Les myopathies distales (MD) constituent un groupe de myopathies génétiques rares et hétérogènes caractérisées par une faiblesse progressive de début distal et dont les explorations suggèrent un processus myopathique. La dystrophie myotonique de Steinert et la dystrophie musculaire facio-scapulo-humérale sont exclues de ce groupe. La classification des MD a considérablement évolué dans les dix dernières années avec l'identification de 17 gènes. Déterminer la proportion des différents sous types de MD dans une étude rétrospective de patients français suivis pour une myopathie distale. Une étude rétrospective a été menée sur 30 patients issus de 24 familles présentant un diagnostic de MD et suivis dans le centre de référence des maladies neuromusculaires et de la SLA de Marseille entre 1989 et 2010. Le diagnostic moléculaire a été obtenu chez 20 patients issus de 15 familles. Les dysferlinopathies étaient le sous type le plus fréquent (n = 5). Les autres diagnostics étaient : myopathie myofibrillaire (n = 3), myopathie héréditaire avec vacuoles bordées de type Nonaka avec mutations du gène GNE (n = 3), myopathie congénitale avec mutation des gènes de la tropomyosine (n = 1) et de la nébuline (n = 1), myopathie distale de début tardif en rapport avec une mutation du gène du récepteur de la ryanodine (RYR1) et myopathie à inclusions héréditaire distale associée à une démence et une maladie de Paget. Un diagnostic moléculaire a pu être obtenu chez 67% des sujets présentant une MD. Des algorithmes basés sur l'âge de début, la sélectivité de l'atteinte au scanner musculaire et les anomalies histologiques ont permis d'orienter avec une bonne sensibilité le diagnostic génétique de ces pathologies.

Four patients with typical signs of congenital muscular dystrophy (C.M.D.), as described in the literature, are reported. In two young sisters born from consanguineous parents the presenting signs were severe congenital hypotonia in one and hypotonia with arthrogryposis in the other. The two other cases were adult patients with a long standing disease, the onset haring been marked by a transient neonatal hypotonia in one and by a congenital torticollis in the other. All 4 patients had progressively increasing muscle retractions, with absent reflexes in three. C.P.K. was moderately increased in all patients. Electromyography demonstrated myopathic abnormalities in 3 cases, associated in 2 cases with misleading pseudo-neurogenic signs. MUscle biopsy showed non specific changes compatible with muscular dystrophy: fibrosis and/or fat involution was marked in all cases, while necrosis of fibers was rarely observed. Histoenzymology and morphometry confirmed the absence of lesion specificity and their results were variable from case to case. A review of 92 published cases demonstrated that the course of the disease is very variable. A fatal outcome occurs in 15% of cases, while the affection becomes worse or remains stable with about the same frequency. A progressive worsening of muscle retractions is a characteristic finding in C.M.D. Genetically, most cases are of recessive autosomic. The current nosology of C.M.D. is probably inadequate, the clinical picture including cases that are likely to be due to different mechanisms that 2 present methods of investigation cannot demonstrate.

BACKGROUND:Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLA2, the gene encoding a β subunit of succinate-CoA ligase, have been reported in 17 patients until now. Mutations in SUCLG1, encoding the α subunit of the enzyme, have been described in two pedigrees only.METHODS AND FINDINGS:In this study, two unrelated patients harbouring three novel pathogenic mutations in SUCLG1 were reported. The first patient had a severe disease at birth. He was compound heterozygous for a missense mutation (p.Pro170Arg) and a c.97+3G>C mutation, which leads to the complete skipping of exon 1 in a minigene expression system. The involvement of SUCLG1 was confirmed by western blot analysis, which showed absence of SUCLG1 protein in fibroblasts. The second patient has a milder phenotype, similar to that of patients with SUCLA2 mutations, and is still alive at 12 years of age. Western blot analysis showed some residual SUCLG1 protein in patient's fibroblasts.CONCLUSIONS:Our results suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are responsible for a very severe disorder with antenatal manifestations, whereas a SUCLA2-like phenotype is found in patients with residual SUCLG1 protein. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.

Le neuropatie ereditarie sensibili alla pressione sono definite da diversi caratteri: ereditarietà autosomica dominante, delezione del gene PMP22, episodi regressivi di paralisi tronculari indolori, occasionalmente, paralisi del plesso brachiale, denervazione all’elettromiografia con riduzione delle velocità di conduzione nervosa nei restringimenti anatomici e zone di ipermielinizzazione focale alla biopsia nervosa.

Introduction. - Pompe's disease, also called glycogen storage disease type 11 or acid maltase deficiency, is an autosomal recessive disease caused by an enzymatic deficiency of acid-alpha-glucosidase (GAA). This deficiency causes an accumulation of intralysosomal glycogen in different organs. The classic form appears in the newborn with a very severe hypotonia and cardiomyopathy, which lead to death before age two. Less frequently, the disease appears only in childhood or in adult life, so called late-onset Pompe's disease. This form causes a very progressive limb-girdle myopathy and restrictive respiratory failure. The diagnosis is based on a low level of GAA either in the muscle biopsy or in the leucocytes. We report six cases of late-onset Pompe's disease from the Languedoc-Roussillon district.Method. - Our work was a retrospective analysis of all cases of Pompe disease diagnosed in adults between 1975 and 2006 at the Montpellier and Nimes Universitary Hospital. We describe the clinical presentation and course of this form and explain the diagnostic approach. Results. The mean age at onset was 44.3 years (range: 36-60 years). The first symptom was fatigability (50%), gait difficulty (50%) and dyspnea (16%). The mean delay from symptom onset to diagnosis was 8.4 years (range: 17 years). Fatal outcome due to respiratory failure was noted in three patients. The mean time between symptom onset and death (four patients) was 20.75 years (range: 37 years). The diagnosis was made on the muscle biopsy showing a low level of GAA. Muscle was strictly normal on the morphologic study in one patient, pointing out the requirement for enzymatic analysis. Molecular confirmation was available in one patient.Discussion. - Late-onset Pompe's disease is a possible cause of limb-girdle myopathy. Respiratory involvement is a characteristic feature. Enzymatic assay of GAA activity on the muscle biopsy is required for certain diagnosis.Conclusion. - it is very important to recognize the adult form of Pompe's disease, a possible cause of limb-girdle myopathy, in order to search for respiratory failure and propose non-invasive ventilation if necessary. Moreover, substitutive therapy (recombinant acid-alpha-glucosidase) has shown efficiency for the classical infantile form of Pompe's disease and such treatment could be proposed for the adult form if larger studies confirm its efficacy. (C) 2008 Elsevier Masson SAS. Tous droits reserves.

Le miopatie infiammatorie (MI) sono un gruppo eterogeneo di entità che hanno in comune un’infiammazione muscolare. Si distinguono tre gruppi. Il primo gruppo è costituito dalle MI primitive, che comprendono le dermatomiositi caratterizzate da segni cutanei, muscolari e viscerali e da un’immunità umorale, così come le polimiositi senza lesione cutanea, ma smembrate in diverse varietà, legate a un’immunità cellulare e spesso associate a malattie autoimmuni. I trattamenti della disimmunità hanno trasformato la loro prognosi. Vi si distinguono due varietà originali, che sono la miosite da macrofagi e le miositi ossificanti. Il secondo gruppo comprende alcune miopatie primitive che si accompagnano a lesioni infiammatorie, ma di significato differente. La miosite da inclusioni deve essere separata dalle dermatopolimiositi. Infine, il terzo gruppo comprende molte miopatie infiammatorie secondarie virali, parassitarie o di forma banale. Dopo la loro individuazione, le varietà di miopatie infiammatorie primitive non sono state oggetto di una classificazione definitiva. Ciò si deve in parte al fatto che i pazienti sono presi in carico da specialisti di discipline molto differenti (neurologi, reumatologi e internisti, specialmente). Così, i neurologi e gli anatomopatologi privilegiano i dati morfologici muscolari, mentre i reumatologi prendono in considerazione in maniera elettiva gli anticorpi sierici. Ciò modifica in particolare il concetto di miositi da sovrapposizione.

Context. - Progressive supranuclear palsy (PSP) is classically characterized by supranuclear ophthalmoplegia, paroxysmal imbalance with backward falling, axial dystonia, rigidity, pseudobulbar palsy and cognitive dysfunction. However, incomplete or atypical clinical presentation has been previously reported, but in all these cases, the patients had at least one of the main clinical features of the disease (ophthalmoplegia, parkinsonian syndrome or cognitive dysfunction).Case report. - A 60-year-old woman presented with nocturnal agitation and choreiform movements. A few months later she developed severe swallowing disorders, caused by achalasia of the upper esophageal sphincter, and responsible for recurrent acute respiratory distress and pneumonia, prevailing to tracheotomy and gastrostomy. She died suddenly two years after the onset of the symptoms.Results. - Postmortem examination of brain revealed a tauopathy, with deposition of abnormal phosphorylated tau in threads and in coiled-shaped as well as globose tangles in the brainstem, subthalamic nuclei and hippocampus. Nuclei of the medulla, including the vagus/solitarius complex and the region of the nucleus ambiguous were especially rich in tau positive inclusions. Ultrastructural analysis of globoid-shaped tangles in the brainstem revealed the presence of straight and paired helicoidal filaments compatible with a PSP.Conclusions. - This case contributes to improve knowledge of the clinical phenotypic range of PSP. in this case, the neuropathological lesions accounted for most of the symptoms. However, the early death of the patient was probably related to the particular distribution of the neuropathological lesions. This case suggests that the initial neuropathological changes in PSP is located in the dorsal brainstem. (C) 2008 Elsevier Masson SAS. Tous droits reserves.

Introduction. The most frequent acute and sub-acute complications of chronic alcoholism are delirium tremens, hepatic encephalopathy and Gayet-Wernicke encephalopathy. Morel laminar sclerosis is a rare and less known complication, often reported with Marchiafava-Bignami disease. Case report. A 57-year-old alcoholic man presented delirium after surgery. Anterograde and retrograde amnesia as well as wrong recognitions appeared progressively and one generalized seizure occurred. He then developed mutism and became bedridden. Magnetic resonance imaging (MRI) showed high-intensity bilateral ternporoparietal signals from white matter on T2-weighted images and high-intensity signals from the parietal cortex on T1-weighted images. The patient died four months after the onset of the delirium. Postmortem examination of the brain showed cortical laminar necrosis with Alzheimer Type II gliosis but without demyelinisation of the corpus callosum. Conclusion. Cortical laminar necrosis with chronic ethylism is usually called Morel's laminar sclerosis. Nevertheless, histology is not typical of this diagnosis, because of necrosis especially of the second (and not the third) layer of the cortex, and because of the absence of lesion of the corpus callosum. MRI data are of interest here because they were rarely reported in cases of Morel's laminar sclerosis.

La myosite à inclusions est une myopathie inflammatoire d'étiologie inconnue. Elle est associée à des pathologies diverses mais rarement à un antécédent de polyomyélite aiguë. N. dossier : HO2005886. Un homme de soixante-sept ans aux antécédents de polyomyélite à sept ans et conservant une monoparésie séquellaire modérée du membre inférieur droit consulta en 2000 pour une aggravation des troubles de la marche avec faiblesse du membre inférieur gauche. Le diagnostic porté alors fut celui de syndrome post polyomyélite. Il consulta deux ans plus tard devant l'apparition d'une faiblesse pour la flexion des doigts touchant les 2 mains et prédominant à gauche. L'examen neurologique montra un déficit asymétrique des fléchisseurs des doigts (4/5 à droite contre 3/5 à gauche) et une atteinte sévère du quadriceps gauche à 2/5. Le reste du testing musculaire était normal en dehors d'un léger déficit ancien des releveurs du pied droit. L'électromyogramme mit en évidence des tracés myogènes dans les deux quadriceps et les jambiers antérieurs. À l'IRM musculaire en séquence T1 il existait un hypersignal et une atrophie marqués des quadriceps avec respect relatif du droit antérieur, ainsi que des fléchisseurs profonds des doigts. Devant cette topographie élective évoquant une myosite à inclusions, une biopsie musculaire fut réalisée et confirma le diagnostic. Des anomalies histologiques typiques de myosite à inclusions ont été décrites chez des patients avec des atteintes neurogènes chroniques. Une des hypothèses propose qu'elles soient l'expression finale commune sur le muscle de diverses atteintes chroniques du SNP. Dans notre cas, il existe non seulement des anomalies histologiques, mais aussi un tableau clinique classique. L'association d'une myosite à inclusions à des antécédents de polyomyélite pourrait ne pas être fortuite. L'étude sémiologique précise permettrait de ne pas négliger d'autres hypothèses que le syndrome post polyomyélite.

Among neuroeosinophilic syndromes, neuromuscular disorders are considered as a special group, including perimyosistis, polymyositis and fasciitis. These three disorders are considered as a continuum. They usually without a recognized cause, and are considered to be spontaneous or exercise-induced. We report the case of a 43 year-old woman who experienced angioedema followed by an histologically proven-fasciitis with eosinophilia after Ramipril (Triatec) use. Causal attribution to Ramipril was considered "plausible". To our knowledge this side effect has never been reported with this drug.

Ces dix dernières années, la consommation des immunoglobulines polyvalentes (IgIV) n'a cessé d'augmenter en France et dans le monde. Les indications neurologiques actuelles des IgIV, se fondant sur les études contrôlées ou ouvertes, sont présentées dans cette revue ainsi que les effets indésirables, le risque viral et le coût de ces IgIV.Contrairement aux autres thérapeutiques immunomodulatrices, les IgIV sont bien tolérées et d'administration aisée. Les études passées et récentes apportent des preuves indéniables quant à l'efficacité des IgIV dans le syndrome de Guillain-Barré, dans les polyradiculonévrites chroniques ou les neuropathies motrices avec blocs de conduction. Dans la myasthénie auto-immune, il existe des preuves tangibles d'efficacité des IgIV au cours des poussées, mais des études complémentaires comparant les IgIV aux autres traitements immunomodulateurs tels que les plasmaphérèses ou les corticoïdes sont attendus. Les IgIV sont réservées en deuxième ou troisième intention de traitement chez les patients présentant une corticorésistance au cours des dermatopolymyosites. Dans les autres indications neurologiques, telles que les neuropathies paranéoplasiques, les myosites à inclusions, la sclérose en plaques, il n'existe pas de preuve d'une efficacité à court et à long terme des IgIV.De nouvelles études contrôlées évaluant les doses minimales efficaces d'IgIV dans les indications neurologiques reconnues, la qualité de vie et leur efficacité à long terme sont nécessaires.La prescription des IgIV en pratique courante devrait se limiter aux affections neurologiques pour lesquelles des études contrôlées et positives ont pu être menées. Pour les autres affections neurologiques dysimmunitaires, les IgIV ne devraient être réservées qu'après échec des thérapeutiques conventionnelles.In the past decade, intravenous immunoglobulins (IVIG) have been widely used and their administration has grown throughout the world. The current indications of IVIG in neurological diseases are discussed on the basis of the passed and current trials. Unlike other immuomodulatory agents, IVIG are well tolerated and have very few side effects and a good viral safety.There is clinical evidence, based on controlled trials, for the effectiveness of IVIG in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal neuropathy with conduction blocks. In myasthenia gravis, the IVIG are effective especially in myasthenic crisis, but their synergistic effect with other treatments, the steroid sparing effect, and their long-term effect are unknown. These issues need to be addressed in further controlled clinical trials. In dermatoploymyositis, IVIG are reserved for steroid resistant patients. There is actually no support or no significant clinical benefit for the routine use of IVIG in other neurological diseases.Further controlled trials are warranted to assess the quality of life, the dose-finding effect and their long-term efficacy in order to improve clinical practices.Routine use of IVIG should be reserved for diseases in which positive controlled trials are available. For the remaining dysimmune diseases, IVIG should be assess in comparison with the other available therapies, taking into consideration the age of the patients, the safety of the IVIG and, in our country, the economic aspect.