical features. Therefore, we reported a rare case in which the 2 conditions concurrently existed. Immune dysfunction might be the pathogenesis of this association, while there is no definite evidence to support it, further studies are needed.
Topics: Male; Humans; Myasthenia Gravis; Pyridostigmine Bromide; Deglutition Disorders
PubMed: 37986404
DOI: 10.1097/MD.0000000000034215 -
PloS One 2023Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial... (Observational Study)
Observational Study
Gulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit-to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.
Topics: Humans; Adenosine Triphosphate; Biological Warfare Agents; DNA, Mitochondrial; Energy Metabolism; Gulf War; Leukocytes, Mononuclear; Persian Gulf Syndrome; Pesticides; Pyridostigmine Bromide; Veterans; Case-Control Studies
PubMed: 37910447
DOI: 10.1371/journal.pone.0287412 -
Environmental Health : a Global Access... Oct 2023During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant...
Cognitive decrements in 1991 Gulf War veterans: associations with Gulf War illness and neurotoxicant exposures in the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) cohorts.
BACKGROUND
During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community.
METHODS
The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI.
RESULTS
Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans.
CONCLUSIONS
This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.
Topics: Humans; Veterans; Persian Gulf Syndrome; Gulf War; Boston; Acetylcholinesterase; Cognition
PubMed: 37794452
DOI: 10.1186/s12940-023-01018-2 -
Journal of Medical Case Reports Sep 2023Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction and causing muscle weakness along with fatigue (myasthenia). When the clinical...
BACKGROUND
Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction and causing muscle weakness along with fatigue (myasthenia). When the clinical manifestations of myasthenia gravis are isolated to the eye muscles, only causing weak eye movements, it is referred to as ocular myasthenia gravis, which can mimic a 1 and ½ syndrome.
CASE PRESENTATION
An African-American female in her fifties with past medical history of hypertension presented to our outpatient clinic with complaints of blurred vision for two weeks. Her symptoms were associated with facial discomfort and a generalized headache. On physical examination upon her initial presentation, there was demonstratable swelling of the left upper eyelid with drooping. Her extraocular movements revealed defects with the abduction and adduction of the right eye, and the left eye would not adduct, although the outward movement was normal. The left eye failed to lift/elevate completely when looking upwards, a pseudo 1 and ½ syndrome. A positive Cogan lid twitch was also noticed. Imaging of the brain and orbit ruled out central causes. Diagnosis of ocular myasthenia gravis was made in accordance with positive anti-acetylcholine receptor antibodies. With 120 mg pyridostigmine oral dose, the patient experienced improvement subjectively and objectively, and the patient was discharged on oral pyridostigmine and prednisone. Six months later, with prednisone having been tapered off, the patient developed a myasthenic crisis and was treated with plasmapheresis and intravenous immunoglobulins. After recovering from the myasthenic crisis, efgartigimod infusions were instituted, which helped our patient restore normal life.
CONCLUSION
Our patient who presented with "blurred vision" was discovered to have binocular diplopia due to significant dysconjugate eye movements. After diligently ruling out central etiologies, we concluded that her presentation was due to a peripheral etiology. Her serologies and her presentation helped confirm a diagnosis of ocular myasthenia gravis. Also, as in most cases, our patient also progressed to develop generalized myasthenia gravis while on pyridostigmine. Efgartigimod infusions instituted after our patient recovered from a myasthenic crisis have helped her restore a normal life.
Topics: Female; Humans; Diplopia; Pyridostigmine Bromide; Prednisone; Vision Disorders; Myasthenia Gravis; Muscle Weakness
PubMed: 37679826
DOI: 10.1186/s13256-023-04089-4 -
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 -
Brain, Behavior, and Immunity Oct 2023Gulf War Illness (GWI) collectively describes the multitude of central and peripheral disturbances affecting soldiers who served in the 1990-1991 Gulf War. While the...
Gulf War Illness (GWI) collectively describes the multitude of central and peripheral disturbances affecting soldiers who served in the 1990-1991 Gulf War. While the mechanisms responsible for GWI remain elusive, the prophylactic use of the reversible acetylcholinesterase inhibitor, pyridostigmine bromide (PB), and war-related stress have been identified as chief factors in GWI pathology. Post-deployment stress is a common challenge faced by veterans, and aberrant cholinergic and/or immune responses to these psychological stressors may play an important role in GWI pathology, especially the cognitive impairments experienced by many GWI patients. Therefore, the current study investigated if an immobilization stress challenge would produce abnormal responses in PB-treated rats three months later. Results indicate that hippocampal cholinergic responses to an immobilization stress challenge are impaired three months after PB administration. We also assessed if an immune or stress challenge reveals deficits in PB-treated animals during hippocampal-dependent learning and memory tasks at this delayed timepoint. Novel object recognition (NOR) testing paired with either acute saline or lipopolysaccharide (LPS, 30 µg/kg, i.p.), as well as Morris water maze (MWM) testing was conducted approximately three months after PB administration and/or repeated restraint stress. Rats with a history of PB treatment exhibited 24-hour hippocampal-dependent memory deficits when challenged with LPS, but not saline, in the NOR task. Similarly, in the same cohort, PB-treated rats showed 24-hour memory deficits in the MWM task. Ultimately, these studies highlight the long-term effects of PB treatment on hippocampal function and provide insight into the progressive cognitive deficits observed in veterans with GWI.
Topics: Rats; Animals; Persian Gulf Syndrome; Gulf War; Lipopolysaccharides; Acetylcholinesterase; Cholinesterase Inhibitors; Pyridostigmine Bromide; Cognitive Dysfunction; Memory Disorders; Disease Models, Animal
PubMed: 37437820
DOI: 10.1016/j.bbi.2023.07.003 -
Environmental Health : a Global Access... Jul 2023Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War...
INTRODUCTION
Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI.
METHODS
Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria.
RESULTS
Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07-3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23-3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12-7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56-6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07-5.62], p ≤ 0.05) among those who met the GWI case criteria.
CONCLUSION
These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.
Topics: Persian Gulf Syndrome; Humans; Apolipoproteins E; Veterans; Pyridostigmine Bromide; Pesticides; Hazardous Substances; Male; Female; Middle Aged; Smoke
PubMed: 37415220
DOI: 10.1186/s12940-023-01002-w -
Neurotoxicology May 2023Gulf War Illness (GWI) is an unrelenting multi-symptom illness with chronic central nervous system and peripheral pathology affecting veterans from the 1991 Gulf War and...
Gulf War Illness (GWI) is an unrelenting multi-symptom illness with chronic central nervous system and peripheral pathology affecting veterans from the 1991 Gulf War and for which effective treatment is lacking. An increasing number of studies indicate that persistent neuroinflammation is likely the underlying cause of cognitive and mood dysfunction that affects veterans with GWI. We have previously reported that fingolimod, a drug approved for the treatment of relapsing-remitting multiple sclerosis, decreases neuroinflammation and improves cognition in a mouse model of Alzheimer's disease. In this study, we investigated the effect of fingolimod treatment on cognition and neuroinflammation in a mouse model of GWI. We exposed C57BL/6 J male mice to GWI-related chemicals pyridostigmine bromide, DEET, and permethrin, and to mild restraint stress for 28 days (GWI mice). Control mice were exposed to the chemicals' vehicle only. Starting 3 months post-exposure, half of the GWI mice and control mice were orally treated with fingolimod (1 mg/kg/day) for 1 month, and the other half were left untreated. Decreased memory on the Morris water maze test was detected in GWI mice compared to control mice and was reversed by fingolimod treatment. Immunohistochemical analysis of brain sections with antibodies to Iba1 and GFAP revealed that GWI mice had increased microglia activation in the hippocampal dentate gyrus, but no difference in reactive astrocytes was detected. The increased activation of microglia in GWI mice was decreased to the level in control mice by treatment with fingolimod. No effect of fingolimod treatment on gliosis in control mice was detected. To explore the signaling pathways by which decreased memory and increased neuroinflammation in GWI may be protected by fingolimod, we investigated the involvement of the inflammatory signaling pathways of protein kinase R (PKR) in the cerebral cortex of these mice. We found increased phosphorylation of PKR in the brain of GWI mice compared to controls, as well as increased phosphorylation of its most recognized downstream effectors: the α subunit of eukaryotic initiation factor 2 (eIF2α), IκB kinase (IKK), and the p65 subunit of nuclear factor-κB (NFκB-p65). Furthermore, we found that the increased phosphorylation level of these three proteins were suppressed in GWI mice treated with fingolimod. These results suggest that activation of PKR and NFκB signaling may be important for the regulation of cognition and neuroinflammation in the GWI condition and that fingolimod, a drug already approved for human use, may be a potential candidate for the treatment of GWI.
Topics: Animals; Male; Mice; Amnesia; Disease Models, Animal; Fingolimod Hydrochloride; Gulf War; Memory Disorders; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases; NF-kappa B; Persian Gulf Syndrome; Protein Kinases; Pyridostigmine Bromide
PubMed: 37160207
DOI: 10.1016/j.neuro.2023.05.006 -
The Turkish Journal of Pediatrics 2023Myasthenia gravis is a chronic, autoimmune disease with muscle weakness. Acetylcholinesterase inhibitors are used in the symptomatic treatment of the disease. Allergic...
BACKGROUND
Myasthenia gravis is a chronic, autoimmune disease with muscle weakness. Acetylcholinesterase inhibitors are used in the symptomatic treatment of the disease. Allergic reaction to pyridostigmine bromide is rare. In the literature, no allergic reaction to pyridostigmine bromide has been reported in the pediatric population.
CASE
A 12-year-old female patient diagnosed with myasthenia gravis consulted our clinic with the complaint of urticaria due to pyridostigmine bromide. The oral challenge test performed with pyridostigmine bromide was positive. As the patient was required to be continue pyridostigmine bromide with no suitable alternatives, it was decided that the patient had to be desensitized to pyridostigmine. During and after the desensitization protocol, no reaction was observed.
CONCLUSIONS
In this report, a successful desensitization protocol for pyridostigmine bromide in a child with myasthenia gravis is discussed.
Topics: Child; Female; Humans; Pyridostigmine Bromide; Acetylcholinesterase; Myasthenia Gravis; Cholinesterase Inhibitors; Muscle Weakness; Hypersensitivity
PubMed: 37114698
DOI: 10.24953/turkjped.2022.386 -
Frontiers in Veterinary Science 2023A 9-year-old male neutered Cockapoo was presented with an acute and progressive history of exercise induced weakness involving all limbs, and bilateral decreased ability...
A 9-year-old male neutered Cockapoo was presented with an acute and progressive history of exercise induced weakness involving all limbs, and bilateral decreased ability to blink. Investigations revealed generalized myasthenia gravis alongside the presence of a thymoma and a cholangiocellular carcinoma. Symptomatic treatment through pyridostigmine bromide was used to control clinical signs, and complete surgical removal of the thymoma and cholangiocellular carcinoma was performed. Serum acetylcholine receptor antibody concentration was measured serially. Clinical remission defined as resolution of clinical signs alongside discontinuation of treatment was achieved by day 251 (8.2 months). Immune remission defined as normalization of serum acetylcholine receptor antibody concentration alongside resolution of clinical signs and discontinuation of treatment was achieved by day 566 (18.5 months). Neurological examination was normal, and the owners did not report any clinical deterioration during the final follow-up appointment on day 752 (24 months), hence outcome was considered excellent. This is the first report describing the temporal evolution of serum acetylcholine receptor antibody concentration in a dog with thymoma-associated myasthenia gravis which achieved immune remission following thymectomy. Treatment was successfully discontinued without any evidence of clinical deterioration thereafter despite serum acetylcholine receptor antibody concentration not normalizing for another 315 days (10 months).
PubMed: 37008354
DOI: 10.3389/fvets.2023.1124702