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Musculoskeletal impairment and functional limitations in a patient affected by mutation in the laminin a-5 gene
Background:
Sacro-iliac joint (SIJ) pain is an often-misdiagnosed cause (up to 30% cases) of atypical low back pain (LBP) that might be treated with a wide range of conservative interventions. However, Platelet-Rich-Plasma (PRP) ultrasound-guided injections at SIJ level in subjects with mitochondrial disorders have not yet been investigated.
Case presentation:
A 52-year-old Caucasian male with fluoroquinolone-related mitochondrial dysfunction referred to a Physical Medicine and Rehabilitation Outpatient, complaining of severe SIJ pain (Numeric Pain Related Scale, NPRS=8). We performed two bilateral PRP ultrasound-guided injections at the sacro-iliac level. PRP is a simple, efficient, and minimally invasive approach. After the first PRP injection, there was a considerable reduction of pain (NPRS=8 vs 5). The second PRP infiltration was performed after 2 weeks and in both cases no adverse events. At the 6-month follow-up evaluation, the patient showed good physical recovery, with the absence of pain (NPRS=0).
Conclusion:
To the best of our knowledge, this is the first report in the literature assessing the safety and effectiveness of PRP ultrasound-guided injections for SIJ pain in a patient affected by mitochondrial disorders. Thus, this case report might have relevant clinical implications in the treatment of SIJ pain in patients affected by this rare pathological condition, albeit further observational studies are warranted to confirm these findings.
Background:
The presence of the vitamin D receptor (VDR) has been recently demonstrated in human muscle supporting the theory of a role of vitamin D in the proliferation and differentiation of muscle cells. So far only few studies investigated the association between vitamin D and muscle performance in post-menopausal women.
Aim:
To define the functional impact of vitamin D deficiency.
Design:
Multicenter retrospective study.
Setting:
Five Italian outpatient services of Physical and Rehabilitation Medicine (PRM).
Population:
Post-menopausal women.
Methods:
We divided the population in two groups based on the threshold of 30 ng/ml as cut-off to define sufficient and insufficient serum levels of 25-hydroxyvitamin D3 [25(OH)D3]. Outcome measures were: appendicular lean mass (ALM); ALM-to-BMI ratio (ALMBMI); total fat mass (FM); visceral adipose tissue (VAT); Hand Grip Strength (HGS); Knee Isometric Extension Strength (KES); Short Physical Performance Battery (SPPB); 4-meter gait speed (4MGS).
Results:
We analyzed the data records of 401 post-menopausal women (mean age 66.93 ± 8.47 years): 203 with hypovitaminosis D (mean age 66.81 ± 8.11 years) and 198 with normal levels of 25(OH)D3 (mean age 67.04 ± 8.84 years). The analysis showed a significant differences between the two groups in terms of: ALMBMI (0.002), FM (p 0.001), VAT mass (0.010), VAT volume (p =0.006), HGS (p<0.001), KES (p<0.001), SPPB score (p <0.001), percentage of people with a 4MGS≤ 0.8 m/s (p<0.001). Furthermore, there were significant correlations (p<0.001) between serum levels of 25(OH)D3 and HGS (r=0.323), KES (r=0.510), and SPPB sit to stand (r=-0.362) and walking sub-scores (r=-0.312).
Conclusion:
This multicenter study demonstrated that post-menopausal women with vitamin D deficiency had a significant reduction of appendicular muscle strength and physical performance.
Clinical rehabilitation impact:
This study reported the frequency of hypovitaminosis D in postmenopausal women and its influence on the reduction of muscle mass, strength, and physical performance in a typical population referring to the physiatrist for musculoskeletal disorders.
The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency.
The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration.
Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes.
Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
Background:
Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. This is an update of a review first published in 2004.
Objectives:
To examine the safety and efficacy of strength training and aerobic exercise training in people with a muscle disease.
Search methods:
We searched the Cochrane Neuromuscular Disease Group Specialized Register (July 2012), CENTRAL (2012 Issue 3 of 4), MEDLINE (January 1946 to July 2012), EMBASE (January 1974 to July 2012), EMBASE Classic (1947 to 1973) and CINAHL (January 1982 to July 2012).
Selection criteria:
Randomised or quasi-randomised controlled trials comparing strength training or aerobic exercise programmes, or both, to no training, and lasting at least six weeks, in people with a well-described diagnosis of a muscle disease.We did not use the reporting of specific outcomes as a study selection criterion.
Data collection and analysis:
Two authors independently assessed trial quality and extracted the data obtained from the full text-articles and from the original investigators. We collected adverse event data from included studies.
Main results:
We included five trials (170 participants). The first trial compared the effect of strength training versus no training in 36 people with myotonic dystrophy. The second trial compared aerobic exercise training versus no training in 14 people with polymyositis and dermatomyositis. The third trial compared strength training versus no training in a factorial trial that also compared albuterol with placebo, in 65 people with facioscapulohumeral muscular dystrophy (FSHD). The fourth trial compared combined strength training and aerobic exercise versus no training in 18 people with mitochondrial myopathy. The fifth trial compared combined strength training and aerobic exercise versus no training in 35 people with myotonic dystrophy type 1.In both myotonic dystrophy trials and the dermatomyositis and polymyositis trial there were no significant differences between training and non-training groups for primary and secondary outcome measures. The risk of bias of the strength training trial in myotonic dystrophy and the aerobic exercise trial in polymyositis and dermatomyositis was judged as uncertain, and for the combined strength training and aerobic exercise trial, the risk of bias was judged as adequate. In the FSHD trial, for which the risk of bias was judged as adequate, a +1.17 kg difference (95% confidence interval (CI) 0.18 to 2.16) in dynamic strength of elbow flexors in favour of the training group reached statistical significance. In the mitochondrial myopathy trial, there were no significant differences in dynamic strength measures between training and non-training groups. Exercise duration and distance cycled in a submaximal endurance test increased significantly in the training group compared to the control group. The differences in mean time and mean distance cycled till exhaustion between groups were 23.70 min (95% CI 2.63 to 44.77) and 9.70 km (95% CI 1.51 to 17.89), respectively. The risk of bias was judged as uncertain. In all trials, no adverse events were reported.
Authors' conclusions:
Moderate-intensity strength training in myotonic dystrophy and FSHD and aerobic exercise training in dermatomyositis and polymyositis and myotonic dystrophy type I appear to do no harm, but there is insufficient evidence to conclude that they offer benefit. In mitochondrial myopathy, aerobic exercise combined with strength training appears to be safe and may be effective in increasing submaximal endurance capacity. Limitations in the design of studies in other muscle diseases prevent more general conclusions in these disorders.
In a prospective study of 225 community dwelling people 75 years and older, we tested the validity of the Tinetti balance scale to predict individuals who will fall at least once during the following year. A score of 36 or less identified 7 of 10 fallers with 70% sensitivity and 52% specificity. With this cut-off score, 53% of the individuals were screened positive and presented a two-fold risk of falling. These characteristics support the use of this test to screen older people at risk of falling in order to include them in a preventive intervention.
The aims of this study were to investigate the Fatigue Severity Scale's Turkish version's validity, reproducibility, internal consistency and parameters. Multiple sclerosis patients' disability levels were determined by the Expended Disability Status Scale and depression status was established with the Beck Depression Inventory. The Fatigue Severity Scale and Beck Depression Inventory were administered through self-report methods and assistance, without guidance, given where needed. An interval of 1 week was allowed between the applications. Seventy-two definitely diagnosed multiple sclerosis patients and matched 76 healthy controls were included. The multiple sclerosis patients' median Expended Disability Status Scale score was 4.0 (1.0-9.5). There were statistically significant differences between multiple sclerosis patients' and healthy controls' Fatigue Severity Scale scores (P<0.001). After controlling for depression, Fatigue Severity Scale scores were lowered, but there was still a significant difference between them (P<0.001). There was no significant difference between the interviews for Fatigue Severity Scale1 and Fatigue Severity Scale2 (P=0.719). Internal consistency for Fatigue Severity Scale was good for multiple sclerosis patients (ICC=0.81, P<0.001). Cronbach's alpha of Fatigue Severity Scale1 was 0.89; Fatigue Severity Scale2 was 0.94. Expended Disability Status Scale scores (P<0.05) and Beck Depression Inventory scores (P<0.001) have a significant effect on the Fatigue Severity Scale. In conclusion, scales have a great importance in following up and assessing the results of treatment strategies. The Turkish validation of the Fatigue Severity Scale is reliable and valid, and is an appropriate tool to assess fatigue in the Turkish multiple sclerosis population.
Background:
The laminin alpha 5 gene (LAMA5) plays a master role in the maintenance and function of the extracellular matrix (ECM) in mammalian tissues, which is critical in developmental patterning, stem cell niches, cancer and genetic diseases. Its mutations have never been reported in human disease so far. The aim of this study was to associate the first mutation in LAMA5 gene to a novel multisystem syndrome.
Methods:
A detailed characterisation of a three-generation family, including clinical, biochemical, instrumental and morphological analysis, together with genetics and expression (WES and RNAseq) studies, was performed.
Results:
The heterozygous LAMA5 mutation c.9418G>A (p.V3140M) was associated with skin anomalies, impaired scarring, night blindness, muscle weakness, osteoarthritis, joint and internal organs ligaments laxity, malabsorption syndrome and hypothyroidism. We demonstrated that the mutation alters the amount of LAMA5 peptides likely derived from protein cleavage and perturbs the activation of the epithelial-mesenchymal signalling, producing an unbalanced expression of Sonic hedgehog and GLI1, which are upregulated in cells from affected individuals, and of ECM proteins (COL1A1, MMP1 and MMP3), which are strongly inhibited. Studies carried out using human skin biopsies showed alteration of dermal papilla with a reduction of the germinative layer and an early arrest of hair follicle downgrowth. The knock-in mouse model, generated in our laboratory, shows similar changes in the tissues studied so far.
Conclusions:
This is the first report of a disease phenotype associated with LAMA5 mutation in humans.
IntroductionThe role of vitamin D supplementation on muscle function and physical performance is still debated. Calcifediol is an available treatment for hypovitaminosis D, particularly for extra-skeletal effects. Aim of this prospective cohort study was to evaluate the effectiveness of calcifediol on serum levels of 25(OH)D3, appendicular muscle strength, physical performance, and prevention of falls in post-menopausal women. Methods
We recruited post-menopausal women aged ≥50 years, referring to an outpatient service for the management of osteoporosis over a 18-month period. We included women with a diagnosis of osteoporosis and/or vitamin D deficiency [serum levels of 25(OH)D3 <30 ng/ml]. All the participants received calcifediol (20 μg, 4 oral drops/day) for a 6-month period. We evaluated at the baseline and after 6 months the following outcomes: serum levels of 25(OH)D3, appendicular muscle strength, using the Isometric Hand Grip Strength Test and the Knee Isometric Extension Strength Test, physical performance, using the Short Physical Performance Battery (SPPB) and the 4-m gait speed (4MGS), and the risk of falls (percentage of fallers and recurrent fallers and mean number of falls). A sub-analysis was performed in patients with vitamin D deficiency. ResultsWe enrolled 113 post-menopausal women, mean aged 68.01 ± 9.13 years. After 6 months of treatment, there was a significant increase in serum levels of 25(OH)D3 (p < 0.001), appendicular muscle strength (p < 0.001), and physical performance (p = 0.002 at SPPB and p = 0.010 at 4MGS, respectively). At 6 months, the percentage of fallers was lower, although not significantly (p = 0.078), whereas there was a significant reduction both in percentage of recurrent fallers and in the mean number of falls (p < 0.001 and p = 0.020, respectively). Conclusion
Calcifediol was significantly effective in improving serum levels of 25(OH)D3 and muscle function and in reducing the percentage of recurrent fallers and the mean number of falls in a cohort of post-menopausal women.
Many osteoporosis clinical practice guidelines are published, and the extent to which physical activity and safe movement is addressed varies. To better inform clinical decision-making, a quality assessment and structured analysis of recommendations was undertaken. Guideline quality varied substantially, and improvement is necessary in physical activity and safe movement recommendations.
Purpose
The purpose of the present study is to survey available osteoporosis clinical practice guidelines (CPGs) containing physical activity and safe movement recommendations in order to assess the methodological quality with which they were developed. An analysis of the various physical activity and safe movement recommendations was conducted to determine variability between CPGs.
Methods
An online literature search revealed 19 CPGs meeting our inclusion criteria. Three independent scorers evaluated CPG quality using the Appraisal of Guidelines for Research and Evaluation version II (AGREE II) instrument. Two separate individuals used a standard table to extract relevant recommendations.
Results
Intra-reviewer AGREE II score agreement ranged from fair to good (intra-class correlation coefficient (ICC) = 0.34 to 0.65). The quality of the 19 included CPGs was variable (AGREE sub-scores: 14 to 100 %). CPGs scored higher in the “scope and purpose” and “clarity of presentation” domains. They scored the lowest in “applicability” and “editorial independence.” Four CPGs were classified as high quality, ten average quality, and five low quality. Most CPGs recommended weight-bearing, muscle-strengthening, and resistance exercises. Information on exercise dosage, progression, and contraindications was often absent. Immobility and movements involving spinal flexion and/or torsion were discouraged.
Conclusions
There were several high-quality CPGs; however, variability in quality and lack of specific parameters for implementation necessitates caution and critical examination by readers. CPG development groups should pay special attention to the clinical applicability of their CPGs as well as fully disclosing conflicts of interest. CPGs were in general an agreement regarding safe physical activity and safe movement recommendations. However, recommendations were often vague and the more specific recommendations were inconsistent between CPGs.
Elderly people experience a gradual loss of muscle strength and a reduction of serum levels of vitamin D and of vitamin D receptor expression in skeletal muscle cells.
The aim of our study was to evaluate the association among serum levels of 25-hydroxy-vitamin D [25(OH)D3], muscle strength, and physical performance in post-menopausal women.
In our retrospective case-control study, we analyzed data from medical records of post-menopausal women aged ≥50 years. We compared subjects with hypovitaminosis D [25(OH)D3 <30 ng/ml] vs. those with normal levels [25(OH)D3 ≥30 ng/ml]. Outcome measures were: Hand Grip Strength Test (HGS) and Knee Extension Strength Test (KES) to evaluate upper and lower limb muscle strength, respectively; Short Physical Performance Battery (SPPB) and usual 4-m gait speed (4MGS) to evaluate physical performance.
We examined 80 patients (mean aged 65.92 ± 7.69 years): forty-six subjects with hypovitaminosis D (mean aged 66.09 ± 7.71 years) and 34 with normal levels of vitamin D (mean aged 65.71 ± 7.78 years). There was a statistically significant difference between hypovitaminosis D group and subjects with normal levels of vitamin D in HGS (12.13 ± 4.34 vs. 19.14 ± 5.59; p < 0.001), KES (11.99 ± 4.04 vs. 16.98 ± 8.43; p = 0.003), SPPB score [8 (5.75-10.25) vs. 12 (10-12); p < 0.001], and proportion of patients with usual 4MGS ≤ 0.8 m/s [29 (63.0 %) vs. 9 (26.5 %); p = 0.002].
In literature, there is no agreement on the association among serum vitamin D levels and muscle function. Our data showed that post-menopausal women with hypovitaminosis D had worse upper and lower limb muscle strength and physical performance than subjects with normal levels of 25(OH)D3.
Our results support the hypothesis that there is a significant positive association among serum 25(OH)D3 levels and upper and lower limb muscle functioning.
This study compared the temporal-distance (TD) gait values of two groups of neurologically impaired subjects with published TD gait values of healthy subjects and analyzed the influence of nine clinical characteristics on TD values in the neurologically impaired subjects. Velocity, cadence, step length, stride length, and ratio of stride length to lower extremity length were recorded for 37 subjects with hemiparesis and 24 subjects with multiple sclerosis. Temporal-distance values were well below normal values, even in functionally independent subjects. Overall, the subjects with hemiparesis had lower values than the subjects with multiple sclerosis. Of the nine characteristics examined, only diagnosis, etiologic factor (for hemiparesis), type of ambulation aid, and functional category were related significantly to TD values. Our findings suggest that TD gait performance goals for patients with neurological impairment should be based on values from impaired rather than healthy subjects and that these goals should be adjusted for the individual patient's diagnosis, etiologic factor, type of ambulation aid, and functional category.
Kilmer DD, McCrory MA, Wright NC, Aitkens SG, Bernauer EM. The effect of a high resistance exercise program in slowly progressive neuromuscular disease. Arch Phys Med Rehabil 1994;75:560-3.
• A 12-week high resistance home exercise program was completed by 10 subjects with slowly progressive neuromuscular diseases (NMD) and 6 normal control subjects (CTL). After evaluating baseline maximal isometric and isokinetic strength of the elbow flexors and knee extensors, subjects completed the home program using adjustable ankle and wrist cuff weights. One side of the body was randomly chosen for exercise. Subjects initially performed 1 set of 10 repetitions on 3 days a week and gradually increased to 5 sets of 10 repetitions on 4 days a week. The NMD group demonstrated significant (p < 0.05) gains in several knee extension isokinetic strength measures but loss of elbow flexion eccentric peak torque and work per degree. The CTL group demonstrated significant gains in all measures of knee extension strength, with improvement of elbow isokinetic eccentric work per degree as well. There was evidence of cross training to the nonexercised limbs for both groups. A high resistance training program, although well tolerated in NMD subjects with mild to moderate weakness, may cause some deleterious effects to diseased skeletal muscle. A high resistance training program appears to offer no advantage over a moderate resistance training program in this population.