OBJECTIVE:Currently, neurologists may primarily rely on blood biomarkers, muscle biopsy, MRI, and genetics in the diagnostic work-up of suspected myopathy. Using expert consensus as diagnostic reference standard, this study addressed the added value of electrodiagnostic medicine (EDX) in diagnosis of myopathies. METHODS:One hundred ninety-four EDX evaluations of patients with a peer-review consensus diagnosis of myopathy were collected by seven European centres. Each patient was given three different consensus diagnoses: (1) the EDX diagnosis solely based on EDX results, (2) the pure clinical diagnosis based on all available information except EDX results, and (3) the final diagnosis including EDX and all additional information. The myopathies were grouped as muscular dystrophy (45), inflammatory myopathy (46), other aetiology (36) or unknown aetiology (67). RESULTS:Higher diagnostic probabilities for myopathy were seen in the final diagnosis compared to the pure clinical diagnosis (p<0.001). Adding EDX information increased the diagnostic probability of myopathy in 67 patients (34.4%). The greatest increase was seen for myopathies of unknown aetiology. CONCLUSIONS:EDX has a major impact in the diagnosis of myopathies of unknown aetiology. In genetically or biopsy proven myopathies, EDX generally supports the diagnosis. SIGNIFICANCE:EDX is still a useful tool in the diagnostic work-up of most patients with suspected myopathy.

L’objectif de ce travail est d’étudier l’histoire naturelle des dystrophinopathies et les corrélations génotype-phénotype grâce au développement de la partie clinique de la banque de données nationale du gène DMD. Près de 70 000 données cliniques ont été collectées chez 600 patients avec une dystrophie musculaire de Duchenne, de Becker ou une forme symptomatique chez une femme, avec un suivi longitudinal moyen de 12ans. Leur analyse permet de préciser l’hétérogénéité phénotypique sur le plan moteur, orthopédique et respiratoire (formes sévère, standard et intermédiaire), sur le plan cardiaque (cardiomyopathie standard, sévère ou absente, absence de corrélation entre les atteintes motrice et cardiaque), et sur le plan cérébral (troubles cognitifs et psychologiques) dans ces trois formes de dystrophinopathie. Cette hétérogénéité phénotypique n’est pas corrélée aux anomalies du gène DMD. Nous proposons un modèle d’analyse du phénotype basé sur la présence ou non d’une atteinte musculaire et cardiaque (décrites par l’âge de début et la vitesse d’évolution) et cérébrale (décrite par le type et la sévérité des troubles cognitifs et psychologiques). L’utilisation de ce modèle d’analyse pour chaque patient et le développement de la banque de données pourraient constituer des outils majeurs pour la recherche clinique et la planification des essais thérapeutiques.

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12 years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum; We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials. (C) 2013 Elsevier Masson SAS. All rights reserved.

In myotonic mystrophy type 1 (DM1), combining respiratory symptom screening and respiratory function testing, is crucial to identify the appropriate time for ventilatory support initiation. Dyspnea has been little investigated in DM1. To provide a multidimensional description of dyspnea, questionnaires assessing dyspnea were administered to 34 consecutive adult patients with DM1 (median (25th-75th centile) age of 36 (28–49), Vital Capacity (VC) of 74 (64–87)% of predicted value). Dyspnea scores were low whatever the questionnaire used: Multidimensional Dyspnea Profile score of 2(0–4.7)/50 for dyspnea sensory descriptor and of 0 (0–4.7)/60 for the emotional descriptor, Visual Analogue Scale score of 0 (0–0)/10 in sitting and supine position and Borg score after six-minute walk test (6MWT) of 2.2 (1.8–4.2)/10. Eleven patients (32%) reported disabling dyspnea in daily living (modified Medical Research Council (mMRC) score ≥ 2). In comparison with patients with mMRC score < 2, patients with mMRC score ≥ 2 had a more severe motor handicap (Muscular Impairment Rating score of 4.0 (4.0–4.0) vs 3.0 (2.0–3.5), p<0.01), a lower 6MWT distance (373 (260–424) vs 436 (346–499)m, p = 0.03) and a lower VC (64 (48–74)% vs 75 (69–89)%, p = 0.02). These data suggest that the mMRC scale might be an easy-to-use and useful tool to assess dyspnea in daily living in DM1 patients. However, the interest of integrating the mMRC dyspnea scale in clinical practice to guide therapeutic management of DM1 patients remains to be assessed in further studies.

Background: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. Aim: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. Methods: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. Results: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset. Conclusion: The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.

Tropomyosins (TM) are a family of highly conserved actin-binding proteins composed of two subunits that form a coiled-coil structure. Skeletal muscle contains two forms of tropomyosin (alpha and beta subunits) localized to the thin filaments where they regulate Ca2+-dependant muscle contraction in association with the troponin complex. The beta subunit is encoded by the TPM2 gene composed of 9 exons of which four are alternatively spliced (exons 1, 2, 6 and 9). Mutations in TPM2 gene have been associated so far with two allelic neuromuscular disorders, autosomal dominant nemaline myopathy (NEM) and distal arthrogryposis (DA). We report an Algerian consanguineous family in which a male child presented at birth with severe hypotonia, distal amyotrophy, arthrogryposis and multiple pterygia, facial dysmorphia, ptosis and ophtalmoplegia. Three first cousins were also affected. Nemaline myopathy was diagnosed on muscle biopsy. After exclusion of ACTA1, TPM3 and NEB genes by linkage studies, a null mutation was identified at a homozygous level in all affected family members. The mutation is localized in exon 6b, specific of the skeletal muscle isoform. A low amount of transcript was detected by quantitative RT-PCR and absence of TPM2 expression in the muscle was confirmed by Western blot analysis. Identification of a null allele mutation in the TNNT1 gene has been reported in the Amish population in association with a lethal form of autosomal recessive nemaline myopathy. By contrast, the null mutation identified in the family is not life-threatening thus indicating a possible mechanism of compensation for total absence of TPM2.

L’électromyographie (EMG) de surface a été et est largement utilisée en kinésiologie et pour l’étude de la fatigue. Son application en clinique reste limitée, alors que les patients expriment leurs attentes d’un examen EMG non invasif. Les professionnels comme le système de santé pourraient tirer bénéfice d’un tel outil d’évaluation de la fonction musculaire en pathologie neuromusculaire, et dans les essais thérapeutiques, objectifs de nos études cliniques sur l’application de cette technique. Les paramètres que nous analysons sont l’enveloppe du signal EMG obtenu lors des contractions volontaires maximales, et le potentiel d’action musculaire composé (PAMC) correspondant. Ces paramètres, non spécifiques, ne peuvent s’appliquer au diagnostic des maladies neuromusculaires, objectif relevant d’autres méthodes évaluées par de nombreuses équipes de recherche. Dans le suivi des lésions nerveuses, ce protocole s’est révélé bien corrélé à l’évolution clinique motrice. Nous l’appliquons aux maladies neuromusculaires chroniques, pour évaluer l’amélioration ou la dégradation de l’activité EMG globale. L’apport respectif en pathologie neuromusculaire des différentes méthodes électrophysiologiques reste à évaluer, et à corréler aux mesures de force, testing manuel ou quantifié, dynamométrie, aux autres techniques envisagées (spectroscopie, imagerie) et aux échelles fonctionnelles.

Objective: To study physiological changes of the compound muscle action potential (CMAP) obtained from stimulation at different sites over the full length of a motor nerve and to study possible effects of anthropometrical factors.Methods: Multicentre study of ulnar motor nerve conduction in five segments to Erb's point performed bilaterally on 100 healthy subjects aged 17-83 years.Results: CMAP amplitude decreased linearly with conduction distance (0.31%/cm) from wrist to Erb's point., CMAP area decreased with the square of conduction distance. Decrease in area was smaller than decrease in amplitude especially distally. CMAP duration increased linearly (0.17%/cm). Amplitude decay correlated with age, height and BMI and dispersion correlated with age and height. There were no correlations between area decay and anthropometrical factors. There was no significant inter-examiner variation.Conclusions: Area decay may be preferred to amplitude decay in the evaluation of conduction block over short segments due to smaller physiological changes and independence of anthropometrical factors. The absence of inter-examiner variation indicates that the results are robust and may be used by other laboratories.Significance: This study provides knowledge of physiological changes of CMAP parameters that may be of importance in the evaluation of nerve pathology, in particular conduction block. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Surface electromyography (SEMG) had been and is still widely used in kinesiology and fatigue studies. Its use in routine clinical neurophysiology remains limited. Patients are requiring non-invasive EMG, which could also benefit to physicians and health care system looking for tools to evaluate muscle function in neuromuscular diseases as well as for therapeutic trials. This is the aim of our clinical studies. We apply SEMG envelope signal analysis acquired from maximal voluntary contractions, and the related compound muscle action potential (CMAP). These unspecific parameters cannot be used for neuromuscular diseases diagnosis, objective under study by many research teams. In nerve lesions follow-up studies, our SEMG procedure is related to motor clinical progression. We are currently evaluating it in chronic neuromuscular diseases. The respective contribution in neuromuscular disorders of the different neurophysiology techniques has still to be confirmed, and compared to force measurement by manual or quantitative testing, dynamometry, other suggested techniques (spectroscopy, imaging) as well as functional scales.

Objective: To present criteria for pathophysiological interpretation of motor and sensory nerve conduction studies and for pathophysiological classification of polyneuropathies suggested by a group of European neurophysiologists.Methods: Since 1992 seven neurophysiologists from six European countries have collected random samples of their electrodiagnostic examinations for peer review medical audit in the ESTEEM (European Standardized Telematic tool to Evaluate Electrodiagnostic Methods) project. Based on existing criteria in the literature, the experience with a patient material of 572 peer reviewed electrodiagnostic examinations, and productive discussions between the physicians at workshops, the collaboration has produced a set of criteria now routinely used at the centres involved in the project.Results: The first part of the paper considers pathophysiology of individual nerve segments. For interpretation of motor and sensory nerve conduction studies, figures showing change in amplitude versus change in conduction velocity/distal latency and change in F-wave frequency versus change in F-wave latency are presented. The suggested boundaries delimit areas corresponding to normal, axonal, demyelinated, or neuropathic nerve segments. Criteria for motor conduction block in upper and lower extremities are schematically depicted using the parameters CMAP amplitude and CMAP duration. The second part of the paper suggests criteria for classification of polyneuropathies into axonal, demyelinating, or mixed using the above-mentioned criteria.Conclusions: The suggested criteria are developed during many years of collaboration of different centres and may be useful for standardization in clinical neurophysiology.Significance: Consistent interpretation of nerve conduction studies is an important step in optimising diagnosis and treatment of nerve disorders. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE:Since 1992, 7 European neurophysiologists have participated in the ESTEEM project concerned with improvements in electrodiagnostic medicine. This study assesses whether the collaboration that includes peer review medical audit has influenced the involved physicians' electrodiagnostic criteria for polyneuropathy (PNP) diagnosing and classification. METHODS:Two sets of each physician's PNP examinations performed early and late in the study were examined for changes in (1) number of studies with abnormal electrophysiological findings required for diagnosing PNP, and (2) agreement between the classifications given by the individual physicians and the peer review group. RESULTS:The average number of abnormal motor nerve segments per patient increased from 4.6 to 6.4 during the study. Although most individual changes were minor, the second set of examinations showed an increased homogeneity among the physicians in the number of abnormal motor nerve segments and abnormal F wave studies, and a tendency towards increased homogeneity in the number of abnormal sensory nerve segments. There was also an increased agreement on pathophysiological PNP classification in the second set of examinations compared to the first set. CONCLUSIONS:The participation in the ESTEEM project seems to have impacted the physicians' clinical routine, possibly as they have accustomed themselves to apply criteria more strictly. SIGNIFICANCE:This study support that international collaboration is a useful step towards improvements in electrodiagnostic medicine.

Table ronde : « Le Normal et le Pathologique » E. Fournier a, J.F. Jabre b, A. Labarre-Vila c, M.R. Magistris d, P. Soichot e, F.C. Wang f a Fédération de neurophysiologie clinique, groupe hospitalier Pitié-Salpêtrière, 47, boulevard de l'hôpital, 75013 Paris, France b Boston VA Medical Center, Harvard-BU Neurology Service, 150 South Huntington, avenue, Boston, MA 02130, États-Unis c Unité ENMG et pathologie neuromusculaire, département de neurologie, CHU, 38043 Grenoble, France d Service de neurologie, hôpital universitaire de Genève, 1211 Genève-XIV, Suisse e Laboratoire EEG-EMG, hôpital général, 21033 Dijon, France f Médecine physique, CHU 4000 Liège, Belgique Présentation (A. Labarre-Vila 3)

Surface electromyography (SEMG) is not yet able to substitute needle EMG for diagnosing neuromuscular diseases in our current clinical neurophysiological practice. Several research groups have been working to reach this goal. Thus, we already have available, though imperfect and open to criticism, tools to apply SEMG to follow-up studies of neuromuscular diseases. There are enough scientific data to integrate validated tools into EMG equipment, to provide recommended electrodes and developed techniques and methods for recording and analysing all SEMG components, so that we could study the suggested standardised parameters in our clinical routine context. Independently of the accuracy of clinical indications for the chosen methods, the requirements of sensitivity, specificity and reproducibility should be as substantial for ENG as for needle or surface EMG. They suppose an equal demanding procedure in doing exams and interpreting results. The respective contribution of ENG and needle or surface EMG is still to be confirmed. Respective value and limitations of the force measurements by manual or quantitative testing, functional scales, SEMG or motor unit number counting are not yet evaluated in follow-up studies of neuromuscular diseases.