Yann Le Fur

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (173)487.73 Total impact

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    ABSTRACT: Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase mutations (SDHx) are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex-vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton MR spectroscopy (167 H-MRS) for identifying SDHx-related PGLs in vivo and non-invasively. Eight patients were prospectively evaluated with single voxel 168 H-MRS. MR spectra from 8 tumors (4 SDHx-related PGLs, 2 sporadic PGLs, 1 cervical schwannoma, and 1 cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx72 related tumor patients. Spectra quality was considered good in 3 cases, medium in 2 cases, poor in 2 cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exihibited a poorer spectra quality compared to other locations. 176 H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, 177 H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.
    Endocrine Related Cancer 06/2015; DOI:10.1530/ERC-15-0246 · 4.91 Impact Factor
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    ABSTRACT: Currently, the physiological factors responsible for exercise intolerance and bioenergetic alterations with age are poorly understood due, at least in part, to the confounding effect of reduced physical activity in the elderly. Thus, in 40 healthy young (22 ± 2 yrs) and old (74 ± 8 yrs) activity matched subjects, we assessed the impact of age on: 1) the relative contribution of the three major pathways of ATP synthesis (oxidative ATP synthesis, glycolysis, and the creatine kinase reaction) and 2) the ATP cost of contraction during high-intensity exercise. Specifically, during supra-maximal plantar flexion (120% of maximal aerobic power), to stress the functional limits of the skeletal muscle energy systems, we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to assess metabolism. Although glycolytic activation was delayed in the old, ATP synthesis from the main energy pathways were not significantly different between groups. Similarly, the inferred peak rate of mitochondrial ATP synthesis was not significantly different between the young (25 ± 8 mM.min(-1)) and old (24 ± 6 mM.min(-1)). In contrast, the ATP cost of contraction was significantly elevated in the old compared to the young (5.1 ± 2.0 and 3.7 ± 1.7 mM.min(-1).W(-1), respectively; P<0.05). Overall, these findings suggest that, when young and old subjects are activity matched, there is no evidence of age-related mitochondrial and glycolytic dysfunction. However, this study does confirm an abnormal elevation in exercise-induced skeletal muscle metabolic demand in the old that may contribute to the decline in exercise capacity with advancing age. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    AJP Regulatory Integrative and Comparative Physiology 06/2015; DOI:10.1152/ajpregu.00522.2014 · 3.53 Impact Factor
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    ABSTRACT: Purpose: Although it has been largely acknowledged that isometric neuromuscular electrostimulation (NMES) exercise induces larger muscle damage than voluntary contractions, the corresponding effects on muscle energetics remains to be determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to have minor slight effects on muscle metabolic response to subsequent dynamic exercise but the magnitude of muscle energetics alterations for NMES EIMD has never been documented. Methods: 31P magnetic resonance spectroscopy measurements were performed in thirteen young healthy males during a standardized rest-exercise-recovery protocol before (D0), two days (D2) and four days (D4) after NMES EIMD on knee extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations (i.e., phosphocreatine [PCr], inorganic phosphate [Pi] and adenosine triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic rates of ATP production and energy cost of contraction (Ec). Results: Resting [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly due to the increased [Pi] (+43% and +32%, respectively) while a significant decrease in resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). [PCr] recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a significantly decreased total rate of ATP production at D4 (-18%) mainly due to an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (-21%). Conclusion: Overall, NMES EIMD led to intramuscular acidosis in resting muscle and mitochondrial impairment in exercising muscle. Alterations of non-contractile processes and/or adaptive mechanisms to muscle damage might account for the decreased Ec during the dynamic exercise.
    Medicine &amp Science in Sports &amp Exercise 06/2015; 47(6). DOI:10.1249/MSS.0000000000000523 · 4.46 Impact Factor
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    ABSTRACT: Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.
    PLoS ONE 06/2015; 10(6):e0128016. DOI:10.1371/journal.pone.0128016 · 3.23 Impact Factor
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    ABSTRACT: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    Clinical Nutrition 03/2015; DOI:10.1016/j.clnu.2015.03.014 · 3.94 Impact Factor
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    ABSTRACT: Exercise efficiency is an important determinant of exercise capacity. However, little is known about the physiological factors that can modulate muscle efficiency during exercise. Accordingly, we examined whether improved O2 availability would 1) impair mitochondrial efficiency and shift the energy production toward aerobic ATP synthesis, 2) reduce the ATP cost of dynamic contraction owing to an improved neuromuscular efficiency, such that 3) whole-body O2 cost would remain unchanged. We used (31)P-Magnetic Resonance Spectroscopy ((31)P-MRS), surface electromyography and pulmonary VO2 measurements in eight active subjects during 6 min of dynamic knee-extension exercise under different fractions of inspired O2 (FiO2, normoxia: 0.21; hyperoxia: 1.0). Pulmonary VO2 (755 ± 111 ml.min(-1) in normoxia and 799 ± 188 ml.min(-1) in hyperoxia, P>0.05) and O2 cost (P>0.05) were not significantly different between normoxia and hyperoxia. In contrast, the total ATP synthesis rate and the ATP cost of dynamic contraction were significantly lower in hyperoxia compared to normoxia (P<0.05). As a result, the ratio between the rate of oxidative ATP synthesis from the quadriceps and pulmonary VO2 was lower in hyperoxia compared to normoxia, but did not reach statistical significance (ATP/VO2: 16 ± 3 mM.ml(-1) in normoxia and 12 ± 5 mM.ml (-1) in hyperoxia, P=0.07). Together, these findings reveal dynamic and independent regulations of mitochondrial and contractile efficiency as a consequence of O2 availability in young active individuals. Furthermore, muscle efficiency appears to be already optimized under normoxic condition and is unlikely to contribute to the well-established improvement in exercise capacity induced by hyperoxia. Copyright © 2014, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology.
    AJP Regulatory Integrative and Comparative Physiology 02/2015; 308(8). DOI:10.1152/ajpregu.00461.2014 · 3.53 Impact Factor
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    ABSTRACT: Background To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers.Methods Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure–posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1+, B1−, and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained.ResultsThe combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA = 10.03 + 1.71; cCho = 1.78 ± 0.55; cCr = 7.29 ± 1.69; cmIns = 5.30 ± 2.67) and in cerebellum (cNAA = 5.28 ± 1.77; cCho = 1.60 ± 0.41; cCr = 6.95 ± 2.15; cmIns = 3.60 ± 0.74).ConclusionA double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain. J. Magn. Reson. Imaging 2014.
    Journal of Magnetic Resonance Imaging 11/2014; 42(2). DOI:10.1002/jmri.24809 · 2.79 Impact Factor
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    ABSTRACT: Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8–9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.
    PLoS ONE 09/2014; 9(9). DOI:10.1371/journal.pone.0109066 · 3.23 Impact Factor
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    ABSTRACT: Purpose: This study compared the metabolic and activation changes induced by electrically-evoked (NMES) and voluntary (VOL) contractions performed at the same submaximal intensity using 31P chemical shift imaging (CSI) and T2 mapping investigations. Methods: Fifteen healthy subjects were asked to perform both NMES and VOL protocols with the knee extensors (i.e., 232 isometric contractions at 30% of maximal force) inside a 3T scanner for two experimental sessions. During the first session, metabolic variations, i.e., phosphocreatine (PCr), inorganic phosphate (Pi) and pH were recorded using localized 31P CSI. During a second session, T2 maps of the knee extensors were obtained at rest and immediately after each exercise. Voxels of interest were selected from the directly stimulated vastus lateralis (VL) and from the non-directly stimulated rectus femoris/vastus intermedius (RF/VI) muscles. Results: PCr depletion recorded throughout the NMES session was significantly larger in the VL as compared to the RF/VI muscles for both conditions (VOL and NMES). A higher occurrence of Pi splitting and a greater acidosis was found during NMES as compared to VOL exercise, illustrating the heterogeneous activation of both slow and fast muscle fibers. T2 changes were greater after NMES as compared to VOL for both muscles but were not necessarily related to the localized metabolic demand. Conclusion: We provided direct evidence that the metabolic demand was strongly related to both the exercise modality and the site of stimulation. On the basis of the occurrence of Pi splitting, we suggested that NMES can activate fast muscle fibers even at low force levels.
    Medicine &amp Science in Sports &amp Exercise 09/2014; 47(5). DOI:10.1249/MSS.0000000000000491 · 4.46 Impact Factor
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    ABSTRACT: Studies examining the effect of aging on skeletal muscle oxidative capacity have yielded equivocal results; however, these investigations may have been confounded by differences in oxygen (O2) delivery, physical activity, and small numbers of participants. Therefore, we evaluated skeletal muscle oxidative capacity and O2 delivery in a relatively large group (N = 40) of young (22 ± 2 years) and old (73 ± 7 years) participants matched for physical activity. After submaximal dynamic plantar flexion exercise, phosphocreatine (PCr) resynthesis (31P magnetic resonance spectroscopy), muscle reoxygenation (near-infrared spectroscopy), and popliteal artery blood flow (Doppler ultrasound) were measured. The phosphocreatine recovery time constant (Tau) (young: 33 ± 16; old: 30 ± 11 seconds), maximal rate of adenosine triphosphate (ATP) synthesis (young: 25 ± 9; old: 27 ± 8 mM/min), and muscle reoxygenation rates determined by the deoxyhemoglobin/myoglobin recovery Tau (young: 48 ± 5; old: 47 ± 9 seconds) were similar between groups. Similarly, although tending to be higher in the old, there were no significant age-related differences in postexercise popliteal blood flow (area under the curve: young: 1,665 ± 227 vs old: 2,404 ± 357mL, p = .06) and convective O2 delivery (young: 293 ± 146 vs old: 404 ± 191 mL, p = .07). In conclusion, when physical activity and O2 delivery are similar, oxidative capacity in the plantar flexors is not affected by aging. These findings reveal that diminished skeletal muscle oxidative capacity is not an obligatory accompaniment to the aging process.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 08/2014; DOI:10.1093/gerona/glu139 · 4.98 Impact Factor
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    ABSTRACT: Although skeletal muscle work efficiency likely plays a key role in limiting mobility of the elderly, the physiological mechanisms responsible for this diminished function remain incompletely understood. Thus, in the quadriceps of young (n=9) and old (n=10) subjects, we measured the cost of muscle contraction (ATP cost) with 31P-magnetic resonance spectroscopy (31P-MRS) during 1) maximal intermittent contractions to elicit a metabolic demand from both cross-bridge cycling and ion pumping and 2) a continuous maximal contraction to predominantly tax cross-bridge cycling. The ATP cost of the intermittent contractions was significantly greater in the old (0.30 ± 0.22 mM.min-1.N m-1) compared to the young (0.13 ± 0.03 mM.min-1.N m-1, P<0.05). In contrast, at the end of the continuous contraction protocol, the ATP cost in the old (0.10 ± 0.07 mM.min-1.N m-1) was not different from the young (0.06 ± 0.02 mM.min-1.N m-1, P=0.2). In addition, the ATP cost of the intermittent contractions correlated significantly with the single leg peak power of the knee-extensors assessed during incremental dynamic exercise (r = -0.55; P<0.05,). Overall, this study reveals an age-related increase in the ATP cost of contraction, likely mediated by an excessive energy demand from ion pumping, which probably contributes to both the decline in muscle efficiency and functional capacity associated with aging.
    Clinical Science 08/2014; 128(3). DOI:10.1042/CS20140274 · 5.63 Impact Factor
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    ABSTRACT: Background Although Magnetic Resonance Imaging has been widely used as a diagnostic tool in neuromuscular disorders, the analysis of images has remained essentially qualitative. Objectives Even if visual scores of deterioration have been proposed and achieve a good sensitivity their specificity remain low. The calculation and mapping of T2 relaxation time, a quantitative index of fat and muscle physical characteristics, can provide reliable information regarding fatty infiltration and inflammatory signs in neuromuscular disorders. Methods In addition to routine images acquired using T1 and STIR sequences, T2 mapping has been obtained from the dominant thigh of 55 patients with various muscle diseases (myositis, myopathies, rhabdomyolysis) and 36 control subjects. Based on the T2 values, we have developed an automatic segmentation method in order to distinguish muscle from fat. Two variables have been defined i.e. the most frequent T2 values (T2mf) and the numbers of T2 values ranging from 60 ms (the upper limit of normal muscle) to 75 ms (the lower limit of fat) expressed as a surface (NT2 60-75ms). Results We observed large T2 variations in patients and controls with a clear positive effect of age (0.23 p<0.001) and no relation to sex. T2mf and NT260–75ms values reduced this variation and were significantly affected by muscle diseases (Table 1). They increased from rabdomyolysis, myositis, to myopathies (Table 2). A diagnostic strategy obtained from a CHAID analysis shows that if STIR images analyses were not convincing to conclude, T2mf and NT260–75ms variable allowed to distinguish patients from controls. Conclusions T2 mapping is a quantitative approach more robust than the sole visual inspection to characterize changes in the muscles of patients with neuromuscular diseases. Additional indices such as T2mf and NT260–75ms provide alternative measures of disease activity which could be used for diagnosis, investigation of the natural history of muscle diseases and the effects of therapeutic strategies. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1602
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):658-658. DOI:10.1136/annrheumdis-2014-eular.1602 · 10.38 Impact Factor
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    ABSTRACT: Object To propose a fast and robust acquisition and post-processing pipeline that is time-compatible with clinical explorations to obtain a proton density (ρ) map used as a reference for metabolic map normalization. This allows inter-subject and inter-group comparisons of magnetic resonance spectroscopic imaging (MRSI) data and longitudinal follow-up for single subjects. Materials and methods A multi-echo T 2* mapping sequence, the XEP sequence for B 1+-mapping and Driven Equilibrium Single Pulse Observation of T 1—an optimized variable flip angle method for T 1 mapping used for both B 1−-mapping and M 0 calculation—were used to determine correction factors leading to quantitative water proton density maps at 3T. Normalized metabolite maps were obtained on a phantom and nine healthy volunteers. To show the potential use of this technique at the individual level, we also explored one patient with low-grade glioma. Results Accurate ρ maps were obtained both on phantom and volunteers. After signal normalization with the generated ρ maps, metabolic concentrations determined by the present method differed from theory by N-acetyl aspartate, choline and creatine levels; illustrating the potential for direct use of this technique in clinical studies. Conclusion The proposed combination of sequences provides a robust ρ map that can be used to normalize metabolic maps in clinical MRSI studies.
    MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 06/2014; 28(1). DOI:10.1007/s10334-014-0451-6 · 2.87 Impact Factor
  • Yann Le Fur · Patrick J Cozzone
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    ABSTRACT: In a previous study, we have shown that modulus post-processing is a simple and efficient tool to both phase correct and frequency align magnetic resonance (MR) spectra automatically. Furthermore, this technique also eliminates sidebands and phase distortions. The advantages of the modulus technique have been illustrated in several applications to brain proton MR spectroscopy. Two possible drawbacks have also been pointed out. The first one is the theoretical decrease in signal-to-noise ratio (SNR) by a factor up to √2 when comparing the spectrum obtained after modulus versus conventional post-processing. The second pitfall results from the symmetrization of the spectrum induced by modulus post-processing, since any resonance or artifact located at the left of the water resonance is duplicated at the right of the water resonance, thus contaminating the region of the spectrum containing the resonances of interest. Herein, we propose a strategy in order to eliminate these two limitations.
    MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 06/2014; 28(1). DOI:10.1007/s10334-014-0444-5 · 2.87 Impact Factor
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    ABSTRACT: Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice, 2 hours after a single intake of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight), through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were accessed strictly noninvasively during a standardized electrostimulation-induced exercise using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared to control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about 2-fold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did alter neither oxidative phosphorylation nor uncoupling protein 3 gene expression at rest. During 6-min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation, but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28% and +21% in 10-mg and 100-mg groups, respectively). ATP cost of contraction was further reduced in 10-mg (-35%) and 100-mg (-45%) groups. Besides, the highest dose also increased the force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.
    AJP Endocrinology and Metabolism 03/2014; 306(10). DOI:10.1152/ajpendo.00520.2013 · 4.09 Impact Factor
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    ABSTRACT: Background Primitive progressive lumbar paravertebral muscle weakness commonly known as Primitive Camptocormia and also referred to as “bent spine syndrome” is characterized by an abnormal trunk posture with marked flexion of the thoraco-lumbar spine on standing and walking. It has been described as a late-onset myopathy with a progressive weakness of the spinal extensor muscles associated to a paravertebral muscles fat invasion on the basis of Magnetic resonance imaging (MRI) investigations. In addition, a few case reports have suggested that primitive camptocormia might not be specific of paravertebral muscles but rather a more general myopathy. However, no data of a proper control have been reported so that a age-bias could have been introduced. Objectives The main purpose of the present study was to quantify fat invasion in thigh muscles of patients with primitive camptocormia using MRI in order to determrine whether camptocormia might be considered as a general myopathy. Methods Eight patients (7 females) were recruited and investigated 16.4±3 years after the onset of the first symptoms. Four age, and sex-matched control women were included. Mean patients and controls age were 78.8±7.9 and 81.8±5 year-old, weight was 60.1±2.3 and 61±1.4 kg, height was 159±3and 156±2 cms. The MRI sequence protocol included axial slices of the thigh using T1-weighted spin echo (TR/TE =544/12, matrix size 512*512, FoV 20 cm, slice thickness 5 mm) at 1.5 T (Vision plus, Siemens). A semi-automatic home-developed tool was used in order to quantify on each slice the muscle, subcutaneous fat (SCC) and infiltrated fat (IF) compartments (1). Results were expressed as means ratios with respect to the total (fat + muscle) fraction. Mann-Whitney tests (p<0.05) were used in order to compare the different fractions between the two groups. Results As summarized in table 1, muscle was the larger compartment in both groups with a similar fatty infiltration. Conclusions On the basis of quantitative MRI measurements, the present results clearly showed that fatty infiltration of thigh muscles, a potential myopathic index, was not larger in patients suffering from a primitive progressive lumbar paravertebral muscle weakness. We also quantified a 20-25% fat infiltration in older subjects. Our results did not confirm those from previous studies suggesting an abnormal muscle fat invasion in primitive camptocormia. However, given that no proper control group was included, the conclusions might have been biased. Muscle fat invasion would then be specific to paravertebral muscles in patients with camptocormia and could not be considered as an index of a general myopathic process. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):281-281. DOI:10.1136/annrheumdis-2012-eular.2337 · 10.38 Impact Factor
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    ABSTRACT: Background Because of its reduced thickness at the carpus level, the MRI identification of cartilage abnormalities has been initially discarded from the usual rheumatologic diagnostic scores and just recently introduced as a qualitative variable related to joint space narrowing. Objectives In the present study we aimed at determining whether carpal cartilage area can be measured using high-field MRI area through a semi-automatic method. We also compared the results related to two different MRI sequences. Methods The study was conducted in 14 healthy volunteers after they provided their written informed consent. MRI investigations were performed at 3T using two 3D sequences i.e. VIBE and DESS for the analysis of carpal cartilage. Cartilage surface was measured on a three-dimensional reconstruction using a conventional image processing radiology software. The protocol received the agreement from the local ethics committee. Results Cartilage measurements performed by two different operators and twice by the same operator showed a very good reproducibility regardless the MRI sequence used. A 15% interindividual variability for the cartilage area was quantified within this control group. Interestingly, the wrist cartilage area was linearly related to the carpal bone height and so for results obtained with both MRI sequences. Conclusions Using high-field MRI, we reported a very reproducible semi-automatic method of cartilage surface measurement in wrist. The measurements were performed on a MRI section accurately defined thanks to 3D acquisitions. The large variability of the corresponding measurements illustrated that cartilage area cannot be used as a stand-alone diagnostic criterion. The standardized linear relationship between wrist cartilage area and carpal bone height captures the natural diversity of these measurements and provides a promising index for future diagnostic and therapeutic studies in the field of rheumatologic diseases. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A1018-A1019. DOI:10.1136/annrheumdis-2013-eular.3073 · 10.38 Impact Factor
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    ABSTRACT: Background Camptocormia also referred to as “bent spine syndrome” is characterized by an abnormal trunk posture with marked flexion of the thoraco-lumbar spine. These clinical signs are most prominent on standing and walking and disappears in the recumbent position. There is definitely a broad spectrum of musculoskeletal and neurological etiologies of this disorder which are likely linked to the referral patter. Camptocormia has been associated with muscular dystrophies, inflammatory myopathies, segmental dystonia, amyotrophic lateral sclerosis, mitochondrial myoapthy, dysferlinopathy and Parkinson disease among others. It has been described as a late-onset (over 50 years-old) myopathy with a progressive weakness of the spinal extensor muscles. Increased CK activity and unspecific EMG changes have been reported while computed tomography and Magnetic resonance imaging (MRI) disclosed fat invasion of paravertebral muscles. However, this fat invasion has never been compared to a proper control group so that the effect of age has been ignored. Objectives The main purpose of the present study was to quantify the potential fatty infiltration of paravertebral muscles in patients with primary camptocormia and to compare the corresponding results with those from a age-matched control group. Methods Patients (4, 3 women) and age and sex-matched controls (4). Patients group has been investigated 16.4 ± 3 years after the symptoms onset. We used a spin echo T1 weighted MRI sequence in order to record axial slices of paravertabral muscles (TR/TE = 544/12, matrix size 512*512, FoV 20 cm, slice thickness 5 mm) at 1.5 T (Vision plus, Siemens). Subcutaneous fat (SCF), fatty infiltration (FIF) and muscle (MF) fractions were quantified using a threshold procedure previously described (1). Results were expressed as ratio related to the total content including muscle and fat contents. Mann-Whitney tests (p < 0.05) were used in order to compare both groups. Results The relative intramuscular fat content was actually larger in controls (61±15%) than in patients (38±15%). Correspondingly, the muscle fraction was larger in patients (62 ±19) as compared to controls (39±15%). However, statistical tests failed to demonstrate any difference thereby suggesting that the fatty infiltration of paravertebral muscles previously reported in patients with camptocormia as a myopathic sign should be revisited in the light of ageing. Conclusions This comparative MRI study between patients with camptocormia and age and sex-matched controls clearly indicate similar fatty and water contents in paravertebral muscles. On that basis, one can argue that the fatty infiltration previously reported in patients with camprocormia as a myopathic sign was rather related to ageing. This preliminary study shoud be extended in a larger cohort. References Mattei, J. P., Y. L. Fur, et al. (2006). “Segmentation of fascias, fat and muscle from magnetic resonance images in humans: the DISPIMAG software.” Magma 19(5): 275-9). Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A326-A326. DOI:10.1136/annrheumdis-2013-eular.1006 · 10.38 Impact Factor
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    ABSTRACT: Impaired skeletal muscle efficiency potentially contributes to the age-related decline in exercise capacity and may explain the altered hemodynamic response to exercise in the elderly. Thus, we examined whether 1) the ATP cost of contraction increases with age, and 2) this results in altered convective O2 delivery to maintain microvascular oxygenation in the calf muscle. To this aim, we used an integrative experimental approach combining phosphorus magnetic resonance spectroscopy (31P-MRS), Doppler ultrasound imaging, and near-infrared spectroscopy (NIRS) during dynamic plantar flexion exercise at 40% of maximal power output (WRmax) in 20 healthy young and 20 older subjects matched for physical activity. The ATP cost of contraction was significantly higher in the old (7.2 ± 4.1 mM.min-1.W-1) compared with the young (2.4 ± 1.9 mM.min-1.W-1, P<0.05) and this was only significantly correlated with plantar flexion WRmax in the old (r=-0.52, P<0.05). Even when differences in power output were taken into account, end-exercise blood flow (old: 259 ± 168; young: 134 ± 40 ml.min-1.W-1, P<0.05) and convective O2 delivery (old: 0.048 ± 0.031; young: 0.026 ± 0.008 L.min-1.W-1, P<0.05) were greater in the old in comparison to the young. In contrast, NIRS oxy-, deoxy-hemoglobin and microvascular oxygenation indices were not significantly different between groups (P>0.05). Therefore, this study reveals that, while the peripheral hemodynamic responses to plantar flexion exercise appear to be appropriate, the elevated energy cost of contraction and associated reduction in WRmax in this muscle group may play a role in limiting exercise capacity with age.
    Clinical Science 11/2013; 126(7-8). DOI:10.1042/CS20130442 · 5.63 Impact Factor

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Institutions

  • 2006–2015
    • Aix-Marseille Université
      • • Centre de Résonance Magnétique Biologique et Médicale (UMR 7339 CRMBM)
      • • Faculté de Médecine
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1980–2015
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • University of Nantes
      Naoned, Pays de la Loire, France
  • 2001–2003
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 1993–1998
    • University Joseph Fourier - Grenoble 1
      • Grenoble Institut des Neurosciences
      Grenoble, Rhône-Alpes, France
  • 1995
    • University of Grenoble
      Grenoble, Rhône-Alpes, France