Towards the Identification of Biomarkers for Muscle Function Improvement in Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. In DM1 patients, skeletal muscle is severely impaired, even atrophied and patients experience a progressive decrease in maximum strength. Strength training for these individuals can improve their muscle function and mass, however, the biological processes involved in these improvements remain unknown. OBJECTIVE: This exploratory study aims at identifying the proteomic biomarkers and variables associated with the muscle proteome changes induced by training in DM1 individuals. METHODS: An ion library was developed from liquid chromatography-tandem mass spectrometry proteomic analyses of Vastus Lateralis muscle biopsies collected in 11 individuals with DM1 pre-and post-training. RESULTS: The proteomic analysis showed that the levels of 44 proteins were significantly modulated. A literature review (PubMed, UniProt, PANTHER, REACTOME) classified these proteins into biological sub-classes linked to training-induced response, including immunity, energy metabolism, apoptosis, insulin signaling, myogenesis and muscle contraction. Linear models identified key variables explaining the proteome modulation, including atrophy and hypertrophy factors. Finally, six proteins of interest involved in myogenesis, muscle contraction and insulin signaling were identified: calpain-3 (CAN3; Muscle development, positive regulation of satellite cell activation), 14-3-3 protein epsilon (1433E; Insulin/Insulin-like growth factor, PI3K/Akt signaling), myosin-binding protein H (MYBPH; Regulation of striated muscle contraction), four and a half LIM domains protein 3 (FHL3; Muscle organ development), filamin-C (FLNC; Muscle fiber development) and Cysteine and glycine-rich protein 3 (CSRP3). CONCLUSION: These findings may lead to the identification for DM1 individuals of novel muscle biomarkers for clinical improvement induced by rehabilitation, which could eventually be used in combination with a targeted pharmaceutical approach to improving muscle function, but further studies are needed to confirm those results.

Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of a CTG triplet repeat expansion in the Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease. OBJECTIVE: This study investigates the effects of 12-week resistance exercise training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n = 11, men) in comparison to control muscle with normal oxidative phosphorylation. METHODS: Immunofluorescence was used to assess protein levels of key respiratory chain subunits of complex I (CI) and complex IV (CIV), and markers of mitochondrial mass and cell membrane in individual myofibres sampled from muscle biopsies. Using control's skeletal muscle fibers population, we classified each patient's fibers as having normal, low or high levels of CI and CIV and compared the proportions of fibers before and after exercise training. The significance of changes observed between pre- and post-exercise within patients was estimated using a permutation test. RESULTS: At baseline, DM1 patients present with significantly decreased mitochondrial mass, and isolated or combined CI and CIV deficiency. After resistance exercise training, in most patients a significant increase in mitochondrial mass was observed, and all patients showed a significant increase in CI and/or CIV protein levels. Moreover, improvements in mitochondrial mass were correlated with the one-repetition maximum strength evaluation. CONCLUSIONS: Remarkably, 12-week resistance exercise training is sufficient to partially rescue mitochondrial dysfunction in DM1 patients, suggesting that the response to exercise is in part be due to changes in mitochondria.

Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1.

Muscle stem cells, the engine of muscle repair, are affected in myotonic dystrophy type 1 (DM1); however, the underlying molecular mechanism and the impact on the disease severity are still elusive. Here, we show using patients' samples that muscle stem cells/myoblasts exhibit signs of cellular senescence in vitro and in situ. Single cell RNAseq uncovers a subset of senescent myoblasts expressing high levels of genes related to the senescence-associated secretory phenotype (SASP). We show that the levels of interleukin-6, a prominent SASP cytokine, in the serum of DM1 patients correlate with muscle weakness and functional capacity limitations. Drug screening revealed that the senolytic BCL-XL inhibitor (A1155463) can specifically remove senescent DM1 myoblasts by inducing their apoptosis. Clearance of senescent cells reduced the expression of SASP, which rescued the proliferation and differentiation capacity of DM1 myoblasts in vitro and enhanced their engraftment following transplantation in vivo. Altogether, this study identifies the pathogenic mechanism associated with muscle stem cell defects in DM1 and opens a therapeutic avenue that targets these defective cells to restore myogenesis.

Individual transcriptomic response to strength training for patients with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not been studied. To determine whether training rescued transcriptomic defects, RNA-Seq was performed on vastus lateralis samples from 9 male patients with DM1 before and after a 12-week strength-training program and 6 male controls who did not undergo training. Differential gene expression and alternative splicing analysis were correlated with the one-repetition maximum strength evaluation method (leg extension, leg press, hip abduction, and squat). While training program-induced improvements in splicing were similar among most individuals, rescued splicing events varied considerably between individuals. Gene expression improvements were highly varied between individuals, and the percentage of differentially expressed genes rescued after training were strongly correlated with strength improvements. Evaluating transcriptome changes individually revealed responses to the training not evident from grouped analysis, likely due to disease heterogeneity and individual exercise response differences. Our analyses indicate that transcriptomic changes are associated with clinical outcomes in patients with DM1 undergoing training and that these changes are often specific to the individual and should be analyzed accordingly.

Psychometric properties of a standardized protocol of muscle strength assessment by hand-held dynamometry in healthy adults: a reliability study.

BACKGROUND: Maximal isometric muscle strength (MIMS) assessment is a key component of physiotherapists' work. Hand-held dynamometry (HHD) is a simple and quick method to obtain quantified MIMS values that have been shown to be valid, reliable, and more responsive than manual muscle testing. However, the lack of MIMS reference values for several muscle groups in healthy adults with well-known psychometric properties limits the use and the interpretation of these measures obtained with HHD in clinic. OBJECTIVE: To determine the intra- and inter-rater reliability, standard error of measurement (SEM) and minimal detectable change (MDC) of MIMS torque values obtained with HHD. METHODS: Intra and Inter-rater Reliability Study. The MIMS torque of 17 muscle groups was assessed by two independent raters at three different times in 30 healthy adults using a standardized HHD protocol using the MEDup™ (Atlas Medic, Québec, Canada). Participants were excluded if they presented any of the following criteria: 1) participation in sport at a competitive level; 2) degenerative or neuromusculoskeletal disease that could affect torque measurements; 3) traumatic experience or disease in the previous years that could affect their muscle function; and 4) use of medication that could impact muscle strength (e.g., muscle relaxants, analgesics, opioids) at the time of the evaluation. Intra- and inter-rater reliability were determined using two-way mixed (intra) and random effects (inter) absolute agreement intraclass correlation coefficients (ICC: 95% confidence interval) models. SEM and MDC were calculated from these data. RESULTS: Intra- and inter-rater reliability were excellent with ICC (95% confidence interval) varying from 0.90 to 0.99 (0.85-0.99) and 0.89 to 0.99 (0.55-0.995), respectively. Absolute SEM and MDC for intra-rater reliability ranged from 0.14 to 3.20 Nm and 0.38 to 8.87 Nm, respectively, and from 0.17 to 5.80 Nm and 0.47 to 16.06 Nm for inter-rater reliability, respectively. CONCLUSIONS: The excellent reliability obtained in this study suggest that the use of such a standardized HHD protocol is a method of choice for MIMS torque measurements in both clinical and research settings. And the identification of the now known metrological qualities of such a protocol should encourage and promote the optimal use of manual dynamometry.

MYTHO is a novel regulator of skeletal muscle autophagy and integrity.

Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.

Periostin as a blood biomarker of muscle cell fibrosis, cardiomyopathy and disease severity in myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy and is caused by an repeat expansion [r(CUG)exp] located in the 3' untranslated region of the DMPK gene. Symptoms include skeletal and cardiac muscle dysfunction and fibrosis. In DM1, there is a lack of established biomarkers in routine clinical practice. Thus, we aimed to identify a blood biomarker with relevance for DM1-pathophysiology and clinical presentation. METHODS: We collected fibroblasts from 11, skeletal muscles from 27, and blood samples from 158 DM1 patients. Moreover, serum, cardiac, and skeletal muscle samples from DMSXL mice were included. We employed proteomics, immunostaining, qPCR and ELISA. Periostin level were correlated with CMRI-data available for some patients. RESULTS: Our studies identified Periostin, a modulator of fibrosis, as a novel biomarker candidate for DM1: proteomic profiling of human fibroblasts and murine skeletal muscles showed significant dysregulation of Periostin. Immunostaining on skeletal and cardiac muscles from DM1 patients and DMSXL mice showed an extracellular increase of Periostin, indicating fibrosis. qPCR studies indicated increased POSTN expression in fibroblasts and muscle. Quantification of Periostin in blood samples from DMSXL mice and two large validation cohorts of DM1 patients showed decreased levels in animals and diseased individuals correlating with repeat expansion and disease severity and presence of cardiac symptoms identified by MRI. Analyses of longitudinal blood samples revealed no correlation with disease progression. CONCLUSIONS: Periostin might serve as a novel stratification biomarker for DM1 correlating with disease severity, presence of cardiac malfunction and fibrosis.

French Translation and Cross-cultural Adaptation of the Scale for the Assessment and Rating of Ataxia.

The Scale for the Assessment and Rating of Ataxia (SARA) is a widely used scale for assessing the severity of ataxia in clinics, natural history studies, and treatment trials worldwide. However, no French translation with validated cross-cultural adaptation is available. This study aimed to translate and adapt the SARA into French. The translation process was conducted according to the ISPOR guidelines for the translation and cultural adaptation process for patient-reported outcomes. A total of five translators, an expert committee, and two physiotherapists took part in the process to assess and ensure comprehension and language equivalences of the final French version. A few misinterpretations were pointed out during the translation process and were changed accordingly by the translation team. The French version of the SARA is ready to be used in clinical and research settings with French-speaking populations living with ataxia.

A rehabilitation program to increase balance and mobility in ataxia of Charlevoix-Saguenay: An exploratory study.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is characterized by balance impairment and mobility limitations, which both increase the risk of falling. The objective of this study was to explore the effects of a rehabilitation program aimed at increasing trunk and lower limb motor control on balance and walking abilities, and accomplishment of activities of daily living. In this exploratory study, a group-supervised rehabilitation program was performed three times a week for 8 weeks (two sessions at a rehabilitation gym and one pool session). Outcome measures included the Ottawa Sitting Scale, Berg Balance Scale, modified Activities-specific Balance Confidence Scale, 30-Second Chair Stand Test, 10-Meter Walk Test, Barthel Index, and Scale for the Assessment and Rating of Ataxia. Significant improvements in balance, trunk control, maximal and self-selected walking speed difference, ataxia severity and accomplishment of specific activities of daily living were noted for the whole group at the end of the program. At the individual level, all participants improved beyond the standard error of measurement in at least two outcome measures. Also, most participants reported many perceived improvements related to balance, posture and functional mobility. This study provides encouraging results on the effects of a rehabilitation program for ambulatory people with ARSACS. Group intervention could have a positive impact on their daily lives and improve the health care service offered to this population. Future studies with larger sample sizes including control groups and other forms of ataxia are necessary to validate our results to generalize them.

Impact of a 12-week Strength Training Program on Fatigue, Daytime Sleepiness, and Apathy in Men with Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disorder causing a plea of impairments, of which fatigue and apathy are some of the most frequent non-muscular symptoms. No curative treatment exists to date, and patients only have access to limited effective care, which are intended to decrease the burden of specific symptoms in daily life. OBJECTIVE: This study aimed to assess whether a 12-week strength training program has an impact on fatigue/daytime sleepiness, apathy, and disease bruden in men with DM1. METHODS: Eleven participants completed the Fatigue and Daytime Sleepiness Scale (FDSS) and the Myotonic Dystrophy Health Index (MDHI) at baseline, at 6 and 12 weeks, and at 6 and 9 months. Also, the Apathy Evaluation Scale (AES) was filled out at baseline, at 12 weeks, and at 6 and 9 months. RESULTS: Results show significant effects of the training program both on apathy and fatigue/daytime sleepiness, effects that are respectively greater at three and six months after the end of the program than at its very end. However, no difference was observed regarding the overall disease burden. CONCLUSION: These findings are promising for patients with DM1 considering that few non-pharmacological treatments are available.

Pharmacological and exercise-induced activation of AMPK as emerging therapies for myotonic dystrophy type 1 patients.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder with variable clinical features. Currently, there is no cure or effective treatment for DM1. The disease is caused by an expansion of CUG repeats in the 3' UTR of DMPK mRNAs. Mutant DMPK mRNAs accumulate in nuclei as RNA foci and trigger an imbalance in the level and localization of RNA-binding proteins causing the characteristic missplicing events that account for the varied DM1 symptoms, a disease mechanism referred to as RNA toxicity. In recent years, multiple signalling pathways have been identified as being aberrantly regulated in skeletal muscle in response to the CUG expansion, including AMPK, a sensor of energy status, as well as a master regulator of cellular energy homeostasis. Converging lines of evidence highlight the benefits of activating AMPK signalling pharmacologically on RNA toxicity, as well as on muscle histology and function, in preclinical DM1 models. Importantly, a clinical trial with metformin, an activator of AMPK, resulted in functional benefits in DM1 patients. In addition, exercise, a known AMPK activator, has shown promising effects on RNA toxicity and muscle function in DM1 mice. Finally, clinical trials involving moderate-intensity exercise also induced functional benefits for DM1 patients. Taken together, these studies clearly demonstrate the molecular, histological and functional benefits of AMPK activation and exercise-based interventions on the DM1 phenotype. Despite these advances, several key questions remain; in particular, the extent of the true implication of AMPK in the observed beneficial improvements, as well as how, mechanistically, activation of AMPK signalling improves the DM1 pathophysiology.

What is Known About Muscle Strength Reference Values for Adults Measured by Hand-Held Dynamometry: A Scoping Review.

Objective: To map the body of existing literature regarding reference values of maximal isometric muscle strength (MIMS) of upper and lower limbs obtained with handheld dynamometers (HHD) in healthy adults to identify potential gaps in the literature and specify future research needs. Data Sources: A scoping review in which PubMed, EMBASE, CINAHL plus, PEDRO, and Cochrane databases were searched before May 1, 2020. Study Selection: All studies using standardized HHD protocols for the purpose of establishing reference values in healthy adult population were included. Two independent reviewers completed an initial screening of article titles and abstracts, and the remaining articles were read in their entirety and screened according to the inclusion and exclusion criteria. Disagreements were discussed, with recourse to a third reviewer when needed. Data Extraction: Data of the selected studies were extracted and charted by 2 independent reviewers using a tested data extraction grid to ensure method standardization. Data were subsequently merged to produce the complete final extracted data. Data Synthesis: Titles and abstracts of 4015 studies were screened, 46 articles were fully reviewed, and 9 manuscripts were selected for the final analysis. A large variability exists between protocols used for muscle testing in terms of type of device, measurement units, subject positioning, and muscle groups tested. Conclusion: The existing literature regarding HHD reference values of MIMS is scarce and presents gaps notably relating to strength units and well-described protocols with known psychometric properties, despite the development and increased availability of high quality HHD. This observation emphasizes the critical need to develop reference values in manual dynamometry in adults to optimize the use of manual dynamometry for diagnostic and prognostic decisions.

Explanatory factors of dynamic balance impairment in myotonic dystrophy type 1.

INTRODUCTION/AIMS: Myotonic dystrophy type 1 (DM1) is a neuromuscular disease affecting many systems and for which muscle weakness is one of the cardinal symptoms. People with DM1 also present with balance-related impairments and high fall risk. The aim of this study was to explore explanatory factors of dynamic balance impairment in the DM1 population. METHODS: A secondary analysis of data collected as part of a larger study was performed. The Mini Balance Evaluation System Test (Mini-BESTest) was used to assess dynamic balance. Age, sex, and CTG repeat length in blood were retrieved from medical records and research files. The maximal isometric muscle strength of five lower limb muscle groups (hip flexors and extensors, knee flexors and extensors, and ankle dorsiflexors) was quantitatively assessed as well as fatigue. Standard multiple regression analysis was used. RESULTS: Fifty-two individuals (31 men) aged between 24 and 81 years were included. The final model explains 65.9% of the balance score; ankle dorsiflexor muscle strength was the strongest explanatory factor, followed by CTG repeat length, age and fatigue to a lesser extent. DISCUSSION: Dynamic balance is impaired in people with DM1. Results of this study suggest that rehabilitation interventions aimed at improving strength of the ankle dorsiflexors and managing fatigue could help to improve dynamic balance in this specific population.

Assessment of muscular strength and functional capacity in the juvenile and adult myotonic dystrophy type 1 population: a 3-year follow-up study.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic, and autosomal dominant disease. Muscle wasting and weakness have been associated with impaired functional capacity and restricted social participation in affected individuals. The disease's presentation is very heterogenous and its progression is still under-documented. OBJECTIVE: The aim of the study was to document the progression of muscular strength and functional capacity in the DM1 population over a 3-year period. METHODS: Twenty-three individuals with juvenile or adult phenotypes of DM1 were recruited to complete clinical assessments in 2016 and 2019. Maximal isometric muscle strength (MIMS) was evaluated with quantified muscle testing and functional capacity was evaluated with the Mini-BESTest, the 10-m walk test at comfortable and maximal speeds, the Timed Up and Go and the 6-min walk test. Participants also completed three questionnaires: DM1-Activ, Upper Extremity Functional Index and Lower Extremity Functional Scale (LEFS). Subgroup analyses were evaluated for sex, phenotype, and type of physical activity practiced during the 3-year period. RESULTS: For the whole group, there was a significant decline in the scores of the Mini-BESTest and the LEFS. Also, MIMS significantly declined for prehension, lateral pinch as well as for hip abductors, knee extensors and ankle dorsiflexors muscle groups. Subgroups analyses revealed that men lost more MIMS than women, and that adult phenotype lost more MIMS than juvenile phenotype. CONCLUSION: Quantified muscle testing is a better indicator of disease progression over a 3-year period than functional tests. Phenotype and sex are important factors that influence the progression of DM1.

Effects and Acceptability of an Individualized Home-Based 10-Week Training Program in Adults with Myotonic Dystrophy Type 1.

BACKGROUND: Muscle weakness is a cardinal sign of myotonic dystrophy type 1, causing important functional mobility limitations and increasing the risk of falling. As a non-pharmacological, accessible and safe treatment for this population, strength training is an intervention of choice. OBJECTIVE: To document the effects and acceptability of an individualized semi-supervised home-based exercise program on functional mobility, balance and lower limb strength, and to determine if an assistive training device has a significant impact on outcomes. METHODS: This study used a pre-post test design and men with the adult form of DM1 were randomly assigned to the control or device group. The training program was performed three times a week for 10 weeks and included three exercises (sit-to-stand, squat, and alternated lunges). Outcome measures included maximal isometric muscle strength, 10-Meter Walk Test, Mini-BESTest, 30-Second Chair Stand Test and 6-minute walk test. RESULTS: No outcome measures showed a significant difference, except for the strength of the knee flexors muscle group between the two assessments. All participants improved beyond the standard error of measurement in at least two outcome measures. The program and the device were well accepted and all participants reported many perceived improvements at the end of the program. CONCLUSIONS: Our results provide encouraging data on the effects and acceptability of a home-based training program for men with the adult form of DM1. These programs would reduce the financial burden on the health system while improving the clinical services offered to this population.

Validity of the Mini-BESTest in adults with myotonic dystrophy type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disease that causes balance problems. The objective of this study was to assess the construct validity of the Mini-BESTest among adults with DM1. METHODS: Fifty-nine individuals with late-onset or adult phenotypes of DM1 were recruited. Participants performed the Mini-BESTest, 10-Meter Walk Test (10mWT), 6-Minute Walk Test (6MWT), and Timed Up & Go (TUG) and were questioned on their tendency to lose balance and whether they fell in the past month. RESULTS: Scores on the Mini-BESTest were significantly different between phenotypes and CTG repeat numbers (P < .02). Significant correlations were found with the 10mWT, 6MWT, and the TUG (r = 0.77-0.84; P < .001). A cutoff score of 21.5 was found to identify fallers with 90% posttest accuracy. DISCUSSION: The Mini-BESTest demonstrates evidence of construct validity when assessing balance in the DM1 population.

Strength-training effectively alleviates skeletal muscle impairments in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic disease characterized by progressive muscle weakness. The aim of this project is to evaluate the effects of a 12-week lower limb strength training program in 11 men with DM1. Maximal isometric muscle strength, 30-second sit-to-stand, comfortable and maximal 10-m walk test (10 mwt) were evaluated at baseline, 6 and 12 weeks, and at 6 and 9 months. The one-repetition maximum strength evaluation method of the training exercises was completed at baseline, 6 and 12 weeks. Muscle biopsies were taken in the vastus lateralis at baseline and 12 weeks to evaluate muscle fiber typing and size (including atrophy/hypertrophy factors). Performance in strength and functional tests all significantly improved by week 12. Maximal isometric muscle strength of the knee extensors decreased by month 9, while improved walking speed and 30 second sit-to-stand performance were maintained. On average, there were no significant changes in fiber typing or size after training. Further analysis showed that individual abnormal hypertrophy factor at baseline could explain the different changes in muscle size among participants. Strength training induces maximal isometric muscle strength and lasting functional gains in DM1. Abnormal hypertrophy factor could be a key component to identify high and low responders to hypertrophy in DM1.

Training program-induced skeletal muscle adaptations in two men with myotonic dystrophy type 1.

OBJECTIVE: The purpose of this side product of another unpublished research project, was to address the effects of a training program on skeletal muscle adaptations of people with myotonic dystrophy type 1 (DM1), under a multifaceted perspective. The objective of this study was to look at training induced muscular adaptations by evaluating changes in muscle strength, myofiber cross-sectional area (CSA), proportion of myofiber types and with indirect markers of muscle growth [proportion of centrally nucleated fibers (CNF) and density of neutrophils and macrophages]. Two men with DM1 underwent a 12-week strength/endurance training program (18 sessions). Two muscle biopsies were obtained pre- and post-training program. RESULTS: Muscular adaptations occurred only in Patient 1, who attended 72% of the training sessions compared to 39% for Patient 2. These adaptations included increase in the CSA of type I and II myofibers and changes in their proportion. No changes were observed in the percentage of CNF, infiltration of neutrophils and macrophages and muscle strength. These results illustrate the capacity of skeletal muscle cells to undergo adaptations linked to muscle growth in DM1 patients. Also, these adaptations seem to be dependent on the attendance. Trial registration Clinicaltrials.gov NCT04001920 retrospectively registered on June 26th, 2019.

Correction to: What is known about the effects of exercise or training to reduce skeletal muscle impairments of patients with myotonic dystrophy type 1? A scoping review.

An incorrect attribution of the first study regarding the effect of exercise in DM1 mouse models needs to be revised.

Intra-Rater Reliability and Concurrent Validity of Quantified Muscle Testing for Maximal Knee Extensors Strength in Men with Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most prevalent degenerative neuromuscular disease in adults. Knee extensor (KE) maximal strength loss is a strong indicator of physical limitations in DM1. A reliable, precise and accessible maximal strength evaluation method needs to be validated for this slowly progressive disease. OBJECTIVE: This paper aims to assess the intra-rater reliability, the standard error of measurement (SEM), the minimal detectable change (MDC), and the concurrent validity of quantified muscle testing (QMT) using a handheld dynamometer with a gold standard: the Biodex isokinetic device. METHODS: Nineteen men with the adult form of DM1 participated in this study by attending 2 visits spaced by one week. The evaluation of KE muscle strength with QMT was completed on the first visit and the same QMT evaluation in addition to the maximal muscle strength evaluation using an isokinetic device were performed on the second visit. RESULTS: The intra-rater reliability was excellent with an intraclass correlation coefficient (ICC) of 0.98 (0.96-0.99 : 95% confidence interval). SEM and MDC values were 1.05 Nm and 2.92 Nm, respectively. Concurrent validity of QMT of KE muscle group with the Biodex was also excellent with a Spearman's correlation of ρ= 0.98. CONCLUSIONS: The excellent concurrent validity and intra-rater reliability, and the small SEM and MDC of the QMT make this test a method of choice, in either a clinical or research setting, to precisely evaluate muscle strength impairments of the KE in men with DM1.