Muscular Impairment Research Articles

Clinical use of bioelectrical impedance analysis in patients affected by myotonic dystrophy type 1: A cross-sectional study.

Myotonic dystrophy type 1 (DM1) is an inherited muscle disorder characterized by slowly progressive weakness due to muscle degeneration. The Muscular Impairment Rating Scale (MIRS) is validated to assess clinical muscle severity of patients with DM1, although the scale is not sensitive enough to assess disease progression in time intervals fit for clinical trials. The aim of this study was to analyze bioelectrical whole body and arm segmental parameters in patients with DM1 to explore a correlation between bioelectrical impedance analysis (BIA) parameters and disease stage. Forty patients with DM1 were enrolled in a cross-sectional study. In all patients, MIRS, handgrip strength (HGS), and BIA were assessed. A Kruskal-Wallis test was used to assess the difference in continuous variables according to MIRS. Correlation between BIA values and HGS were made by Pearson's coefficient analysis. A linear regression analysis was performed. Eighteen of 40 patients were men (45%). The median age of the cohort was 42 y (30-58 y). Four patients (10%) were classified as MIRS 1; 20 (50%) MIRS 2; 11 (27.5%) MIRS 3; and 5 (12.5%) as MIRS 4. A correlation was observed between phase angle and MIRS (P = 0.0001). MIRS correlated with other BIA values such as resistance, impedance ratio, and capacitance (P = 0.005, P = 0.0001, P = 0.0006, respectively). At linear regression analysis, segmental resistance, phase angle, impedance ratio, and capacitance of both arms significantly correlated with HGS. Results from the study support the use of BIA as a suitable procedure for staging DM1 muscle involvement and as a measure of muscle disease outcome, in clinical practice and in clinical trial design of therapeutic drugs.

De novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia

Endotoxemia caused by bacterial lipopolysaccharides (LPSs) leads to severe skeletal muscular deterioration, starting with higher membrane permeability and decline in resting membrane potential (RMP). However, the molecular mechanism of such changes remains unclear. Here, we evaluated the possible involvement of connexin43- and connexin45-based hemichannels (Cx43 and Cx45 HCs, respectively) as putative mediators of sarcolemmal dysfunctions induced by LPS in control (Cx43fl/flCx45fl/fl) and Cx43/Cx45 expression-deficient (Cx43fl/flCx45fl/fl:Myo-Cre) skeletal mice myofibers. At 5 h of endotoxemia, control myofibers presented Cx43 and Cx45 proteins forming functional HCs. Additionally, myofibers from endotoxic control mice showed dye uptake in vivo, which was inhibited by carbenoxolone, a Cx HC blocker. A similar increase in membrane permeability was observed in myofibers freshly isolated from skeletal muscle of mice treated for 5 h with LPS, which was blocked by the Cx HC blocker and was absent in myofibers from mice simultaneously treated with LPS and boldine, which is a Cx HC blocker. The increase in sarcolemmal permeability was mimicked by isolated myofibers treated with pro-inflammatory cytokines (TNF-α and IL-1β) and occurred at 5 h after treatment. Endotoxemia also induced a significant increase in basal intracellular Ca2+ signal and a drop in RMP in control myofibers. These two changes were not elicited by myofibers deficient in Cx43/Cx45 expression. Therefore, sarcolemmal dysfunction characterizing endotoxemia is largely explained by the expression of functional Cx43 and Cx45 HCs. Hence, current therapy options for individuals suffering from endotoxic shock could be greatly improved with selective Cx HC inhibitors avoiding the underlying skeletal muscle dysfunction.

Differential Effect of Obesity on Muscular Strength in Adults with Cerebral Palsy

Cerebral palsy (CP) is a non-progressive and permanent neurological disorder that is characterized by muscular deterioration and atrophy. The major clinical problem with CP is early development of cardiovascular disease with increased rates of mortality. Due to the inevitability of motor dysfunction adults with CP can develop health risk factors such as obesity at a higher rate compared to the general population. Limited information is available to identify levels of obesity and its relation to muscular function in adults with CP. PURPOSE: To determine whether severity of obesity may affect muscular function and strength in adults with CP. METHODS: We studied total of sixteen adults with and without CP. Muscular strength (i.e., torque, work, and power) during knee extension and flexion was measured at 90, 150, and 210 °/sec in the lower extremity using Humac Norm Isokinetic Dynamometer. Maximal isometric forearm muscular strength was measured using a handgrip dynamometer. Body mass index (BMI), waist to hip ratio, and whole-body scan from Dual Energy X-Ray Absorptiometry were used to identify the levels of obesity. RESULTS: Compared to control, individuals with CP had similar BMI (26.8±3.0 CP vs. 22.9±1.0 control kg/m2; P>0.05), % body fat (35.2±4.5 CP vs. 28.4±3.7 control %; P>0.05), and % leg fat (40.7±4.3 CP vs. 30.5±4.1 control %; P>0.05). However, waist to hip ratio was significantly greater in CP (0.90±0.02 CP vs. 0.80±0.02 control; P<0.05); muscular strength was significantly lower in CP compared to control (e.g., knee extensor peak torque at 90°/sec; 25.9±8.1 CP vs. 72.5±12.2 control ft-lb; P<0.05). There was no relationship between BMI and extensor/flexor peak torque in both groups; however, there was a linear relationship between waist to hip ratio and extensor/flexor peak torque only in CP group (R2=0.34). A strong inverse relationship between % leg fat and extensor/flexor peak torque was observed in both groups (R2=0.79). CONCLUSION: These findings suggest that central obesity rather than BMI appeared to influence muscular strength in CP adults. In addition, less fat in the legs rather than the total body may contribute for higher leg muscular strength in adults with CP. Supported by Central RSCA and Undergraduate Research Grant, SJSU

Lower extremity muscle pathology in myotonic dystrophy type 1 assessed by quantitative MRI.

ObjectiveTo determine the value of quantitative MRI in providing imaging biomarkers for disease in 20 different upper and lower leg muscles of patients with myotonic dystrophy type 1 (DM1).MethodsWe acquired images covering these muscles in 33 genetically and clinically well-characterized patients with DM1 and 10 unaffected controls. MRIs were recorded with a Dixon method to determine muscle fat fraction, muscle volume, and contractile muscle volume, and a multi-echo spin-echo sequence was used to determine T2 water relaxation time (T2water), reflecting putative edema.ResultsMuscles in patients with DM1 had higher fat fractions than muscles of controls (15.6 ± 11.1% vs 3.7 ± 1.5%). In addition, patients had smaller muscle volumes (902 ± 232 vs 1,097 ± 251 cm3), smaller contractile muscle volumes (779 ± 247 vs 1,054 ± 246 cm3), and increased T2water (33.4 ± 1.0 vs 31.9 ± 0.6 milliseconds), indicating atrophy and edema, respectively. Lower leg muscles were affected most frequently, especially the gastrocnemius medialis and soleus. Distribution of fat content per muscle indicated gradual fat infiltration in DM1. Between-patient variation in fat fraction was explained by age (≈45%), and another ≈14% was explained by estimated progenitor CTG repeat length (r2 = 0.485) and somatic instability (r2 = 0.590). Fat fraction correlated with the 6-minute walk test (r = −0.553) and muscular impairment rating scale (r = 0.537) and revealed subclinical muscle involvement.ConclusionThis cross-sectional quantitative MRI study of 20 different lower extremity muscles in patients with DM1 revealed abnormal values for muscle fat fraction, volume, and T2water, which therefore may serve as objective biomarkers to assess disease state of skeletal muscles in these patients.ClinicalTrials.gov identifierNCT02118779.

The Effects of Chronic Electrical Stimulation Evaluation Functional and Electrical Properties of Muscle in a Small Group of Patients with Congenital Muscle Disorders

BackgroundIn the case of Congenital Muscle Disorders like Myotonic Dystrophy type 1 (DM1) the rehabilitative interventions have always been aimed at muscle strengthening, increasing of fatigue resistance and improving of aerobic metabolism efficiency whereas the electrical membrane fault has always been addressed pharmacologically. Neuromuscular electrical stimulation (NMES) is a useful therapeutic tool in sport medicine and in the rehabilitation of many clinical conditions characterized by motor impairment such as stroke, cerebral palsy and spinal cord injury.The aim of our pilot study was to evaluate the effects of chronic electrical stimulation both on functional and electrical properties of muscle in a small group of patients with condenital muscle disorders.Materials and methodsfive DM1 patients and one patient with Congenital Myotonia (CM) performed a home electrical stimulation of the tibialis anterior muscle lasting 15 days with a frequency of two daily sessions of 60 minutes each. Muscle strength was assessed according to the MRC scale (Medical Research Council) and functional tests (10 Meter Walking Test, 6 Minutes Walking Test – MWT and Timed Up and Go Test – TUG test) were performed. We analyzed the average rectified value of sEMG signal amplitude (ARV) to characterize the sarcolemmal excitability.ResultsAfter the treatment an increase of muscle strength in those DM1 patients with a mild strength deficit was observed. In all subjects an improvement of 10 MWT was recorded. Five patients improved their performance in the 6 MWT. In TUG test 4 out of 6 patients showed a slight reduction in execution time. All patients reported a subjective improvement when walking. A complete recovery of the normal increasing ARV curve was observed in 4 out of 5 DM1 patients; the CM patient didn't show modification of the ARV pattern.ConclusionsNMES determined a clear‐cut improvement of both the muscular weakness and the sarcolemmal excitability alteration in our small group of DM1 patients. Therefore this rehabilitative approach, if confirmed by further extensive studies, could be considered early in the management of muscular impairment in these patients. An attractive hypothesis to explain our encouraging result could be represented by a functional inhibition of small conductance calcium‐activated potassium channels expressed 3 (SK3) in muscle of DM1 subjects.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Uncovering health and social care needs among myotonic dystrophy patients: Utility of the Needs and Provisions Complexity Scale.

Myotonic dystrophy type 1 (DM1) is a slowly progressive multisystem disorder. Guidelines recommend multidisciplinary follow-up. We aimed to investigate the presence of unmet health and social care needs among patients with DM1 and whether unmet needs correlated with motor function, cognitive impairments, or quality of life. Patients were 22 adults with DM1. "Needs and Provisions Complexity Scale" (NPCS) was applied to evaluate the individual's needs and provision of health and social services. The Muscular Impairment Rating Scale (MIRS) was used to measure motor function and disease stage. All patients underwent neuropsychological testing. The EQ-5D-3L questionnaire was used to evaluate the patients' health-related quality of life (HRQoL). Median time from diagnosis was 11years (range: 1-40). Twenty patients had developed needs related to social care, personal care, and rehabilitation that had not been met, whereas need for medical follow-up was largely met. The more pronounced the muscular impairment, the more unmet needs were experienced by DM1 patients (r=0.50, P=0.019). Degree of unmet needs did not correlate with full-scale IQ (r=-0.27, P=0.23) or HRQoL (r=-0.14, P=0.55). Using NPCS, we discovered that patients with DM1 had unmet needs with respect to social care, personal care, and rehabilitation although their need for medical follow-up was met. Thus, the use of NPCS helped bring our practice in better accordance with guidelines. A higher MIRS grade should alert the clinician to the likelihood of unmet needs.

Post-stroke shoulder pain subtypes classifying criteria: towards a more specific assessment and improved physical therapeutic care

BackgroundPost-stroke Shoulder Pain (PSSP) is a common stroke-related syndrome that prolongs hospitalization and diminishes quality of life. PSSP studies were unsuccessful in clarifying pathophysiological mechanisms. Therefore, cohort's studies with greater variety of the sample and larger follow-up period could provide additional clinical data and may improve medical care. ObjectiveTo classify people with PSSP and identify intergroup clinical differences, providing additional data useful for therapeutic care planning. MethodsOne thousand individuals with stroke were selected from all levels of one health Area and followed up during one year. Demographic data, stroke clinical characteristics, stroke-related symptoms and rehabilitation parameters were collected. The shoulder muscle impairment was used to group participants into three clinical profiles: severe muscular impairment, moderate muscular impairment and low muscular impairment groups. ResultsA total of 119 individuals were diagnosed with PSSP. The suggested classification criteria showed two groups that differed significantly in relation to the onset and duration of PSSP, presence of sensory and speech impairment, and spasticity. The outcomes did not firmly support the existence of a third suggested PSSP subtype. ConclusionsPSSP may vary in onset, clinical manifestations, severity and syndrome duration. These results highlight the course of different clinical profiles and require multidisciplinary management approaches.

The role of fat grafting in prepectoral breast reconstruction

Prepectoral breast reconstruction has reemerged as a promising alternative to submuscular implants, as they place the patient at lower risk for pain, muscular impairment, and animation deformity. However, the thinner amount of overlying tissue in prepectoral reconstruction presents its own unique set of challenges. A "rippling" deformity is seen in some prepectoral patients, which is typically corrected with fat grafting. This report details our recommended technique for fat grafting in the prepectorally implanted patient.

Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is a slowly progressive myopathy characterized by varying multisystemic involvement. Several cerebral features such as brain atrophy, ventricular enlargement, and white matter lesions (WMLs) have frequently been described. The aim of this study is to investigate the structural organization of the brain that defines the disease through multimodal imaging analysis, and to analyze the relation between structural cerebral changes and DM1 clinical and neuropsychological profiles. 31 DM1 patients and 57 healthy controls underwent an MRI scan protocol, including T1, T2 and DTI. Global gray matter (GM), global white matter (WM), and voxel-level Voxel Based Morphometry (VBM) and voxel-level microstructural WM abnormalities through Diffusion Tensor Imaging (DTI) were assessed through group comparisons and linear regression analysis with age, degree of muscular impairment (MIRS score), CTG expansion size and neuropsychological outcomes from a comprehensive assessment. Compared with healthy controls, DM1 patients showed a reduction in both global GM and WM volume; and further regional GM decrease in specific primary sensory, multi-sensory and association cortical regions. Fractional anisotropy (FA) was reduced in both total brain and regional analysis, being most marked in frontal, paralimbic, temporal cortex, and subcortical regions. Higher ratings on muscular impairment and longer CTG expansion sizes predicted a greater volume decrease in GM and lower FA values. Age predicted global GM reduction, specifically in parietal regions. At the cognitive level, the DM1 group showed significant negative correlations between IQ estimate, visuoconstructive and executive neuropsychological scores and both global and regional volume decrease, mainly distributed in the frontal, parietal and subcortical regions. In this study, we describe the structural brain signatures that delineate the involvement of the CNS in DM1. We show that specific sensory and multi-sensory - as well as frontal cortical areas - display potential vulnerability associated with the hypothesized neurodegenerative nature of DM1 brain abnormalities.

Myocardial fibrosis by late gadolinium enhancement cardiovascular magnetic resonance in myotonic muscular dystrophy type 1: highly prevalent but not associated with surface conduction abnormality

BackgroundConduction disease and arrhythmias represent a major cause of mortality in myotonic muscular dystrophy type 1 (MMD1). Permanent pacemaker (PPM) implantation is the cornerstone of therapy to reduce cardiovascular mortality in MMD1. Cardiovascular magnetic resonance (CMR) studies demonstrate a high prevalence of myocardial fibrosis in MMD1, however the association between CMR myocardial fibrosis with late gadolinium enhancement (CMR-LGE) and surface conduction abnormality is not well established in MMD1.We investigated whether myocardial fibrosis by CMR-LGE is associated with surface conduction abnormalities meeting criteria for PPM implantation according to current guidelines in a cohort of patients with genetically confirmed MMD1.MethodsPatients with genetically confirmed MMD1 were retrospectively evaluated. 12-lead electrocardiography (ECG) performed within 6 months of CMR was necessary for inclusion. The severity and extent of MMD1 was quantified using a validated Muscular Impairment Rating Scale (MIRS). Based on current guidelines for device-based therapy of cardiac rhythm abnormalities, we defined surface conduction abnormality as the presence of ECG alterations meeting criteria for PPM implant (class I or II indications): PR interval > 200 ms (type I atrioventricular (AV) block) and/or mono or bifascicular block (QRS > 120 ms), or evidence of advanced AV block. Balanced steady-state free precession sequences (bSSFP) were used for assessment of left ventricular (LV) volumes and ejection fraction. MOdified Look-Locker Inversion Recovery (MOLLI) acquisition schemes were used to acquire T1 maps. Patients’ charts were reviewed up to 12 months post-CMR for occurrence of PPM implantation.ResultsFifty-two patients (38% male, 41 ± 14 years) were included. Overall, 31 (60%) patients had a surface conduction abnormality and 22 (42%) demonstrated midwall myocardial fibrosis by CMR-LGE. After a median of 57 days from CMR exam, 15 patients (29%) underwent PPM implantation. Subjects with vs. without surface conduction abnormality had significantly longer disease length (15.5 vs. 7.8 years, p = 0.015) and higher disease severity on the MIRS scale (p = 0.041). High prevalence of myocardial fibrosis by CMR-LGE was detected in subjects with and without surface conduction abnormality with no significant difference between the two cohorts (42% vs. 43%, p = 0.999). By multivariate logistic regression analysis, disease length was the only independent variable associated with surface conduction abnormality (OR 1.071, 95%CI 1.003–1.144, p = 0.040); while CMR-LGE was not associated with conduction abnormality (ρ = − 0.009, p = 0.949).ConclusionsMyocardial fibrosis by CMR-LGE is highly prevalent in MMD1 but not related to surface conduction abnormality meeting current guideline criteria for PPM implantation .

Physiotherapy for Children with CLN2 Disease

Abstract CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, genetic, paediatric-onset, neurodegenerative lysosomal storage disorder characterised by seizures, ataxia, rapid loss of motor function and language ability, dementia, visual loss and early death. Physiotherapy plays an important role in the management of CLN2 disease, aiming to maintain the best possible functioning and autonomy of the child, support the child’s participation in everyday life, limit secondary complications and maintain or improve quality of life. This article discusses the physiotherapeutic treatment of children diagnosed with CLN2 disease. Based on the author’s clinical experience, frequent muscular impairments associated with CLN2 disease, their impact on affected children’s sensorimotor abilities and autonomy, and physiotherapy interventions are described. Common muscular deficits included abnormal muscle tone leading to poor trunk control, difficulty standing upright, often accompanied by equinus contractures and movement disorders such as myoclonus. The use of orthotic and adaptive medical devices that support an erect posture in locomotion and positioning appear to be particularly beneficial for prolonging sensorimotor control, communication and food intake. In conclusion, early initiation of physiotherapy is recommended and should include the provision of adaptive walking, standing, sitting and positioning aids.

Relationships between muscular impairments, pain, and disability in patients with chronic nonspecific low back pain: a cross sectional study.

To clarify the significance of mechanical impairments, pain, and functional limitations as predictors of chronic low back pain (LBP). Ninety patients with chronic nonspecific low back pain (CNSLBP) were prospectively studied with clinical tests and questionnaires. Changes in muscle extensibility and endurance tests were evaluated and changes assessed in LBP intensity on numeric rating scale 0–10 and severity with Oswestry Disability Index (ODI) 0–100. In the present study we found significant associations between the 4 muscle extensibility and 2 endurance tests and pain at nonspecific patients with chronic LBP (P<0.005). The 2 muscle extensibility and 1 endurance tests were in complete equilibrium with ODI disability and hence showed similar results (P<0.005). The associations between the muscle extensibility and endurance tests and pain were significantly elevated in patients with nonspecific chronic LBP.

Atypical and severe manifestations of chikungunya virus infection in French Guiana: A hospital-based study.

BackgroundFrench Guiana (FG) was the first country in South America to declare chikungunya virus infection (CHIKV). The outbreak affected about 16,000 persons between February 2014 and October 2015, with several atypical cases, but only two fatal cases. We aimed to describe the clinical presentation of patients hospitalized for CHIKV infection, to estimate and identify risk factors of unusual and severe forms in adult patients.Materials and methodsA monocentric retrospective study was conducted in Cayenne hospital, the main city and the main hospital in FG, from March 1st 2014 to August 31st 2015. All patients admitted for at least one night with a biological diagnosis of CHIKV infection during the 2014/2015 outbreak were included, except pregnant women and children under 15 years.ResultsDuring the study period, 285 patients with a diagnosis of CHIKV infection were hospitalized in Cayenne hospital, among whom 96 nonpregnant adults were studied. Five were classified as severe forms (5.2%) and 23 as unusual forms (23.9%). The most frequent atypical and/or severe form was neurological (n = 20), followed by cardio-respiratory failure (acute respiratory failure n = 4, acute heart failure n = 2), digestive and hepatic disorders (acute hepatitis n = 3, acute pancreatitis n = 2), renal disorders (acute renal failure n = 5) and muscular impairment (rhabdomyolysis n = 3).ConclusionDuring the outbreak, hospitalizations were frequent, particularly for common forms, driven by algic clinical presentations and concerns due to the novelty of this infection. Despite atypical neurological and liver forms of CHIKV infection, case-fatality was low in French Guiana. No specific risk factor of atypical and/or severe forms was found in our study.

Efficacy of Multi-exon Skipping Treatment in Duchenne Muscular Dystrophy Dog Model Neonates

Duchenne muscular dystrophy (DMD) is caused by mutations in DMD, which codes for dystrophin. Because the progressive and irreversible degeneration of muscle occurs from childhood, earlier therapy is required to prevent dystrophic progression. Exon skipping by antisense oligonucleotides called phosphorodiamidate morpholino oligomers (PMOs), which restores the DMD reading frame and dystrophin expression, is a promising candidate for use in neonatal patients, yet the potential remains unclear. Here, we investigate the systemic efficacy and safety of early exon skipping in dystrophic dog neonates. Intravenous treatment of canine X-linked muscular dystrophy in Japan dogs with a 4-PMO cocktail resulted in ∼3%-27% in-frame exon 6-9 skipping and dystrophin restoration across skeletal muscles up to 14% of healthy levels. Histopathology was ameliorated with the reduction of fibrosis and/or necrosis area and centrally nucleated fibers, significantly in the diaphragm. Treatment induced cardiac multi-exon skipping, though dystrophin rescue was not detected. Functionally, treatment led to significant improvement in the standing test. Toxicity was not observed from blood tests. This is the first study to demonstrate successful multi-exon skipping treatment and significant functional improvement in dystrophic dogs. Early treatment was most beneficial for respiratory muscles, with implications for addressing pulmonary malfunction in patients.

Why Do Individuals with Cirrhosis Fall? A Mechanistic Model for Fall Assessment, Treatment, and Research.

Falls are prevalent for people with cirrhosis and commonly lead to loss of independence, reduced quality of life, and mortality. Despite a critical need for fall prevention in this population, cirrhosis-specific fall-related mechanisms are not well understood. We posit that most falls in this patient population are due to a coalescence of discrete subclinical impairments that are not typically detected at the point of care. The combined effect of these subtle age- and disease-related neurocognitive and muscular impairments leads to the inability to respond successfully to a postural perturbation within the available 300 to 400ms. This article provides a conceptual model of physiological resilience to avoid a fall that focuses on attributes that underlie the ability to withstand a postural perturbation and their clinical evaluation. Evidence supporting this model in cirrhosis and other high fall risk conditions will be synthesized and suggestions for fall assessment and treatment will be discussed.

Systemic alterations induced by phospholipase A2 , BmooTX-I, isolated from Bothrops moojeni snake venom.

Ophidic accidents are among the problems of public health in Brazil. The components from bothropic venom are responsible for many systemic clinical complications resulting from envenomation. The present work aimed to analyse the systemic changes induced in mice after intraperitoneal administration of BmooTX-I, a myotoxic acidic phospholipase A2 isolated from Bothrops moojeni venom. Urinalysis was performed and the following plasma biochemical markers were documented: urea, creatinine and uric acid (renal function); glucose and amylase (pancreatic function); alanine aminotransferase, alkaline phosphatase and gamma-GT (intra- and extrahepatic function); creatine kinase and enzymatic lactate (muscle function). Our results showed that after the intraperitoneal injection of BmooTX-I the urine of these animals showed glycosuria, proteinuria, haematuria, bacteriuria, bilirubinuria, polyuria and nitrite. The plasma biochemical analysis showed alterations in levels of urea, creatinine and uric acid. Amylase concentration was not altered significantly, but the plasma glucose increased significantly compared to controls. The plasma levels of alanine aminotransferase and alkaline phosphatase decreased and increased, respectively, in these same animals. On the other hand, the plasma γGT concentration did not undergo significant modification compared to the control group. The plasma concentration of CK increased, while the enzymatic lactate concentration decreased after the injection of the BmooTX-I. Therefore, in mice BmooTX-I is capable of causing systemic alterations which manifest as renal, muscular, hepatic and pancreatic impairment.

Neuropsychological and Psychological Functioning Aspects in Myotonic Dystrophy Type 1 Patients in Italy

Introduction: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant genetic illness, characterized by a progressive loss of strength. Important deficits in cognitive functioning and a significant prevalence of psychiatric disorders have been previously reported.Methods:A neuropsychological and psychological assessment was carried out in 31 DM1 patients (61% males) in order to measure the cognitive functioning and explore their personality profiles. The MMSE Mini-Mental State Examination, Frontal Assessment Battery (FAB), ENB-2 Battery assessing memory (short term, long term and working memory), integration capacities, visual-spatial ability, attention (selective, divided, shifting/switching) executive functions, praxis, discrimination and logic capabilities and psychopathology Symptom Check List 90-R (SCL-90-R) were administered. The neuropsychological and psychological evaluation of DM1 patients was carried out taking into consideration the clinical parameters (CTG repeat, age at onset, disease duration, Muscular Impairment Rate Scale (MIRS), Medical Research Council Scale (MRC) and the Epworth Sleepiness Scales (EPS)).Results: Regarding psychopathology 19.4% of patients scored a moderate or high level of symptoms intensity index (GSI), 12.9% reported a high number of symptoms (PST) and 16.1% reported a high intensity level of the perceived symptoms (PSDI). Fatigue and daytime sleepiness resulted as being associated with higher levels of psychoticism (PSY). Only 1 patient reported a severe impairment in the spatial and temporal orientation, memory, language, praxis, attention and calculation. Longer disease duration was also associated with cognitive impairment evaluated through ENB-2 (p < 0.05).Discussions and Conclusions:There are indications of the utility of neuropsychological and psychological screening and support for these patients and their families due to the link between disease duration and cognitive performances. A proposal of a clinical protocol, with an illustration of a clinical case report of a family is presented.

Sarcolab pilot study into skeletal muscle\u2019s adaptation to long-term spaceflight

Spaceflight causes muscle wasting. The Sarcolab pilot study investigated two astronauts with regards to plantar flexor muscle size, architecture, and function, and to the underlying molecular adaptations in order to further the understanding of muscular responses to spaceflight and exercise countermeasures. Two crew members (A and B) spent 6 months in space. Crew member A trained less vigorously than B. Postflight, A showed substantial decrements in plantar flexor volume, muscle architecture, in strength and in fiber contractility, which was strongly mitigated in B. The difference between these crew members closely reflected FAK-Y397 abundance, a molecular marker of muscle’s loading history. Moreover, crew member A showed downregulation of contractile proteins and enzymes of anaerobic metabolism, as well as of systemic markers of energy and protein metabolism. However, both crew members exhibited decrements in muscular aerobic metabolism and phosphate high energy transfer. We conclude that countermeasures can be effective, particularly when resistive forces are of sufficient magnitude. However, to fully prevent space-related muscular deterioration, intersubject variability must be understood, and intensive exercise countermeasures programs seem mandatory. Finally, proteomic and metabolomic analyses suggest that exercise benefits in space may go beyond mere maintenance of muscle mass, but rather extend to the level of organismic metabolism.

Validation of the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1

We aimed to validate the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1 (DM1). Fifty patients with adult-onset, genetically confirmed DM1 were evaluated by Nine Hole Peg Test and re-evaluated at one week. Myotonia was not a limiting factor. The first test was compared with that performed by normal subjects (n = 28). Contextually, patients underwent handgrip and three-finger pinch assessments by handheld dynamometer. The Nine Hole Peg Test showed high intra-rater and inter-rater reliability in DM1 [ICC 0.86/0.83 for dominant and 0.90/0.88 for non-dominant hand, respectively]. Inverse correlation with handgrip and pinch strength values (r = −0.4; p < 0.01) and direct correlation with Muscular Impairment Rating Scale (r = 0.4; p < 0.01) were found for both DH and NDH. The test was able to differentiate severe DM1 patients, stratified by extent of muscle impairment, from mildly affected and normal controls, with a sensitivity of 97% and 95% for dominant hand and non-dominant hand, respectively (p < 0.0001). In conclusion, we showed that the Nine Hole Peg Test is a reliable, valid and sensitive test of dexterity in DM1, and that it can be considered as a candidate outcome measure to monitor natural history of disease and, possibly, therapeutic response in clinical trials.

Progressive Resistance Training Improves Torque Capacity and Strength in Mobility-Limited Older Adults.

Progressive resistance training (PRT) is consistently shown to improve muscle strength in older adults. The efficacy of PRT to improve muscle fatigue in older adults with demonstrated mobility limitations remains unclear. Mobility-limited (Short Physical Performance Battery [SPPB] ≤ 9) older adults (age 70-92 years) were recruited for this study and randomized to either PRT or home-based flexibility (FLEX) 3 d/wk for 12 weeks. Muscle fatigue and strength outcomes were assessed at baseline and 12 weeks. The primary outcome was torque capacity, a composite measure of strength and fatigue, defined as the sum of peak torques from an isokinetic fatigue test. Seventy participants were randomized (mean [SD] age 78.9 [5.4] years; 60% female; mean [SD] SPPB 7.5 [1.6]). At follow-up, the PRT group improved significantly in torque capacity, mean between-group difference (95% confidence interval) 466.19 (138.4, 793.97) Nm (p = .006), and maximal strength 127.3 (60.96, 193.61) Nm (p = .0003), when compared with FLEX group. Neither group demonstrated significant changes in muscle fatigue or torque variability. Twelve weeks of PRT improved torque capacity, as well as strength in mobility-limited older adults. These results demonstrate PRT improves multiple age-related muscular impairments.