Grip strength is a variable which may be important to measure and follow in various populations. A new dynamometer with high accuracy and sensitivity has recently been developed to assess grip ...strength. The objectives of this work were to provide norms of maximal isometric grip strength measured with this new dynamometer (the MyoGrip device), to assess the reliability of measurements, to compare the measurements obtained with MyoGrip and Jamar dynamometers and finally to establish predictive equations from a population of healthy subjects (children and adults).
Measurements of maximal isometric grip strength using the MyoGrip and the Jamar (which is considered as the gold-standard) were performed on 346 healthy subjects aged from 5 to 80 years. Test-retest reliability for both devices was assessed on 77 subjects. Predictive equations were computed on subjects younger than 60 years of age in order to avoid the effects of aging on strength.
This study provides norms for isometric grip strength for health subjects from 5 to 80 years. Reliability of the MyoGrip device was excellent (intraclass correlation coefficient: 0.967). Despite good correlation between devices, the Jamar tended to overestimate maximal grip strength by about 14 %. A single predictive equation for men and women, adults and children incorporating hand circumference only can be used to compute the predicted theoretical maximal grip strength.
The MyoGrip device is a reliable tool for measuring isometric grip strength. Owing to its unique metrological features, it can be used in very weak patients or in any situation where high precision and accuracy are required.
Introduction/Aims
Current upper limb assessments in pediatric spinal muscular atrophy (SMA) may not adequately capture change with disease progression. Our aim was to examine the relationship between ...motor function, strength, and hand/finger mobility of the upper limb in treatment‐naïve children with SMA Types 2 and 3 to assess new methods to supplement current outcomes.
Methods
The Revised Upper Limb Module (RULM), grip and pinch strength, and hand/finger mobility data were collected from 19 children with SMA Types 2 and 3 aged 5.2–16.9 years over a year.
Results
A median loss between 0.5 and 2.5 points in the RULM was seen across all SMA subgroups with the biggest median loss recorded between 10 and 14 years of age. The grip strength loss was −0.06 kg (−4.69 to 3.49; IQR, 1.21); pinch improvement of 0.05 (−0.65 to 1.27; IQR, 0.48); hand/finger mobility test improvement of 4 points (−24 to 14; IQR, 6.75) for the whole cohort. Significant correlations were found between the RULM and grip strength (p < .001), RULM and pinch strength (p < .001), RULM and revised Brooke (p < .001), grip strength and pinch strength (p < .001).
Discussion
The combined use of the RULM, dynamometry, and hand mobility provide insight about correlations between function and strength in children with SMA. The RULM and grip strength assessments captured a significant decline in upper limb function, whereas the pinch and finger/hand mobility showed an improvement over the course of 1 year and these results should be considered for future studies.
Upper limb function, strength, and hand/finger mobility in treatment‐naïve children with spinal muscular atrophy Types 2 and 3 were assessed by the Revised Upper Limb Module (RULM) and high‐precision dynamometry.
Spinal muscular atrophy (SMA) is a monogenic disorder caused by loss of function mutations in the survival motor neuron 1 gene, which results in a broad range of disease severity, from neonatal to ...adult onset. There is currently a concerted effort to define the natural history of the disease and develop outcome measures that accurately capture its complexity. As several therapeutic strategies are currently under investigation and both the FDA and EMA have recently approved the first medical treatment for SMA, there is a critical need to identify the right association of responsive outcome measures and biomarkers for individual patient follow-up. As an approved treatment becomes available, untreated patients will soon become rare, further intensifying the need for a rapid, prospective and longitudinal study of the natural history of SMA Type 2 and 3. Here we present the baseline assessments of 81 patients aged 2 to 30 years of which 19 are non-sitter SMA Type 2, 34 are sitter SMA Type 2, 9 non-ambulant SMA Type 3 and 19 ambulant SMA Type 3. Collecting these data at nine sites in France, Germany and Belgium established the feasibility of gathering consistent data from numerous and demanding assessments in a multicenter SMA study. Most assessments discriminated between the four groups well. This included the Motor Function Measure (MFM), pulmonary function testing, strength, electroneuromyography, muscle imaging and workspace volume. Additionally, all of the assessments showed good correlation with the MFM score. As the untreated patient population decreases, having reliable and valid multi-site data will be imperative for recruitment in clinical trials. The pending two-year study results will evaluate the sensitivity of the studied outcomes and biomarkers to disease progression.
ClinicalTrials.gov (NCT02391831).
Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease caused by mutations in the dystrophin gene. Gene therapy using highly functional microdystrophin genes and ...recombinant adeno-associated virus (rAAV) vectors is an attractive strategy to treat DMD. Here we show that locoregional and systemic delivery of a rAAV2/8 vector expressing a canine microdystrophin (cMD1) is effective in restoring dystrophin expression and stabilizing clinical symptoms in studies performed on a total of 12 treated golden retriever muscular dystrophy (GRMD) dogs. Locoregional delivery induces high levels of microdystrophin expression in limb musculature and significant amelioration of histological and functional parameters. Systemic intravenous administration without immunosuppression results in significant and sustained levels of microdystrophin in skeletal muscles and reduces dystrophic symptoms for over 2 years. No toxicity or adverse immune consequences of vector administration are observed. These studies indicate safety and efficacy of systemic rAAV-cMD1 delivery in a large animal model of DMD, and pave the way towards clinical trials of rAAV-microdystrophin gene therapy in DMD patients.
Introduction: Assessment of muscle mechanical properties may provide clinically valuable information for follow‐up of patients with Duchenne muscular dystrophy (DMD) through the course of their ...disease. In this study we aimed to assess the effect of DMD on stiffness of relaxed muscles using elastography (supersonic shear imaging). Methods: Fourteen DMD patients and 13 control subjects were studied. Six muscles were measured at 2 muscle lengths (shortened and stretched): gastrocnemius medialis (GM); tibialis anterior (TA); vastus lateralis (VL); biceps brachii (BB); triceps brachii (TB); and abductor digiti minimi (ADM). Results: Stiffness was significantly higher in DMD patients compared with controls for all the muscles (main effect for population, P < 0.033 in all cases), except for ADM. The effect size was small (d = 0.33 for ADM at both muscle lengths) to large (d = 0.86 for BB/stretched). Conclusions: Supersonic shear imaging is a sensitive non‐invasive technique to assess the increase in muscle stiffness associated with DMD. Muscle Nerve 51: 284–286, 2015
Introduction/Aims
Mutations amenable to skipping of specific exons have been associated with different motor progression in Duchenne muscular dystrophy (DMD). Less is known about their association ...with long‐term respiratory function. In this study we investigated the features of respiratory progression in four DMD genotypes relevant in ongoing exon‐skipping therapeutic strategies.
Methods
This was a retrospective longitudinal study including DMD children followed by the UK NorthStar Network and international AFM Network centers (May 2003 to October 2020). We included boys amenable to skip exons 44, 45, 51, or 53, who were older than 5 years of age and ambulant at first recorded visit. Subjects who were corticosteroid‐naive or enrolled in interventional clinical trials were excluded. The progression of respiratory function (absolute forced vital capacity FVC and calculated as percent predicted FVC%) was compared across the four subgroups (skip44, skip45, skip51, skip53).
Results
We included 142 boys in the study. Mean (standard deviation) age at first visit was 8.6 (2.5) years. Median follow‐up was 3 (range, 0.3‐8.3) years. In skip45 and skip51, FVC% declined linearly from the first recorded visit. From the age of 9 years, FVC% declined linearly in all genotypes. Skip44 had the slowest (2.7%/year) and skip51 the fastest (5.9%/year) annual FVC% decline. The absolute FVC increased progressively in skip44, skip45, and skip51. In skip53, FVC started declining from 14 years of age.
Discussion
The progression of respiratory dysfunction follows different patterns for specific genotype categories. This information is valuable for prognosis and for the evaluation of exon‐skipping therapies.
Background
Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1‐year longitudinal data from ...quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) in a placebo‐controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.
Methods
Quantitative MRI and 31P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year‐1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross‐sectional area (cCSA), and water T2 in global leg and thigh segments, muscle groups, individual muscles, as well as 31P MRS indices in quadriceps or triceps surae. Analyses covered patient‐control comparisons, annual change assessments via standard t‐tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, 31P MRS, functional, strength, and clinical parameters.
Results
The quadriceps and gastrocnemius medialis muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps. In the placebo group, the median 1‐year FF increase in the quadriceps was 3.2% (P < 0.001), whereas in the sirolimus group, it was 0.7% (P = 0.033). Both groups experienced a significant decrease in cCSA in the quadriceps after 1 year (P < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (P < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T2 values were highest in the quadriceps muscles of both groups, significantly exceeding control values in both groups (P < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T2 increased significantly only in the sirolimus group's quadriceps (P < 0.01). Multiple 31P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T2 and FF at baseline and the change in FF (P < 0.001). Additionally, significant correlations were observed between FF, cCSA, water T2, and functional and strength outcome measures.
Conclusions
This study has demonstrated that quantitative MRI/31P MRS can discern measurable differences between placebo and sirolimus‐treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.
ABSTRACT
Introduction: The MG‐QOL15 is a validated, health‐related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze ...its clinimetric properties. Methods: We first performed Rasch analysis on >1,300 15‐item Myasthenia Gravis Quality of Life scale (MG‐QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG‐QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on >1,300 MG‐QOL15r scales. Results: The MGQOL15r performed slightly better than the MG‐QOL15. The 3‐response option MG‐QOL15r demonstrated better clinimetric properties than the 4‐ or 5‐option scales. Relative distributions of item and person location estimates showed good coverage of disease severity. Conclusions: The MG‐QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG‐QOL15. Muscle Nerve 54: 1015–1022, 2016
Key points
Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non‐volitional method for assessing diaphragm contractility in humans, yet it ...requires invasive procedures such as oesophageal and gastric catheter balloons.
Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown.
Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure.
This approach provides a novel fully non‐invasive and non‐volitional tool for the assessment of diaphragm contractility in humans.
Measuring twitch transdiaphragmatic pressure (Pdi,tw) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of Pdi requires invasive oesophageal and gastric catheter‐balloons. Ultrafast ultrasound is a non‐invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and Pdi,tw, and how these indices might be used to estimate Pdi,tw. CMS was performed in 13 healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. Pdi,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1 kHz framerate. Maximal diaphragm axial velocity (Vdi,max) and diaphragm thickening fraction (TFdi,tw) were computed. Intra‐session reliability was assessed. Repeated‐measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra‐session reliability was strong for Pdi,tw and Vdi,max and moderate for TFdi,tw. Vdi,max correlated with Pdi,tw in all subjects (0.64 < ρ < 1.00, R = 0.75; all P < 0.05). TFdi,tw correlated with Pdi,tw in eight subjects only (0.85 < ρ < 0.93, R = 0.69; all P < 0.05). Coupling ultrafast ultrasound and CMS shows promise for the non‐invasive and fully non‐volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow‐up of diaphragm contractility in clinical populations.
Key points
Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non‐volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons.
Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown.
Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure.
This approach provides a novel fully non‐invasive and non‐volitional tool for the assessment of diaphragm contractility in humans.
The aim of the present study was to assess the reliability of shear elastic modulus measurements performed using supersonic shear imaging (SSI) in nine resting muscles (i.e. gastrocnemius medialis, ...tibialis anterior, vastus lateralis, rectus femoris, triceps brachii, biceps brachii, brachioradialis, adductor pollicis obliquus and abductor digiti minimi) of different architectures and typologies. Thirty healthy subjects were randomly assigned to the intra-session reliability (n = 20), inter-day reliability (n = 21) and the inter-observer reliability (n = 16) experiments. Muscle shear elastic modulus ranged from 2.99 (gastrocnemius medialis) to 4.50 kPa (adductor digiti minimi and tibialis anterior). On the whole, very good reliability was observed, with a coefficient of variation (CV) ranging from 4.6% to 8%, except for the inter-operator reliability of adductor pollicis obliquus (CV = 11.5%). The intraclass correlation coefficients were good (0.871 ± 0.045 for the intra-session reliability, 0.815 ± 0.065 for the inter-day reliability and 0.709 ± 0.141 for the inter-observer reliability). Both the reliability and the ease of use of SSI make it a potentially interesting technique that would be of benefit to fundamental, applied and clinical research projects that need an accurate assessment of muscle mechanical properties.
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