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Neurology India 2021Polymyositis is a group of muscle disease characterised by progressive muscle inflammation and predominantly muscle weakness. It usually presents subacutely with...
Polymyositis is a group of muscle disease characterised by progressive muscle inflammation and predominantly muscle weakness. It usually presents subacutely with proximal weakness and mild diffuse muscular pain. Some patients have atypical presentation like early respiratory difficulty, Motor neuron disease (MND), or isolated dysphagia which leads to delay in diagnosis and treatment. We present one such case.
Topics: Deglutition Disorders; Humans; Motor Neuron Disease; Muscle Weakness; Myositis; Polymyositis
PubMed: 34747820
DOI: 10.4103/0028-3886.329582 -
Neural Plasticity 2021This study presents single-fiber electromyography (EMG) analysis for assessment of paretic muscle changes after stroke. Single-fiber action potentials (SFAPs) were...
This study presents single-fiber electromyography (EMG) analysis for assessment of paretic muscle changes after stroke. Single-fiber action potentials (SFAPs) were recorded from the first dorsal interosseous (FDI) muscle bilaterally in 12 individuals with hemiparetic stroke. The SFAP parameters, including the negative peak duration and the peak-peak amplitude, were measured and further used to estimate muscle fiber diameter through a model based on the quadratic function. The SFAP parameters, fiber density, and muscle fiber diameter derived from the model were compared between the paretic and contralateral muscles. The results show that SFAPs recorded from the paretic muscle had significantly smaller negative peak duration than that from the contralateral muscle. As a result, the derived muscle fiber diameter of the paretic muscle was significantly smaller than that of the contralateral muscle. The fiber density of the paretic muscle was significantly higher than that of the contralateral muscle. These results provide further evidence of remodeled motor units after stroke and suggest that paretic muscle weakness can be due to both complex central and peripheral neuromuscular alterations.
Topics: Action Potentials; Aged; Electromyography; Female; Humans; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle, Skeletal; Paresis; Stroke
PubMed: 34434227
DOI: 10.1155/2021/3045990 -
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 -
The American Journal of Pathology Aug 2020Alzheimer disease (AD) is characterized by deterioration of cognitive capabilities with an estimated 44 million individuals worldwide living with it. Beyond memory... (Review)
Review
Alzheimer disease (AD) is characterized by deterioration of cognitive capabilities with an estimated 44 million individuals worldwide living with it. Beyond memory deficits, the most common AD co-morbidities include swallowing defects (muscle), fractures (bone, muscle), and heart failure. The underlying causes of these co-morbidities and their role in AD pathophysiology are currently unknown. This review is the first to summarize the emerging picture of the cardiac and musculoskeletal deficits in human AD. We present the involvement of the heart, characterized by diastolic heart failure, the presence of amyloid deposits, and electrophysiological changes, compared with age-matched control subjects. The characteristic musculoskeletal defects in AD come from recent clinical studies and include potential underlying mechanisms (bone) in animal models. These studies detail a primary muscle weakness (without a loss of muscle mass) in patients with mild cognitive impairment, with progression of cognitive impairment to AD associating with ongoing muscle weakness and the onset of muscle atrophy. We conclude by reviewing the loss of bone density in patients with AD, paralleling the increase in fracture and fall risk in specific populations. These studies paint AD as a systemic disease in broad strokes, which may help elucidate AD pathophysiology and to allow for new ways of thinking about therapeutic interventions, diagnostic biomarkers, and the pathogenesis of this multidisciplinary disease.
Topics: Alzheimer Disease; Cognitive Dysfunction; Disease Progression; Heart; Humans; Muscle Weakness; Muscle, Skeletal
PubMed: 32407731
DOI: 10.1016/j.ajpath.2020.04.013 -
Molecular Brain Dec 2023Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It... (Review)
Review
Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion channels and alteration in neuronal excitability represent a hallmark of the disease, manifesting not only during the symptomatic period but also in the early pre-symptomatic stages. In this review, we delve into these alterations observed in ALS patients and preclinical disease models, and explore their consequences on neuronal activities. Furthermore, we discuss the potential of ion channels as therapeutic targets in the context of ALS.
Topics: Humans; Amyotrophic Lateral Sclerosis; Motor Neurons; Ion Channels; Muscle Weakness
PubMed: 38102715
DOI: 10.1186/s13041-023-01070-6 -
Clinical and Translational Science Jul 2021Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately,...
Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator-induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin-angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1-7 (Ang1-7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1-7 protects the diaphragm against MV-induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1-7 shielded diaphragm fibers against MV-induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1-7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1-7 has the therapeutic potential to protect against VIDD by preventing MV-induced contractile dysfunction and atrophy of both slow and fast muscle fibers.
Topics: Angiotensin I; Animals; Diaphragm; Disease Models, Animal; Female; Humans; Infusions, Intravenous; Muscle Contraction; Muscle Weakness; Muscular Disorders, Atrophic; Oxidative Stress; Peptide Fragments; Rats; Respiration, Artificial
PubMed: 33742769
DOI: 10.1111/cts.13015 -
Annals of the New York Academy of... May 2021Aging is a chronic, complicated process that leads to degenerative physical and biological changes in living organisms. Aging is associated with permanent, gradual... (Review)
Review
Aging is a chronic, complicated process that leads to degenerative physical and biological changes in living organisms. Aging is associated with permanent, gradual physiological cellular decay that affects all aspects of cellular mechanobiological features, including cellular cytoskeleton structures, mechanosensitive signaling pathways, and forces in the cell, as well as the cell's ability to sense and adapt to extracellular biomechanical signals in the tissue environment through mechanotransduction. These mechanobiological changes in cells are directly or indirectly responsible for dysfunctions and diseases in various organ systems, including the cardiovascular, musculoskeletal, skin, and immune systems. This review critically examines the role of aging in the progressive decline of the mechanobiology occurring in cells, and establishes mechanistic frameworks to understand the mechanobiological effects of aging on disease progression and to develop new strategies for halting and reversing the aging process. Our review also highlights the recent development of novel bioengineering approaches for studying the key mechanobiological mechanisms in aging.
Topics: Aging; Biomechanical Phenomena; Cytoskeleton; Disease Progression; Elasticity; Humans; Mechanotransduction, Cellular; Muscle Weakness; Musculoskeletal System
PubMed: 33231326
DOI: 10.1111/nyas.14529 -
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 -
Brazilian Journal of Cardiovascular... Jun 2021In heart transplantation (HT) recipients, several factors are critical to promptly adopting appropriate rehabilitation strategies and may be important to predict...
INTRODUCTION
In heart transplantation (HT) recipients, several factors are critical to promptly adopting appropriate rehabilitation strategies and may be important to predict outcomes way after surgery. This study aimed to determine preoperative patient-related risk factors that could adversely affect the postoperative clinical course of patients undergoing HT.
METHODS
Twenty-one hospitalized patients with heart failure undergoing HT were evaluated according to respiratory muscle strength and functional capacity before HT. Mechanical ventilation (MV) time, reintubation rate, and intensive care unit (ICU) length of stay were recorded, and assessed postoperatively.
RESULTS
Inspiratory muscle strength as absolute and percentpredicted values were strongly correlated with MV time (r=-0.61 and r=-0.70, respectively, at P<0.001). Concerning ICU length of stay, only maximal inspiratory pressure (MIP) absolute and percent-predicted values were significantly associated. The absolute |MIP| was significantly negatively correlated with ICU length of stay (r=-0.58 at P=0.006) and the percent-predicted MIP was also significantly negatively correlated with ICU length of stay (r=-0.68 at P=0.0007). No associations were observed between preoperative functional capacity, age, sex, and clinical characteristics and MV time and ICU length of stay in the cohort included in this study. Patients with respiratory muscle weakness had a higher prevalence of prolonged MV, reintubation, and delayed ICU length of stay.
CONCLUSION
An impairment of preoperative MIP was associated with poorer short-term outcomes following HT. As such, inspiratory muscle strength is an important clinical preoperative marker in patients undergoing HT.
Topics: Heart Transplantation; Humans; Intensive Care Units; Maximal Respiratory Pressures; Muscle Weakness; Respiration, Artificial; Respiratory Muscles
PubMed: 33438847
DOI: 10.21470/1678-9741-2020-0344