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Resume Les formes autosomiques recessives de la maladie de Charcot-Marie-Tooth (AR-CMT) sont caracterisees par un debut infantile et un phenotype severe comparativement aux formes dominantes. Les maladies de CMT reliees aux mutations du gene de la periaxine (PRX) sont rares et sont caracterisees par une demyelinisation majeure restreinte aux nerfs peripheriques. A la suite de la decouverte d’une grande frequence d’une mutation particuliere de la periaxine a l’Ile de La Reunion (E1085fsX4 homozygote), nous avons examine tous les patients francais connus comme porteurs de mutation du gene de la periaxine , soit 24 dont 18 issus de l’Ile de La Reunion (6 familles et 10 cas sporadiques). Les six autres patients sont originaires de la Metropole et sont issus de deux familles comportant deux sujets atteints et deux autres cas sporadiques. On denombre 17 femmes et sept hommes. La marche est acquise avec retard, en moyenne a 3,4 ± 1,6 ans. Un patient n’a jamais acquis la marche. L’index CMTNS (Charcot Marie Tooth Neuropathy Score) est en moyenne a 24,5 ± 8,1. Sept patients ont perdu la marche en moyenne vers 24 ± 22 ans. D’autres symptomes sont notes : une scoliose majeure presente au dela de 12 ans, parfois compliquee d’un syndrome respiratoire restrictif, une deformation des pieds, d’un strabisme, d’un glaucome et d’une myopie. Lorsque les vitesses de conduction sont enregistrables, il existe un ralentissement majeur de la vitesse de conduction motrice du nerf median ( periaxine doit etre envisagee chez les patients presentant une neuropathie demyelinisante severe de debut infantile associee a une scoliose. Le pronostic fonctionnel est pejoratif etant donne que 29 % des patients sont en fauteuil roulant et presentent une insuffisance respiratoire restrictive. Ainsi, le conseil genetique est recommande au sein de ces familles consanguines.

Revue Neurologique - In Press.Proof corrected by the author Available online since samedi 25 avril 2015

Resume La myopathie facio-scapulohumerale est une affection autosomique dominante dont le locus a ete identifie dans la region telomerique du chromosome 4 en 4q3S. Elle parait avoir un taux de mutation elevee. Observation Une enfant presente des l'enfance les signes d'une forme severe de myopathie facio-scapulohumerale en l'absence d'antecedents familiaux. Le diagnostic ne sera confirme qu'a l'âge de 23 ans grâce a l'etude moleculaire retrouvant la deletion. Celle-ci est retrouvee avec une faible intensite chez le pere, qui apparait comme porteur d'une mutation sous forme d'une mosaique germinale sans expression clinique. Conclusion Cette observation illustre la possibilite de forme severe de la myopathie facio-scapulohumerale et le caractere dominant de l'affection que la clinique simple ne permet pas de reconnaitre. Elle souligne donc l'importance de l'enquete en biologie moleculaire et les difficultes du conseil genetique.

Setting: Tuberculin testing is an accepted method for screening pregnant women for tuberculosis. The interpretation of tuberculin reactivity in bacillus Calmette-Guerin (BCG)-immunized pregnant women is still in debate. Objective: Four related issues were addressed: (1) The effect of pregnancy on tuberculin reactivity; (2) the effect of age differential on tuberculin reactivity; (3) the effect of repeated immunization with BCG; and (4) the risk of developing tuberculosis during pregnancy or a 3-year post-partum period. Design: We performed tuberculin testing in 840 healthy Chilean women in the 32nd to 34th week of pregnancy; 807 had been immunized with 1 or more doses of BCG. There were 3 age groups: 177 were ≥ 19 years old, 534 were 20–29 years old, and 129 were ≥ 30 years old. All women in the study were followed at least 3 years post-partum. Results: Women ≤ 19 years old and non-pregnant women of similar age studied in the same geographical area had a similar distribution of the size of tuberculin reactions. Over 50% of all BCG-immunized women in each group had tuberculin reactions ≥ 10 mm. A differential effect of different doses of BCG was significant only in 20- to 29-year-old women. None of the women in this study developed tuberculosis during pregnancy or a 3-year post-partum observation period. Conclusions: Healthy, BCG-immunized pregnant women may have positive tuberculin reactions without having an increased risk for tuberculosis. The incidence of tuberculosis and the BCG immunization status need to be considered in the development of policy recommendations for diagnosis and treatment of Mycobacterium tuberculosis infection in pregnant women.

The proportion of tuberculin reactors in a population and the intensity of tuberculin reactions have been shown to increase with increasing exposure to mycobacterial infection, eg, repeated BCG immunization. These observations suggested that tuberculin reactivity would become uniformly high in individuals with a high mycobacterial load who did not have a known cause of anergy. Since tuberculin reactivity has been measured to evaluate the possible genetic regulation of responses to mycobacteria in humans, it is important to study its behavior under conditions of ongoing, maximal exposure to mycobacteria. In the present study, we determined the mean size of tuberculin reactivity in BCG-immunized and unimmunized patients with pulmonary tuberculosis of recent onset, and the stability of tuberculin reactions during and after treatment of pulmonary tuberculosis.Serial tuberculin testing was performed on patients with newly diagnosed active pulmonary tuberculosis diagnosed over a period of 2 years at the National Institute for Respiratory Diseases in Santiago, Chile. The first tuberculin test was performed at the time of diagnosis in 58 patients. Repeated tuberculin testing was performed 2 weeks later in 15 patients with initial reaction sizes15 mm. Four additional tuberculin tests were performed, one each at 3-months intervals in 42 patients regardless of the size of the initial tuberculin reaction.Tuberculin reactions at entry had a unimodal distribution in patients both with and without BCG scars (14.8 +/- 5.0 mm and 16.5 +/- 5.2 mm, respectively). A second tuberculin test in patients with initial reaction sizes15 mm showed a moderate, statistically significant increase in the mean reaction size (PPD1: 10.1 +/- 3.2 mm; PPD2: 11.9 +/- 4.8 mm). Repeated tuberculin testing over 1 year revealed no significant changes in reaction size. The mean reaction sizes were 15.8 +/- 5.0 mm at entry, 15.5 +/- 5.4 mm at 3 months, 17.2 +/- 5.2 mm at 6 months, 17.0 +/- 5.1 mm at 9 months, and 16.7 +/- 54 mm at 12 months. The standard deviation of a random observation within patients was 5.3 mm. The largest variations due to increased reactivity after 6 months of treatment were observed in patients with reaction15 mm at entry compared with hyperergic patients, and in BCG-immunized patients compared to unimmunized patients.In the presence of an ongoing mycobacterial infection, patients without anergizing conditions express a tuberculin reactivity that is relatively constant during and after treatment of pulmonary tuberculosis. The size and stability of the reactions seem to be determined by individual conditions that include the tuberculin reactivity at the time of diagnosis and the BCG immunization status.

Necrotizing autoimmune myopathy (NAM) is a group of severe acquired myopathies, characterized by prominent myofiber necrosis with little or no muscle inflammation. They can be misdiagnosed as muscular dystrophies, preventing initiation of appropriate therapy. Specific auto-antibody anti-Signal recognition protein is observed in 16% of cases. Recently, auto-antibodies against 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) were identified in NAM patients by one group, especially in statin exposed patients. Here we report the first European series of patients. We detected and quantified anti-HMGCR auto-antibodies using addressable laser bead immunoassay that we developed. Patients (n = 38) were 44 ± 19 years old (3 pediatric cases) and sex ratio male: female was 0.22. Statin exposure was recorded in 40% of patients. Patients suffered from myalgia (44%), and had a muscular deficit (92%). Subacute onset (less than 6 months) was noted for most of them (n = 18), nevertheless 10 patients had a slow progressive muscular deficit (10 months to years). Severe proximal weakness was observed (72%) and three patients were bedridden at the diagnosis. All patients had increase CK level (6630 ± 5990 UI/L). CK level correlated with muscular strength (r2 = −0.64, p = 0.005) and to anti-HMGR titer (r2 = −0.5, p = 0.04). None patients presented signs of pulmonary involvement. Mean duration of treatments (steroids, immunosupressant and/or IgIV) was 30.1 ± 36.1 [3–42] months, and to date it was not possible to stop the treatment for any patient. This the first study confirming the observation and the description of anti-HMGCR NAM. The majority of patients we detected was statin-naive, had a severe weakness and need prolonged treatments. Anti-HMGCR auto-antibodies testing may be warranted in dystrophic like patients. Anti-HMGR titer correlates with CK level suggesting their role in physiopathogenesis.

1. Intradermal or subplantar injection of soluble snake venom phospholipase A2 (PLA2) evoked a brisk inflammatory response, with cutaneous vascular permeability increase and paw oedema. 2. These inflammatory processes are mainly the result of arachidonic acid cascade activation and mast cell degranulation. 3. Copper, iron and zinc have an inhibitory effect on vascular permeability increase and paw oedema induced by PLA2. 4. Copper and iron could have not only a direct effect on PLA2 but on enzymes of arachidonic acid cascade. 5. However, zinc have a moderate antiinflammatory activity. This effect could be the result to inhibit PLA2 induced mast cell degranulation.

Eleven patients with IgM anti-MAG monoclonal gammopathy of undetermined significance and neuropathy have been treated with high-dose intravenous immunoglobulins (400 mg/kg/day for five days). Eight patients had a subjective improvement and underwent two more courses. In five cases a clear-cut improvement was noted on ataxia and disability scales. Serum IgM levels and nerve conduction velocities remained unchanged.

Resume Les auteurs rapportent le cas d'un patient de 12 ans, presentant une comitialite a crises partielles complexes, evoluant vers un tableau d'epilepsie avec pointes-ondes continues au cours du sommeil. L'introduction du clobazam est suivie chez ce patient d'une amelioration spectaculaire. Les particularites de cette observation sont discutees, ainsi que le role du Clobazam dans la reversibilite des troubles.

Summary Two cases of predominantly motor polyneuropathy attributable to the inhalation of a glue containing n-hexane with methylethylcetone are reported. Electromyographic study shows neurogenic changes with fibrillation potentials at rest in distal muscles and reduced conduction velocities. These findings can be related to the presence of axonal failure and segmental demyelination. Delayed conduction of the brain stem auditory evoked responses suggests an involvement of the central nervous system.

Demyelinating lesions of MS are infiltrated by activated T-lymphocytes and macrophages with secretion of soluble factors. This results in the synthesis of oligoclonal immunoglobulin (IgG) by plasma cells. The activated T-lymphocytes migrate from the peripheral blood to the CNS. This hyperactive state is linked to a selective loss of the suppressor/inducer T-cell subset. Administration of a soluble factor — interferon γ — enhances the immune response by promoting class II antigen expression on macrophages or astrocytes, resulting in a relapse. However, the reason for T-cell activation in peripheral blood is not known, nor is the antigen. Myelin basic protein (MBP) has been considered to be the target since MBP is able to induce chronic relapsing allergic eccephalomyelitis (CRAE) in an animal model of MS. Yet other myelin antigens have succeeded in inducing CRAE in animal models, and anti-MBP antibodies have been found in healthy individuals. The possibility that the hyperimmune state results from a viral infection has not yet been proven. It is known that in Caucasians, a genetic susceptibility factor is linked to class II MHC. Using MRI it has been found that the presence of new plaques was not regularly correlated with relapses, which indicates that MS is an ongoing pathology process. Most drugs used in MS influence the Immune response but have potential toxicity. Monoclonal antibodies offer the opportunity of specific targeting of T-cells and are promising for the future.

Summary In two cases with recurrent palsies, the results of electrophysiological studies led to nerve biopsy showing typical tomacula. The first case was an inherited neuropathy with liability to pressure palsies. The second case was an apparently sporadic painless recurrent brachial neuropathy. Electrophysiological alterations were diffuse and sensory fibres of the median nerve between index and wrist were the most involved. Conduction blocks were observed without palsy in narrow anatomical passageways where nerve compressions are frequent (ulnar nerve at the elbow, peroneal nerve at the fibula). A compression by a neighbouring anatomical structure could make the prognosis worse and justify nerve decompression. The nerves with slowest conduction have the most important risk of palsy and the patients should be given advice to avoid their compression.