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Skeletal Muscle Aug 2023Critical illness is hallmarked by severe stress and organ damage. Fibroblast growth factor 21 (FGF21) has been shown to rise during critical illness. FGF21 is a...
BACKGROUND
Critical illness is hallmarked by severe stress and organ damage. Fibroblast growth factor 21 (FGF21) has been shown to rise during critical illness. FGF21 is a pleiotropic hormone that mediates adaptive responses to tissue injury and repair in various chronic pathological conditions. Animal studies have suggested that the critical illness-induced rise in FGF21 may to a certain extent protect against acute lung, liver, kidney and brain injury. However, FGF21 has also been shown to mediate fasting-induced loss of muscle mass and force. Such loss of muscle mass and force is a frequent problem of critically ill patients, associated with adverse outcome. In the present study, we therefore investigated whether the critical illness-induced acute rise in FGF21 is muscle-protective or rather contributes to the pathophysiology of critical illness-induced muscle weakness.
METHODS
In a catheterised mouse model of critical illness induced by surgery and sepsis, we first assessed the effects of genetic FGF21 inactivation, and hence the inability to acutely increase FGF21, on survival, body weight, muscle wasting and weakness, and markers of muscle cellular stress and dysfunction in acute (30 h) and prolonged (5 days) critical illness. Secondly, we assessed whether any effects were mirrored by supplementing an FGF21 analogue (LY2405319) in prolonged critical illness.
RESULTS
FGF21 was not required for survival of sepsis. Genetic FGF21 inactivation aggravated the critical illness-induced body weight loss (p = 0.0003), loss of muscle force (p = 0.03) and shift to smaller myofibers. This was accompanied by a more pronounced rise in markers of endoplasmic reticulum stress in muscle, without effects on impairments in mitochondrial respiratory chain enzyme activities or autophagy activation. Supplementing critically ill mice with LY2405319 did not affect survival, muscle force or weight, or markers of muscle cellular stress/dysfunction.
CONCLUSIONS
Endogenous FGF21 is not required for sepsis survival, but may partially protect muscle force and may reduce cellular stress in muscle. Exogenous FGF21 supplementation failed to improve muscle force or cellular stress, not supporting the clinical applicability of FGF21 supplementation to protect against muscle weakness during critical illness.
Topics: Animals; Mice; Critical Illness; Endoplasmic Reticulum Stress; Muscle Weakness; Disease Models, Animal; Sepsis
PubMed: 37537627
DOI: 10.1186/s13395-023-00320-4 -
Medicine Oct 2022Pancytopenia and epilepsia are rare complications of Graves' disease (GD). Muscle weakness is a physical sign of GD. It is extremely rare for GD patients to present 3...
RATIONALE
Pancytopenia and epilepsia are rare complications of Graves' disease (GD). Muscle weakness is a physical sign of GD. It is extremely rare for GD patients to present 3 symptoms at the same time.
PATIENT CONCERNS
A 35-year-old female was admitted to hospital for dizziness for 1 day. The results of laboratory examination on admission showed pancytopenia and hypothyroidism. Her clinical manifestations include pancytopenia, epilepsy, and muscle weakness.
DIAGNOSIS
Graves' hyperthyroidism.
INTERVENTIONS
She received endotracheal intubation, ventilator, antithyroid drugs, and hormone therapy.
OUTCOME
The patient was discharged after treatment.
LESSON
Severe complications caused by GD are rare and require antithyroid therapy. Although glucocorticoid is not recommended by the guidelines, it can effectively improve thrombocytopenia.
Topics: Adult; Antithyroid Agents; Epilepsy; Female; Glucocorticoids; Graves Disease; Humans; Hyperthyroidism; Muscle Weakness; Pancytopenia
PubMed: 36254023
DOI: 10.1097/MD.0000000000031042 -
Revista de Neurologia Sep 2013Acute muscle weakness, a common disorder in pediatrics, can occur from impairment of any part of the motor unit, including the upper motor neuron, lower motor neuron,... (Review)
Review
Acute muscle weakness, a common disorder in pediatrics, can occur from impairment of any part of the motor unit, including the upper motor neuron, lower motor neuron, peripheral nerve, neuromuscular junction or muscle. It usually manifests itself as an acute or hyperacute motor disorder of progressive or rapidly progressive course. Acute muscle weakness is a neuromuscular emergency, especially if it affects the respiratory or oropharyngeal musculature. The location of the motor weakness and associated neurological signs and symptoms usually indicate the location of the lesion. The onset, speed and clinical evolution, as well as other data from the patient's history, suggest the pathophysiological differential diagnosis. Successful treatment depends on the immediate and correct differential diagnosis. This paper presents the main differential diagnosis of main neuromuscular diseases that cause acute muscle weakness in children.
Topics: Acute Disease; Autoimmune Diseases; Child; Humans; Metabolism, Inborn Errors; Motor Neurons; Muscle Hypotonia; Muscle Weakness; Muscular Diseases; Neurologic Examination; Neuromuscular Diseases; Neuromuscular Junction; Ophthalmoplegia; Peripheral Nerves; Peripheral Nervous System Diseases; Physical Examination; Virus Diseases
PubMed: 23897142
DOI: No ID Found -
Neurology Dec 2017To describe the phenomenon of acute illness-associated weakness (AIAW) in patients with dystroglycanopathy (DG), determine the frequency of this phenomenon in DGs, and...
OBJECTIVE
To describe the phenomenon of acute illness-associated weakness (AIAW) in patients with dystroglycanopathy (DG), determine the frequency of this phenomenon in DGs, and compare it to the frequency in Duchenne-Becker muscular dystrophy (DBMD).
METHODS
Patients enrolled in a DG natural history study provided medical history, including major illnesses or hospitalizations, at enrollment and annually. We noted a recurring syndrome of profound transient weakness in the setting of febrile illness. To determine the frequency of this phenomenon in the DG cohort and compare it to a cohort with another membrane-related muscular dystrophy, DBMD, we surveyed patients (e-survey tool), collecting demographics and information about episodes of sudden progression of weakness and events surrounding the episodes.
RESULTS
Surveys were completed by 52 (56.6%) patients with DG and 51 (27.3%) patients with DBMD. AIAW was reported in 12 (23%) patients with DG and 2 (4%) patients with DBMD (odds ratio 7.35; 95% confidence interval 1.55, 34.77; = 0.005). Altogether (history or survey), 21 patients with DG, with mutations in , , , , or , reported AIAW. These events typically occurred in children <7 years old, and the preceding illness usually included respiratory symptoms. In 10 (47.6%) patients with DG, AIAW preceded the diagnosis of muscular dystrophy.
CONCLUSIONS
People with DG, across genotypes, can experience acute, transient weakness associated with a febrile illness, a phenomenon that rarely occurs in DBMD. The physiologic basis of this phenomenon is unknown.
CLINICALTRIALSGOV IDENTIFIER
NCT00313677.
Topics: Adolescent; Adult; Age of Onset; Child; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Dystroglycans; Female; Fever; Genotype; Humans; Infant; Male; Muscle Proteins; Muscle Weakness; Muscular Dystrophy, Duchenne; Young Adult
PubMed: 29101272
DOI: 10.1212/WNL.0000000000004720 -
Intensive Care Medicine Sep 2017We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive... (Review)
Review
We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.
Topics: Age Factors; Biomedical Research; Critical Care; Deglutition Disorders; Delirium; Frailty; Humans; Intensive Care Units; Length of Stay; Muscle Strength; Muscle Weakness; Neuromuscular Diseases; Outcome Assessment, Health Care; Respiratory System
PubMed: 28289812
DOI: 10.1007/s00134-017-4757-5 -
Orphanet Journal of Rare Diseases May 2018GNE myopathy is an ultra-rare autosomal recessive disease, which starts as a distal muscle weakness and ultimately leads to a wheelchair bound state. Molecular research... (Review)
Review
GNE myopathy is an ultra-rare autosomal recessive disease, which starts as a distal muscle weakness and ultimately leads to a wheelchair bound state. Molecular research and animal modelling significantly moved forward understanding of GNE myopathy mechanisms and suggested therapeutic interventions to alleviate the symptoms. Multiple therapeutic attempts are being made to supplement sialic acid depleted in GNE myopathy muscle cells. Translational research field provided valuable knowledge through natural history studies, patient registries and clinical trial, which significantly contributed to bringing forward an era of GNE myopathy treatment. In this review, we are summarising current GNE myopathy, scientific trends and open questions, which would be of significant interest for a wide neuromuscular diseases community.
Topics: Animals; Distal Myopathies; Humans; Muscle Weakness; Muscle, Skeletal; N-Acetylneuraminic Acid; Research Design
PubMed: 29720219
DOI: 10.1186/s13023-018-0802-x -
Heart & Lung : the Journal of Critical... 2023Patients with coronary heart disease (CHD) are susceptible to lung function problems caused by respiratory muscle weakness. Many CHD patients show complications of...
BACKGROUND
Patients with coronary heart disease (CHD) are susceptible to lung function problems caused by respiratory muscle weakness. Many CHD patients show complications of respiratory muscle weakness, but the risk factors remain unclear.
OBJECTIVE
To explore the risk factors for inspiratory muscle weakness in CHD.
METHODS
This study enrolled 249 patients with CHD who underwent maximal inspiratory pressure (MIP) measurement between April 2021 and March 2022.According to the percentage of MIP (MIP/Predicted normal value [PNV]), patients were divided into the inspiratory muscle weakness (IMW) (n = 149) (MIP/PNV<70%) and control groups (n = 100) (MIP/PNV≥70༅). Clinical information and MIP of the two groups were collected and analyzed.
RESULTS
The incidence of IMW was 59.8% (n = 149). Age (P < 0.001); history of heart failure (P < 0.001), hypertension (P = 0.04), and peripheral artery disease (PAD) (P = 0.001); left ventricular end-systolic dimension (P = 0.035); presence of segmental motion abnormality of the ventricular wall (P = 0.030); and high density lipoprotein cholesterol (P = 0.001) and N-terminal brain natriuretic peptide (NT-proBNP) levels (P < 0.001) in the IMW group were significantly higher than those in the control group. The proportion of anatomic complete revascularization (P = 0.009), left ventricular ejection fraction (P = 0.010), and alanine transaminase (P = 0.014) and triglycerides levels (P = 0.014) in the IMW group were significantly lower than those in the control group. Logistic regression analysis showed that anatomic complete revascularization (OR=0.350, 95%CI 0.157-0.781) and NT-proBNP level (OR=1.002, 95%CI 1.000-1.004) were independent risk factors for IMW.
CONCLUSION
The independent risk factors for decreased IMW in patients with CAD were anatomic incomplete revascularization and NT-proBNP level.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Coronary Disease; Muscle Weakness; Risk Factors; Natriuretic Peptide, Brain; Peptide Fragments; Biomarkers
PubMed: 36878105
DOI: 10.1016/j.hrtlng.2023.02.019 -
Disease Markers 2021Heart failure (HF) is a global medical problem that characterizes poor prognosis and high economic burden for the health system and family of the HF patients. Although... (Review)
Review
Heart failure (HF) is a global medical problem that characterizes poor prognosis and high economic burden for the health system and family of the HF patients. Although modern treatment approaches have significantly decreased a risk of the occurrence of HF among patients having predominant coronary artery disease, hypertension, and myocarditis, the mortality of known HF continues to be unacceptably high. One of the most important symptoms of HF that negatively influences tolerance to physical exercise, well-being, social adaptation, and quality of life is deep fatigue due to HF-related myopathy. Myopathy in HF is associated with weakness of the skeletal muscles, loss of myofibers, and the development of fibrosis due to microvascular inflammation, metabolic disorders, and mitochondrial dysfunction. The pivotal role in the regulation of myocardial and skeletal muscle rejuvenation, attenuation of muscle metabolic homeostasis, and protection against ischemia injury and apoptosis belongs to myokines. Myokines are defined as a wide spectrum of active molecules that are directly synthesized and released by both cardiac and skeletal muscle myocytes and regulate energy homeostasis in autocrine/paracrine manner. In addition, myokines have a large spectrum of pleiotropic capabilities that are involved in the pathogenesis of HF including cardiac remodeling, muscle atrophy, and cardiac cachexia. The aim of the narrative review is to summarize the knowledge with respect to the role of myokines in adverse cardiac remodeling, myopathy, and clinical outcomes among HF patients. Some myokines, such as myostatin, irisin, brain-derived neurotrophic factor, interleukin-15, fibroblast growth factor-21, and growth differential factor-11, being engaged in the regulation of the pathogenesis of HF-related myopathy, can be detected in peripheral blood, and the evaluation of their circulating levels can provide new insights to the course of HF and stratify patients at higher risk of poor outcomes prior to sarcopenic stage.
Topics: Biomarkers; Collagen; Decorin; Fibronectins; Growth Differentiation Factors; Heart Failure; Humans; Muscle Weakness
PubMed: 33520013
DOI: 10.1155/2021/6644631 -
European Journal of Physical and... Jun 2010The aim of this review was to examine the contribution of muscle weakness to postural stability in healthy older adults and to determine the relationship between muscle... (Review)
Review
BACKGROUND AND AIM
The aim of this review was to examine the contribution of muscle weakness to postural stability in healthy older adults and to determine the relationship between muscle weakness and balance impairment.
DESIGN
A comprehensive search of electronic databases was performed from earliest record to February 2010. All study designs that contained a measure of muscle strength or muscle power and balance performance in older adults were examined. Population. Participants (>or=60 years) included healthy, community-dwelling cohorts, nursing home residents, frail, mobility- or functionally-limited adults but not persons with pathophysiological conditions or disease.
METHODS
Interventions of progressive resistance or power training to increase muscle strength/power were examined but studies that included balance or multimodal training were excluded.
RESULTS
A total of 74 papers were eligible for review; 45 with strength measures only; 5 with power measures only and 24 papers containing both strength and power outcomes. Overall, 54% (27/50) of studies reported significantly improved strength and balance measures and 73% (16/22) showed improved power and balance following resistance/power training intervention, whereas 84% and 86% of cross sectional studies observed significant associations between balance and strength/power outcomes respectively.
CONCLUSION
The findings suggest that there is some evidence for the contribution of muscle strength and muscle power to balance performance in older adults. There is, however, weak evidence for the cause and effect relationship between muscle function and balance performance. Clinical Rehabilitation Impact. Inconsistencies in the literature can be attributed to methodological limitations.
Topics: Accidental Falls; Aged; Databases, Bibliographic; Female; Humans; Male; Muscle Weakness; Postural Balance; Resistance Training; Risk Factors
PubMed: 20485224
DOI: No ID Found -
The European Respiratory Journal Apr 2012Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant... (Review)
Review
Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology. Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure. As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.
Topics: Critical Illness; Energy Metabolism; Humans; Intensive Care Units; Muscle Proteins; Muscle Weakness; Risk Factors
PubMed: 21965224
DOI: 10.1183/09031936.00090011