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BMJ Case Reports Sep 2020Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by...
Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation.
Topics: Adult; Asthenia; Biopsy; Connectin; Diagnosis, Differential; Dyspnea; Female; Genetic Diseases, Inborn; Humans; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Mutation; Palliative Care; Respiratory Insufficiency
PubMed: 32912888
DOI: 10.1136/bcr-2020-235378 -
The American Journal of Emergency... Aug 2022Unilateral paralysis is an alarming symptom with broad differential diagnoses, including stroke, Todd's paralysis, myelopathy, and peripheral neuropathy. Hypokalemic... (Review)
Review
Unilateral paralysis is an alarming symptom with broad differential diagnoses, including stroke, Todd's paralysis, myelopathy, and peripheral neuropathy. Hypokalemic paralysis (HP), a neuromuscular disorder associated with muscle dysfunction, is caused by hypokalemia and manifests as symmetric proximal extremity muscle weakness. Unilateral paralysis has rarely been reported in the literature. Once hypokalemia is corrected, HP is usually reversible. Delayed diagnosis and treatment may result in fatal consequences. Here, we report an atypical case of unilateral weakness along with a review of the literature on unilateral HP.
Topics: Humans; Hypokalemia; Hypokalemic Periodic Paralysis; Muscle Weakness; Paralysis; Stroke
PubMed: 35527097
DOI: 10.1016/j.ajem.2022.04.042 -
International Journal of Environmental... Nov 2020The COVID-19 pandemic has recently been the cause of a global public health emergency. Frequently, elderly patients experience a marked loss of muscle mass and strength... (Review)
Review
The COVID-19 pandemic has recently been the cause of a global public health emergency. Frequently, elderly patients experience a marked loss of muscle mass and strength during hospitalization, resulting in a significant functional decline. This paper describes the impact of prolonged immobilization and current pharmacological treatments on muscular metabolism. In addition, the scientific evidence for an early strength intervention, neuromuscular electrical stimulation or the application of heat therapy during hospitalization to help prevent COVID-19 functional sequels is analyzed. This review remarks the need to: (1) determine which potential pharmacological interventions have a negative impact on muscle quality and quantity; (2) define a feasible and reliable pharmacological protocol to achieve a balance between desired and undesired medication effects in the treatment of this novel disease; (3) implement practical strategies to reduce muscle weakness during bed rest hospitalization and (4) develop a specific, early and safe protocol-based care of functional interventions for older adults affected by COVID-19 during and after hospitalization.
Topics: Aged; COVID-19; Hospitalization; Humans; Muscle Weakness; Pandemics; Time Factors
PubMed: 33255233
DOI: 10.3390/ijerph17238715 -
European Journal of Immunology Sep 2022Polymyositis (PM) is a chronic autoimmune inflammatory myopathy resulting in muscle weakness. The limited approved therapies and their poor efficacy contribute to its...
Polymyositis (PM) is a chronic autoimmune inflammatory myopathy resulting in muscle weakness. The limited approved therapies and their poor efficacy contribute to its comorbidity. We investigated the therapeutic use of ONX 0914 and KZR-616, selective inhibitors of the immunoproteasome, in C protein-induced myositis (CIM), a mouse model of PM that closely resembles the human disease. Diseased mice (day 13 postimmunization) were treated with 10 mg/kg ONX 0914, KZR-616, or vehicle on alternate days until day 28. Endpoints included muscle strength assessed by a grip strength meter, serum creatine kinase activity, histology, and immunohistochemistry analysis. Treatment with ONX 0914 or KZR-616 prevented the loss of grip strength in mice after CIM induction, while vehicle-treated animals displayed progressive muscle weakness. Immunoproteasome inhibition lowered PM-associated leukocyte infiltration of the muscle and prevented increased serum creatine kinase levels. LMP7-deficient mice were resistant to CIM induction, as they showed no alterations in grip strength or creatine kinase (CK) levels or muscular alterations. In conclusion, selective inhibition of the immunoproteasome displays therapeutic efficacy in a preclinical mouse model of PM with suppression of muscle inflammation and preservation of muscle strength. Positive results from this study support the rationale for using KZR-616 in clinical studies.
Topics: Animals; Creatine Kinase; Humans; Mice; Morpholines; Muscle Weakness; Polymyositis; Proteasome Endopeptidase Complex
PubMed: 35733374
DOI: 10.1002/eji.202249851 -
Tuberkuloz Ve Toraks Jun 2023This study aimed to investigate whether inspiratory muscle strength was associated with bacterial colonization and other clinical outcomes and whether bacterial...
INTRODUCTION
This study aimed to investigate whether inspiratory muscle strength was associated with bacterial colonization and other clinical outcomes and whether bacterial colonization was associated with clinical outcomes in patients with non-cystic fibrosis bronchiectasis (NCFB).
MATERIALS AND METHODS
Eighty-six patients were enrolled in a cross-sectional study. Patients were divided into two groups according to the presence of inspiratory muscle weakness and bacterial colonization. Parameters were compared between groups.
RESULT
Bronchiectasis etiologies were post-infectious, Kartagener's syndrome, and primary ciliary dyskinesia. The median value of MIP was -68, and MEP was 89 cm H2O in all patients. Although the ratio of bacterial colonization was similar to patients without inspiratory muscle weakness, the inspiratory muscle weakness group had a higher number of females, lower FEV1, FVC, ISWT, CRQ, higher MRC, E-FACED, SGRQ, number of hospitalization (p<0.05). When colonized and non-colonized patients were compared, MIP, and MEP were similar in spite of adjusted BMI, age, and sex. FEV1, FVC, ISWT, and ESWT were lower, and E-FACED scores (p<0.05) were higher in colonized patients.
CONCLUSIONS
Although inspiratory muscle strength was not associated with bacterial colonization in NCFB patients, it is an important factor that could be linked to disease severity, pulmonary functions, quality of life, and exercise capacity. Bacterial colonization was also associated with severe disease, deteriorated pulmonary functions, and exercise capacity.
Topics: Female; Humans; Cross-Sectional Studies; Quality of Life; Bronchiectasis; Fibrosis; Muscle Weakness; Muscles
PubMed: 37345393
DOI: 10.5578/tt.20239914 -
BMC Pharmacology & Toxicology Sep 2021In septic mice, supplementing parenteral nutrition with 150 mg/day 3-hydroxybutyrate-sodium-salt (3HB-Na) has previously shown to prevent muscle weakness without...
BACKGROUND
In septic mice, supplementing parenteral nutrition with 150 mg/day 3-hydroxybutyrate-sodium-salt (3HB-Na) has previously shown to prevent muscle weakness without obvious toxicity. The main objective of this study was to identify the toxic threshold of 3HB-Na supplementation in septic mice, prior to translation of this promising intervention to human use.
METHODS
In a centrally-catheterized, antibiotic-treated, fluid-resuscitated, parenterally fed mouse model of prolonged sepsis, we compared with placebo the effects of stepwise escalating doses starting from 150 mg/day 3HB-Na on illness severity and mortality (n = 103). For 5-day survivors, also the impact on ex-vivo-measured muscle force, blood electrolytes, and markers of vital organ inflammation/damage was documented.
RESULTS
By doubling the reference dose of 150 mg/day to 300 mg/day 3HB-Na, illness severity scores doubled (p = 0.004) and mortality increased from 30.4 to 87.5 % (p = 0.002). De-escalating this dose to 225 mg still increased mortality (p ≤ 0.03) and reducing the dose to 180 mg/day still increased illness severity (p ≤ 0.04). Doses of 180 mg/day and higher caused more pronounced metabolic alkalosis and hypernatremia (p ≤ 0.04) and increased markers of kidney damage (p ≤ 0.05). Doses of 225 mg/day 3HB-Na and higher caused dehydration of brain and lungs (p ≤ 0.05) and increased markers of hippocampal neuronal damage and inflammation (p ≤ 0.02). Among survivors, 150 mg/day and 180 mg/day increased muscle force compared with placebo (p ≤ 0.05) up to healthy control levels (p ≥ 0.3).
CONCLUSIONS
This study indicates that 150 mg/day 3HB-Na supplementation prevented sepsis-induced muscle weakness in mice. However, this dose appeared maximally effective though close to the toxic threshold, possibly in part explained by excessive Na intake with 3HB-Na. Although lower doses were not tested and thus might still hold therapeutic potential, the current results point towards a low toxic threshold for the clinical use of ketone salts in human critically ill patients. Whether 3HB-esters are equally effective and less toxic should be investigated.
Topics: 3-Hydroxybutyric Acid; Acid-Base Equilibrium; Aldosterone; Animals; Brain; Dietary Supplements; Dose-Response Relationship, Drug; Infusions, Parenteral; Ketones; Kidney; Liver; Male; Maximum Tolerated Dose; Mice, Inbred C57BL; Muscle Weakness; Sepsis; Severity of Illness Index; Mice
PubMed: 34544493
DOI: 10.1186/s40360-021-00517-7 -
International Journal of Environmental... Nov 2023Japanese diet adherence has been inversely correlated with muscle weakness. In this study, we aimed to validate that association. Longitudinal data from 1699 individuals...
Japanese diet adherence has been inversely correlated with muscle weakness. In this study, we aimed to validate that association. Longitudinal data from 1699 individuals aged ≥50 years (mean age 62.5 ± 6.9 years, 50.4% female) at two time points (2007 and 2011) were used. Participants without muscle weakness from several regions in Japan were included. The 12-component revised Japanese Diet Index (rJDI12) classified by tertiles assessed adherence to the Japanese dietary pattern. Muscle weakness was defined as a handgrip strength of ˂18 kg for females and ˂28 kg for males based on the Asian Working Group for Sarcopenia criteria 2019. A multivariate logistic approach was used to determine the relationship between rJDI12 tertile and the occurrence of muscle weakness by calculating the odds ratio (OR) and its 95% confidence interval (95% CI) throughout the observation period. Muscle weakness was negatively correlated with the highest rJDI12 tertile (OR [95% CI] 0.891 [0.814, 0.973] for T3). This association was consistent in sensitivity analyses with multiple imputations of missing values. Closely following the Japanese dietary pattern appears to reduce the occurrence of muscle weakness among the aging population in this study, suggesting it may prevent frailty and sarcopenia in the aging population.
Topics: Aged; Female; Humans; Male; Middle Aged; Cohort Studies; Diet; East Asian People; Hand Strength; Muscle Weakness; Sarcopenia
PubMed: 37998296
DOI: 10.3390/ijerph20227065 -
American Journal of Respiratory and... Apr 2023Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. This study investigated diaphragm... (Clinical Trial)
Clinical Trial
Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. This study investigated diaphragm muscle strength in patients after COVID-19 and its relationship to unexplained dyspnea on exertion. Fifty patients previously hospitalized with COVID-19 (14 female, age 58 ± 12 yr, half of whom were treated with mechanical ventilation, and half of whom were treated outside the ICU) were evaluated using pulmonary function testing, 6-minute-walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm function data were compared with values from a healthy control group. Moderate or severe dyspnea on exertion was present at 15 months after hospital discharge in approximately two-thirds of patients. No significant pulmonary function or echocardiography abnormalities were detected. Twitch transdiaphragmatic pressure was significantly impaired in patients previously hospitalized with COVID-19 compared with control subjects, independent of initial disease severity (14 ± 8 vs. 21 ± 3 cm HO in mechanically ventilated patients vs. control subjects [ = 0.02], and 15 ± 8 vs. 21 ± 3 cm HO in nonventilated patients vs. control subjects [ = 0.04]). There was a significant association between twitch transdiaphragmatic pressure and the severity of dyspnea on exertion ( = 0.03). Diaphragm muscle weakness was present 15 months after hospitalization for COVID-19 even in patients who did not require mechanical ventilation, and this weakness was associated with dyspnea on exertion. The current study, therefore, identifies diaphragm muscle weakness as a correlate for persistent dyspnea in patients after COVID-19 in whom lung and cardiac function are normal. Clinical trial registered with www.clinicaltrials.gov (NCT04854863).
Topics: Aged; Female; Humans; Middle Aged; COVID-19; Diaphragm; Dyspnea; Hospitalization; Muscle Weakness; Muscular Diseases; Thoracic Diseases
PubMed: 36596223
DOI: 10.1164/rccm.202206-1243OC -
Gait & Posture Jul 2022The C-Mill interactive treadmill allows for a safe walking-adaptability assessment, unveiling reduced walking adaptability in polio survivors compared to healthy...
BACKGROUND
The C-Mill interactive treadmill allows for a safe walking-adaptability assessment, unveiling reduced walking adaptability in polio survivors compared to healthy individuals, possibly related to their high fall rate. However, evidence on its validity and reproducibility is scarce.
RESEARCH QUESTION
What is the validity and reproducibility of C-Mill walking-adaptability assessment in polio survivors?
METHODS
Polio survivors with a history and/or fear of falling (n = 46) performed two walking-adaptability assessments, 1-2 weeks apart, including target-stepping tests (with 0%, 20% and 30% inter-target variance) and obstacle-avoidance tests (anticipatory and reactive). We examined (1) face validity by determining Group effects (for subgroups stratified for fall frequency, fear of falling and leg muscle weakness) and Condition effects (for difficulty level) on walking-adaptability outcomes, (2) construct validity by correlating walking-adaptability and balance outcomes, and (3) content validity by establishing possible ceiling effects. We determined whether face-validity findings were reproducible over test occasions and calculated Intraclass Correlation Coefficients (ICC) and the 95% Limits of Agreement (LoA) for walking-adaptability outcomes.
RESULTS
Walking-adaptability outcomes differed in to-be-expected directions for subgroups stratified for fall frequency and leg muscle weakness and for difficulty levels, all reproducible over test occasions. Correlations between walking-adaptability and balance outcomes were mainly low (r < 0.587). Ceiling effects were present for anticipatory obstacle-avoidance and balance outcomes, but not for reactive obstacle avoidance. ICCs [95% confidence intervals] were good for the challenging 20% (0.80[0.67-0.88]) and 30% target-stepping conditions (0.74[0.57-0.85]) and for the reactive obstacle-avoidance (0.76[0.59-0.86]) condition, but not for 0% target-stepping and anticipatory obstacle-avoidance (ICC<0.62) conditions. Likewise, the narrowest LoA were observed for the 20% and 30% target-stepping conditions.
SIGNIFICANCE
We proved face, construct and content validity of C-Mill walking-adaptability assessment in polio survivors with a history of falls and/or fear of falling. Adding walking-adaptability assessment, particularly the more challenging tests given their superior reproducibility, to currently used clinical tests could improve fall-risk evaluation in this population.
Topics: Fear; Gait; Humans; Muscle Weakness; Poliomyelitis; Postural Balance; Reproducibility of Results; Survivors; Walking
PubMed: 35772347
DOI: 10.1016/j.gaitpost.2022.06.008 -
Scientific Reports Mar 2021The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal... (Meta-Analysis)
Meta-Analysis
The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles. We collected data published from 1990 to April 2020 using PubMed, Cochrane Library, EMBASE, and SciELO. Risk of bias for observational studies was assessed regarding the ROBIN-I scale. Studies with less than five patients (case reports) were selected for an additional qualitative analysis. We used the software Comprehensive Meta-Analysis at the confidence level of 0.05. We identified 23 studies for qualitative analysis (17 case-reports), and five studies were eligible for quantitative analysis. From case reports, 21 patients presented muscle weakness and confirmatory biopsy for CQ/HCQ induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of CQ/HCQ, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy. No study presented randomized samples. The chronic use of CQ/HCQ may be a risk for drug-induced myopathy. There is substantiated need for proper randomized trials and controlled prospective studies needed to assess the clinical and subclinical stages of CQ/HCQ -induced muscle myopathy.
Topics: Adult; Aged; Creatine Kinase; Fructose-Bisphosphate Aldolase; Humans; Hydroxychloroquine; L-Lactate Dehydrogenase; Middle Aged; Muscle Weakness; Muscle, Skeletal; Observational Studies as Topic
PubMed: 33758324
DOI: 10.1038/s41598-021-86079-4