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B Eymard

Publications and source records attributed to B Eymard.

At least 19 recordsLinked to original sources
PubMed1997

[Autoimmune myasthenia: recent physiopathological data].

AUTOIMMUNE DISEASE: Myasthenia gravis is a one of the rare autoimmune diseases with a well-defined antigen. Autoantibodies directed against the muscular acetylcholine receptor (AChR) play a key role, blocking the acetylchoroquine binding site and provoking accelerated receptor degradation; complement destroys the post-synaptic membrane. Disease severity is correlated with extent of AChR loss. THYMUS: Involvement of the thymus is suggested by the beneficial effect of thymectomy and by histological and functional anomalies (modified cellular composition, abnormally activated lymphocytes, sensitivization of certain lymphocytes to AChR). "ANTIBODY NEGATIVE" DISEASE: The lack of anti-AChR antibodies detectable at immunoprecipitation, evidences the complexity of myastenia gravis pathogenesis. These "antibody-negative" forms are distinct from seropositive forms which have a high frequency of pure occular involvement and from infantile forms where the thymus regresses. "Antibody-negative" myastenia gravis might be mediated by antibodies directed against other endplate tardets. CLINICAL DIVERSITY: Our understanding of mechanisms responsible for the diversity of the clinical expression highlight the role of the AChR polymophism (with and adult and fetal expression). GENETIC PREDISPOSITION: Several factors involved in disease pathogenesis have been identified, including genetic factors: the HLA system, AChR alpha chain gene polymorphism, and immunoglobulin and T-cell antigen-receptor gene polymorphism.

Humans↗
PubMed1997

Localized proton magnetic resonance spectroscopy in patients with adult adrenoleukodystrophy. Increase of choline compounds in normal appearing white matter.

OBJECTIVES: To describe the changes in the results of magnetic resonance imaging and spectroscopy occurring in the normal-appearing white matter of patients with adult adrenoleukodystrophy and to present evidence of a particular change that may serve as a marker for the follow-up of the disease. DESIGN: Neurologic, magnetic resonance imaging, and localized proton spectroscopic examinations were performed in 11 patients with adult adrenoleukodystrophy and compared with 11 sex- and age-matched controls. PATIENTS: Eleven patients with adult adrenoleukodystrophy participated in a trial of dietary therapy with glyceryl trioleate and glyceryl trierucate (Lorenzo's oil) in the Fédération de Neurologie and the Institut National de la Santé et de la Recherche Médicale, Unité 134, at the Hôpital de la Salpêtrière in Paris, France. RESULTS: The results of magnetic resonance imaging of the white matter were normal in 2 patients and showed areas of mild symmetrical hypersignals on T2-weighted images and fluid attenuated inversion recovery sequences, localized in the posterior white matter in 9 patients. The results of spectroscopy indicated that the peak of the area of choline-containing compounds was increased at long echo times in patients with adult adrenoleukodystrophy, which may reflect very long-chain fatty acid accumulation in this disease. The peak of the area of myo-inositol-containing compounds was increased at short echo times in patients with adult adrenoleukodystrophy, which may indicate a rise in this metabolite concentration. The N-acetylaspartate-creatine amplitude ratio was significantly decreased in patients with motor deficit. The significance of this finding remains to be established. CONCLUSIONS: The results of localized proton magnetic resonance spectroscopy show abnormalities in the cerebral white matter of patients with adult adrenoleukodystrophy, which may contribute to the understanding of the pathophysiologic characteristics of the disease. Although changes in the results of spectroscopy found in this disease are not specific, the increase of choline-containing compounds may reflect the accumulation of very long-chain fatty acids in the central nervous system. Localized proton magnetic resonance spectroscopy may prove a valuable technique, in addition to magnetic resonance imaging, for noninvasive investigation of patients with adult adrenoleukodystrophy undergoing future clinical trials.

Adrenoleukodystrophy↗
PubMed1997

Cranial MRI findings in myotonic dystrophy.

MRI was performed in 13 patients with the adult form of myotonic dystrophy (MD) and compared with that of sex- and age-matched normal controls. There was some cerebral atrophy in the patients and marked thickening of the skull in three of them, associated with ossification of the falx cerebri in two. We found high-signal areas on T2-weighted images in the white matter in 9 (70%) of the patients; five showed high-signal areas in the subcortical white matter of the temporal lobes. These findings were associated with intellectual impairment in only one patient, who had a history of a difficult birth and temporal lobe epilepsy.

Adult↗
PubMed1997

The fetal/adult acetylcholine receptor antibody ratio in mothers with myasthenia gravis as a marker for transfer of the disease to the newborn.

High anti-fetal/anti-adult muscle anti-acetylcholine receptor (AChR) antibody (Ab) titer ratio is predictive of the occurrence of neonatal myasthenia gravis in a first child. The aim of the present study was to determine whether the ratio between the levels of antibodies is an intrinsic property of the mother's sera or varies with physiologic status such as pregnancy. We performed a longitudinal study of the levels of Ab directed against both fetal and adult AChRs and the ratio between them in 11 mothers with myasthenia gravis (MG). Sera were taken during, before, and after pregnancy. Absolute levels of Ab varied considerably during the time of observation as indicated by analyzing the maximum change between any two sample times during the study (adult mean percentage change 45.9 +/- 26.4; fetal 42.51 +/- 22.05). In contrast to this, the anti-fetal/anti-adult muscle AChR Ab titer ratio was much less variable (mean percentage change 16.66 +/- 10.11; p < 0.0033). The levels of the two Ab types yielded a correlation of 0.918, consistent with the stability of the ratio between them. This stability of ratio has practical value in the management of pregnancy and infant care in mothers with MG because the ratio at any time, before or during pregnancy, will predict whether the child will contract neonatal MG. We determined this for the first child, but further studies are necessary to establish if this remains true for subsequent pregnancies.

Antibodies↗
PubMed1997

Primary adhalinopathy (alpha-sarcoglycanopathy): clinical, pathologic, and genetic correlation in 20 patients with autosomal recessive muscular dystrophy.

Primary adhalin (or alpha-sarcoglycan) deficiency due to a defect of the adhalin gene localized on chromosome 17q21 causes an autosomal recessive myopathy. We evaluated 20 patients from 15 families (12 from Europe and three from North Africa) with a primary adhalin deficiency with two objectives: characterization of the clinical phenotype and analysis of the correlation with the level of adhalin expression and the type of gene mutation. Age at onset and severity of the myopathy were heterogeneous: six patients were wheel-chair bound before 15 years of age, whereas five other patients had mild disease with preserved ambulation in adulthood. The clinical pattern was similar in all the patients with symmetric characteristic involvement of trunk and limb muscles, calf hypertrophy, and absence of cardiac dysfunction. Immunofluorescence and immunoblot studies of muscle biopsy specimens showed a large variation in the expression of adhalin. The degree of adhalin deficiency was fairly correlated with the clinical severity. There were 15 different mutations (10 missense, five null). Double null mutations (three patients) were associated with severe myopathy, but in the other cases (null/missense and double missense) there was a large variation in the severity of the disease.

Adolescent↗
PubMed1996

Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function.

Arthrogryposis multiplex congenita (AMC), characterized by multiple joint contractures developing in utero, results from lack of fetal movement. Some cases are genetically determined, but AMC occasionally complicates pregnancy in patients with myasthenia gravis (MG) suggesting involvement of circulating maternal antibodies. We previously demonstrated antibodies that inhibited the function of fetal acetylcholine receptor (AChR) in one healthy woman with an obstetric history of recurrent AMC. Here we study sera from this woman, from one other with a similar history, and from three (one asymptomatic) whose babies had neonatal MG and AMC. All five maternal sera had high titers of antibodies that inhibited alpha-Bungarotoxin (alpha-BuTx) binding to fetal AChR, and their sera markedly inhibited fetal AChR function with little effect on adult AChR function. Moreover, in a further survey, 3 of 20 sera from anti-AChR negative AMC mothers inhibited fetal AChR function significantly at 1:100 dilution. These results demonstrate the role of antibodies to fetal AChR and perhaps other muscle antigens in some cases of AMC. More generally, they suggest that placental transfer of antibodies directed at fetal antigens should be considered as a cause of other recurrent fetal or perinatal disorders.

Adult↗
PubMed1996

Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon.

BACKGROUND: In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. METHODS AND RESULTS: In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39 +/- 0.39 versus 4.00 +/- 0.67, P = .00003) and regional (anterior, 2.39 +/- 0.64 versus 3.87 +/- 0.92, P = .002; septal, 2.60 +/- 0.48 versus 4.00 +/- 0.70, P = .0003; lateral, 2.26 +/- 0.58 versus 4.16 +/- 1.11, P = .0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size (r = -.77, P = .009). CONCLUSIONS: The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Adult↗
PubMed1996

Paramyotonia congenita: genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene.

Sodium channel disorders include hyperkalemic periodic paralysis (hyperPP), paramyotonia congenita (PC) and potassium-aggravated myotonia (PAM). PC is a myotonic syndrome characterized by cold-induced muscle stiffness and weakness. In this paper, we report two families. The first is affected by PC with cold-induced stiffness and no weakness, in addition to hyperPP. This family displays the Arg1448Cys mutation in the sodium channel gene originally described in pure PC families. The fact that families with the same mutation present distinct phenotypes indicates that other factors, genetic or environmental, may modulate the expression of the disease in sodium channel disorders. The second family was unusual because patients presented cold-induced weakness without stiffness. A mutation was found in the sodium channel gene that changed an isoleucine into a threonine at position 693. These two families demonstrate that sodium channel mutations may cause either cold-induced stiffness or weakness.

Adult↗
PubMed1996

[Oculopharyngeal myopathies: value of myotomy of the superior sphincter of the esophagus. Apropos of a case].

Since 3 years, a 74 year-old man suffered of swallowing impairment, weight loss, bilateral ptosis and proximal muscular weakness. Electron microscopy disclosed intranuclear tubular filaments and confirmed the diagnosis of oculopharyngeal muscular dystrophy. Upper oesophageal sphincter myotomy was performed with complete improvement. Four months after surgery, swallowing disorders were not recurrent and weight gain was substantial.

Aged↗
PubMed1996

MR quantification of muscle fatty replacement in McArdle's disease.

McArdle's disease is an energy-dependent disorder of skeletal muscle caused by the inability to break down glycogen. The aim of this study was to quantify fatty replacement in patients with McArdle's disease. Calf and thigh axial spin echo T1-weighted magnetic resonance (MR) images (repetition time 500 ms, echo time 25 ms) were obtained at 0.5 T in nine patients with McArdle's disease (age 51 +/- 16 years, range 26-74) and nine sex- and age-matched healthy subjects (age 52 +/- 16 years, range 29-78) to quantify intramuscular fat. Regions of interest were drawn manually, encompassing the largest cross section of muscle. A fatty replacement index (IF) was determined from histograms of signal in the regions of interest in calf and thigh muscles. In normal subjects, IF = 3.6 +/- 2.8% in calf and 4.9 +/- 2.3% in thigh. In patients, IF = 11 +/- 9.3% in calf and 13.5 +/- 10.4% in thigh, significantly different from IF values in normal subjects (p = .03). IF correlated well with age in patients (p = .03). In older patients, up to 25% of the muscle volume was replaced by fat. Patients with McArdle's disease, usually weakly disabled, exhibit significant muscle fatty replacement on MR images. These findings suggest a progressive muscle loss over time related to the disease process.

Adipose Tissue↗
PubMed1996

Chromosome 15-linked limb-girdle muscular dystrophy: clinical phenotypes in Reunion Island and French metropolitan communities.

Erb's type limb-girdle muscular dystrophy (LGMD) was identified and clinically studied in detail in a small community living in the Reunion Island (RI). It was linked to chromosome 15q and related to mutations in the muscle specific calpain 3 gene. A series of cases were afterwards clinically and genetically identified in the French metropolitan community. The phenotype was identical to the RI type in the great majority of cases, although clinical differences were noticed in a few cases. Six different mutations were identified in the RI families, whereas a series of 39 mutations were detected in the French metropolitan families, all different from those present in the RI patients. Phenotype-genotype correlations were attempted in both communities.

Adolescent↗
PubMed1995

X-linked vacuolated myopathy: complement membrane attack complex on surface membrane of injured muscle fibers.

We describe a probable recessive X-linked myopathy characterized by the presence of vacuolated muscle fibers. Four males and their shared maternal grandfather were affected. Clinical characteristics include juvenile onset, very slow progression, and predominant proximal muscle involvement. The clinical picture and the morphological findings are compared with those previously described in a family. By immunofluorescence, all histologically abnormal muscle fibers, in particular those vacuolated, showed a strong deposition of the complement C5b-9 membrane attack complex over the whole muscle fiber surface. Weak immunostaining for membrane attack complex was also found in endomysial capillaries and perimysial vessel walls. Muscle fibers showed sarcolemmal immunolabeling with anti-major histocompatibility complex I, which was also present on the margins of many vacuoles. All vacuoles were stained by antidystrophin antibody, which colocalized in most of them with antilaminin immunostaining. Taken together, these results suggest that the deposition of membrane attack complex on the damaged cell surface membrane could be important in the pathogenesis of this muscle disorder, and that the membrane-bounded vacuoles could be a consequence of sarcolemmal invagination.

Adult↗
PubMed1995

Chronic progressive external ophthalmoplegia with ragged-red fibers: clinical, morphological and genetic investigations in 43 patients.

The evaluation of the severity of progressive external ophthalmoplegia (PEO) with ragged-red fibers in muscle, at the onset of the disease, when PEO is most often the only presenting symptom, is a difficult problem in neurological practice. In order to address that issue, we have performed a comparative analysis of the clinical, morphological and molecular characteristics of 43 patients affected with that form of ocular myopathy. Quantification of mitochondrial accumulation was performed with an image analysis application on muscle sections stained with succinate dehydrogenase histochemical reaction. The proportion of muscle fibres appearing as cytochrome c oxidase deficient was used as an index of the muscle-energy defect. Muscle mitochondrial DNA deletions were detected, localized and quantitated by Southern blot analysis. Point mutations were screened in five transfer RNA genes in the mtDNA (tRNA(Leucine (UUR)), tRNA(Lysine), tRNA(Glutamine), tRNA(Isoleucine) and tRNA(Formylmethionine)) by a denaturing gradient gel electrophoresis technique. This investigation confirmed the high frequency of mtDNA deletions or point mutations in PEO. At the onset of the disease, no clinical, morphological or molecular features could predict whether PEO would remain isolated or become part of a more severe multisystem disease. However, patients with mtDNA deletions were characterized by more severe ophthalmoplegia of earlier onset. Their muscle alterations were roughly parallel in severity to the proportion of deleted mtDNA molecules in muscle. Patients with a multitissular disease and mtDNA deletions were always sporadic cases and their clinical presentation was, most often, closely related to Kearns Sayre syndrome.

Adolescent↗
PubMed1995

Quantitative analysis by polymerase chain reaction of growth hormone receptor gene expression in human liver and muscle.

A single form of GH receptor (GHR) messenger RNA (mRNA) of 4.5 kilobases, encoding the full-length GHR, has been found in man. To measure the absolute number of mRNA molecules encoding the GHR in human tissues, we developed a quantitative polymerase chain reaction assay. An internal control RNA was constructed by inserting a 50-basepair fragment of the rat PRL receptor complementary DNA into a portion of the human GHR complementary DNA. The internal control RNA and the target mRNA were amplified together with the same set of primers. Twenty-four cycles of amplification were used to satisfy an exponential phase of amplification. It was possible to detect as few as 500 molecules of target mRNA/micrograms total RNA. In 3 liver samples obtained from normal donors at the time of transplant, the amount of GHR mRNA ranged from 0.5 +/- 0.1 to 1.4 +/- 0.4 x 10(6) molecules/micrograms total RNA. These results were confirmed by slot blot analysis of the same samples. The number of receptor transcripts did not appear to be correlated with the receptor-binding capacity found in the 3 liver samples. In 7 muscle biopsies, GH receptor mRNA varied between 4.0 +/- 0.4 and 34.6 +/- 1.4 x 10(4) molecules/micrograms total RNA. This technique allows direct measurement of GHR gene expression in human tissues and represents a valuable tool, particularly for tissues such as muscle, in which the receptor protein cannot be measured using conventional binding assays.

Base Sequence↗
PubMed1995

A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype.

We describe two adult siblings who had had mild GM2 gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM2 gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide. HEXA gene analysis proved that the patients are compound heterozygotes for the previously identified G533-->A mutation and for a new mutation, G1171-->A, at exon 11. This new mutation affects a conserved amino acid and results in a Val-->Met substitution at position 391 of the HEXA gene. Full sequence of the alpha-subunit cDNA of Hex A revealed no other mutation. Assays for Hex A activities in patients suspected of having GM2 gangliosidosis should be performed with the sulfated substrate 4-methylumbelliferyl N-acetylglucosamine 6-sulfate.

Adult↗
PubMed1995

[Role of the thymus in the physiopathology of myasthenia].

In myasthenia gravis (MG), the frequency of histologic abnormalities (hyperplasia in young patients, thymoma in older cases) and clinical improvement after thymectomy indicate involvement of the thymus in the pathophysiology of the disease. MG patient thymuses are characterized by the following features: increased amount of B cells (in hyperplasia) and functional abnormalities, mainly activation of B, T and epithelial cells. Moreover, thymic lymphocytes are sensitized to acetylcholine receptor (AChR): first, AChR specific T and B lines can be grown from MG thymus cultures, second, cultured thymic lymphocytes proliferate in the presence of AChR and produce anti-AChR antibodies. AChR molecules are expressed in thymic myoid cells and AChR-like molecules could be displayed at the surface of other cell types. Thus, autosensitization conditions are combined in MG thymus, and potential mechanisms are discussed. It could be a primary event, autosensitization of lymphocytes to AChR taking place initially in the thymus. Or it could be a secondary process, lymphocytes sensitized to AChR in the periphery could be trapped by myoid cells and restimulated in the thymus. In thymoma, autoimmunization occurs differently: the autoimmune process could be initiated by the tumor epithelial cells which express an AChR-like protein. The possible role of severe architectural disturbance in MG thymus (particularly in thymoma), altering thymic lymphocyte selection and maturation is also discussed.

Female↗
PubMed1994

[Severe cardiomyopathy revealing amylopectinosis. Two cases in adolescents from the same family].

Type IV glycogen storage disease, also termed Andersen's disease or amylopectinosis, is a rare autosomic recessive hereditary disease usually caused by a deficit in glycogen branching enzyme. We report our observation of two siblings with type IV glycogen storage disease who had normal branching enzyme activity. The initial symptom was severe heart failure. A 14-year-old boy, born to consanguinous parents, was seen for severe global heart failure. Growth retardation had been diagnosed since the age of 6 and abnormal fatigability since the age of 12. Muscle and endomyocardium biopsies revealed abnormal glycogen storage with normal branching enzyme activity. The patient's condition improved after symptomatic treatment, but death occurred due to infectious complications after orthoptic heart transplantation. One year later, the proband's 12-year-old sister, with an uneventful personal medical history, was hospitalized for severe left ventricular failure. Muscle and liver biopsies demonstrated the same anomalies, again without branching enzyme deficiency in the liver. Heart failure was controlled with symptomatic care and the patient's current condition remains satisfactory. This observation demonstrates the clinical expression of familial type IV glycogen storage disease in patients with normal branching enzyme activity. Age at onset is quite variable, reported from 5 to 70 years, as is the clinical course before diagnosis.

Adolescent↗