Myoadenylate deaminase (MAD) is an enzyme active in skeletal muscle, probably during exercise of moderate intensity but certainly during vigorous exercise, when the deamination of AMP leads to increased levels of IMP and ammonia. There is controversy about the clinical significance of MAD deficiency. The main objective of the present study was to investigate the extent to which genetically confirmed MAD deficiency affects muscle function under conditions of maximal short-term electrically induced activation. The left hand was immobilized and adductor pollicis muscle function was investigated. To exclude the influence of central factors, such as the patient's motivation, the ulnar nerve was maximally electrically activated and force output was measured at the thumb. Sixty rapid shortening contractions resulted in a decrease of maximal power to 34.2±5.4% and 33.3±6.3% (means±S.D.) of the values for unfatigued muscle in the control and MAD-deficient subjects respectively (P > 0.05; n = 7). Maximal isometric forces and shortening velocities did not differ between groups in unfatigued, fatigued or recovered muscle. None of the subjects experienced exercise-related muscle aches or cramps. In conclusion, MAD deficiency does not appear to affect adductor pollicis muscle force, shortening velocity and relaxation, either during or after maximal short-term activation.
The influence of adipose tissue thickness (ATT) on near-IR spectroscopy (NIRS) measurements in vivo was studied in the human flexor digitorum superficialis muscle at rest and during sustained isometric handgrip exercise. NIRS was used for the quantitative measurement of muscle O(2) consumption (mV.O(2)) and forearm blood flow (FBF) in 78 healthy subjects. Skinfold thickness ranged from 1.4 to 8.9 mm within the group. Resting mV.O(2) was 0.11+/-0.04 ml of O(2).min(-1).100 g(-1), and FBF was 1.28+/-0.82 ml.min(-1).100 ml(-1). There was a negative correlation (r=-0.70, P< or =0.01), indicating a decrease in mV.O(2) with increasing ATT. mV.O(2) in the 10 leanest subjects appeared to be twice as high as that in the 10 subjects with the highest ATT. A poor correlation (r=0.29, P< or =0.01) was found between ATT and FBF. The gender difference that we found for mV.O(2) was due to the difference in ATT between female and male subjects. No correlation was found between maximum voluntary contraction and mV.O(2), nor between maximum voluntary contraction and ATT, indicating that the contraction force did not confound our results. These results show that ATT has a substantial confounding influence on in vivo NIRS measurements, and that it is essential to incorporate this factor into future NIRS muscle studies in order to justify comparisons between different groups. To facilitate such comparisons, upper and lower boundaries for normal values of mV.O(2) and FBF in relation to ATT are presented.
Quality of life (QoL) in children with facioscapulohumeral dystrophy (FSHD) seems plausible decreased. Little is known about factors influencing QoL in children with FSHD. Our objective is to explore factors contributing to the QoL of children, adolescents, and young adults with FSHD, to describe how they experience life with FSHD, and to report their support needs.
To determine the clinical phenotype and outcome in hepatitis E virus–associated neuralgic amyotrophy (HEV-NA).
Methods:
Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection.
Results:
Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12–2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months.
Conclusions:
Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted.
Abstract Introduction/Aims Functional performance tests are the gold standard to assess disease progression and treatment effects in neuromuscular disorders. These tests can be confounded by motivation, pain, fatigue, and learning effects, increasing variability and decreasing sensitivity to disease progression, limiting efficacy assessment in clinical trials with small sample sizes. We aimed to develop and validate a quantitative and objective method to measure skeletal muscle volume and fat content based on whole‐body fat‐referenced magnetic resonance imaging (MRI) for use in multisite clinical trials. Methods Subjects aged 18 to 65 years, genetically confirmed facioscapulohumeral muscular dystrophy 1 (FSHD1), clinical severity 2 to 4 (Ricci's scale, range 0–5), were enrolled at six sites and imaged twice 4–12 weeks apart with T1‐weighted two‐point Dixon MRI covering the torso and upper and lower extremities. Thirty‐six muscles were volumetrically segmented using semi‐automatic multi‐atlas‐based segmentation. Muscle fat fraction (MFF), muscle fat infiltration (MFI), and lean muscle volume (LMV) were quantified for each muscle using fat‐referenced quantification. Results Seventeen patients (mean age ± SD, 49.4 years ±13.02; 12 men) were enrolled. Within‐patient SD ranged from 1.00% to 3.51% for MFF and 0.40% to 1.48% for MFI in individual muscles. For LMV, coefficients of variation ranged from 2.7% to 11.7%. For the composite score average of all muscles, observed SDs were 0.70% and 0.32% for MFF and MFI, respectively; composite LMV coefficient of variation was 2.0%. Discussion We developed and validated a method for measuring skeletal muscle volume and fat content for use in multisite clinical trials of neuromuscular disorders.
It is unclear whether Charcot-Marie-Tooth (CMT) disease, type 1A, causes auditory processing disorders. Therefore, auditory processing abilities were investigated in five CMT1A patients with normal hearing.Previous studies have failed to separate peripheral from central auditory processing disorders.Five genetically confirmed CMT1A cases in patients with normal hearing underwent behavioral and objective testing. Pure tone audiometry, speech audiometry, and OAE assessment were followed-up by an auditory processing test battery comprising sentences-in-noise test, pattern recognition tests, words-in-noise test, dichotic digit test, filtered speech test, binaural fusion test, and categorical speech perception test. Subsequently, ABR and ERP measurements were conducted.Either the behavioral or objective test scores of 4 out of the 5 CMT1A patients did not differ significantly from those of subjects with normal hearing. Significantly lower scores of one patient on auditory processing tests and ABR measurements could be ascribed to subnormal hearing.The authors conclude that CMT1A patients with normal peripheral hearing have auditory processing abilities that were not indicative for an auditory processing disorder. Furthermore, the presence of a peripheral hearing loss complicates the interpretation of auditory processing abilities.
Pericytes are multipotent, vessel-associated progenitors that exhibit high proliferative capacity, can cross the blood-muscle barrier, and have the ability to home to muscle tissue and contribute to myogenesis. Consequently, pericyte-based therapies hold great promise for muscular dystrophies. A complex multi-system disorder exhibiting muscular dystrophy for which pericytes might be a valuable cell source is myotonic dystrophy type 1 (DM1). DM1 is caused by an unstable (CTG)n repeat in the DMPK gene and characterized by skeletal muscle weakness, muscle wasting, and myotonia. We have successfully isolated alkaline phosphatase-positive pericytes from skeletal muscle of DM1 patients and a transgenic mouse model. Intranuclear (CUG)n RNA foci, a pathogenic DM1 hallmark, were identified in human and mouse pericytes. Notably, pericytes from DM1 patients maintained similar growth parameters and innate myogenic characteristics in vitro compared to cells from unaffected controls. Our in vitro results thus demonstrate the potential of pericytes to ameliorate muscle features in DM1 in a therapeutic setting.
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