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Stroke-related sarcopenia (SRS) is characterized by progressive systemic muscle loss and decreased function and is thought to be primarily affected by catabolic-anabolic imbalance, but there is a lack of specific treatment. Our study evaluated whether β-hydroxybutyrate (BHB) improves SRS through regulation in protein synthesis and proteolysis. BHB reduced infarct volume, increased muscle mass and muscle fiber cross-sectional area. Delayed administration of BHB, when the infarct volume was stable, improved the balance beam score and time of rotarod and the above SRS indicators. Mechanistically, BHB increased the total contents of H3K9bhb in gastrocnemius muscles of tMCAO mice and enhanced the endogenous binding of H3K9bhb with Foxo3a promoter in response to the transcription inhibition of Foxo3a. Our study indicated BHB alleviated SRS, which was partly mediated by H3K9bhb, and then inhibited FOXO3a. BHB also promoted protein synthesis, muscle regeneration and proliferation to maintain protein metabolic homeostasis and ultimately ameliorated SRS.

Sang-Hun Lee,1 Hangseok Choi,2 Keon-Yeup Kim,1 Hyung-Soo Lee,3 Jin-Man Jung1 1Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea; 2Medical Science Research Center, Korea University College of Medicine, Seoul, South Korea; 3Department of Medicine, Graduate School, Kyung Hee University, Seoul, South KoreaCorrespondence: Jin-Man Jung, Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Gojan 1-Dong, Danwon-Gu, Ansan, Gyeonggi-Do, 15355, South Korea, Tel +82-31-412-5150, Fax +82-31-412-5154, Email dr.jinmanjung@gmail.comPurpose: Several studies have examined the clinical impact of poststroke and stroke-related sarcopenia on stroke recovery. However, few studies have investigated the effect of sarcopenia detected shortly after stroke on functional prognosis. We predicted functional outcomes using early screening for sarcopenia in patients with acute ischemic stroke. We also examined the effect of sarcopenia detected shortly after stroke on functional prognosis.Patients and Methods: Patients diagnosed with acute ischemic stroke within 2 days of symptom onset were consecutively enrolled at a tertiary university hospital. Appendicular skeletal muscle mass (ASM) was measured using dual-energy X-ray absorptiometry during early hospitalization. Sarcopenia was diagnosed based on low ASM and strength criteria of the Asian Working Group for Sarcopenia (AWGS) and European Working Group on Sarcopenia in Older People (EWGSOP2). The primary outcome was poor functional outcome, defined as a modified Rankin score of 4– 6 and all-cause mortality at 3 months.Results: Of the 653 patients, 214 (32.8%) and 174 (26.6%) had sarcopenia according to the AWGS and EWGSOP2 criteria, respectively. Irrespective of the definition, the sarcopenia group had a significantly higher proportion of patients with poor functional outcomes and all-cause mortality. Multivariate logistic regression analysis revealed that height-adjusted ASM was independently associated with poor functional outcomes (odds ratio: 0.61; 95% confidence interval: 0.40– 0.91; P < 0.005), and they were negatively correlated. However, the association between 3-month mortality, skeletal muscle mass, and sarcopenia was not sustained in multivariate analyses.Conclusion: Height-adjusted ASM associated with sarcopenia is a potential predictor of poor functional outcomes at 3 months in patients with acute stroke. However, owing to the limitations of this study, further research is required to confirm these findings.Keywords: stroke-related sarcopenia, skeletal muscle mass, functional outcome, prognosis

The prevalence of stroke-related sarcopenia has been noted; however, epidemiological data and interventions that increase or reduce the incidence of stroke-related sarcopenia remain lacking. Studies on stroke-related sarcopenia were included in association or interventional analyses. All analyses were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two evaluators independently extracted the data. Female stroke patients had a higher preference for sarcopenia than male patients (pooled odds ratio [OR] = 0.670, 95 % CI 0.533–0.842, p = 0.001). Although stroke patients without drug use have improved skeletal muscle mass index (SMI) (MD = 0.272, 95 % CI 0.087–0.457, p = 0.004), handgrip strength (HGS) was not significantly altered (MD = −0.068, 95 % CI −0.221–0.076, p = 0.354). Stroke patients with nutrient interventions have improved SMI (MD = −0.354, 95 % CI −0.635- −0.073, p = 0.014) and HGS (MD = −0.394, 95 % CI −0.678- −0.111, p = 0.006); the synergistic effect of rehabilitation exercise has not been ruled out. Whether a sex difference exists in these interventions remains to be investigated. The underlying pathological mechanisms and potential therapeutic strategies for this disease are discussed. Sex difference, proteostasis, and mitochondrial function may impact the incidence of stroke-related sarcopenia. Understanding the underlying pathological mechanisms and potential therapeutic targets for this disease will provide new insights into disease treatment, prevention, and drug development. • Epidemiological data and interventions that increase or reduce the incidence of stroke-related sarcopenia remain lacking. • Female stroke patients had a higher preference for sarcopenia than male patients. • Without drug use improves skeletal muscle mass index (SMI) but not handgrip strength (HGS) in stroke patients. • Nutrient interventions may improve SMI and HGS in stroke patients. • Understanding disease's pathological mechanisms will provide new insights into treatment, prevention, and drug development. [ABSTRACT FROM AUTHOR]

[Display omitted] • BHB reduced infarct volume, increased muscle mass and muscle fiber CSA of tMCAO mice. • Delayed administration of BHB after tMCAO, when the infarct volume was stable, improved the balance beam score and time of rotarod and increased muscle mass and muscle fiber CSA. • BHB increased the total contents of H3K9bhb and enhanced the endogenous binding of H3K9bhb with FOXO3a promoter in response to the transcription inhibition of FOXO3a. • BHB promoted protein synthesis, muscle regeneration and proliferation to maintain protein metabolic homeostasis and ultimately ameliorated SRS. Stroke-related sarcopenia (SRS) is characterized by progressive systemic muscle loss and decreased function and is thought to be primarily affected by catabolic-anabolic imbalance, but there is a lack of specific treatment. Our study evaluated whether β-hydroxybutyrate (BHB) improves SRS through regulation in protein synthesis and proteolysis. BHB reduced infarct volume, increased muscle mass and muscle fiber cross-sectional area. Delayed administration of BHB, when the infarct volume was stable, improved the balance beam score and time of rotarod and the above SRS indicators. Mechanistically, BHB increased the total contents of H3K9bhb in gastrocnemius muscles of tMCAO mice and enhanced the endogenous binding of H3K9bhb with Foxo3a promoter in response to the transcription inhibition of Foxo3a. Our study indicated BHB alleviated SRS, which was partly mediated by H3K9bhb, and then inhibited FOXO3a. BHB also promoted protein synthesis, muscle regeneration and proliferation to maintain protein metabolic homeostasis and ultimately ameliorated SRS. [ABSTRACT FROM AUTHOR]

Background & Aims: Muscle atrophy is an early event that occurs after stroke, but there are few reports on the changes in skeletal muscle thickness in acute stroke. This study investigated the factors contributing to reduced muscle thickness in patients with acute stroke., Methods: In total, 51 patients with stroke and the National Institute of the Health Stroke Scale (NIHSS) > 3 were included in our study. They were admitted to our hospital between July 2017 and May 2020. The quadriceps muscle thickness was measured with an ultrasound device within 2 days after admission and 14 days later. The collected data included age, sex, body mass index, stroke type, neuromuscular electrical stimulation, NIHSS, serum albumin at admission, start of enteral nutrition, Functional Oral Intake Scale (FOIS), start of mobilization and ambulation, number of physical and occupational therapy units, C-reactive protein at admission and whether surgery had been performed. These data were retrospectively retrieved from medical documents. A dietician calculated energy intake, protein intake, and energy adequacy. Multiple regression analysis was used to identify the factors associated with reduced quadriceps muscle thickness. The independent variables were NIHSS, date of start of enteral feeding, protein intake, FOIS, date of mobilization, and date of start of ambulation training., Results: The rate of change in quadriceps muscle thickness of the paretic limb was -15.3 % (interquartile range, -46.1-14.8 %). Multiple regression analysis showed that the factors responsible for the decrease in muscle thickness on the paretic side were FOIS (β: 0.376; 95 % Cl, 0.999 to 4.541) and the start date of ambulation (β: -0.378; 95 % Cl, -2.575 to -0.543), with a multiple correlation coefficient of 0.456., Conclusion: The FOIS and the start date of ambulation after acute stroke were related to the rate of reduction in muscle thickness on the paretic side., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare for this study., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

• Stroke-related sarcopenia is considered to be a kind of secondary sarcopenia. • The exact mechanism of sarcopenia in stroke patients is still unclear. • Some simple and convenient rehabilitation scores and clinical tests can be used for the screening. • It is necessary to pay attention to stroke-related sarcopenia. Sarcopenia is a syndrome characterized by progressive systemic muscle loss and decreased function. The loss of systemic muscle mass and decreased function after stroke can't be explained by brain injury alone, and it is considered to be a kind of secondary sarcopenia, which is called stroke-related sarcopenia. More and more evidence shows that stroke-related sarcopenia can promote the occurrence and development of sarcopenia through a variety of pathogenesis, such as immobilization, impaired feeding, sympathetic activation, inflammation and denervation. Post-stroke disability brings difficulties to the screening and diagnosis of sarcopenia. Simple and easy rehabilitation scores and clinical tests can be used for the determination of body function under specific conditions of stroke, as well as for the screening stroke-related sarcopenia. At present, there is still no particularly effective way to stop its progress,however, the combination of rehabilitation exercise, nutrition supply and drugs may delay or even prevent the development of stroke-related sarcopenia. This article reviews the latest progress in the pathogenesis, screening, evaluation and treatment of stroke-related sarcopenia to provide reference for clinical treatment and rehabilitation of stroke. [ABSTRACT FROM AUTHOR]