Publications by authors named "Nadja Scherbakov"

38 Publications

Comment on: "Experimental ischaemic stroke induces transient cardiac athrophy" by Veltkamp et al.

J Cachexia Sarcopenia Muscle 2020 12;11(6):1865-1866

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1002/jcsm.12638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749586PMC
December 2020

Comment on 'Weight loss in heart failure is associated with increased mortality only in non-obese patients without diabetes' by Niedziela et al.

J Cachexia Sarcopenia Muscle 2020 12 26;11(6):1867-1868. Epub 2020 Nov 26.

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1002/jcsm.12649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749531PMC
December 2020

Early rehabilitation after stroke: relationship between the heart rate variability and functional outcome.

ESC Heart Fail 2020 10 30;7(5):2983-2991. Epub 2020 Jul 30.

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Berlin, Germany.

Aims: Impaired autonomic nervous system regulation is frequently observed in patients with stroke. The aim of this prospective study was to evaluate the impact of cardiac autonomic tone on functional outcome after the early post-stroke rehabilitation.

Methods And Results: One hundred and three consecutive patients (67 ± 11 years, body mass index (BMI) 27.1 ± 5.4 kg/m , 64% men) with ischaemic (84% of patients) and haemorrhagic stroke were studied. Depressed heart rate variability (HRV), as a surrogate marker of increased sympathetic tone, was defined by the standard deviation of NN intervals < 100 ms and HRV triangular index ≤ 20 assessed from a 24 h Holter electrocardiogram at admission to rehabilitation (23 ± 16 days after stroke). Twenty-two per cent of patients had depressed HRV at baseline and were comparable with patients with normal HRV with regard to their functional [Barthel Index (BI), modified Rankin Scale (mRS), and Rivermead Motor Assessment (RMA)] and biochemical status. After a 4-week follow-up, 70% of patients with depressed HRV showed a cumulative functional disability, defined by mRS ≥ 4, BI ≤ 70, and RMA ≤ 5, in contrast to patients with normal HRV (35%, P = 0.003). Patients with depressed HRV showed a worse functional status by BI (-16%, P < 0.001), RMA (-12%, P < 0.05), and mRS (+16%, P < 0.01), compared with patients with normal HRV. Cumulative functional disability was associated with depressed HRV (odds ratio 4.25, 95% confidence interval 1.56-11.54, P < 0.005) after adjustment for age, sex, and body mass index (odds ratio 4.6, 95% confidence interval 1.42-14.97, P < 0.05).

Conclusions: The presence of autonomic cardiovascular dysregulation in patients with subacute stroke was associated with adverse functional outcome after the early post-stroke rehabilitation.
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http://dx.doi.org/10.1002/ehf2.12917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524118PMC
October 2020

Acute effects of oral triglyceride load on dynamic changes in peripheral endothelial function in heart failure patients with reduced ejection fraction and healthy controls.

Nutr Metab Cardiovasc Dis 2020 10 2;30(11):1961-1966. Epub 2020 Jun 2.

Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Germany; Department of Cardiology (Virchow Klinikum), Charité Universitätsmedizin Berlin, German Centre for Cardiovascular Research (DZHK), Partner site Berlin, Germany; Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin (CSB), Germany. Electronic address:

Bachground: Postprandial hyperlipaemia impairs endothelial function, possibly via oxidative-stress-mediated mechanisms. The aim of this study was to evaluate the acute effects of an oral triglyceride load (OTGL) on peripheral endothelial function in heart failure patients with reduced ejection fraction (HFrEF) compared to healthy controls.

Design: Prospective cross-sectional.

Methods: We enrolled 47 patients with HFrEF and 20 healthy controls. Peripheral endothelial function was assessed with EndoPAT2000 technology using a reactive hyperaemia index (RHI) and pulse wave amplitude (PWA) at baseline (after 8-h overnight fasting) as well as 1, 2, 3 and 4-h post-OTGL consumption (250-ml cream drink). Pulse wave amplitude index (PWAI) was calculated as a ratio of PWA at each time point to the baseline PWA.

Results: RHI at baseline was lower in HFrEF patients compared to controls (1.7 ± 0.3 and 2.3 ± 0.6, respectively; P = 0.001). The OTGL accounted for a physiologic increase in PWA in healthy controls (p = 0.01), but this change was not observed in HFrEF patients. After 4 h, vasodilator response was significantly increased in healthy controls but not patients with HFrEF (2.3 ± 1.3 vs. 1.3 ± 0.8 respectively, P < 0.05).

Conclusions: The main finding of this study was the impaired postprandial dynamic changes in peripheral endothelial function in patients with HFrEF compared to healthy controls. A high-fat load that caused acute hypertriglyceridaemia significantly increased resting blood flow and peak flow at reactive hyperaemia in healthy subjects. By contrast, patients with HFrEF exhibited impaired dynamic changes in peripheral endothelial function after oral triglyceride load.
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http://dx.doi.org/10.1016/j.numecd.2020.05.018DOI Listing
October 2020

Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome.

ESC Heart Fail 2020 06 10;7(3):1064-1071. Epub 2020 Mar 10.

Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Augustenburger Platz 1, 13353, Berlin, Germany.

Aims: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from various studies showing cerebral hypoperfusion and orthostatic intolerance. The peripheral endothelial dysfunction (ED) has not been sufficiently investigated in patients with ME/CFS. The aim of the present study was to examine peripheral endothelial function in patients with ME/CFS.

Methods And Results: Thirty-five patients [median age 40 (range 18-70) years, mean body mass index 23.8 ± 4.2 kg/m , 31% male] with ME/CFS were studied for peripheral endothelial function assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of ME/CFS was based on Canadian Criteria. Nine of these patients with elevated antibodies against β2-adrenergic receptor underwent immunoadsorption, and endothelial function was measured at baseline and 3, 6, and 12 months follow-up. ED was defined by reactive hyperaemia index ≤1.81. Twenty healthy subjects of similar age and body mass index were used as a control group. Peripheral ED was found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P < 0.05). Patients with ED, in contrast to patients with normal endothelial function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ± 16, P = 0.04), as well as more severe fatigue-related symptoms (8.62 ± 0.87 vs. 7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile range 7.0-10.0) vs. 7.5 (interquartile range 6.0-9.25), P = 0.04]. Peripheral ED showed correlations with more severe immune-associated symptoms (r = -0.41, P = 0.026), such as sore throat (r = -0.38, P = 0.038) and painful lymph nodes (r = -0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = -0.59, P = 0.005). There were no differences between the patient group with ED and the patient group with normal endothelial function regarding demographic, metabolic, and laboratory parameters. Further, there was no difference in soluble vascular cell adhesion molecule and soluble intercellular adhesion molecule levels. At baseline, peripheral ED was observed in six patients who underwent immunoadsorption. After 12 months, endothelial function had improved in five of these six patients (reactive hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06).

Conclusions: Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.
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http://dx.doi.org/10.1002/ehf2.12633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261521PMC
June 2020

Body weight changes and incidence of cachexia after stroke.

J Cachexia Sarcopenia Muscle 2019 06 24;10(3):611-620. Epub 2019 Jan 24.

BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Germany.

Background: Body weight loss is a frequent complication after stroke, and its adverse effect on clinical outcome has been shown in several clinical trials. The purpose of this prospective longitudinal single-centre observational study was to investigate dynamical changes of body composition and body weight after ischemic stroke and an association with functional outcome.

Methods: Sixty-seven consecutive patients (age 69 ± 11 years, body mass index 27.0 ± 4.1 kg/m , 42% female patient, mean ± SD) with acute ischemic stroke with mild to moderate neurological deficit (National Institute of Health Stroke Scale median 4, ranged 0-12) were analysed in the acute phase (4 ± 2 days) and at 12 months (389 ± 26 days) follow-up. Body composition was examined by dual energy X-ray absorptiometry. Cachexia was defined according to the consensus definition by body weight loss ≥5% within 1 year and additional clinical signs. Lean tissue wasting was considered if a ratio of upper and lower limbs lean mass sum to squared height (kg/m ) was ≤5.45 kg/m for female patient and ≤7.25 kg/m for male patient.

Results: According to the body weight changes after 12 months, 42 (63%) patients had weight gain or stable weight, 11 (16%) patients had moderate weight loss, and 14 (21%) patients became cachectic. A relative decline of 19% of fat tissue and 6.5% of lean tissue was observed in cachectic patients, while no changes of lean tissue were observed in non-cachectic patients after 12 months. The modified Rankin Scale was 48% higher (2.1 ± 1.6, P < 0.05), Barthel Index was 22% lower (71 ± 39, P < 0.01), and handgrip strength was 34% lower (21.9 ± 13.0, P < 0.05) in cachectic compared to non-cachectic patients after 12 months. The low physical performance if defined by Barthel Index <60 points was linked to the lean tissue wasting (OR 44.8, P < 0.01), presence of cachexia (OR 20.8, P < 0.01), and low body mass index <25 kg/m (OR 11.5, P < 0.05). After adjustment for cofounders, lean tissue wasting remained independently associated with the low physical performance at 12 months follow-up (OR 137.9, P < 0.05).

Conclusions: In this cohort study, every fifth patient with ischemic stroke fulfilled the criteria of cachexia within 12 months after index event. The incidence of cachexia was 21%. Cachectic patients showed the lowest functional and physical capacity.
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http://dx.doi.org/10.1002/jcsm.12400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596391PMC
June 2019

Cachexia as a common characteristic in multiple chronic disease.

J Cachexia Sarcopenia Muscle 2018 Dec 13;9(7):1189-1191. Epub 2019 Jan 13.

Department of Cardiology (CVK), Charité-Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1002/jcsm.12388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351667PMC
December 2018

Do we need a reference standard for the muscle mass measurements?

ESC Heart Fail 2018 10;5(5):741-744

Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1002/ehf2.12356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165936PMC
October 2018

Heart-brain Interactions in Heart Failure.

Card Fail Rev 2018 Aug;4(2):87-91

Centre for Stroke Research Berlin, Charité University Hospital Berlin, Germany.

Heart failure (HF) is a complex disease with a growing incidence worldwide. HF is accompanied by a wide range of conditions which affect disease progression, functional performance and contribute to growing healthcare costs. The interactions between a failing myocardium and altered cerebral functions contribute to the symptoms experienced by patients with HF, affecting many comorbidities and causing a poor prognosis. This article provides a condensed version of the 2018 position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association. It addresses the reciprocal impact on HF of several pathological brain conditions, including acute and chronic low perfusion of the brain, and impairment of higher cortical and brain stem functions. Treatment-related interactions - medical, interventional and device-related - are also discussed.
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http://dx.doi.org/10.15420/cfr.2018.14.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125712PMC
August 2018

Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME.

PLoS One 2018 15;13(3):e0193672. Epub 2018 Mar 15.

Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Introduction: Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases.

Methods: 10 patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with IA with an IgG-binding column for 5 days. We assessed severity of symptoms as outcome parameter by disease specific scores. Antibodies were determined by ELISA and B cell phenotype by flow cytometry.

Results: IgG levels dropped to median 0.73 g/l (normal 7-16 g/l) after the 4th cycle of IA, while IgA and IgM levels remained unchanged. Similarly, elevated ß2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later ß2 autoantibodies were significantly lower compared to pretreatment. Frequency of memory B cells significantly decreased and frequency of plasma cells increased after the 4th IA cycle. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting moderate to marked improvement for 6-12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening.

Conclusions: IA can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development. Data from our pilot trial warrants further studies in CFS/ME.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193672PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854315PMC
June 2018

Cardiac muscle wasting in individuals with cancer cachexia.

ESC Heart Fail 2017 11 15;4(4):458-467. Epub 2017 Jul 15.

Center for Stroke Research Berlin, Charite Universitätsmedizin Berlin, Berlin, Germany.

Aims: Cachexia is a severe complication of cancer that adversely affects the course of the disease and is associated with high rates of mortality. Patients with cancer manifest symptoms, such as fatigue, shortness of breath, and impaired exercise tolerance, which are clinical signs of chronic heart failure. The aim of this study was to evaluate cardiac muscle wasting in cancer individuals.

Methods And Results: We retrospectively analysed 177 individuals who died of cancer, including 58 lung, 60 pancreatic, and 59 gastrointestinal (GI) cancers, and 42 cancer-free controls who died of other, non-cardiovascular reasons. Cancer cachexia (CC) was defined based on clinical and/or pathological diagnosis, body mass index (BMI) <20.0 kg/m and/or oedema-free body weight loss of 5.0% during the previous year or less. The pathology reports were analysed for BMI, heart weight (HW), and left and right ventricular wall thicknesses (LVWT and RVWT, respectively). The analysis of clinical data included recording of biochemical parameters and medication data of study patients. CC was detected in 54 (30.5%) subjects. Individuals with CC had a significantly lower HW than non-cachectic subjects (363.1 ± 86.2 vs. 447.0 ± 128.9 g, P < 0.001) and control group (412.9 ± 75.8 g, P < 0.05). BMI correlated with HW in cases with GI cancer (r = 0.44, P < 0.001), lung cancer (r = 0.53, P < 0.0001), and pancreatic cancer (r = 0.39, P < 0.01).

Conclusions: Body weight loss in individuals with lung, pancreatic, and GI cancers is accompanied by a decrease in HW. In patients with CC who receive cancer treatment, screening for cardiac muscle wasting may have clinical importance.
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http://dx.doi.org/10.1002/ehf2.12184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695173PMC
November 2017

Sleep-Disordered Breathing in Acute Ischemic Stroke: A Mechanistic Link to Peripheral Endothelial Dysfunction.

J Am Heart Assoc 2017 Sep 11;6(9). Epub 2017 Sep 11.

Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Sleep-disordered breathing (SDB) after acute ischemic stroke is frequent and may be linked to stroke-induced autonomic imbalance. In the present study, the interaction between SDB and peripheral endothelial dysfunction (ED) was investigated in patients with acute ischemic stroke and at 1-year follow-up.

Methods And Results: SDB was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit. SDB was defined by apnea-hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (EndoPAT-2000). ED was defined by reactive hyperemia index ≤1.8. Forty-one stroke patients underwent 1-year follow-up (390±24 days) after stroke. SDB was observed in 57% patients with acute ischemic stroke. Compared with patients without SDB, ED was more prevalent in patients with SDB (32% versus 64%; <0.01). After adjustment for multiple confounders, presence of SDB remained independently associated with ED (odds ratio, 3.1; [95% confidence interval, 1.2-7.9]; <0.05). After 1 year, the prevalence of SDB decreased from 59% to 15% (<0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized SDB, compared with patients with persisting SDB (<0.05).

Conclusions: SDB was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral ED. Normalized ED in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between SDB and ED.

Clinical Trial Registration: URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00000514.
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http://dx.doi.org/10.1161/JAHA.117.006010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634268PMC
September 2017

Longer-term impact of hemiparetic stroke on skeletal muscle metabolism-A pilot study.

Int J Cardiol 2017 Mar 21;230:241-247. Epub 2016 Dec 21.

Center for Stroke Research Berlin, Charité Medical School Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany; Department of Cardiology, Charité Medical School Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address:

Background: Hemiparetic stroke leads to structural and metabolic alterations of skeletal muscle tissue, thereby contributing to functional impairment associated with stroke. In situ metabolic processes at tissue level in skeletal muscle have not been investigated. We hypothesize that muscular metabolic capacity is limited after hemiparetic stroke, and that changes affect rather the paretic than non-paretic limb.

Methods: Nine male hemiparetic stroke survivors (age, 62±8years; BMI, 28±4kg/m; median stroke latency, 23months ranging from 7 to 34months poststroke) underwent dynamic in situ measurements of carbohydrate and lipid metabolism at fasting condition and during oral glucose tolerance testing, using bilateral microdialysis. Results were compared to 8 healthy male subjects of similar age and BMI.

Results: Tissue perfusion, fasting and postprandial profiles of interstitial metabolites glucose, pyruvate, lactate and glycerol did not differ between paretic and non-paretic muscle. Patients displayed higher fasting and postprandial dialysate glycerol levels compared to controls (P<0.001) with elevated plasma FFA (fasting FFA; 0.63±0.23 vs. 0.29±0.17mmol/L; P=0.004). Glycolytic activity was higher in patients vs. controls, with increased lactate production upon glucose load (P<0.001).

Conclusions: An elevated lipolytic and glycolytic activity on tissue level suggests an impaired substrate metabolism with blunted oxidative metabolism in bilateral skeletal muscle in patients after hemiparetic stroke. Muscular metabolic properties did not differ between paretic and non-paretic leg. Further work is needed to investigate the clinical impact of this impaired muscular metabolic capacity in post-stroke patients.
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http://dx.doi.org/10.1016/j.ijcard.2016.12.143DOI Listing
March 2017

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation.

J Cachexia Sarcopenia Muscle 2016 03 27;7(1):60-7. Epub 2015 Oct 27.

Center for Stroke Research CSB Charite Universitätsmedizin Berlin Germany; German Centre for Cardiovascular Research (DZHK), partner site Berlin Germany; Department of Cardiology Charite Universitätsmedizin Berlin Germany.

Background: C-terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub-fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke.

Methods: Patients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m(2)) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA.

Results: CAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p < 0.001). Simple regression analyses revealed an association between CAF22 levels and parameters of physical performance, hand grip strength, and phase angle, a BIA derived measure of the muscle cellular integrity. Improvement of the handgrip strength of the paretic arm during rehabilitation was independently related to the recovery of CAF22 serum levels only in those patients who showed increased lean mass during the rehabilitation.

Conclusions: CAF22 serum profiles showed a dynamic elevation and recovery in the subacute phase after acute stroke. Further studies are needed to explore the potential of CAF22 as a serum marker to monitor the muscle status in patients after stroke.
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http://dx.doi.org/10.1002/jcsm.12068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799857PMC
March 2016

Searching for a relevant definition of sarcopenia: results from the cross-sectional EPIDOS study.

J Cachexia Sarcopenia Muscle 2016 03 2;7(1):100-1. Epub 2015 Dec 2.

Center for Stroke Research CSB Charite University Medical School Berlin Germany; German Centre for Cardiovascular Research (DZHK) Berlin Germany; Department of Cardiology Charite University Medical School Berlin Germany.

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http://dx.doi.org/10.1002/jcsm.12090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799861PMC
March 2016

Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation, and cachexia in chronic heart failure.

Eur Heart J 2016 06 9;37(21):1684-91. Epub 2016 Feb 9.

Department of Cardiology and Pneumology, University Medical Center Göttingen, Georg-August University, Göttingen, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Goettingen, Goettingen, Germany.

Aims: Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia.

Methods And Results: Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction ≤40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment.

Conclusion: Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship.
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http://dx.doi.org/10.1093/eurheartj/ehw008DOI Listing
June 2016

Influence of essential amino acids on muscle mass and muscle strength in patients with cerebral stroke during early rehabilitation: protocol and rationale of a randomized clinical trial (AMINO-Stroke Study).

BMC Neurol 2016 Jan 22;16:10. Epub 2016 Jan 22.

Center for Stroke Research Berlin CSB, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Patients with stroke are at a high risk for long-term handicap and disability. In the first weeks after stroke muscle wasting is observed frequently. Early post-stroke rehabilitation programs are directed to improve functional independence and physical performance. Supplementation with essential amino acids (EAAs) might prevent muscle wasting and improve rehabilitation outcome by augmenting muscle mass and muscle strength. We aim to examine this in a double blinded, randomized placebo-controlled clinical trial.

Methods: Patients with ischemic or haemorrhagic stroke will be enrolled at begin of the early post-stroke rehabilitation in a parallel group interventional trial. Oral supplementation of EAAs or placebo will be given for 12 weeks in a double blinded manner. Physical and functional performance will be assessed by exercise testing before supplementation of EAAs as well as at discharge from the in-patient rehabilitation, at 12 weeks and 1 year afterwards.

Discussion: This is the first randomized double-blinded placebo-controlled clinical study aiming to assess the effect of the EAAs supplementation on muscle strength, muscle function and physical performance in stroke patients during early post-stroke rehabilitation. Supplementation of EAAs could prevent muscle mass wasting and improve functional independence after stroke.

Trial Registration: The study is registered at the German registry for clinical trials as well as at World Health Organization (WHO; number DRKS00005577).
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http://dx.doi.org/10.1186/s12883-016-0531-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722757PMC
January 2016

The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure.

Int J Cardiol 2016 Feb 2;205:6-12. Epub 2015 Dec 2.

Innovative Clinical Trials, Department of Cardiology and Pneumology, University of Medicine Göttingen, Germany; Applied Cachexia Research, Department of Cardiology, Charité-University Medical School, Campus Virchow-Klinikum Berlin, Germany. Electronic address:

Unlabelled: Anaemia and iron deficiency (ID) are important co-morbidities in patients with chronic heart failure (HF) and both may lead to reduced exercise capacity.

Methods: We enrolled 331 out-patients with stable chronic HF (mean age: 64 ± 11 years, 17% female, left ventricular ejection fraction [LVEF] 35 ± 13%, body mass index [BMI] 28.5 ± 5.2 kg/m(2), New York Heart Association [NYHA] class 2.2 ± 0.7, chronic kidney disease 35%, glomerular filtration rate 61.7 ± 20.1 mL/min). Anaemia was defined according to World Health Organization criteria (haemoglobin [Hb] < 13 g/dL in men, < 12 g/dL in women). ID was defined as serum ferritin < 100 μg/L or ferritin < 300 μg/L with transferrin saturation (TSAT) < 20%. Exercise capacity was assessed as peak oxygen consumption (peak VO2) by spiroergometry and 6-minute walk test (6MWT).

Results: A total of 91 (27%) patients died from any cause during a mean follow-up of 18 months. At baseline, 98 (30%) patients presented with anaemia and 149 (45%) patients presented with ID. We observed a significant reduction in exercise capacity in parallel to decreasing Hb levels (r = 0.24, p < 0.001). In patients with anaemia and ID (n = 63, 19%), exercise capacity was significantly lower than in patients with ID or anaemia only. Cox regression analysis showed that after adjusting for NYHA, age, hsCRP and creatinine anaemia is an independent predictor of mortality in patients with HF (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.33-0.97, p = 0.04).

Conclusion: The impact of anaemia on reduced exercise capacity and on mortality is stronger than that of ID. Anaemia remained an independent predictor of death after adjusting for clinically relevant variables.
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http://dx.doi.org/10.1016/j.ijcard.2015.11.178DOI Listing
February 2016

Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

Eur J Heart Fail 2015 Dec 9;17(12):1283-93. Epub 2015 Oct 9.

Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.

Aims: Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure.

Methods And Results: We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P < 0.0001), peak oxygen consumption (R = - 0.5, P < 0.0001), 6-min walk distance (R = - 0.32, P < 0.0001), and gait speed (R = - 0.2, P = 0.001), as well as with parameters of kidney and liver function, iron metabolism and storage.

Conclusion: CAF shows good sensitivity for the detection of skeletal muscle wasting in patients with heart failure. Its assessment may be useful to identify patients who should undergo additional testing, such as detailed body composition analysis. As no other biomarker is currently available, further investigation is warranted.
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http://dx.doi.org/10.1002/ejhf.400DOI Listing
December 2015

Insulin resistance in heart failure: differences between patients with reduced and preserved left ventricular ejection fraction.

Eur J Heart Fail 2015 Oct 21;17(10):1015-21. Epub 2015 Jul 21.

Center for Stroke Research Berlin, Charite Universitätsmedizin Berlin, Germany.

Aims: Insulin resistance (IR) is a characteristic feature of heart failure (HF) pathophysiology that affects symptoms and mortality. Differences in the pathophysiological profile of IR in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not characterized in detail. The aim of this study was to evaluate features of IR in HFpEF vs. HFrEF.

Methods And Results: We included 18 patients with HFrEF (EF 30 ± 11%, body mass index (BMI) 26.5 ± 3.3 kg/m(2)), 22 HFpEF patients (EF 63 ± 7%, BMI 28.6 ± 4.8 kg/m(2)), and 20 healthy controls of similar age, all without diabetes mellitus. Patients were in stable ambulatory condition and on stable medical regimens for HF. IR was assessed at fasting steady state by the homeostasis model assessment (HOMA) index and within the physiological range of insulin-glucose interactions by the short insulin sensitivity test (SIST). Fasting-state IR was observed in HFpEF and in HFrEF in comparison with controls (HOMA 1.9, interquartile range (IQR) 1.5-3.6 vs. HOMA 3.1, IQR 1.4-3.7 vs. controls 1.2, IQR 1.8-0.9, respectively; analysis of variance P < 0.001), but no statistical difference was observed between HFpEF and HFrEF. The dynamic test over the physiological range of insulin-glucose interactions revealed a more severe IR in HFrEF as compared with HFpEF. Thus, glucose levels remained the highest in HFrEF (76 (64-89) mg/dL) at the end of the SIST compared with HFpEF and controls (68 (58-79) and 56 (44-66) mg/dL, respectively, P < 0.001).

Conclusion: IR is present in non-diabetic patients with HFpEF and HFrEF. However, distinct differences in the insulin sensitivity characteristics in HFpEF and HFrEF become apparent by more advanced testing. Patients with HFrEF showed more severe IR.
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http://dx.doi.org/10.1002/ejhf.317DOI Listing
October 2015

Muscle wasting in ageing and chronic illness.

ESC Heart Fail 2015 Jun;2(2):58-68

University Medical Center Göttingen, Heart Center Göttingen, Department of Cardiology and Pneumology, Göttingen, Germany.

Purpose: As life expectancy increases, muscle wasting is becoming a more and more important public health problem. This review summarizes the current knowledge of pathophysiological mechanisms underlying muscle loss in ageing and chronic diseases such as heart failure and discusses evolving interventional strategies.

Recent Findings: Loss of skeletal muscle mass and strength is a common phenomenon in a wide variety of disorders associated with ageing and morbidity-associated catabolic conditions such as chronic heart failure. Muscle wasting in ageing but otherwise healthy human beings is referred to as sarcopenia. Unlike cachexia in advanced stages of chronic heart failure, muscle wasting per se is not necessarily associated with weight loss. In this review, we discuss pathophysiological mechanisms underlying muscle loss in sarcopenia and cachexia, highlight similarities and differences of both conditions, and discuss therapeutic targets and possible treatments, such as exercise training, nutritional support, and drugs. Candidate drugs to treat muscle wasting disease include myostatin antagonists, ghrelin agonists, selective androgen receptor molecules, megestrol acetate, activin receptor antagonists, espindolol, and fast skeletal muscle troponin inhibitors.

Summary: Present approaches to muscle wasting disease include exercise training, nutritional support, and drugs, although particularly the latter remain currently restricted to clinical studies. Optimizing skeletal muscle mass and function in ageing and chronic illness including heart failure is one of the chapters that are far from finished and gains future potential for new therapeutic interventions to come.
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http://dx.doi.org/10.1002/ehf2.12033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410534PMC
June 2015

Ischemic stroke and heart failure: facts and numbers.

ESC Heart Fail 2015 Mar 30;2(1):1-4. Epub 2015 Mar 30.

Center for Stroke Research Berlin (CSB), Charite Universitätsmedizin Berlin, Berlin, Germany.

Heart failure (HF) is pandemic in the modern society. Comorbidities of HF come increasingly to the fore in today's patient presentation and demand multidisciplinary treatment concepts. Ischemic stroke is a major comorbidity in HF patients and frequently contributes to the adverse outcome and functional dependency. Patients with HF are two-fold to three-fold more likely to suffer an ischemic stroke, have more than two times higher mortality and show worse functional outcome after stroke compared with non-HF subjects. The risk of recurrent stroke is about two-fold elevated in patients with HF. The risk of stroke increased with time duration of HF from 18 per 100 cases in the first year of HF to 47 per 1000 patients within the next 4-5 years. Moreover, so called 'silent' strokes (clinically asymptomatic brain lesions) are two to four times more likely in HF patients. In turn, 10-24% of stroke patients have HF. Specific characteristics of the interaction between ischemic stroke and HF have been uncovered in recent years. However, gaps in present knowledge need to be addressed in future studies. What are the detailed pathophysiologic links beyond atrial fibrillation, stroke patterns, and time courses in the interaction? What implication has HF with preserved versus reduced ejection fraction? Does treatment of HF prevents ischemic stroke or reduces stroke-related sequelae? This editorial provides a condensed overview on current insights and presents facts and numbers on the interaction between heart failure and ischemic stroke.
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http://dx.doi.org/10.1002/ehf2.12026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746959PMC
March 2015

Stroke-related sarcopenia: specific characteristics.

J Am Med Dir Assoc 2015 Apr 10;16(4):272-6. Epub 2015 Feb 10.

Center for Stroke Research CSB, Charite University Medical School, Berlin, Germany; Department of Cardiology, Charite University Medical School, Berlin, Germany. Electronic address:

Sarcopenia is characterized by muscle wasting and is primarily a disease of the elderly. A stroke-specific sarcopenia has been described recently. Stroke-related sarcopenia has a number of features that distinguish it from the age-related sarcopenia. The disability from stroke depends on the brain lesion leading to impairment of the efferent neuronal pathways. However, the alterations of structural and functional muscle capacity are secondary and depend rather on complex pathophysiological reactions including imbalanced efferent neurovegetative control, systemic and local metabolic imbalance, feeding difficulties, and inflammation. Muscle structural changes start to develop within hours after stroke, followed by rapid reduction of muscle mass. The pathophysiological mechanisms leading to the muscle mass decline are still not understood in details. This review provides insights into the specific features of the stroke-related sarcopenia. Recent research achievements in this area and clinical implications will be discussed.
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http://dx.doi.org/10.1016/j.jamda.2014.12.007DOI Listing
April 2015

Catabolic signaling and muscle wasting after acute ischemic stroke in mice: indication for a stroke-specific sarcopenia.

Stroke 2014 Dec 28;45(12):3675-83. Epub 2014 Oct 28.

From the Department of Innovative Clinical Trials, University Medical Centre, Göttingen, Germany (J.S., S.v.H., S.D.A.); Centre for Stroke Research Berlin (S.S., K.P., A.R., N.S., U.D., W.D.), Applied Cachexia Research, Department of Cardiology, Virchow-Klinikum (A.T., S.v.H., S.D.A.), Departments of Neurology and Experimental Neurology (A.R., O.E., A.M., U.D.), NeuroCure Clinical Research Center (A.M.), and Experimental and Clinical Research Center (M.B.), Charité-Universitätsmedizin Berlin, Berlin, Germany; and German Center for Cardiovascular Diseases (DZHK), Partner Site, Berlin, Germany (U.D., W.D.).

Background And Purpose: Muscle wasting is a common complication accompanying stroke. Although it is known to impair poststroke recovery, the mechanisms of subacute catabolism after stroke have not been investigated in detail. The aim of this study is to investigate mechanisms of local and systemic catabolism and muscle wasting (sarcopenia) in a model of ischemic stroke systematically.

Methods: Changes in body composition and catabolic activation in muscle tissue were studied in a mouse model of acute cerebral ischemia (temporal occlusion of the middle cerebral artery). Tissue wasting (nuclear magnetic resonance spectroscopy), tissue catabolism (caspases-3 and -6, myostatin), and proteasome activity were assessed. Food intake, activity levels, and energy expenditure were assessed, and putative mechanisms of postischemic wasting were tested with appropriate interventions.

Results: Severe weight loss in stroke animals (day 3: weight loss, -21.7%) encompassed wasting of muscle (-12%; skeletal and myocardium) and fat tissue (-27%). Catabolic signaling and proteasome activity were higher in stroke animals in the contralateral and in the ipsilateral leg. Cerebral infarct severity correlated with catabolic activity only in the contralateral leg but not in the ipsilateral leg. Lower energy expenditure in stroke animals together with normal food intake and activity levels suggests compensatory mechanisms to regain weight. Interventions (high caloric feeding, β-receptor blockade, and antibiotic treatment) failed to prevent proteolytic activation and muscle wasting.

Conclusions: Catabolic pathways of muscle tissue are activated after stroke. Impaired feeding, sympathetic overactivation, or infection cannot fully explain this catabolic activation. Wasting of the target muscle of the disrupted innervation correlated to severity of brain injury. Our data indicate the presence of a stroke-specific sarcopenia.
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http://dx.doi.org/10.1161/STROKEAHA.114.006258DOI Listing
December 2014

Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.

J Neurosci 2014 Sep;34(39):13222-33

Divisions of Physiology, and

After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons.
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http://dx.doi.org/10.1523/JNEUROSCI.1209-13.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172810PMC
September 2014

How to determine a metabolically healthy body composition in cardiovascular disease.

J Am Coll Cardiol 2014 Sep;64(11):1182-3

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http://dx.doi.org/10.1016/j.jacc.2014.05.063DOI Listing
September 2014

Intestinal blood flow in patients with chronic heart failure: a link with bacterial growth, gastrointestinal symptoms, and cachexia.

J Am Coll Cardiol 2014 Sep;64(11):1092-102

Department of Gastroenterology, Charité, Campus Mitte, Berlin, Germany.

Background: Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia.

Objectives: The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF.

Methods: A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured.

Results: Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A-antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia.

Conclusions: Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia.
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http://dx.doi.org/10.1016/j.jacc.2014.06.1179DOI Listing
September 2014

Response to the letter to the editor from Xue and Varadhan titled "What is missing in the validation of frailty instruments?".

J Am Med Dir Assoc 2014 Feb;15(2):147

Center for Stroke Research Berlin-CSB, Charité-Universitätsmedizin, Berlin, Germany.

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http://dx.doi.org/10.1016/j.jamda.2013.11.014DOI Listing
February 2014

Stroke induced Sarcopenia: muscle wasting and disability after stroke.

Int J Cardiol 2013 Dec 14;170(2):89-94. Epub 2013 Oct 14.

Centre for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Germany.

Stroke is the second leading cause of death and the leading cause of disability in Western countries. More than 60% of patients remain disabled, 50% of patients suffer from hemiparesis and 30% remain unable to walk without assistance. The skeletal muscle is the main effector organ accountable for disability in stroke. This disability is primarily attributed to the brain lesion; however less attention is paid to structural, metabolic and functional alterations of muscle tissue after stroke. Hemiparetic stroke leads to various muscle abnormalities: A combination of denervation, disuse, inflammation, remodelling and spasticity accounts for a complex pattern of muscle tissue phenotype change and atrophy. The molecular mechanisms of muscle degradation after stroke are only incompletely understood. Reinnervation, fibre-type shift, disuse atrophy, and local inflammatory activation are only some of the key features yet to be explained. Only limited data is available today on clinical muscle changes after stroke that results from few studies in a mere 500 patients. Despite its importance for optimum post stroke recovery, stroke-related sarcopenia is not considered in current guidelines for stroke therapy or rehabilitation and measurement tools to address sarcopenia are infrequently used. This lack of robust evidence on muscle pathology after stroke and on treatment strategies needs to be addressed in an interdisciplinary integrated approach. This review provides an overview on current pathophysiologic insights and on clinical relevance of sarcopenia in stroke patients and on measurement tools to address the problem in the clinical setting.
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http://dx.doi.org/10.1016/j.ijcard.2013.10.031DOI Listing
December 2013

Investigation of changes in body composition, metabolic profile and skeletal muscle functional capacity in ischemic stroke patients: the rationale and design of the Body Size in Stroke Study (BoSSS).

J Cachexia Sarcopenia Muscle 2013 Sep 13;4(3):199-207. Epub 2013 Mar 13.

Center for Stroke Research Berlin-CSB, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Background: Stroke is steadily increasing in prevalence. Muscle tissue wasting and functional changes are frequently observed in stroke, but this has not been studied in detail yet. There is a lack of data to support guideline recommendations on how to target muscle wasting in stroke patients. We hypothesise that pathophysiological metabolic profiles and muscle functional and structural impairment are developing in stroke patients, which are associated with stroke severity and outcome after stroke.

Methods: The Body Size in Stroke Study (BoSSS) is a prospective, longitudinal observation study that will explore associations between the metabolic profile, body tissue wasting and particular metabolic and functional changes in skeletal muscle tissue in stroke patients. Consecutive patients with acute stroke (n = 150) will be enrolled due to lacunar or territorial ischemic infarct in the area of the middle cerebral artery. Patients will be studied at annual intervals after 12 and 24 months. For comparison, healthy controls of similar age and patients with chronic heart failure will be used as control groups. The main objective is to study changes in body composition in stroke patients. Secondary, the study will focus on changes in insulin sensitivity of adipose tissue and skeletal muscle. Furthermore, measurements of endothelial function and peripheral blood flow will provide insight in the vascular regulation in stroke patients.

Conclusion: This study will be the largest observational study providing insights into the metabolic and functional changes of muscle tissue in patients with acute ischemic stroke. The new data will increase our understanding of the pathophysiologic tissue wasting in stroke disease and help to develop new therapeutic strategies.
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http://dx.doi.org/10.1007/s13539-013-0103-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774919PMC
September 2013