Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults.

Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. INTRODUCTION: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. METHODS: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). RESULTS: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. CONCLUSION: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young.

Diagnostic power of the non-ischaemic forearm exercise test in detecting glycogenosis type V.

BACKGROUND AND PURPOSE: This was a retrospective study to assess the diagnostic value of the non-ischaemic forearm exercise test in detecting McArdle's disease. METHODS: The study is a retrospective diagnostic study over 15 years (1999-2013) on a referred sample of patients suffering from exercise intolerance and various muscle complaints, generally with elevated creatine kinase (CK). In all, 1226 patients underwent the non-ischaemic forearm exercise test. Blood lactate, ammonia and CK levels were analyzed. DNA analyses and/or muscle biopsies were assessed to confirm the diagnosis of McArdle's disease. The results of 60 volunteers were used to compare with the results of study subjects. RESULTS: In this cohort, 40 patients were finally diagnosed with McArdle's disease. Absolute values of lactate and ammonia rise were used to discriminate all McArdle patients from healthy patients. A sensitivity and specificity of respectively 100% and 99.7% were calculated. The 24-h CK level showed no significant difference from the CK level at the day of the test and confirms the safety of the test. CONCLUSIONS: This study has formally assessed the diagnostic value of the non-ischaemic forearm exercise test in the detection of McArdle's disease. Very high sensitivity and specificity were observed. Furthermore, the test is easy to set up and to perform, it is non-traumatic and cost effective. It may circumvent a muscle biopsy in McArdle patients presenting the most common mutations. Hence, it is a perfect and safe screening instrument to detect patients with McArdle's disease. Glycogen storage disease type III patients, however, may show similar patterns to McArdle patients.

Diagnostic measures for sarcopenia and bone mineral density.

SUMMARY: Currently used diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. These diagnostic measures associate differently to bone mineral density (BMD), as an example of muscle-related clinical outcome. These differences should be taken into account when studying sarcopenia. INTRODUCTION: Diagnostic measures for sarcopenia utilize different measures of muscle mass, muscle strength, and physical performance. To understand differences between these measures, we determined the association with respect to whole body BMD, as an example of muscle-related clinical outcome. METHODS: In the European cross-sectional study MYOAGE, 178 young (18-30 years) and 274 healthy old participants (69-81 years) were recruited. Body composition and BMD were evaluated using dual-energy X-ray densitometry. Diagnostic measures for sarcopenia were composed of lean mass as percentage of body mass, appendicular lean mass (ALM) as percentage of body mass, ALM divided by height squared (ALM/height(2)), knee extension torque, grip strength, walking speed, and Timed Up and Go test (TUG). Linear regression models were stratified for sex and age and adjusted for age and country, and body composition in separate models. RESULTS: Lean mass and ALM/height(2) were positively associated with BMD (P < 0.001). Significance remained in all sex and age subgroups after further adjustment for fat mass, except in old women. Lean mass percentage and ALM percentage were inversely associated with BMD in old women (P < 0.001). These inverse associations disappeared after adjustment for body mass. Knee extension torque and handgrip strength were positively associated with BMD in all subgroups (P < 0.01), except in old women. Walking speed and TUG were not related to BMD. CONCLUSIONS: The associations between diagnostic measures of sarcopenia and BMD as an example of muscle-related outcome vary widely. Differences between diagnostic measures should be taken into account when studying sarcopenia.

Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial.

AIM: This study aimed to gain a better understanding of the psychological impact of participating in a clinical trial for patients with Pompe disease (Acid Maltase Deficiency). Attitudes and expectations of adult patients with neuromuscular diseases regarding medical trials are as yet unreported. In order to learn about the psychological consequences of participating in a clinical trial, we conducted a prospective assessment of patients with late-onset Pompe Disease, a rare genetic condition, for which no treatment had been available before. This psychological study was carried out as an ancillary study to the randomized double-blind placebo-controlled trial described elsewhere (van der Ploeg et al., 2010). SUBJECTS AND METHODS: We assessed patients (n=8) at inclusion, and at 12 and 18 months for six psychological dimensions: depression (Beck Depression Inventory, BDI), hopelessness (Beck Hopelessness Scale, BHS), anxiety (STAI A-B), quality of life (Whoqol-26), social adjustment (S.A.S-self-report) and locus of control (IPC Levenson). We produced a self-administered questionnaire in order to assess the attitudes, motivations and expectations of patients during the trial. RESULTS: At 12 months, mean social adjustment (SAS-SR, P=0.02) had improved, and at 18 months mean depression score had improved as well (BDI, P=0.03). The quality of life of patients (Whoqol-26) remained unchanged. Throughout the study, patients were more likely to have an internal locus of control than an external one (IPC Levenson). The self-administered questionnaire showed that patients' expectations were disproportionate compared to the medical information they had received starting the trial. For all patients, the first motivation for being enrolled in a clinical trial was "to help research", for half of them the motivation was to "improve their health". Whether patients believed to be part of one group or another (placebo or treatment) depended on their subjective perception of improvement during the trial. CONCLUSION: Given the small sample size, the conclusions of this study are preliminary. However, findings do suggest that there is a positive psychological impact of participating in a treatment trial. Moreover, the patients' reactions upon unblinding have led us to recommend that patients be asked whether they would like their group assignation disclosed to them or not.

The French Pompe registry. Baseline characteristics of a cohort of 126 patients with adult Pompe disease.

Pompe disease is a rare autosomal recessive muscle lysosomal glycogenosis, characterised by limb-girdle muscle weakness and frequent respiratory involvement. The French Pompe registry was created in 2004 with the initial aim of studying the natural history of French patients with adult Pompe disease. Since the marketing in 2006 of enzyme replacement therapy (alglucosidase alfa, Myozyme(®)), the French Pompe registry has also been used to prospectively gather the biological and clinical follow-up data of all adult patients currently treated in France. This report describes the main clinical and molecular features, at the time of inclusion in the French registry, of 126 patients followed up in 21 hospital-based neuromuscular or metabolic centres. Sixty-five men and 61 women have been included in the registry. Median age at inclusion was 49 years, and the median age at onset of progressive limb weakness was 35 years. Fifty-five percent of the patients were walking without assistance, 24% were using a stick or a walking frame, and 21% were using a wheelchair. Forty-six percent of the patients needed ventilatory assistance, which was non-invasive in 35% of the cases. When performed, muscle biopsies showed specific features of Pompe disease in less than two-thirds of the cases, confirming the importance of acid alpha-glucosidase enzymatic assessment to establish the diagnosis. Molecular analysis detected the common c.-32-13T>G mutation, in at least one allele, in 90% of patients. The French Pompe registry is so far the largest country-based prospective study of patients with Pompe disease, and further analysis will be performed to study the impact of enzyme replacement therapy on the progression of the disease.

Central and peripheral components of exercise-related fatigability in myotonic dystrophy type 1.

BACKGROUND: Fatigue frequently occurs in myotonic dystrophy type 1 (DM1), but its pathophysiology remains unclear. This study assessed central and peripheral components of exercise-related fatigability in patients with DM1, compared to controls. METHODS: Examinations were performed before and after a contraction of the abductor digiti minimi (ADM) muscle sustained for 45 s at 60% of maximal voluntary contraction (MVC). Myoelectric activity was recorded using high spatial resolution surface EMG during twitch stimulations and MVC and was characterized by root mean square, mean power frequency (MPF), and muscle fiber conduction velocity (MFCV). Peripheral nerve excitability was assessed by stimulating the ulnar nerve at the wrist with ADM recordings. Motor cortex excitability testing to transcranial magnetic stimulation included measures of intracortical facilitation and inhibition of motor evoked potentials (MEPs) in ADM muscle. RESULTS: At baseline, patients with DM1 showed altered peripheral nerve and cortical excitability (reduced intracortical facilitation) associated with impaired myoelectric properties. During the fatiguing exercise, the force remained stable, while MPF and MFCV decreased in both DM1 and control groups. After exercise, only refractoriness was reduced in patients with DM1, whereas controls showed marked neuromuscular and cortical changes. CONCLUSION: Patients with DM1 showed altered excitability of various cortical and neuromuscular components at baseline. However, most of excitability parameters did not vary after exercise in patients with DM1, in contrast to controls. This suggests that excitability properties, frankly altered at baseline, were not prone to be affected further after exercise in patients with DM1.

Measuring perfusion and bioenergetics simultaneously in mouse skeletal muscle: a multiparametric functional-NMR approach.

A totally noninvasive set-up was developed for comprehensive NMR evaluation of mouse skeletal muscle function in vivo. Dynamic pulsed arterial spin labeling-NMRI perfusion and blood oxygenation level-dependent (BOLD) signal measurements were interleaved with (31)P NMRS to measure both vascular response and oxidative capacities during stimulated exercise and subsequent recovery. Force output was recorded with a dedicated ergometer. Twelve exercise bouts were performed. The perfusion, BOLD signal, pH and force-time integral were obtained from mouse legs for each exercise. All reached a steady state after the second exercise, justifying the pointwise summation of the last 10 exercises to compensate for the limited (31)P signal. In this way, a high temporal resolution of 2.5 s was achieved to provide a time constant for phosphocreatine (PCr) recovery (τ(PCr)). The higher signal-to-noise ratio improved the precision of τ(PCr) measurement [coefficient of variation (CV) = 16.5% vs CV = 49.2% for a single exercise at a resolution of 30 s]. Inter-animal summation confirmed that τ(PCr) was stable at steady state, but shorter (89.3 ± 8.6 s) than after the first exercise (148 s, p < 0.05). This novel experimental approach provides an assessment of muscle vascular response simultaneously to energetic function in vivo. Its pertinence was illustrated by observing the establishment of a metabolic steady state. This comprehensive tool offers new perspectives for the study of muscle pathology in mice models.

Home-based exercise in autoimmune myasthenia gravis: A randomized controlled trial.

The tolerance of exercise and its effects on quality of life in myasthenia gravis are not currently backed up by strong evidence. The aim of this study was to determine whether exercise as an adjunct therapy is well tolerated and can improve health-related quality of life (HRQoL) in stabilized, generalized autoimmune myasthenia gravis (gMG). We conducted a parallel-group, multi-center prospective RCT using computer-generated block randomization. Adults with stabilized, gMG, and no contra-indication to exercise, were eligible. Participants received usual care alone or usual care and exercise. The exercise intervention consisted of 3-weekly 40 min sessions of an unsupervised, moderate-intensity home rowing program over 3 months. The primary endpoint was the change in HRQoL from randomization to post-intervention. Assessor-blinded secondary endpoints were exercise tolerance and effects on clinical, psychological and immunological status. Of 138 patients screened between October 2014 and July 2017, 45 were randomly assigned to exercise (n = 23) or usual care (n = 20). Although exercise was well tolerated, the intention-to-treat analysis revealed no evidence of improved HRQoL compared to usual care (MGQOL-15-F; mean adjusted between-groups difference of -0.8 points, 95%CI -5.4 to 3.7). Two patients hospitalized for MG exacerbation were from the usual care group.

Periodic salbutamol in facioscapulohumeral muscular dystrophy: a randomized controlled trial.

OBJECTIVE: To evaluate the effects on muscle strength of salbutamol administered for 6 months using a periodic regimen in patients presenting with facioscapulohumeral muscular dystrophy (FSHD). DESIGN: Placebo-controlled double-blind randomized study. SETTING: Three clinical centers involved in neuromuscular disorders. PARTICIPANTS: Ambulatory patients (N=112), 56 per group, with genetically confirmed FSHD, age 18 to 60 years. INTERVENTIONS: Salbutamol (sustained released formulation) administered orally at a daily dose of 16 mg using a periodic dosage regimen (3 wks on, 1 wk off). MAIN OUTCOME MEASURES: Muscle strength was assessed with quantitative muscle testing (QMT), manual muscle testing (MMT), and timed motor tests. Patients were evaluated at baseline, and 3 and 6 months later. Plasma drug assays were carried out at each visit. RESULTS: There was no significant change with periodic use of salbutamol in the total composite QMT z-score, MMT score, or timed motor tests. Salbutamol was well tolerated. Lack of efficacy did not seem to be related to plasma concentrations, which were within the expected range. CONCLUSIONS: Results from this study and previous controlled trials preclude at present the use of salbutamol as routine treatment for FSHD, even if we cannot exclude improvement from anabolic effects with a longer duration of treatment.

Quantitative myotonia assessment using force relaxation curve modelling.

The lack of a robust quantitative measure of myotonia has been underlined in previous studies. Recent publications have proposed methods to quantify myotonia based on the measurement of force relaxation times during maximal contractions. However, they present several drawbacks mainly due to unstable force, odd peaks or digital noise. A possible solution to this issue consists in fitting the force curve with a convenient regression model. The aim of this study was, therefore, to provide a regression model in order to fit the force relaxation time curve automatically and to provide a robust index for quantitative assessment of myotonia in clinical settings. Force curves were fitted by an asymmetric sigmoidal function. The inverse function was then used to compute various absolute and relative relaxation times automatically. These variables were calculated for 16 controls and 16 patients with myotonic dystrophy type 1 (DM1). All variables were significantly increased in DM1 patients compared to controls. For instance, the relaxation time between 40 and 60% of the initial contraction level was 18.2 (SD: 3.3) ms in controls and 40.1 (SD: 17.7) ms in DM1 patients. All relaxation variables were highly discriminant. Force curve modelling provides an objective and effective quantification of myotonia.

Scapular dyskinesis in myotonic dystrophy type 1: clinical characteristics and genetic investigations.

OBJECTIVE: To study scapular winging or other forms of scapular dyskinesis (condition of alteration of the normal position and motion of the scapula) in myotonic dystrophy type 1 (DM1), which is generally considered to be a distal myopathy, we performed an observational cohort study. METHODS: We performed a prospective cohort study on the clinical features and progression over time of 33 patients with DM1 and pronounced, mostly asymmetric scapular winging or other forms of scapular dyskinesis. We also explored if scapular dyskinesis in DM1 has the same genetic background as in facioscapulohumeral muscular dystrophy type 1 (FSHD1). RESULTS: The cohort included patients with congenital (n = 3), infantile (n = 6) and adult-onset DM1 (n = 24). Scapular girdle examination showed moderate shoulder girdle weakness (mean MRC 3) and atrophy of trapezius, infraspinatus, and rhomboid major, seemingly similar as in FSHD1. Shoulder abduction and forward flexion were limited (50-70°). In five patients, scapular dyskinesis was the initial disease symptom; in the others it appeared 1-24 years after disease onset. Follow-up data were available in 29 patients (mean 8 years) and showed mild to severe increase of scapular dyskinesis over time. In only three patients, DM1 coexisted with a FSHD mutation. In all other patients, FSHD was genetically excluded. DM2 was genetically excluded in nine patients. The clinical features of the patients with both DM1 and FSHD1 mutations were similar to those with DM1 only. CONCLUSION: Scapular dyskinesis can be considered to be part of DM1 in a small proportion of patients. In spite of the clinical overlap, FSHD can explain scapular dyskinesis only in a small minority. This study is expected to improve the recognition of shoulder girdle involvement in DM1, which will contribute to the management of these patients.

Respiratory and upper limb function as outcome measures in ambulant and non-ambulant subjects with Duchenne muscular dystrophy: A prospective multicentre study.

The field of translational research in Duchenne muscular dystrophy (DMD) has been transformed in the last decade by a number of therapeutic targets, mostly studied in ambulant patients. A paucity of studies focus on measures that capture the non-ambulant stage of the disease, and the transition between the ambulant and non-ambulant phase. In this prospective natural history study, we report the results of a comprehensive assessment of respiratory, upper limb function and upper limb muscle strength in a group of 89 DMD boys followed in 3 European countries, 81 receiving corticosteroids, spanning a wide age range (5-18 years) and functional abilities, from ambulant (n = 60) to non-ambulant (n = 29). Respiratory decline could be detected in the early ambulatory phase using Peak Expiratory Flow percentage predicted (PEF%), despite glucocorticoid use (mean annual decline: 4.08, 95% CI [-7.44,-0.72], p = 0.02 in ambulant; 4.81, 95% CI [-6.79,-2.82], p < 0.001 in non-ambulant). FVC% captured disease progression in non-ambulant DMD subjects, with an annual loss of 5.47% (95% CI [-6.48,-4.45], p < 0.001). Upper limb function measured with the Performance of Upper Limb (PUL 1.2) showed an annual loss of 4.13 points (95% CI [-4.79,3.47], p < 0.001) in the non-ambulant cohort. Measures of upper limb strength (MyoGrip and MyoPinch) showed a continuous decline independent of the ambulatory status, when reported as percentage predicted (grip force -5.51%, 95% CI [-6.54,-4.48], p < 0.001 in ambulant and a slower decline -2.86%; 95% CI -3.29,-2.43, p < 0.001, in non-ambulant; pinch force: -2.66%, 95% CI [-3.82,-1.51], p < 0.001 in ambulant and -2.23%, 95% CI [-2.92,-1.53], p < 0.001 in non-ambulant). Furthermore, we also explored the novel concept of a composite endpoint by combining respiratory, upper limb function and force domains: we were able to identify clear clinical progression in patients in whom an isolated measurement of only one of these domains failed to appreciate the yearly change. Our study contributes to the field of natural history of DMD, linking the ambulant and non-ambulant phases of the disease, and suggests that composite scores should be explored further.

Inter-hemispheric asymmetry of motor corticospinal excitability in major depression studied by transcranial magnetic stimulation.

BACKGROUND: Imaging and electroencephalographic studies have reported inter-hemispheric asymmetries in frontal cortical regions associated with depression. This study aimed at comparing motor corticospinal excitability assessed by methods of transcranial magnetic stimulation (TMS) between the right and left hemispheres in patients with major depression and healthy controls. METHOD: Patients with major depression (n=35) and healthy controls (n=35) underwent a bilateral study of various motor corticospinal excitability parameters, including rest motor threshold (RMT), corticospinal silent period (CSP) duration and intra-cortical inhibition (ICI) and facilitation (ICF). Indexes of asymmetry were calculated, and the relationships between excitability parameters and clinical scores of depression were statistically analyzed. RESULTS: Depressed patients showed a reduced excitability of both excitatory (RMT, ICF) and inhibitory (CSP, ICI) processes in the left hemisphere, compared to the right hemisphere and to healthy controls. CONCLUSION: The present results confirmed the existence of inter-hemispheric asymmetries in frontal cortex activities of depressed patients in favor of a left-sided reduced excitability. This neurophysiological approach may help to guide repetitive TMS procedures in the treatment of depressive disorders.

Stimulus-response curve of human motor nerves: multicenter assessment of various indexes.

The value of various indexes to characterize the stimulus-response curve of human motor nerves was assessed in 40 healthy subjects recruited from four European centers of investigation (Créteil, Lausanne, Liège, Marseille). Stimulus-response curves were established by stimulating the right median and ulnar motor nerves at the wrist, with stimulus durations of 0.05 and 0.5 ms. The following parameters were studied: the threshold intensity of stimulation to obtain 10% (I 10), 50% (I 50), and 90% (I 90) of the maximal compound muscle action potential, the ratios I 10/I 50, I 90/I 50, (I 90 - I 10)/I 10, (I 90-I 50)/I 50, and (I 50 - I 10)/I 10, and the slopes of the stimulus-response curves with or without normalization to I 50. For each parameter, within-center variability and reproducibility (in a test-retest study) were assessed and between-center comparisons were made. For most of the parameters, the results varied significantly within and between the centers. Within the centers, only the ratios I 10/I 50 and I 90/I 50 were found constant and reproducible. Between the centers, the absolute intensity thresholds (I 10, I 50, I 90) and the ratio I 90/I 50 did not show significant differences at stimulus duration of 0.5 ms, whatever the stimulated nerve. The reduced variability and good reproducibility of the ratios I 10/I 50 and I 90/I 50 open perspectives in neurophysiological practice for the use of these indexes of the stimulus-response curve, a rapid and noninvasive test.

Simulation analysis of interference EMG during fatiguing voluntary contractions. Part II--changes in amplitude and spectral characteristics.

Capabilities of amplitude and spectral methods for information extraction from interference EMG signals were assessed through simulation and preliminary experiment. Muscle was composed of 4 types of motor units (MUs). Different hypotheses on changes in firing frequency of individual MUs, intracellular action potential (IAP) and muscle fibre propagation velocity (MFPV) during fatigue were analyzed. It was found that changes in amplitude characteristics of interference signals (root mean square, RMS, or integrated rectified value, IEMG) detected by intramuscular and surface electrodes differed. RMS and IEMG of surface detected interference signals could increase even under MU firing rate reduction and without MU synchronisation. IAP profile lengthening can affect amplitude characteristics more significantly than MU firing frequency. Thus, an increase of interference EMG amplitude is unreliable to reflect changes in the neural drive. The ratio between EMG amplitude and contraction response can hardly characterise the so-called 'neuromuscular efficiency'. The recently proposed spectral fatigue indices can be used for quantification of interference EMG signals. The indices are practically insensitive to MU firing frequency. IAP profile lengthening and decrease in MFPV enhanced the index value, while recruitment of fast fatigable MUs reduced it. Sensitivity of the indices was higher than that of indices traditionally used.

Simulation analysis of interference EMG during fatiguing voluntary contractions. Part I: What do the intramuscular spike amplitude-frequency histograms reflect?

Decline in amplitude of EMG signals and in the rate of counts of intramuscularly recorded spikes during fatigue is often attributed to a progressive reduction of the neural drive only. As a rule, alterations in intracellular action potential (IAP) are not taken into account. To test correctness of the hypothesis, the effect of various discharge frequency patterns as well as changes in IAP shape and muscle fibre propagation velocity (MFPV) on the spike amplitude-frequency histogram of intramuscular interference EMG signals were simulated and analyzed. It was assumed that muscle was composed of four types of motor units (MUs): slow-twitch fatigue resistant, fast-twitch fatigue resistant, fast intermediate, and fast fatigable. MFPV and IAP duration at initial stage before fatigue as well as their changes differed for individual MU types. Fatigability of individual MU types in normal conditions as well as in the case of ischaemic or low oxygen conditions due to restricted blood flow was also taken into account. It was found that spike amplitude-frequency histogram is poorly sensitive to MU firing frequency, while it is highly sensitive to IAP profile lengthening. It is concluded that spike amplitude-frequency analysis can hardly provide a correct measure of MU rate-coding pattern during fatigue.

[Manual and quantitative muscle testing in neuromuscular disorders. How to assess the consistency of strength measurements in clinical trials?]. / Testing musculaire manuel et quantifié dans les maladies neuromusculaires. Comment assurer la qualité des mesures de force dans les protocoles cliniques?

Evaluation of functional capacities of patients suffering of neuromuscular disorders, particularly muscle strength, is a critical issue for their diagnosis and follow-up. Within the framework of the natural history of any given disease, such an evaluation may improve the clinician's knowledge of the pathophysiological processes involved, and may help to anticipate and sometimes prevent deleterious consequences as the disease progresses. It is also helpful for identifying correlation between the severity of organic damage and the functional impact of the disease. The measurement of functional capacities must be done with accuracy, sensitivity and reliability, essentially when used as an outcome measure for therapeutic trials. Several evaluation tools for measuring muscle strength are available. They are usually classified into two groups: manual muscle testing (MMT) methods and quantified muscle testing (QMT) methods. In this article, we present the principles of strength measurements, and the different tools and materials that are commonly used in clinical settings. Their limitations and drawbacks are illustrated through several examples. Although QMT is theoretically and potentially more consistent than MMT to precisely follow the muscle capacities of the patients, precise and robust procedures must be elaborated and validated for each tested muscle function. Strength measurements must be performed by trained and experimented clinical evaluators. This issue is critical in the follow up of multicentric therapeutic trials. Inter-rater reliability must be assessed to guarantee the statistical power of the trial.

[Nerve excitability studies in the assessment of dysimmune neuropathies]. / Etude de l'excitabilité nerveuse dans l'exploration des neuropathies dysimmunitaires.

INTRODUCTION: Various changes in axonal membrane excitability might explain negative symptoms in dysimmune neuropathies, e.g., acute or chronic inflammatory demyelinating neuropathies or multifocal neuropathies with persistent conduction blocks. Several electrophysiological methods have recently been designed to specifically assess such axonal membrane excitability changes. STATE OF ART: Resting and action potentials are related to ionic movements through the axonal membrane, mainly involving various types of sodium and potassium channels, as well as the ATP-dependent Na+/K+ pump. The functional status of these channels and pumps can be assessed in man, by studying the excitability recovery cycle after a single impulse, the strength-duration and stimulus-response curves, and the effects of hyperpolarization and depolarization depending on activity (voluntary contraction), ischemia or application of prolonged subthreshold currents. Various features of altered axonal membrane excitability might characterize dysimmune neuropathies, according to the course of the disease and its treatment. PERSPECTIVES: This electrophysiological approach allowed changes in axonal membrane properties to be objectively determined. In particular, some results obtained with these methods could explain the rapid action of intravenous immunoglobulins, and various pathophysiological mechanisms of conduction block or axonal degeneration. CONCLUSIONS: Nerve excitability studies appeared to be useful for the diagnosis and the follow-up of dysimmune neuropathies. New therapeutical strategies for such neuropathies will be probably developed in the future intending to improve nerve function by acting on axonal membrane excitability.

[Pathophysiology and treatment of fatigue in multiple sclerosis]. / Physiopathologie et traitement de la fatigue dans la sclérose en plaques.

Patients suffering from multiple sclerosis (MS) frequently complain of fatigue (53 to 92 percent depending on studies). Fatigue can be one of the most disabling symptoms of MS and presents as physical or mental fatigue in daily living activities. Besides this permanent feeling of exhaustion, MS patients can suffer from an abnormal tiredness and lack of energy after a given motor or mental task, which defines fatigability. A number of studies explored the origins of fatigue and fatigability by means of subjective and objective tools. The implication of central nervous system dysfunctions has been established in several studies; however the contribution of peripheral nervous system factors and systemic abnormalities associated with inflammatory and immunological parameters was also suggested. The aim of this review is to present the different types of fatigue and fatigability occurring in MS patients, their origins, the investigation tools which allow the quantification of fatigue and fatigability and characterization of their mechanisms. The currently available therapeutic strategies that have been proposed to relieve this disabling symptom are presented.

The prevalence of malnutrition according to the new ESPEN definition in four diverse populations.

BACKGROUND & AIMS: Consensus on the definition of malnutrition has not yet been reached. Recently, The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed a consensus definition of malnutrition. The aim of the present study was to describe the prevalence of malnutrition according to the ESPEN definition in four diverse populations. METHODS: In total, 349 acutely ill middle-aged patients, 135 geriatric outpatients, 306 healthy old individuals and 179 healthy young individuals were included in the study. Subjects were screened for risk of malnutrition using the SNAQ. The ESPEN definition of malnutrition, i.e. low BMI (< 18.5 kg/m(2)) or a combination of unintentional weight loss and low FFMI or low BMI was applied to all subjects. RESULTS: Screening identified 0, 0.5, 10 and 30% of the healthy young, the healthy old, the geriatric outpatients and the acutely ill middle-aged patients as being at risk of malnutrition. The prevalence of malnutrition ranged from 0% in the healthy young, 0.5% in healthy old individuals, 6% in the geriatric outpatients to 14% in the acutely ill middle-aged patients. Prevalence of low FFMI was observed in all four populations (14-33%), but concurred less frequently with weight loss (0-13%). CONCLUSIONS: Using the ESPEN definition, 0%-14% malnutrition was found in the diverse populations. Further work is needed to fully address the validity of a two-step approach, including risk assessment as an initial step in screening and defining malnutrition. Furthermore, assessing the predictive validity of the ESPEN definition is needed.