Adults with neuromuscular diseases like spinal muscular atrophy or Duchenne muscular dystrophy require full-time use of a wheelchair (WC) and perform all activities of daily living in a sitting ...position. Optimal configuration of the WC and seating system is essential to maintain the health and quality of life of users. However, few recommendations for configuration exist. The aim of this study was to identify and select 10 WC seating criteria that ensure an optimal sitting posture for health and quality of life. A four round Delphi method was used to collect the opinions of WC users and health professionals (HP), separately. First, the HP were asked if they believed that different criteria would apply to each disease. Then the HP and SMA II and DMD WC user experts responded to electronic surveys in 4 rounds. Overall, 74 experts took part: 31 HP, 21 WC users with SMA II and 22 WC users with DMD. In total, 52% of HP believed that different criteria would apply to each disease. Ten criteria were identified by the HP for SMA II and 10 for DMD. Of the 40 criteria selected, 30 (75%) were common to each panel. Six topics were similar across panels: comfort, access to the joystick, prevention of pain, stability, pressure management and power seat functions. However, power seat functions did not reach consensus between HP and WC users (30-33% of agreement for HP and 93-100% for the WC user panels, p < 0.001). Adults with SMA II and DMD had similar WC seating needs. Therefore, the same recommendations can be applied to these groups. Further research is necessary to understand the impact of cost on the prescription of power seat functions by health professionals.
Pompe disease is a rare neuromuscular disease caused by a deficiency of the lysosomal enzyme acid α-glucosidase. The late-onset Pompe disease (LOPD) in adults is characterized by weakness of ...ventilatory, axial, and proximal extremity muscles. These muscle impairments progressively impair various motor functions such as locomotion and postural control. Nearly 87% of adults with LOPD (aLOPD) report walking problems, and more than 80% report instability and falls. Knowledge of these motor functions is now sufficient to provide a clear and comprehensive overview of motor function in aLOPD. Therefore, this scoping review aimed to summarize current knowledge about motor function in aLOPD. It specifically targeted neuromuscular performance, locomotion, and postural control.
A systematic search in MEDLINE (through PubMed), EMBASE, and Cochrane databases was conducted until May 2021. We included studies providing primary data on at least 4 participants, exploring neuromuscular performance, locomotion, and/or postural control in aLOPD. Risk of bias analysis was assessed using tools appropriate to the study designs; the risk of bias 2 (Cochrane tool) for randomized controlled trials, risk of bias in Nonrandomized Studies - of Interventions (Cochrane tool) for nonrandomized interventional trials, and the Newcastle-Ottawa Scale for cohort studies and case-control studies.
The search identified 2,885 articles. After screening, 58 articles were included in the analysis. In these studies, 88% explored locomotion, 83% neuromuscular performance, and 3% postural control. This review showed that aLOPD experience symmetrical weakness, concerning especially the hip and lumbar muscles. Locomotor activities are limited with a distance reduction, spatiotemporal gait parameter modification, and an increased pelvic drop and tilt. Balance disorders are also observed especially in the anteroposterior direction.
We performed the first review on motor function characteristics in aLOPD. Although a significant amount of knowledge was synthesized in this review, our study also highlighted the lack of current research on this topic. Maximal muscle strength was the only neuromuscular performance studied, and gait biomechanics and postural control were poorly explored in LOPD. Relationships between the degree of muscle weakness and motor function alterations also remain to be determined in aLOPD.
Update on new muscle glycogenosis Laforêt, Pascal; Malfatti, Edoardo; Vissing, John
Current opinion in neurology,
10/2017, Letnik:
30, Številka:
5
Journal Article
Recenzirano
The field of muscle glycogenoses has progressed in recent years by the identification of new disorders, and by reaching a better understanding of pathophysiology of the disorders and the physiology ...of glycogen metabolism.
In this review, we describe the clinical and pathological features of the three most recently described muscle glycogenoses caused by recessive mutations in GYG1, RBCK1 and PGM1. The three involved enzymes play different roles in glycogen metabolism. Glycogenin-1 (GYG1) is involved in the initial steps of glycogen synthesis, whereas phosphoglucomutase catalyzes two metabolic pathways; the connection between galactose and glycogen on one side, and glucose metabolism on the other side. The metabolic consequences of mutations in the ubiquitin ligase gene RBCK1 are still poorly understood. GYG1 deficiency has been associated with cardiomyopathies with abnormal storage material in the heart, but most cases present with a polyglucosan body myopathy without cardiac involvement.
The recent identification of new glycogenosis not only allows to improve the knowledge of glycogen metabolism, but also builds bridges with protein glycosylation and immune system.
•Maximum strength was the only neuromuscular performance affected in Pompe disease•Our study highlights a proximal-distal gradient in muscle weakness intensity•The weakest muscles were the hip ...extensors followed by hip abductors and abductors•Instrumented assessment of the weakest muscles is essential•Neural and muscular fibers factors of aLOPD are as functional as those of controls
Adults with late-onset Pompe disease (aLOPD) are characterized by muscular contractile tissue deterioration. However, their neuromuscular performances are poorly known. We aimed to compare maximal muscle strength, activation, explosive strength and neuromuscular fatigue between aLOPD and controls. We studied 20 aLOPD and 20 matched controls. Isometric maximum voluntary contraction (MVC) torque was obtained for the hip, knee and ankle muscles. The voluntary activation level (VAL) during knee extensor MVC was assessed using interpolated twitch technique. Explosive strength was evaluated for knee and ankle muscles through the rate of torque development (RTD) during fast contractions. Neuromuscular fatigue was measured during a 30-second contraction of knee flexors and extensors. All muscle MVC torques were significantly lower in aLOPD than controls (p <0.05). The weakest muscles were the hip extensors followed by hip abductors and abductors. Raw value of RTD was lower in aLOPD for the majority of muscles (p <0.05). No intergroup differences were reported for normalized RTD, VAL and neuromuscular fatigue (p-values> 0.05). Our study shows that maximal strength was the only neuromuscular characteristic affected in aLOPD with a proximal-distal intensity gradient. This suggests that the surviving muscle tissue of aLOPD is as functionally efficient as that of control individuals.
Abstract Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three ...main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan’s anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin.
To study fat and carbohydrate metabolism during exercise in patients with glycogenin-1 (GYG1) deficiency, and to study whether IV glucose supplementation can alleviate exercise intolerance in these ...patients.
This is a case-control study with 4 patients with GYG1 deficiency and 4 healthy controls. Patients performed 1 hour of cycling at 50% of their maximal workload capacity, while controls cycled at the same absolute workloads as patients. Heart rate was measured continuously, and production and utilization of fat and glucose was assessed by stable isotope technique. The following day, patients repeated the exercise, this time receiving an IV 10% glucose supplement.
Glucose utilization during exercise was similar in patients and controls, while palmitate utilization was greater in patients compared to controls. However, exercise-induced increases in lactate were attenuated to about half normal in patients. This was also the case during a handgrip exercise test. Glucose infusion improved exercise tolerance in patients, and lowered heart rate by on average 11 beats per minute during exercise.
The findings suggest that patients with GYG1 deficiency not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion.
To assess whether bezafibrate increases fatty acid oxidation (FAO) and lowers heart rate (HR) during exercise in patients with carnitine palmitoyltransferase (CPT) II and very long-chain acyl-CoA ...dehydrogenase (VLCAD) deficiencies.
This was a 3-month, randomized, double-blind, crossover study of bezafibrate in patients with CPT II (n = 5) and VLCAD (n = 5) deficiencies. Primary outcome measures were changes in FAO, measured with stable-isotope methodology and indirect calorimetry, and changes in HR during exercise.
Bezafibrate lowered low-density lipoprotein, triglyceride, and free fatty acid concentrations; however, there were no changes in palmitate oxidation, FAO, or HR during exercise.
Bezafibrate does not improve clinical symptoms or FAO during exercise in patients with CPT II and VLCAD deficiencies. These findings indicate that previous in vitro studies suggesting a therapeutic potential for fibrates in disorders of FAO do not translate into clinically meaningful effects in vivo.
This study provides Class I evidence that bezafibrate 200 mg 3 times daily is ineffective in improving changes in FAO and HR during exercise in adults with CPT II and VLCAD deficiencies.
• Distribution of muscles involvement helps in directing the diagnosis towards a myopathy.• The main relevant clinical data was the correlation between age and disease severity.• A general ...symmetrical muscle alteration was noticed except for the subscapularis.• Subscapularis, anterior serratus and quadratus femoris muscles were mainly involved.
This study describes muscle involvement on whole-body MRI (WB-MRI) scans at different stages of McArdle disease. WB-MRI was performed on fifteen genetically confirmed McArdle disease patients between ages 25 to 80. The degree of fatty substitution was scored for 60 muscles using Mercuri's classification. All patients reported an intolerance to exercise and episodes of rhabdomyolysis. A mild fixed muscle weakness was observed in 13/15 patients with neck flexor weakness in 7/15 cases, and proximal muscle weakness in 6/15 cases. A moderate scapular winging was observed in five patients. A careful review of the MRI scans, as well as hierarchical clustering of patients by Mercuri scores, pointed out recurrent muscle changes particularly in the subscapularis, anterior serratus, erector spinae and quadratus femoris muscles. WB-MRI imaging provides clinically relevant information and is a useful tool to orient toward the diagnosis of McArdle disease.
Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we ...identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.
About 1% of the world's population uses a wheelchair. Wheelchair use is a well-known risk of pressure injury. A connected pressure detection system could help to prevent this complication that is ...linked to long durations of sitting, provided that user expectations are understood. The aim of this study was to explore the needs of wheelchair users (WU) regarding connected pressure detection systems to prevent pressure injury. A cross-section survey-based study of WU was conducted, using an anonymous electronic questionnaire posted from July 2019 to June 2020. Eighty-eight people responded. The majority were power wheelchair users (72.7%); one third (33.0%) had already sustained a pressure injury; only 17.0% knew of the existence of pressure detection systems, nevertheless 78.4% believed that they could be useful in daily life. The feature that received the highest rating was a pressure warning alarm (4.2/5 points). The majority (71.6%) preferred reminder-alerts to be set according to their habits and not according to medical guidelines. In conclusion, pressure detecting systems were perceived as useful to prevent pressure injuries by both manual and power wheelchair users. Work is needed to inform potential users of the existence of such systems.
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