No sign of weakness: a systematic review and meta-analysis of hip and calf muscle strength after anterior cruciate ligament injury.

OBJECTIVE: We aimed to determine hip and lower-leg muscle strength in people after ACL injury compared with an uninjured control group (between people) and the uninjured contralateral limb (between limbs). DESIGN: Systematic review with meta-analysis. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Scopus, Cochrane CENTRAL and SportDiscus to 28 February 2023. ELIGIBILITY CRITERIA: Primary ACL injury with mean age 18-40 years at time of injury. Studies had to measure hip and/or lower-leg muscle strength quantitatively (eg, dynamometer) and report muscle strength for the ACL-injured limb compared with: (i) an uninjured control group and/or (ii) the uninjured contralateral limb. Risk of bias was assessed according to Cochrane Collaboration domains. RESULTS: Twenty-eight studies were included (n=23 measured strength ≤12 months post-ACL reconstruction). Most examined hip abduction (16 studies), hip extension (12 studies) and hip external rotation (7 studies) strength. We found no meaningful difference in muscle strength between people or between limbs for hip abduction, extension, internal rotation, flexion or ankle plantarflexion, dorsiflexion (estimates ranged from -9% to +9% of comparator). The only non-zero differences identified were in hip adduction (24% stronger on ACL limb (95% CI 8% to 42%)) and hip external rotation strength (12% deficit on ACL limb (95% CI 6% to 18%)) compared with uninjured controls at follow-ups >12 months, however both results stemmed from only two studies. Certainty of evidence was very low for all outcomes and comparisons, and drawn primarily from the first year post-ACL reconstruction. CONCLUSION: Our results do not show widespread or substantial muscle weakness of the hip and lower-leg muscles after ACL injury, contrasting deficits of 10%-20% commonly reported for knee extensors and flexors. As it is unclear if deficits in hip and lower-leg muscle strength resolve with appropriate rehabilitation or no postinjury or postoperative weakness occurs, individualised assessment should guide training of hip and lower-leg strength following ACL injury. PROSPERO REGISTRATION NUMBER: CRD42020216793.

Neural drive and motor unit characteristics after anterior cruciate ligament reconstruction: implications for quadriceps weakness.

Purpose: The purpose of this investigation was to compare the quality of neural drive and recruited quadriceps motor units' (MU) action potential amplitude (MUAPAMP) and discharge rate (mean firing rate (MFR)) relative to recruitment threshold (RT) between individuals with anterior cruciate ligament reconstruction (ACLR) and controls. Methods: Fourteen individuals with ACLR and 13 matched controls performed trapezoidal knee extensor contractions at 30%, 50%, 70%, and 100% of their maximal voluntary isometric contraction (MVIC). Decomposition electromyography (dEMG) and torque were recorded concurrently. The Hoffmann reflex (H-reflex) and central activation ratio (CAR) were acquired bilaterally to detail the proportion of MU pool available and volitionally activated. We examined MUAPAMP-RT and MFR-RT relationships with linear regression and extracted the regression line slope, y-intercept, and RT range for each contraction. Linear mixed effect modelling used to analyze the effect of group and limb on regression line slope and RT range. Results: Individuals with ACLR demonstrated lower MVIC torque in the involved limb compared to uninvolved limb. There were no differences in H-reflex or CAR between groups or limbs. The ACLR involved limb demonstrated smaller mass-normalized RT range and slower MU firing rates at high contraction intensities (70% and 100% MVIC) compared to uninvolved and control limbs. The ACLR involved limb also demonstrated larger MU action potentials in the VM compared to the contralateral limb. These differences were largely attenuated with relative RT normalization. Conclusions: These results suggest that persistent strength deficits following ACLR may be attributable to a diminished quadriceps motor neuron pool and inability to upregulate the firing rate of recruited MUs.

Muscle weakness as an additional criterion for grading sarcopenia-related prognosis in patients with cancer.

BACKGROUND: Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated. METHODS: Data on muscle strength by handgrip (HG) dynamometry and total-body SMM estimated by bioelectrical impedance analysis (BIA) of Italian and German patients with cancer observed prospectively until death or censoring were analysed (N = 1076). Patients were stratified in four risk categories based on low HG (<10th percentiles of age and gender-specific normative values) and low total-body SMM according to SMM index cutoffs (<10.75 and <6.75 kg/m2 in men and women, respectively). RESULTS: During a median follow-up of 58 months [25th-75th percentile, 37-60], 566 patients had died. Patients presenting low HG in combination or not with low SMM were characterised by shorter median survival (12.7 vs. 27.2 months, respectively; p < 0.001) compared to those with low SMM/normal HG and normal SMM/normal HG (>60 months for both). After adjusting for sex, age, body mass index and percentage of weight loss, disease's stage, performance status and type of cancer, compared to reference category (normal HG and SMM; N = 210) the hazard ratios were: low SMM/normal HG (N = 342), 0.83 [95% confidence interval, CI, 0.67-1.02] (p = 0.073); normal SMM/low HG (N = 158), 1.19 [95% CI, 1.07-1.32] (p = 0.002); low SMM/low HG (N = 366), 1.39 [95% CI, 1.27-1.53] (p < 0.001). CONCLUSIONS: Muscle weakness was found to be a more powerful predictor of survival than BIA-estimated SMM and should be considered as an additional key feature of sarcopenia in patients with cancer.

The Manual Therapy and Strengthening for the Hip (MASH) Trial: Protocol for a Multisite Randomized Trial of a Subgroup of Older Adults With Chronic Back and Hip Pain.

OBJECTIVE: Chronic low back pain (CLBP) is a disabling and costly condition for older adults that is difficult to properly classify and treat. In a cohort study, a subgroup of older adults with CLBP who had elevated hip pain and hip muscle weakness was identified; this subgroup differentiated itself by being at higher risk for future mobility decline. The primary purpose of this clinical trial is to evaluate whether a hip-focused low back pain (LBP) treatment provides better disability and physical performance outcomes for this at-risk group compared with a spine-focused LBP treatment. METHODS: This study is a multisite, single-blinded, randomized controlled, parallel arm, Phase II trial conducted across 3 clinical research sites. A total of 180 people aged between 60 and 85 years with CLBP and hip pain are being recruited. Participants undergo a comprehensive baseline assessment and are randomized into 1 of 2 intervention arms: hip-focused or spine-focused. They are treated twice weekly by a licensed physical therapist for 8 weeks and undergo follow-up assessments at 8 weeks and 6 months after randomization. Primary outcome measures include the Quebec Low Back Disability Scale and the 10-Meter Walk Test, which are measures of self-report and performance-based physical function, respectively. IMPACT: This multicenter, randomized clinical trial will determine whether a hip-focused or spine-focused physical therapist intervention results in improved disability and physical performance for a subgroup of older adults with CLBP and hip pain who are at increased risk of mobility decline. This trial will help further the development of effective interventions for this subgroup of older adults with CLBP.

Increased short interval intracortical inhibition in participants with previous hamstring strain injury.

PURPOSE: Cortical mechanisms may contribute to weakness in participants with previous hamstring strain injury. This study aims to examine intra-cortical inhibition (SICI) and corticospinal excitability in previously injured participants. METHODS: In this cross-sectional study, TMS was used to examine SICI, silent period, silent period: MEP ratios and area under the stimulus response curve in the biceps femoris and medial hamstrings. Comparisons were made between participants with (n = 10) and without (n = 10) previous hamstring strain injury. Motor threshold and isometric knee flexor strength were also compared between participants and the relationship between strength and SICI in control and previously injured participants was examined. RESULTS: Isometric knee flexor strength was lower in previously injured limbs compared with control limbs (mean difference = - 41 Nm (- 26%) [95% CI = - 80 to - 2 Nm], p = 0.04, Cohen's d = - 1.27) and contralateral uninjured limbs (mean difference = - 23 Nm (- 17%), [95% CI = - 40 to - 6 Nm], p = 0.01, Cohen's d = - 0.57). Previously injured limbs exhibited smaller responses to paired pulse stimulation (i.e. greater levels of SICI) in the biceps femoris compared with control limbs (mean difference = - 19%, [95% CI = - 34 to - 5%], p = 0.007, Cohen's d = - 1.33). Isometric knee flexor strength was associated with the level of SICI recorded in the biceps femoris in previously injured participants (coefficient = 23 Nm [95% CI = 7-40 Nm], adjusted R2 = 0.31, p = 0.01). There were no differences in markers of corticospinal excitability between previously injured and control limbs (all p > 0.24, all Cohen's d < 0.40). CONCLUSION: Athletes with previous injury in the biceps femoris exhibit increased SICI in this muscle compared with control participants. Increased SICI is related to lower levels of hamstring strength, and rehabilitation programs targeting the removal of intra-cortical inhibition should be considered.

Magnetic twitch assessment of diaphragm and quadriceps weakness in critically ill mechanically ventilated patients.

Critically ill mechanically ventilated (MV) patients develop significant muscle weakness, which has major clinical consequences. There remains uncertainty, however, regarding the severity of leg weakness, the precise relationship between muscle strength and thickness, and the risk factors for weakness in MV patients. We therefore measured both diaphragm (PdiTw) and quadriceps (QuadTw) strength in MV patients using magnetic stimulation and compared strength to muscle thickness. Both PdiTw and QuadTw were profoundly reduced for MV patients, with PdiTw 19 % of normal and QuadTw 6% of normal values. There was a poor correlation between strength and thickness for both muscles, with thickness often remaining in the normal range when strength was severely reduced. Regression analysis revealed reductions in PdiTw correlated with presence of infection (p = 0.006) and age (p = 0.007). QuadTw best correlated with duration of MV (p = 0.036). Limb muscles are profoundly weak in critically ill patients, with a severity that mirrors the level of weakness observed in the diaphragm.

Respiratory Characteristics in Patients With Major Burn Injury and Smoke Inhalation.

This study aimed to evaluate pulmonary function measurements and respiratory muscle parameters in patients with major burn injury and smoke inhalation. The inclusion criteria included patients who were diagnosed with a smoke inhalation burn or a major burn of more than 20% of total body surface area (TBSA). All subjects underwent a pulmonary function test, respiratory muscle strength test, peak cough flow and fluoroscopic diaphragmatic movement measurement, and 6-minute walk test before starting pulmonary rehabilitation. Evaluations were conducted on the 88th day after the injury, the average time of admission to the Department of the Rehabilitation Medicine for burn rehabilitation after the completion of the acute treatment. The average degree of burns of the total 67 patients was 34.6% TBSA. All parameters in the patient group were significantly lower than the healthy controls, and a mild restrictive pattern of impairment with a reduction in diffusing capacity and more reduced expiratory muscle, than inspiratory muscle strength were observed. Peak cough flow, respiratory muscle strength, and forced vital capacity in the patient group with inhalation burn were significantly lower than in those without inhalation burn. The conditions of the majority of patients with major burn and inhalation injury were consistent with restrictive impairment and significant reduction in diffusion capacity. The patients had expiratory muscle weakness, decreased diaphragmatic movement, and exercise capacity impairment.

Prognostic factors for recurrent idiopathic clubfoot deformity: a systematic literature review and meta-analysis.

Background and purpose - After initial clubfoot correction through Ponseti treatment, recurrence rates range from 26% to 48%. Even though various factors have been associated with increased recurrence risk, systematic assessments of the prognostic capacity of recurrence risk factors and their clinical relevance are lacking. Therefore we assessed clinically relevant prognostic factors for recurrent idiopathic clubfoot deformity after initial correction through Ponseti treatment. Methods - PubMed, Embase, Cinahl, and Web of Science were systematically searched for studies investigating the association between clinically relevant factors and recurrence rates. Prognostic factors were qualitatively assessed and included in the meta-analysis if ≥ 2 studies investigated the same factor and methods were comparable. Results - 34 articles were included in the qualitative synthesis, of which 22 were also included in the meta-analysis. Meta-analysis revealed that poor evertor muscle activity (OR = 255, 95% CI 30-2,190), brace non-compliance (OR = 10, CI 5-21), no additional stretching (OR = 31, CI 10-101), more casts (OR = 3.5, CI 1.6-7.8), lower education level of parents (OR = 1.8, CI 1.2-2.6), non-marital status of parents (OR = 1.8, CI 1.1-3.0), and higher Dimeglio scores (OR = 1.9, CI 1.2-3.3) were associated with higher recurrence rates. Interpretation - Brace non-compliance and poor evertor muscle activity have been identified as main recurrence risk factors and are therefore important to be closely monitored during clinical follow-up of clubfoot patients. Adding additional stretching during the bracing protocol might be promising in the quest to prevent relapse, but scientific evidence for clear clinical treatment recommendations is still limited.

Prevalence and predictive factors for bilateral carpal tunnel syndrome by electrodiagnosis: A retrospective study.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common compressive neuropathy. Patients who have unilateral symptoms are frequently found to have bilateral CTS by electrodiagnostic (EDx) study. We aimed to (a) study the prevalence and identify the predictive factors for bilateral CTS diagnosed by EDx; and (b) develop a model to predict bilateral CTS. METHODS: The retrospective clinical and EDx data of patients with CTS were collected and analyzed using the Chi-squared test and multiple logistic regression analysis. A model was fitted, and the best cutoff point determined. Calibration and discrimination performance of the model were performed. RESULTS: A total of 327 patients with a mean age of 50.0 years were enrolled. Most were women (82.6%), and the most common presenting symptom was hand numbness (93.6%). The median duration of symptoms was 60 days. The prevalence of bilateral CTS was 80.7%. In the multivariate analysis, the predictive factors for bilateral CTS were the presence of bilateral symptoms (AOR 6.7 [95%CI 3.1-14.3]), thenar muscle weakness (AOR 3.9 [95%CI 1.3-11.6]), and age ≥ 45 years (AOR 2.5 [95%CI 1.3-4.6]). The logistic regression model was fitted, and the best cutoff point determined. The area under the receiver operating curve (AUC) was 0.76. The respective optimism-corrected C index and Somers' D was 0.762 and 0.524. CONCLUSION: The prevalence of bilateral CTS was 80.7%. Our findings suggest bilateral CTS was predicted with adequate diagnostic accuracy by bilateral symptoms, age ≥ 45 years, and thenar muscle weakness.

Changes in motor paralysis involving upper extremities of outpatient chronic stroke patients from temporary rehabilitation interruption due to spread of COVID-19 infection: An observational study on pre- and post-survey data without a control group.

BACKGROUND: Outpatient rehabilitation was temporarily suspended because of coronavirus disease (COVID-19), and there was a risk that patients' activities of daily living (ADLs) would decrease and physical functions unmaintained. Therefore, we investigated the ADLs and motor functions of chronic stroke patients whose outpatient rehabilitation was temporarily interrupted. METHODS: In this observational study, the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and Barthel Index (BI) scores of 49 stroke hemiplegic patients at 6 and 3 months before rehabilitation interruptions were retrospectively determined and were prospectively investigated on resumption of outpatient rehabilitation. Presence or absence of symptoms and difficulties caused by the interruption period (IP) was investigated using a binomial method. Deltas were analyzed using a generalized linear model (GLM) according to the survey period. Age, sex, severity of FMA-UE immediately post-resumption and post-onset period were used as covariates. For survey items showing significant model fit, the 95% confidence interval of minimum detectable change (MDC95) was calculated, and the amount of change was compared. Questionnaire responses were tested via proportion ratio. Statistical significance was set at 5%. RESULTS: The FMA-UE part A and total scores were significantly model fit depending on periods. The estimated FMA-UE total score decreased by 1.64 (z = -2.38, p = 0.02) during the 3-month IP. No fits were observed by GLM in other parts of the FMA-UE, ARAT, or BI. The calculated MDC95 was 3.58 for FMA-UE part A and 4.50 for FMA-UE overall. Answers to questions regarding sleep disturbance and physical pain were significantly biased toward "no" in the psychosomatic function items (p<0.05). There was no bias in the distribution of answers to questions regarding joint stiffness, muscle weakness, muscle stiffness, and difficulty in moving arms and hands. All 16 questions regarding activities and participation items were significantly biased toward answers "no" (p<0.05). CONCLUSIONS: The FMA-UE part A and total scores were affected. Patients complained of subjective symptoms related to upper limb paralysis after the IP. Since ADLs of patients were maintained, the therapist can recommend that patients not receiving outpatient treatments be evaluated in relation to the shoulder, elbow, and forearm and instructed on self-training to maintain motor function.

Diagnostic delay in patients with FKRP-related muscular dystrophy.

Diagnostic journey for people with FKRP mutations participating in a dystroglycanopathy natural history study (n = 68; NCT00313677) was analyzed. Earliest symptoms and age at muscular dystrophy diagnosis were abstracted from subject-reported medical history and record review. Initial signs/symptoms were classified as chronic motor dysfunction (e.g., delayed motor milestones, weakness, falling; n = 40, 59%), elevated transaminases (n = 7, 10%), or acute/intermittent symptoms (myoglobinuria, myalgia, febrile illness-associated acute weakness; n = 21, 31%). Median time from sign/symptom onset to diagnosis was 6.5 years and differed by symptom group: 7.5 years for motor group, 9 years for acute/intermittent group, and 4 years for elevated transaminases group. The sign/symptom category that most commonly resulted in a diagnosis was chronic motor dysfunction (n = 45). Of those without clear weakness as first symptom (n = 55), 36.4% were not diagnosed with MD until weakness became apparent. Median time to diagnosis was shortest for those with febrile illness-associated acute weakness (0.25 years). Median time from first sign/symptom to MD diagnosis has decreased incrementally from 18.8 years for those with onset in the 1970s to < 10 years for symptom onset occurring after 2000. Awareness of disease presentation variability will aid in earlier diagnosis, which is increasingly important with treatments in development.

Effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions: A scoping review.

BACKGROUND: In the field of orthotics, the use of three-dimensional (3D) technology as an alternative to the conventional production process of orthoses is growing. PURPOSE: This scoping review aimed to systematically map and summarize studies assessing the effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions, and to identify knowledge gaps. METHODS: The Cochrane Library, PubMed, EMBASE, CINAHL, Web of Science, IEEE, and PEDro were searched for studies of any type of 3D-printed orthoses for traumatic and chronic hand conditions. Any outcome related to the effectiveness of 3D-printed orthoses was considered. Two reviewers selected eligible studies, charted data on study characteristics by impairment type, and critically appraised the studies, except for case reports/series. RESULTS: Seventeen studies were included: four randomized controlled trials, four uncontrolled trials, four case series and five case reports. Only three studies had a sample size >20. Impairments described were forearm fractures (n = 5), spasticity (n = 5), muscle weakness (n = 4), joint contractures (n = 2) and pain (n = 1). Four poor to fair quality studies on forearm fractures supported the effectiveness of 3D-printed orthoses on hand function, functionality, and satisfaction. One good quality study on spasticity demonstrated the effectiveness of 3D-printed orthoses on hand function. One poor quality pain study reported limited positive effects on satisfaction. Studies on muscle weakness and joint contractures showed no benefits. CONCLUSION: Current literature addressing the effectiveness of 3D-printed orthoses for traumatic and chronic hand conditions consists primarily of small and poor methodological quality studies. There is a need for well-designed controlled trials including patient-related outcomes, production time and cost analyses.

Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19.

Post-acute consequences of COVID-19, also termed long COVID, include signs and symptoms persisting for more than 12 weeks with prolonged multisystem involvement; most often, however, malnutrition is ignored. METHOD: The objective was to analyze persistent symptoms, nutritional status, the evolution of muscle strength and performance status (PS) at 6 months post-discharge in a cohort of COVID-19 survivors. RESULTS: Of 549 consecutive patients hospitalized for COVID-19 between 1 March and 29 April 2020, 23.7% died and 288 patients were at home at D30 post-discharge. At this date, 136 of them (47.2%) presented persistent malnutrition, a significant decrease in muscle strength or a PS ≥ 2. These patients received dietary counseling, nutritional supplementation, adapted physical activity guidance or physiotherapy assistance, or were admitted to post-care facilities. At 6 months post-discharge, 91.0% of the 136 patients (n = 119) were evaluated and 36.0% had persistent malnutrition, 14.3% complained of a significant decrease in muscle strength and 14.9% had a performance status > 2. Obesity was more frequent in patients with impairment than in those without (52.8% vs. 31.0%; p = 0.0071), with these patients being admitted more frequently to ICUs (50.9% vs. 31.3%; p = 0.010). Among those with persistent symptoms, 10% had psychiatric co-morbidities (mood disorders, anxiety, or post-traumatic stress syndrome), 7.6% had prolonged pneumological symptoms and 4.2% had neurological symptoms. CONCLUSIONS: Obese subjects as well as patients who have stayed in intensive care have a higher risk of functional loss or undernutrition 6 months after a severe COVID infection. Malnutrition and loss of muscle strength should be considered in the clinical assessment of these patients.

Histopathological characteristics of cervical extensor tissue in patients with dropped head syndrome.

BACKGROUND: To date, the histopathologic characteristics of dropped head syndrome (DHS) have not been reported sufficiently. The present study investigates the histopathology of biopsy specimens from the cervical paravertebral region in patients with DHS. METHODS: Histopathological parameters were evaluated in biopsy specimens of the cervical paravertebral soft tissue from 15 patients with DHS. RESULTS: Among the 15 cases of DHS examined, skeletal muscle was identified in 7 cases, all of which showed necrosis, microvessel proliferation and atrophy. The ligament was identified in 12 cases, 8 of which showed degeneration. The lag time between the onset of symptoms and the performance of a biopsy in all 8 cases, which showed degeneration was over 3 months. Microvessel proliferation in the ligament was observed in 1 of the 4 cases, in which the lag time between the onset of symptoms and the performance of a biopsy was less than 3 months (acute or subacute phase), and in 7 of the 8 cases, in which the lag time between the symptoms and the performance of a biopsy was over 3 months (chronic phase). Chronic inflammation in the ligament was identified in 1 of the 12 cases. CONCLUSIONS: The identification of necrosis, microvessel proliferation, and atrophy in the skeletal muscle of patients with DHS and the presence of ligament degeneration and microvessel proliferation in the chronic but not acute or subacute phases may suggest that persistent skeletal muscle damage of the cervical paravertebral region causes subsequent ligament damage in patients with DHS.

Insulin resistance and muscle weakness are synergistic risk factors for silent lacunar infarcts: the Bunkyo Health Study.

Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65-84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94-2.48], Low; 1.86 [1.02-3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98-2.02], Low; 1.49 [1.04-2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64-11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk.

miRNome profiling in Duchenne muscular dystrophy; identification of asymptomatic and manifesting female carriers.

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder that occurs due to inactivating mutations in DMD gene, leading to muscular dystrophy. Prediction of pathological complications of DMD and the identification of female carriers are important research points that aim to reduce disease burden. Herein, we describe a case of a late DMD patient and his immediate female family members, who all carry same DMD mutation and exhibited varied degrees of symptoms. In our study, we sequenced the whole miRNome in leukocytes and plasma of the family members and results were validated using real-time PCR. Our results highlighted the role of miR-409-3p, miR-424-5p, miR-144-3p as microRNAs that show correlation with the extent of severity of muscular weakness and can be used for detection of asymptomatic carriers. Cellular and circulating levels of miR-494-3p had shown significant increase in symptomatic carriers, which may indicate significant roles played by this miRNA in the onset of muscular weakness. Interestingly, circulating levels of miR-206 and miR-410-3p were significantly increased only in the severely symptomatic carrier. In conclusion, our study highlighted several miRNA species, which could be used in predicting the onset of muscle and/or neurological complications in DMD carriers.