Skeletal muscle structure and function in response to electrical stimulation in moderately impaired COPD patients. Influence of complete spinal cord injury on skeletal muscle within 6 mo of injury. Acute skeletal muscle wasting in critical illness. Neuromuscular electrical stimulation attenuates thigh skeletal muscles atrophy but not trunk muscles after spinal cord injury. Atrophy responses to muscle inactivity. I. Cellular markers of protein deficits. Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients. Muscle atrophy, inflammation and clinical outcome in incident and prevalent dialysis patients. The effects of exercise training on muscle atrophy in haemodialysis patients. Observational study of spinal muscular atrophy type I and implications for clinical trials Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study. Mechanisms of Chronic Muscle Wasting and Dysfunction after an Intensive Care Unit Stay. A Pilot Study. Early type II fiber atrophy in intensive care unit patients with nonexcitable muscle membrane Muscle atrophy is prevented in patients with acute spinal cord injury using functional electrical stimulation Skeletal muscle microbiopsy: a validation study of a minimally invasive technique Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid Qualitative Ultrasound in Acute Critical Illness Muscle Wasting [Validity of the motor function measurement scale when routinely used in the follow-up of adult outpatients in a neuromuscular center].
STUDY OBJECTIVE To determine the structural and functional consequences of high-frequency neuromuscular electrical stimulation ( hf-NMES ) in a group of moderately impaired out patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN A prospect i ve , cross-over r and omized trial . SETTING An university-based , tertiary center . PATIENTS AND MATERIAL S Seventeen patients ( FEV(1)=49.6+/-13.4 % predicted , Medical Research Council dyspnoea grade s II-III ) underwent 6-weeks hf-NMES ( 50Hz ) and sham stimulation of the quadriceps femoris in a r and omized , cross-over design . Knee strength was measured by isokinetic dynamometry ( peak torque ) and leg muscle mass ( LMM ) by DEXA ; in addition , median cross-sectional area ( CSA ) of type I and II fibres and capillary-fibre ratio were evaluated in the vastus lateralis . The 6-min walking distance ( 6MWD ) was also determined . RESULTS At baseline , patients presented with well-preserved functional capacity , muscle strength and mass : there was a significant relationship between strength and type II CSA ( P<0.05 ) . NMES was not associated with significant changes in peak torque , LMM or 6MWD as compared to sham ( P>0.05 ) . At micro-structural level , however , electrical stimulation increased type II , but decreased type I , CSA ; no change , however , was found in the relative fibre distribution or capillary : fibre ratio ( P<0.05 ) . There was no significant association between individual changes in structure and function with training ( P>0.05 ) . Post-NMES increase in type II CSA was inversely related to baseline mass and strength ( P<0.05 ) . CONCLUSION NMES may promote a modest degree of type II muscle fibre hypertrophy in COPD patients with well-preserved functional status . These micro-structural changes , however , were not translated into increased volitional strength in this sub- population This study examined the influence of  spinal cord injury ( SCI )  on affected skeletal muscle . The right vastus lateralis muscle was biopsied in 12 patients as soon as they were clinical ly stable ( average 6 wk after SCI ) , and 11 and 24 wk after injury . Sample s were also taken from nine able-bodied controls at two time points 18 wk apart . Surface electrical stimulation ( ES ) was applied to the left quadriceps femoris muscle to assess fatigue at these same time intervals . Biopsies were analyzed for fiber type percent and cross-sectional area ( CSA ) , fiber type-specific succinic dehydrogenase ( SDH ) and alpha-glycerophosphate dehydrogenase ( GPDH ) activities , and myosin heavy chain percent . Controls showed no change in any variable over time . Patients showed 27 - 56 % atrophy ( P = 0.000 ) of type I , IIa , and IIax+IIx fibers from 6 to 24 wk after injury , result ing in fiber CSA approximately one-third that of controls . Their fiber type specific SDH and GPDH activities increased ( P < /= 0.001 ) from 32 to 90 % over the 18 wk , thereby approaching or surpassing control values . The relative CSA of type I fibers and percentage of myosin heavy chain type I did not change . There was apparent conversion among type II fiber subtypes ; type IIa decreased and type IIax+IIx increased ( P < /= 0.012 ) . Force loss during ES did not change over time for either group but was greater ( P = 0.000 ) for SCI patients than for controls overall ( 27 vs. 9 % ) . The results indicate that vastus lateralis muscle shows marked fiber atrophy , no change in the proportion of type I fibers , and a relative independence of metabolic enzyme levels from activation during the first 24 wk after clinical ly complete SCI . Over this time , quadriceps femoris muscle showed moderately greater force loss during ES in patients than in controls . It is suggested that the predominant response of mixed human skeletal muscle within 6 mo of SCI is loss of contractile protein . Therapeutic interventions could take advantage of this to increase muscle mass IMPORTANCE Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment . OBJECTIVE To perform a comprehensive prospect i ve characterization of skeletal muscle wasting , defining the pathogenic roles of altered protein synthesis and breakdown . DESIGN , SETTING , AND PARTICIPANTS Sixty-three critically ill patients ( 59 % male ; mean age : 54.7 years [ 95 % CI , 50.0 - 59.6 years ] ) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 ( 95 % CI , 21.9 - 25.2 ) were prospect ively recruited within 24 hours following intensive care unit ( ICU ) admission from August 2009 to April 2011 at a university teaching and a community hospital in Engl and . Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours , to spend more than 7 days in critical care , and to survive ICU stay . MAIN OUTCOMES AND MEASURES Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area ( CSA ) on days 1 , 3 , 7 , and 10 . In a subset of patients , the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7 . Histopathological analysis was performed . In addition , muscle protein synthesis , breakdown rates , and respective signaling pathways were characterized . RESULTS There were significant reductions in the rectus femoris CSA observed at day 10 ( −17.7 % [ 95 % CI , −25.9 % to 8.1 % ] ; P < .001 ) . In the 28 patients assessed by all 3 measurement methods on days 1 and 7 , the rectus femoris CSA decreased by 10.3 % ( 95 % CI , 6.1 % to 14.5 % ) , the fiber CSA by 17.5 % ( 95 % CI , 5.8 % to 29.3 % ) , and the ratio of protein to DNA by 29.5 % ( 95 % CI , 13.4 % to 45.6 % ) . Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 ( −15.7 % ; 95 % CI , −27.7 % to 11.4 % ) compared with single organ failure ( −3.0 % ; 95 % CI , −5.3 % to 2.1 % ) ( P < .001 ) , even by day 3 ( −8.7 % [ 95 % CI , −59.3 % to 50.6 % ] vs −1.8 % [ 95 % CI , −12.3 % to 10.5 % ] , respectively ; P = .03 ) . Myofiber necrosis occurred in 20 of 37 patients ( 54.1 % ) . Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1 ( 0.035%/hour ; 95 % CI , 0.023 % to 0.047%/hour ) compared with rates observed in fasted healthy controls ( 0.039%/hour ; 95 % CI , 0.029 % to 0.048%/hour ) ( P = .57 ) and increased by day 7 ( 0.076 % [ 95 % CI , 0.032%-0.120%/hour ] ; P = .03 ) to rates associated with fed controls ( 0.065%/hour [ 95 % CI , 0.049 % to 0.080%/hour ] ; P = .30 ) , independent of nutritional load . Leg protein breakdown remained elevated throughout the study ( 8.5 [ 95 % CI , 4.7 to 12.3 ] to 10.6 [ 95 % CI , 6.8 to 14.4 ] μmol of phenylalanine/min/ideal body weight × 100 ; P = .40 ) . The pattern of intracellular signaling supported increased breakdown ( n = 9 , r = −0.83 , P = .005 ) and decreased synthesis ( n = 9 , r = −0.69 , P = .04 ) . CONCLUSIONS AND RELEVANCE Among these critically ill patients  , muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure . These findings may provide insights into skeletal muscle wasting in critical illness The current study examined the effects of 12weeks of surface neuromuscular electrical stimulation ( NMES ) and ankle weights on the cross-sectional areas ( CSAs ) of three thigh [ Gracilis ( Gra ) , Sartorious ( Sar ) and Adductor ( Add ) ] as well as two trunk [ hip flexor ( HF ) and back extensor ( BE ) ] muscle groups in men with spinal cord injury ( SCI ) . Seven individuals with chronic motor complete SCI were r and omly assigned into a resistance training + diet ( RT+diet ; n=4 ) or diet control ( n=3 ) groups . The RT+diet group underwent twice weekly training with surface NMES and ankle weights for 12weeks . Training composed of four sets of 10 repetitions of leg extension exercise while sitting in their wheelchairs . Both groups were asked to monitor their dietary intake . Magnetic resonance images were captured before and after 12weeks of interventions . Gra muscle CSA showed no change before and after interventions . A significant interaction ( P=0.001 ) was noted between both groups as result of 9 % increase and 10 % decrease in the Gra muscle CSA of the RT+diet and diet groups , respectively . Sar muscle CSA increased [ 1.7±0.4 - 2.5±0.5cm(2 ) ; P=0.029 ] in the RT+diet group with no change [ 2.9±1.4 - 2.6±1.3cm(2 ) ] in the diet group ; with interaction noted between both groups ( P=0.002 ) . Analysis of covariance indicated that Add muscle CSA was 38 % greater in the RT+diet compared to the diet group ( P=0.025 ) after 12weeks ; a trend of interaction was also noted between both groups ( P=0.06 ) . HF and BE muscle groups showed no apparent changes in CSA in both groups . The results suggested that surface NMES can delay the process of progressive skeletal muscle atrophy after chronic SCI . However , the effects are localized to the trained thigh muscles and do not extend to the proximal trunk muscles The goal of this study was to use the model of spinal cord isolation ( SI ) , which blocks nearly all neuromuscular activity while leaving the motoneuron muscle-fiber connections intact , to characterize the cellular processes linked to marked muscle atrophy . Rats r and omly assigned to normal control and SI groups were studied at 0 , 2 , 4 , 8 , and 15 days after SI surgery . The slow soleus muscle atrophied by approximately 50 % , with the greatest degree of loss occurring during the first 8 days . Throughout the SI duration , muscle protein concentration was maintained at the control level , whereas myofibrillar protein concentration steadily decreased between 4 and 15 days of SI , and this was associated with a 50 % decrease in myosin heavy chain ( MHC ) normalized to total protein . Actin relative to the total protein was maintained at the control level . Marked reductions occurred in total RNA and DNA content and in total MHC and actin mRNA expressed relative to 18S ribosomal RNA . These findings suggest that two key factors contributing to the muscle atrophy in the SI model are 1 ) . a reduction in ribosomal RNA that is consistent with a reduction in protein translational capacity , and 2 ) . insufficient mRNA substrate for translating key sarcomeric proteins comprising the myofibril fraction , such as MHC and actin . In addition , the marked selective depletion of MHC protein in the muscles of SI rats suggests that this protein is more vulnerable to inactivity than actin protein . This selective MHC loss could be a major contributor for the previously reported loss in the functional integrity of SI muscles . Collectively , these data are consistent with the involvement of pretranslational and translational processes in muscle atrophy due to SI Fully se date d patients , being treated in the intensive care unit ( ICU ) , experience substantial skeletal muscle loss . Consequently , survival rate is reduced and full recovery after awakening is compromised . Neuromuscular electrical stimulation ( NMES ) represents an effective method to stimulate muscle protein synthesis and alleviate muscle disuse atrophy in healthy subjects . We investigated the efficacy of twice-daily NMES to alleviate muscle loss in six fully se date d ICU patients admitted for acute critical illness [ n=3 males , n=3 females ; age 63 ± 6 y ; APACHE II ( Acute Physiology and Chronic Health Evaluation II ) disease-severity-score : 29 ± 2 ] . One leg was subjected to twice-daily NMES of the quadriceps muscle for a period of 7 ± 1 day whereas the other leg acted as a non-stimulated control ( CON ) . Directly before the first and on the morning after the final NMES session , quadriceps muscle biopsies were collected from both legs to assess muscle fibre-type-specific cross-sectional area ( CSA ) . Furthermore , phosphorylation status of the key proteins involved in the regulation of muscle protein synthesis was assessed and mRNA expression of selected genes was measured . In the CON leg , type 1 and type 2 muscle-fibre-CSA decreased by 16 ± 9 % and 24 ± 7 % respectively ( P<0.05 ) . No muscle atrophy was observed in the stimulated leg . NMES increased mammalian target of rapamycin ( mTOR ) phosphorylation by 19 ± 5 % when compared with baseline ( P<0.05 ) , with no changes in the CON leg . Furthermore , mRNA expression of key genes involved in muscle protein breakdown either declined [ forkhead box protein O1 ( FOXO1 ) ; P<0.05 ] or remained unchanged [ muscle atrophy F-box ( MAFBx ) and muscle RING-finger protein-1 ( MuRF1 ) ] , with no differences between the legs . In conclusion , NMES represents an effective and feasible interventional strategy to prevent skeletal muscle atrophy in critically ill comatose patients BACKGROUND & AIMS Muscle wasting is considered the best marker of protein-energy wasting in end-stage renal disease ( ESRD ) . We tested the usefulness of a simple observer subjective muscle atrophy ( MA ) grading in relation to morbidity and mortality in ESRD patients . METHODS In two different ESRD cohorts ( 265 incident patients starting dialysis and 221 prevalent hemodialysis patients ) , each patient 's degree of MA was visually grade d by a trained nurse on a scale from 1 to 4 as part of the subjective global assessment . This score was confronted with inflammatory and nutritional indexes as well as objective measurements of muscle atrophy . Patients were then prospect ively followed for up to four or six years , depending on the cohort . RESULTS Thirty percent of the incident and 39 % of the prevalent patients presented signs of MA . Across worsening MA scale , nutritional and anthropometric markers of muscle loss were incrementally poorer . Inflammation markers as well as the proportion of women became progressively higher . Female sex , presence of cardiovascular disease , inflammation and low insulin-like growth factor-1 levels were associated with increased significant odd ratios of MA in each cohort . After adjustment for age , sex , inflammation , diabetes , cardiovascular disease , glomerular filtration rate and /or time on hemodialysis , the hazard ratio of death for moderate/severe MA was 2.62 ( 95 % CI : 1.34 , 5.13 ; p=0.001 ) and 3.04 ( 95 % CI : 1.61 , 5.71 ; p=0.0001 ) in the incident and prevalent cohorts respectively . CONCLUSION Increased MA is more common in female dialysis patients and associated with inflammation , poor nutritional and anthropometric status , as well as a 3-fold increased 4 - 6 year mortality . Our data support the use of frequent MA and /or nutritional assessment s in the clinical practice BACKGROUND Patients with end-stage renal disease on haemodialysis ( HD ) have limited work capacity . Many structural and functional alterations in skeletal muscles contribute to this disability . METHODS To evaluate the effects of exercise training on uraemic myopathy , seven HD patients ( mean age 44.1+/-17.2 years ) were studied . Open muscle biopsies were taken from their vastus lateralis muscle before and after a 6-month exercise rehabilitation programme and examined by routine light- and transmission electron-microscopy . Histochemical stainings of frozen sections were performed and morphometric analysis was also applied to estimate the proportion of each fibre type and the muscle fibre area . Spiroergometric and neurophysiological testing and peak extension forces of the lower limbs were measured before and after exercise training . RESULTS All patients showed impaired exercise capacity , which was associated with marked muscular atrophy ( mean area 2548+/-463 microm2 ) and reduction in muscle strength and nerve conduction velocity . All types of fibres were atrophied , but type II were more affected . The ultrastructural study showed severe degenerative changes in skeletal muscle fibres , mitochondria , and capillaries .  Exercise training had an impressive effect on muscular atrophy ; in particular the proportion of type II fibres increased by 51 % and mean muscle fibre area by 29 % . Favourable changes were also seen on the structure and number of capillaries and mitochondria . These results were confirmed by a 48 % increase in VO2 peak and a 29 % in exercise time , as well as an improvement in the peak muscle strength of the lower limbs and in nerve conduction velocity . CONCLUSIONS Skeletal muscle atrophy in HD patients contribute to their poor exercise tolerance . The application of an exercise training rehabilitation programme improved muscle atrophy markedly , and therefore had beneficial effects in overall work performance Objectives : Prospect i ve cohort study to characterize the clinical features and course of spinal muscular atrophy type I ( SMA-I ) . Methods : Patients were enrolled at 3 study sites and followed for up to 36 months with serial clinical , motor function , laboratory , and electrophysiologic outcome assessment s. Intervention was determined by published st and ard of care guidelines . Palliative care options were offered . Results : Thirty-four of 54 eligible subjects with SMA-I ( 63 % ) enrolled and 50 % of these completed at least 12 months of follow-up . The median age at reaching the combined endpoint of death or requiring at least 16 hours/day of ventilation support was 13.5 months ( interquartile range 8.1–22.0 months ) . Requirement for nutritional support preceded that for ventilation support . The distribution of age at reaching the combined endpoint was similar for subjects with SMA-I who had symptom onset before 3 months and after 3 months of age ( p = 0.58 ) . Having 2 SMN2 copies was associated with greater morbidity and mortality than having 3 copies . Baseline electrophysiologic measures indicated substantial motor neuron loss . By comparison , subjects with SMA-II who lost sitting ability ( n = 10 ) had higher motor function , motor unit number estimate and compound motor action potential , longer survival , and later age when feeding or ventilation support was required . The mean rate of decline in The Children 's Hospital of Philadelphia Infant Test for Neuromuscular Disorders motor function scale was 1.27 points/year ( 95 % confidence interval 0.21–2.33 , p = 0.02 ) . Conclusions : Infants with SMA-I can be effectively enrolled and retained in a 12-month natural history study until a majority reach the combined endpoint . These outcome data can be used for clinical trial design Although loss of muscle mass is considered a cause of diminished muscle strength with aging , little is known regarding whether composition of aging muscle affects strength . The skeletal muscle attenuation coefficient , as determined by computed tomography , is a noninvasive measure of muscle density , and lower values reflect increased muscle lipid content . This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees/s in 2,627 men and women aged 70 - 79 yr participating in baseline studies of the Health ABC Study , a longitudinal study of health , aging , and body composition .  Strength was higher in men than in women ( 132.3 + /- 34.5 vs. 81.4 + /- 22.0 N x m , P < 0.01 ) . Men had greater muscle attenuation values ( 37.3 + /- 6.5 vs. 34.7 + /- 7.0 Hounsfield units ) and muscle cross-sectional area ( CSA ) at the midthigh than women ( 132.7 + /- 22.4 vs. 93.3 + /- 17.5 cm(2 ) , P < 0.01 for both ) . The strength per muscle CSA ( specific force ) was also higher in men ( 1.00 + /- 0.21 vs. 0.88 + /- 0.21 N x m x cm(-2 ) ) . The attenuation coefficient was significantly lower for hamstrings than for quadriceps ( 28.7 + /- 8.7 vs. 41.1 + /- 6.9 Hounsfield units , P < 0.01 ) . Midthigh muscle attenuation values were lowest ( P < 0.01 ) in the eldest men and women and were negatively associated with total body fat ( r = -0.53 , P < 0.01 ) . Higher muscle attenuation values were also associated with greater specific force production ( r = 0.26 , P < 0.01 ) . Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women . These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity RATIONALE Critical illness survivors often experience permanent functional disability due to intensive care unit (ICU)-acquired weakness . The mechanisms responsible for long-term weakness persistence versus resolution are unknown . OBJECTIVES To delineate cellular mechanisms underlying long-term weakness persistence in ICU survivors . METHODS We conducted a nested , prospect i ve study of critically ill patients mechanically ventilated for 7 days or longer . The patients were recruited from the RECOVER program  and serially assessed over 6 months after ICU discharge . Twenty-seven of 82 patients consented to participate ; 15 and 11 patients were assessed at 7 days and 6 months after ICU discharge , respectively . MEASUREMENTS AND MAIN RESULTS We assessed motor functional capacity , quadriceps size , strength , and voluntary contractile capacity and performed electromyography , nerve conduction studies , and vastus lateralis biopsies  for histologic , cellular , and molecular analyses . Strength and quadriceps cross-sectional areas were decreased 7 days after ICU discharge . Weakness persisted to 6 months and correlated with decreased function . Quadriceps atrophy resolved in 27 % patients at 6 months . Muscle mass reconstitution did not correlate with resolution of weakness , owing to persistent impaired voluntary contractile capacity . Compared with Day 7 , increased ubiquitin-proteasome system-mediated muscle proteolysis , inflammation , and decreased mitochondrial content all normalized at 6 months . Autophagy markers were normal at 6 months . Patients with sustained atrophy had decreased muscle progenitor ( satellite ) cell content . CONCLUSIONS Long-term weakness in ICU survivors results from heterogeneous muscle pathophysiology with variable combinations of muscle atrophy and impaired contractile capacity . These findings are not explained by ongoing muscle proteolysis , inflammation , or diminished mitochondrial content . Sustained muscle atrophy is associated with decreased satellite cell content and compromised muscle regrowth , suggesting impaired regenerative capacity Objective : Intensive care unit-acquired weakness indicates increased morbidity and mortality . Nonexcitable muscle membrane after direct muscle stimulation develops early and predicts intensive care unit-acquired weakness in se date d , mechanically ventilated patients . A comparison of muscle histology at an early stage in intensive care unit-acquired weakness has not been done . We investigated whether nonexcitable muscle membrane indicates fast-twitch myofiber atrophy during the early course of critical illness . Design : Prospect i ve observational study . Setting : Two intensive care units at Charité University Medicine , Berlin . Patients : Patients at increased risk for development of intensive care unit-acquired weakness , indicated by Sepsis-related Organ Failure Assessment scores ≥8 on 3 of 5 consecutive days within their first week in the intensive care unit . Interventions : None . Measurements and Main Results : Electrophysiological compound muscle action potentials after direct muscle stimulation and muscle biopsies were obtained at median days 7 and 5 , respectively . Patients with nonexcitable muscle membranes ( n = 15 ) showed smaller median type II cross-sectional areas ( p < .05 ) , whereas type I muscle fibers did not compared with patients with preserved muscle membrane excitability ( compound muscle action potentials after direct muscle stimulation ≥3.0 mV ; n = 9 ) . We also observed decreased mRNA transcription levels of myosin heavy chain isoform IIa and a lower densitometric ratio of fast-to-slow myosin heavy chain protein content . Conclusion : We suggest that electrophysiological nonexcitable muscle membrane predicts preferential type II fiber atrophy in intensive care unit patients during early critical illness Severe muscle atrophy occurs rapidly following traumatic spinal cord injury ( SCI ) . Previous research shows that neuromuscular or ‘ functional ’ electrical stimulation ( FES ) , particularly FES-cycle ergometry ( FES-CE ) can cause muscle hypertrophy in individuals with chronic SCI ( > 1 year post-injury ) . However , the modest degree of hypertrophy in these already atrophied muscles has lessened earlier hopes that FES therapy would reduce secondary impairments of SCI . It is not known whether FES treatments are effective when used to prevent , rather than reverse , muscle atrophy in individuals with acute SCI . This study explored whether unloaded isometric FES contractions ( FES-IC ) or FES-CE decreased subsequent muscle atrophy in individual with acute SCI ( <3 months post-injury ) . Twenty-six subjects , 14–15 weeks post-traumatic SCI , were assigned to control , FES-IC , or FES-CE against progessively increasing resistance . Subjects were involved in the study for 3 or 6 months . Total body lean body mass ( TB-LBM ) , lower limb lean body mass ( LL-LBM ) , and gluteal lean body mass ( G-LBM ) were determined before the study , and at 3 and 6 months using dual energy X-ray absorptiometry ( DEXA ) . Controls lost an average of 6.1 % , 10.1 % , 12.4 % , after 3 months and 9.5 % , 21.4 % , 26.8 % after 6 months in TB-LBM , LL-LBM and G-LBM respectively . Subjects in the FES-IC group consistently lost less lean body mass than controls , however , only 6 month G-LBM loss was significantly attenuated in this group relative to the controls . In the FES-CE group , LL-LBM and G-LBM loss were prevented at both 3 and 6 months , and TB-LBM loss was prevented at 6 months . In addition , FES-CE significantly increased G-LBM and LL-LBM after 6 months of training relative to pre-training levels . Within the control group , there was no significant relationship between LL-LBM loss ( 3 and 6 months ) and the number of days between injury and baseline measurement . In summary , this study shows that FES-CE , but not FES-IC , training prevents muscle atrophy in acute SCI after 3 months of training , and causes significant hypertrophy after 6 months . The magnitude of differences in regionalized LBM between controls and FES-CE subject raises hopes that such treatment may indeed be beneficial in preventing secondary impairments of SCI if employed before extensive post-injury atrophy occurs The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease ( COPD ) is of growing interest , but often requires biopsies , usually with the Bergström technique . The current study was design ed to test the validity of a minimally invasive technique : the microbiopsy . In 17 patients with COPD and four normal subjects , two specimens of the vastus lateralis were taken percutaneously under local anaesthesia , one with a 16-gauge needle ( microbiopsy ) and the other with the Bergström needle .  The enzymatic activity of citrate synthase ( CS ) and phosphofructokinase ( PFK ) , and the myosin heavy chain ( MyoHC ) composition were measured for both techniques . The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy . The microbiopsy sample weight reached 55±17 mg . The two techniques showed excellent agreement for CS activity and MyoHC composition . The PFK activity did not differ statistically between the techniques , but the agreement was moderate . The agreement between both biopsy techniques was stable over time . The median ( range ) fibre number within the microbiopsy specimens was 144 ( 38–286 ) . In conclusion , the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects , compared with the Bergström technique Background Spinal muscular atrophy ( SMA ) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn , result ing in hypotonia and muscle weakness . The disease is caused by deletion or mutation in the telomeric copy of SMN gene ( SMN1 ) and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene ( SMN2 ) . The SMN2 mRNA lacks exon 7 , result ing in a production of lower amounts of the full-length SMN protein . Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene . One of these drugs is the valproic acid ( VPA ) , a histone deacetylase inhibitor . Methods Twenty-two patients with type II and III SMA , aged between 2 and 18 years , were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test ( Medical Research Council scale-MRC ) , the Hammersmith Functional Motor Scale ( HFMS ) , and the Barthel Index . Results After 12 months of therapy , the patients did not gain muscle strength . The group of children with SMA type II presented a significant gain in HFMS scores during the treatment . This improvement was not observed in the group of type III patients . The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result . There was an improvement of the daily activities at the end of the VPA treatment period . Conclusion Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease . Trial Registration Clinical Trials.gov : Objectives : A rapid and early loss of skeletal muscle mass underlies the physical disability common amongst survivors of critical illness . However , skeletal muscle function depends not only on its quantity but its quality , which may be adversely affected . We set out to characterise the changes in macroscopic muscle echogenicity and fascial characteristics that occur early in critical illness , and to relate these to microscopic histologically defined myofibre necrosis and fascial pathology . Design and Setting : Prospect i ve two center observational study . Patients : Thirty subjects comprising a subgroup of patients recruited to the Musculoskeletal Ultrasound in Critical Illness : Longitudinal Evaluation ( MUSCLE ) study . Measurements and Main Results : Comparisons were made between sequential Vastus Lateralis histological specimens and ultrasound assessment of Rectus Femoris echogenicity . Change in muscle echogenicity was greater in patients who developed muscle necrosis ( n = 15 ) than in those who did not ( 8.2 % [ 95 % CI , –5.3 to 21.7 ] vs –15.0 % [ 95 % CI , –28.9 to –1.09 ] ; p = 0.016 ) . The area under receiver operator curve for ultrasound echogenicity ’s prediction of myofiber necrosis was 0.74 ( 95 % CI , 0.565 to 0.919 ; p = 0.024 ) increasing to 0.85 ( 95 % CI , 0.703 to –0.995 ; p = 0.003 ) with the removal of those with potential iatrogenic muscle damage . Fasciitis was observed in 18 of 30 biopsies ( 60 % ) . Conclusions : Myofiber necrosis and fascial inflammation can be detected noninvasively using ultrasound in the critically ill . Fasciitis precedes and frequently accompanies muscle necrosis . These findings may have functional implication s for survivors of critical illness INTRODUCTION The Motor Function Measure ( MFM ) is widely used to assess severity and progression of neuromuscular diseases . Validity was established in a group of patients aged 6 - 60 years with suspected or confirmed diagnosis of neuromuscular diseases , Duchenne Muscular Dystrophy being the most frequent diagnosis in the population tested . OBJECTIVES Our aim was to check the validity of the MFM in a hospital department specialized in neuromuscular diseases in the follow-up of adult out- patients presenting a myopathy , such population being very different from the MFM validation group in terms of age and sub-groups of myopathy . METHODS One hundred patients were r and omly selected in the Reference Center for Neuromuscular Diseases of Nice ( France ) between 2005 and 2007 . Were collected : the  MFM score , manual muscular testing ( MMT ) of lower and upper limb , face and spine , Brooke and Vignos scores . MFM and its three dimensions D1 ( st and ing position and transfers ) , D2 ( axial and proximal limb motor function ) and D3 ( distal motor function ) were compared to the other scores with the Spearman Correlation Coefficient and the Principal Component Analysis . RESULTS Patients were aged 18 - 78 years . The most frequent diagnoses were Steinert 's Muscular Dystrophy ( DM1 ) and Facio-ScapuloHumeral Dystrophy ( FSHD ) ( 30 % and 29 % ) .  MFM  was significantly correlated to all other scores except for Face MMT . However , Face MMT was correlated to D1 and D2 in DM1 patients and to D2 in FSHD patients . DISCUSSION Our results confirm the validity of the  MFM  in adult patients with muscular diseases . However , the  MFM global score and its three dimensions D1 , D2 and D3 are variously correlated with the facial and axial muscle testing . Therefore , we recommend using separately the three dimensions D1 , D2 , D3 ( rather than the global score ) and , if more accuracy is required , the facial and axial muscle testing
Our meta analysis of a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA according to fiber type and gender .
Skeletal muscle atrophy is a major systemic impairment in chronic diseases .
Yet its determinants have been hard to identify because a clear research definition has not been agreed upon .
The reduction in muscle fiber cross-sectional area ( CSA ) is a widely acknowledged marker of muscle atrophy , but no reference values for the muscle fiber CSA at the age of the onset of chronic disease have ever been published .