Self-reported outcomes and quality of life of patients with non-dystrophic myotonia: The French IMPACT 2022 survey.

Non-dystrophic myotonias (NDM) are disabling genetic diseases that impact quality of life. To reduce the impact of NDM, patients develop coping strategies such as lifestyle adaptation and avoiding key triggers. To understand how myotonia affects patients' lives, the IMPACT survey, an online questionnaire on patient-reported outcomes, was developed based on international IMPACT questionnaire. The French IMPACT 2022 survey was completed by 47 NDM French patients. Besides muscle stiffness (98%), patients reported muscle pain (83%), falls (70%) and anxiety (77%). These issues negatively impacted abilities to work/study (49%), daily life at home (49%) and overall mobility outside (49%). Most patients (96%) reported ongoing pharmacological treatment (mexiletine, 91%) associated with improvement in muscle stiffness (100%) and reduction in falls (94%), muscle pain (87%) and anxiety (80%). Patients were moderately satisfied (19.1%), satisfied (42.6%) and very satisfied (29.8%) with the current management; 32% rated their quality of life positively (≥ 8 on 10-point scale). In conclusion, this French survey confirms the impact of myotonia on daily life and quality of life. The improvement in patient-reported outcomes in treated participants highlights the importance of managing myotonia with effective treatments. More work should be initiated to assess the importance of NDM symptom management and patients' adherence and compliance to treatment.

Current clinical management of CIDP with immunoglobulins in France: An expert opinion.

Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.

Deep phenotyping of facioscapulohumeral muscular dystrophy type 2 by magnetic resonance imaging.

BACKGROUND AND PURPOSE: The aim was to define the radiological picture of facioscapulohumeral muscular dystrophy 2 (FSHD2) in comparison with FSHD1 and to explore correlations between imaging and clinical/molecular data. METHODS: Upper girdle and/or lower limb muscle magnetic resonance imaging scans of 34 molecularly confirmed FSHD2 patients from nine European neuromuscular centres were analysed. T1-weighted and short-tau inversion recovery (STIR) sequences were used to evaluate the global pattern and to assess the extent of fatty replacement and muscle oedema. RESULTS: The most frequently affected muscles were obliquus and transversus abdominis, semimembranosus, soleus and gluteus minimus in the lower limbs; trapezius, serratus anterior, latissimus dorsi and pectoralis major in the upper girdle. Iliopsoas, popliteus, obturator internus and tibialis posterior in the lower limbs and subscapularis, spinati, sternocleidomastoid and levator scapulae in the upper girdle were the most spared. Asymmetry and STIR hyperintensities were consistent features. The pattern of muscle involvement was similar to that of FSHD1, and the combined involvement of trapezius, abdominal and hamstring muscles, together with complete sparing of iliopsoas and subscapularis, was detected in 91% of patients. Peculiar differences were identified in a rostro-caudal gradient, a predominant involvement of lower limb muscles compared to the upper girdle, and in the higher percentage of STIR hyperintensities in FSHD2. CONCLUSION: This multicentre study defines the pattern of muscle involvement in FSHD2, providing useful information for diagnostics and clinical trial design. Both similarities and differences between FSHD1 and FSHD2 were detected, which is also relevant to better understand the pathogenic mechanisms underlying the FSHD-related disease spectrum.

Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis.

OBJECTIVES: Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis. MATERIALS AND METHODS: Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients. INTERPRETATION: Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate myopathy and congenital miosis.

We present three members of an Italian family affected by tubular aggregate myopathy (TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine kinase (CK) elevation and congenital miosis consistent with a Stormorken-like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a similar pattern of muscle involvement that correlated with clinical severity. The lower limbs were more severely affected than the scapular girdle, and thighs were more affected than legs. Molecular analysis revealed a novel c.290C>G (p.S97C) mutation in ORAI1 in all affected patients. Functional assays in both human embryonic kidney (HEK) cells and myotubes showed an increased rate of Ca2+ entry due to a constitutive activation of the CRAC channel, consistent with a 'gain-of-function' mutation. In conclusion, we describe an Italian family harboring a novel heterozygous c.290C>G (p.S97C) mutation in ORAI1 causing a mild- and late-onset TAM and congenital miosis via constitutive activation of the CRAC channel. Our findings extend the clinical and genetic spectrum of the ORAI1-related TAM.

EFNS review on the role of muscle biopsy in the investigation of myalgia.

BACKGROUND: Myalgia, defined as any pain perceived in muscle, is very common in the general population and a frequent cause for referral to neurologists, rheumatologists and internists in general. It is however only rarely due to primary muscle disease and often referred from ligaments, joints, bones, the peripheral and central nervous system. A muscle biopsy should only be performed if this is likely to be diagnostically useful. At present no 'guidelines' exist. METHODS: An EFNS panel of muscle specialists was set to review relevant studies from PubMed dating as far back as 1/1/1990. Only Class IV studies were available and therefore the recommendations arrived at are 'best practice recommendations' based on information harvested from the literature search and expert opinion. RESULTS: Muscle cramps should be recognized while drugs, infections, metabolic/ endocrinological and rheumatological causes of myalgia should be identified from the history and examination and pertinent laboratory tests. A muscle biopsy is more likely to be diagnostically useful if myalgia is exertional and if one or more of the following apply: i) there is myoglobinuria, (ii) there is a second wind phenomenon, (iii) there is muscle weakness, (iv) there is muscle hypertrophy /atrophy, (v) there is hyperCKemia (>2-3× normal), and (vi) there is a myopathic EMG. CONCLUSIONS: Patients presenting with myalgia can be recommended to have a biopsy based on careful history and examination and on simple laboratory screening.

[Facioscapulohumeral muscular dystrophy type 2]. / Dystrophie musculaire facio-scapulo-humérale de type 2.

INTRODUCTION: In recent years, the advances of knowledge in clinical, genetic and epigenetic features of facioscapulohumeral muscular dystrophy (FSHD) allowed the identification of two forms of FSHD, the classical autosomal dominant FSHD type 1, and FSHD type 2 characterized by an identical clinical phenotype but associated with a different (epi)genetic defect. STATE OF THE ART: In the large majority of FSHD1 patients, the identification of D4Z4 pathogenic contraction on a permissive chromosome 4 is sufficient for diagnosis, while FSHD2 diagnosis is complicated by the fact that the genetic defect associated with this disease is not known yet and a complete D4Z4 genotype and a D4Z4 specific methylation test are required. Indeed, FSHD2 patients display a non-contracted D4Z4 allele on chromosomes 4, at least one permissive chromosome 4QA and a profound hypomethylation of both chromosomes 4 and 10. A common pathophysiological pathway has been hypothesized for FSHD1 and FSHD2 in order to explain the identical clinical phenotype and the highly similar epigenetic changes found in patients affected by these diseases. According to this hypothesis, chromatin relaxation - due to pathogenic D4Z4 contraction in FSHD1 patients, and to important hypomethylation of this locus in FSHD2 patients - would allow the last D4Z4 unit to encode for a toxic DUX4 transcript. This transcript would be stable only when encoded from a permissive chromosome 4 carrying a polyadenylation signal immediately distal to the last D4Z4 unit on chromosome 4. PERSPECTIVES: Since, to express clinical phenotype, FSHD2 patients have to carry both 4QA chromosome and hypomethylated D4Z4 on chromosomes 4 and 10, digenic transmission has been hypothesized for this disease. The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene. CONCLUSIONS: The identification, among patients carrying a FSHD phenotype, of FSHD2, a new disease with distinct (epi)genetic features but having a common pathophysiological pathway with FSHD1, suggests the possibility of developping new therapeutic strategies suitable for both diseases.

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.

[Phenotypic heterogeneity and phenotype-genotype correlations in dystrophinopathies: Contribution of genetic and clinical databases]. / Variabilité phénotypique et corrélations génotype-phénotype des dystrophinopathies : contribution des banques de données.

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 12years 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.

The effect of tibialis anterior weakness on foot drop and toe clearance in patients with facioscapulohumeral dystrophy.

BACKGROUND: Facioscapulohumeral dystrophy is a genetic disease characterized by progressive muscle weakness leading to a complex combination of postural instability, foot drop during swing and compensatory strategies during gait that have been related to an increased risk of falling. The aim is to assess the effect of tibialis anterior muscle weakness on foot drop and minimum toe clearance of patients with facioscapulohumeral dystrophy during gait. METHODS: Eight patients allocated to a subgroup depending on the severity of tibialis anterior muscle weakness, assessed by manual muscle testing (i.e., severe and mild weakness), and eight matched control participants underwent gait analysis at self-selected walking speeds. FINDINGS: Walking speed, for all facioscapulohumeral dystrophy patients, and step length, for patients with severe weakness only, were significantly decreased compared to control participants. Minimum toe clearance was similar across all groups, but its variability was increased only for patients with severe weakness. A greater foot drop was systematically observed for patients with severe weakness during swing and only in late swing for patients with mild weakness. Individual strategies to compensate for foot drop remain unclear and may depend on other muscle impairment variability. INTERPRETATION: Although all patients were able to control the average height of their foot trajectory during swing, patients with severe tibialis anterior muscle weakness exhibited increased foot drop and minimum toe clearance variability. Manual muscle testing is a simple, cheap and effective method to assess tibialis anterior muscle weakness and seems promising to identify facioscapulohumeral dystrophy patients with an increased risk of tripping.

EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia.

OBJECTIVE: To provide evidence-based guidelines to general neurologists for the assessment of patients with pauci- or asymptomatic hyperCKemia. BACKGROUND: Recent epidemiologic studies show that up to 20% of 'normal' individuals have an elevated creatine kinase activity in the serum (sCK). The possibility of a subclinical myopathy is often raised, and patients may be unnecessarily denied treatment with statins. SEARCH STRATEGY: Electronic databases including Medline, the Cochrane Library and the American Academy of Neurology were searched for existing guidelines. Articles dealing with series of patients investigated for asymptomatic/pauci-symptomatic hyperCKemia and articles dealing with myopathies that can present with asymptomatic hyperCKemia were identified and reviewed. RESULTS: The only guidelines found were those approved by the Italian Association of Myology Committee, and the only relevant articles identified describe class IV studies. RECOMMENDATIONS: HyperCKemia needs to be redefined as values beyond 1.5 times the upper limit of normal (which itself needs to be appropriately defined). Pauci- or asymptomatic hyperCKemia with no apparent medical explanation may be investigated with a muscle biopsy if one or more of the following are present; the sCK is >or=3x normal, the electromyogram is myopathic or the patient is <25 years of age. In addition, women with sCK<3 times normal may be offered DNA testing because of the possibility of carrying a dystrophin mutation.

[Retinal involvement and genetic myopathy]. / Atteinte rétinienne et myopathies génétiques.

INTRODUCTION: In genetic diseases, association between retinal and muscular involvement is uncommon, quite specific and frequently allows the diagnosis. In this context, three types of retinal involvement have been described: retinitis pigmentosa (RP), pattern retinal dystrophy (PRD) and exudative retinitis resembling Coats disease (CD). STATE OF THE ART: The association between RP, PRD and muscle weakness is highly evocative of a mitochondrial disorder. Extra ocular muscles may be affected, but limb girdle or distal weakness can also be present in association or not with symptoms and signs of multisystemic involvement. In a large number of patients suffering from facioscapulohumeral muscular dystrophy (FSHD), retinal vessels telangectasia can be found at the fundoscopic examination. This finding, which corresponds to a developmental abnormality of peripheral retinal blood vessels, is not progressive and remains clinically asymptomatic. Nevertheless, a few patients with FSHD can develop an exsudative retinopathy resembling Coats disease with the risk of the major complication, recurrent retinal detachments. PERSPECTIVES AND CONCLUSIONS: Considering the diagnostic interest and the deleterious consequences that may follow retinal involvement, close collaboration between the neurologist and ophthalmologist is needed in order to establish the diagnosis, detect complications early, and set up appropriate therapies.

[Validity of the motor function measurement scale when routinely used in the follow-up of adult outpatients in a neuromuscular center]. / Analyse de validité de la "Mesure de la fonction motrice" (MFM) en pratique de consultation adulte d'un centre de référence pour maladies neuromusculaires.

INTRODUCTION: The Motor Function Measure (MFM) is widely used to assess severity and progression of neuromuscular diseases. Validity was established in a group of patients aged 6-60 years with suspected or confirmed diagnosis of neuromuscular diseases, Duchenne Muscular Dystrophy being the most frequent diagnosis in the population tested. OBJECTIVES: Our aim was to check the validity of the MFM in a hospital department specialized in neuromuscular diseases in the follow-up of adult out-patients presenting a myopathy, such population being very different from the MFM validation group in terms of age and sub-groups of myopathy. METHODS: One hundred patients were randomly selected in the Reference Center for Neuromuscular Diseases of Nice (France) between 2005 and 2007. Were collected: the MFM score, manual muscular testing (MMT) of lower and upper limb, face and spine, Brooke and Vignos scores. MFM and its three dimensions D1 (standing position and transfers), D2 (axial and proximal limb motor function) and D3 (distal motor function) were compared to the other scores with the Spearman Correlation Coefficient and the Principal Component Analysis. RESULTS: Patients were aged 18-78 years. The most frequent diagnoses were Steinert's Muscular Dystrophy (DM1) and Facio-ScapuloHumeral Dystrophy (FSHD) (30% and 29%). MFM was significantly correlated to all other scores except for Face MMT. However, Face MMT was correlated to D1 and D2 in DM1 patients and to D2 in FSHD patients. DISCUSSION: Our results confirm the validity of the MFM in adult patients with muscular diseases. However, the MFM global score and its three dimensions D1, D2 and D3 are variously correlated with the facial and axial muscle testing. Therefore, we recommend using separately the three dimensions D1, D2, D3 (rather than the global score) and, if more accuracy is required, the facial and axial muscle testing.

Mechanisms underlying Andersen's syndrome pathology in skeletal muscle are revealed in human myotubes.

Andersen's syndrome is a rare disorder that has been defined with a triad: periodic paralysis, cardiac arrhythmia, and development anomalies. Muscle weakness has been reported in two-thirds of the patients. KCNJ2 remains the only gene linked to Andersen's syndrome; this gene encodes for the alpha-subunit of the strong inward-rectifier K+ channel Kir2.1. Several studies have shown that Andersen's syndrome mutations lead to a loss of function of the K+ channel activity in vitro. However, ex vivo studies on isolated patient muscle tissue have not been reported. We have performed muscle biopsies of controls and patients presenting with clinically and genetically defined Andersen's syndrome disorder. Myoblasts were cultured and characterized morphologically and functionally using the whole cell patch-clamp technique. No morphological difference was observed between Andersen's syndrome and control myoblasts at each passage of the cell culture. Cellular proliferation and viability were quantified in parallel with direct cell counts and showed no difference between control and Andersen's syndrome patients. Moreover, our data show no significant difference in myoblast fusion index among Andersen's syndrome and control patients. Current recordings carried out on myotubes revealed the absence of an inwardly rectifying Ba2+-sensitive current in affected patient cells. One consequence of the Ik1 current loss in Andersen's syndrome myotubes is a shift of the resting membrane potential toward depolarizing potentials. Our data describe for the first time the functional consequences of Andersen's syndrome mutations ex vivo and provide clues to the K+ channel pathophysiology in skeletal muscle.

Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients.

BACKGROUND: The Fragile X Mental retardation-Related 1 (FXR1) gene belongs to the fragile X related family, that also includes the Fragile X Mental Retardation (FMR1) gene involved in fragile X syndrome, the most common form of inherited mental retardation. While the absence of FMRP impairs cognitive functions, inactivation of FXR1 has been reported to have drastic effects in mouse and xenopus myogenesis. Seven alternatively spliced FXR1 mRNA variants have been identified, three of them being muscle specific. Interestingly, they encode FXR1P isoforms displaying selective RNA binding properties. METHODS AND RESULTS: Since facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy characterised by altered splicing of mRNAs encoding muscle specific proteins, we have studied the splicing pattern of FXR1 mRNA in myoblasts and myotubes of FSHD patients. We show here that FSHD myoblasts display an abnormal pattern of expression of FXR1P isoforms. Moreover, we provide evidence that this altered pattern of expression is due to a specific reduced stability of muscle specific FXR1 mRNA variants, leading to a reduced expression of FXR1P muscle specific isoforms. CONCLUSION: Our data suggest that the molecular basis of FSHD not only involves splicing alterations, as previously proposed, but may also involve a deregulation of mRNA stability. In addition, since FXR1P is an RNA binding protein likely to regulate the metabolism of muscle specific mRNAs during myogenesis, its altered expression in FSHD myoblasts may contribute to the physiopathology of this disease.

[Anti-MAG paraproteinemic demyelinating polyneuropathy: a clinical, biological, electrophysiological and anatomopathological descriptive study of a 13-patients' cohort]. / Les polyneuropathies avec IgM monoclonale anti-MAG : étude descriptive clinique, biologique, électrophysiologique et anatomopathologique d'une cohorte de 13 patients.

INTRODUCTION: Polyneuropathies associated with IgM paraproteinemia and anti-myelin associated glycoprotein (MAG) antibodies (MAG-PN) have to be differentiated from chronic inflammatory demyelinating polyneuropathies. METHODS: In a retrospective study, we have analyzed clinical, electrophysiological, biological and pathological data from MAG-PN patients. RESULTS: Seven male and six female patients were followed in the department for a mean 2 years (0.5-6.5 years). Mean age at diagnosis was 61 years (44.5-85.5 years). Patients had symmetrical bilateral paresthesia (11/13) and hypoesthesia (11/13) prominent in the lower limbs. Nine patients developed gait ataxia and four patients had moderate distal weakness in the lower limbs. Mean Overall Neuropathy Limitation Scale was 2.3 (0-5). Nerve conduction study showed demyelinating features though delayed distal motor latency on median (206 % of normal value) and ulnar nerves (150% of normal value). Seven out of thirteen patients had at least two nerves with terminal latency index below 0.25. IgM paraproteinemia was of undetermined significance in ten cases and three patients had non-Hodgkin lymphoma. IgM deposits and widening of the peripheral myelin were observed in 5/7 sural nerve biopsies. Anti-MAG antibodies were detected in the sera of all patients using enzyme-linked immunosorbent assay and in 8/12 patients using western blot analysis. CONCLUSIONS: MAG-PN have distinctive clinical, electrophysiological and pathological features. It is a chronic, slowly progressive, predominantly sensory and ataxic neuropathy. Disability is usually moderate. Electrophysiological study shows distal demyelinating process and is highly suggestive of MAG-PN in more than one half of our patients. Several techniques may detect anti-MAG antibodies, they have to be associated to improve sensitivity and specificity of the test.

Comparison of high-frequency and ultrahigh-frequency probes in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: High-frequency ultrasound (HFUS 18-20 MHz) performed on patients with chronic inflammatory demyelinating polyneuropathy (CIDP) shows a focal enlargement, particularly in the proximal segments of upper-arm motor nerves. Ultrahigh frequency ultrasound (UHFUS 30-70 MHz), having a higher spatial resolution, enables a better characterization of nerve structures. The aim of this study was to compare the two ultrasound probes in the evaluation of motor nerve characteristics in CIDP patients. METHODS: Eleven patients with definite or probable CIDP underwent an ultrasound evaluation of median and ulnar nerves, bilaterally. Nerve and fascicle cross-sectional area (CSA), vascularization, and echogenicity were assessed. RESULTS: Nerve and fascicle CSA were increased in the proximal segments, especially in the median nerve, in 9/11 patients and in 10/11 patients at the HFUS and UHFUS evaluations, respectively. A statistically significant difference between CSA values obtained with the two probes was found only for fascicle values. UHFUS allowed for a more precise estimation of fascicle size and number than the HFUS. We were able to identify nerve vascularization in 4/11 patients at UHFUS only. CONCLUSION: UHFUS gives more detailed information on the changes in the internal nerve structure in CIDP patients. In particular, it permits to better characterize fascicle size and morphology, and to have a precise estimation of their number. Its frequency range also allows to evaluate nerve vascularization. SIGNIFICANCE: Ultrasound evaluation could become an adjunctive diagnostic tool for CIDP. Further studies are needed to validate the examined parameters as biomarkers for the evaluation and follow-up of CIDP patients.

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.

[McArdle disease (gycogenosis type V): analysis of clinical, biological and genetic features of five French patients]. / Maladie de McArdle (glycogénose de type V) : étude clinique, biochimique et génétique d'une cohorte de cinq patients français.

INTRODUCTION: McArdle disease (glycogenosis type V) is an autosomal recessive metabolic myopathy. Defect in glycogen breakdown is due to mutations of the gene for myophosphorylase (PYGM). Among patients of the department, we searched for correlations between disease phenotype, biochemistry analysis of muscle samples and PYGM genotype. METHODS: We included five patients whose muscle biopsy showed deposits of glycogen and negative histochemical staining for myophosphorylase. RESULTS: All patients exhibited exercise intolerance and high serum CK levels (mean 4400). Two of them had an acute renal insufficiency caused by rhabdomyolysis. One patient developed moderate late-onset muscle weakness of the proximal part of upper limbs. Muscle glycogen concentration was high (three times the normal). Myophosphorylase activity was undetectable in four muscle samples out of five. Two patients were homozygous and two other heterozygous for the R50X mutation of PYGM. The other one had a novel missense mutation S814N. Patients homozygous for R50X mutation had higher CK levels (8080 versus 1457, p=0.046), but disease severity and muscle glycogen concentrations were equivalent. CONCLUSIONS: Our patients had typical clinical and laboratory features of McArdle disease. Diagnosis was suggested by exercise intolerance with high CK levels. The R50X mutation was the most common (60% of the mutated alleles). We found no relationship between clinical severity, PYGM genotype and biochemistry analysis of muscle samples.