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W Nix

Publications and source records attributed to W Nix.

At least 19 recordsLinked to original sources
PubMed2003

Variation in the classification of polyneuropathies among European physicians.

OBJECTIVE: Considerable debate still exists regarding the classification of polyneuropathies (PNPs) into predominantly demyelinating, predominantly axonal loss, mixed or unclassified. This study was designed to determine the variation among physicians in the classification of PNPs by using the European Standardized Telematic tool to Evaluate Electromyography knowledge-based systems and Methods (ESTEEM) multicenter database. METHODS: Seven physicians from 6 laboratories in Europe sent a total of 156 prospectively collected cases of PNP with electromyography (EMG) data including diagnosis (examination diagnosis) to the database. Each physician interpreted the electrophysiological data from all cases (interpretation diagnosis) and a final diagnosis was given at the consensus meetings of the group (consensus diagnosis). RESULTS: Comparison of each physician's examination diagnosis with his/her interpretation diagnosis, i.e. intra-physician variation, showed a change towards less classified PNPs (P < 0.05). Interpretation diagnoses showed large inter-physician variation in the classification of PNPs. The consensus group was more cautious than individual physicians in classifying PNPs as mixed and axonal. The probability of the consensus diagnosis increased with increasing number of abnormal motor and sensory segments tested. CONCLUSIONS: Recognition of variation in classification of PNP as shown in this study and suggesting standards of good clinical practice developed by a consensus group may increase the quality of EMG practice.

Consensus↗
PubMed2000

Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease.

Thymomas are the only tumors that are proven to generate mature T cells from immature precursors. It is unknown, however, whether intratumorous thymopoiesis has an impact on the peripheral T-cell pool and might thus be related to the high frequency of thymoma-associated myasthenia gravis. This study shows, using fluorescence-activated cell sorting-based analyses and T-cell proliferation assays, that thymopoiesis and T-cell function in thymomas correspond with immunologic alterations in the blood. Specifically, the proportion of circulating CD45RA(+)CD8(+) T cells is significantly increased in patients with thymoma compared with normal controls, in accordance with intratumorous T-cell development that is abnormally skewed toward the CD8(+) phenotype. Moreover, it is primarily the proportion of circulating CD45RA(+)CD8(+) T cells that decreases after thymectomy. The results also demonstrate that T cells reactive toward recombinant autoantigens are distributed equally between thymomas and blood, whereas T-cell responses to foreign antigen (ie, tetanus toxoid) are seen only among circulating T cells and not among thymoma-derived T cells. These functional studies support the hypothesis that thymopoiesis occurring within thymomas alters the peripheral T-cell repertoire. Because many thymomas are enriched with autoantigen-specific T cells, a disturbance of circulating T-cell subset composition by export of intratumorous T cells may contribute to paraneoplastic autoimmune disease arising in patients with thymoma. (Blood. 2000;96:3872-3879)

Adolescent↗
PubMed1999

Association of acetylcholine receptor alpha-subunit gene expression in mixed thymoma with myasthenia gravis.

OBJECTIVE: To investigate the association of MG with the transcription of muscular or neuronal acetylcholine receptor (AChR) subunit genes in thymomas. BACKGROUND: Many steps in the pathogenesis of MG have been elucidated but, with rare exceptions, its etiology is unknown. In patients with MG with thymoma, the tumor probably elicits autoimmunity to AChR, but it is enigmatic why MG develops in some patients but not in others. METHODS: Reverse transcriptase (RT)-PCR, immunohistochemistry, and immunofluorescence studies were carried out to investigate AChR expression in 35 patients with thymoma. Statistical analysis was used to specify significant differences between thymoma subtypes. RESULTS: Considering all thymomas (n = 35), no correlation was found between MG status and AChR gene expression as detected by RT-PCR. However, when histologically defined thymoma subtypes were studied separately, transcription of the muscular AChR P3A- alpha-subunit gene was significantly associated (alpha < 0.01) with the occurrence of MG in mixed thymomas (n = 17), but not in thymomas of the cortical type. For the other muscular AChR subunits (P3A+ alpha isoform, beta, gamma, delta, and epsilon) and the alpha2 and beta4 neuronal AChR subunits, no such correlation was detected. CONCLUSIONS: Expression of the P3A AChR alpha-subunit gene might be important for the pathogenesis of MG in mixed thymomas, suggesting etiologic heterogeneity of paraneoplastic MG among patients with histologically different thymoma subtypes.

Adult↗
PubMed1999

Neurofilament is an autoantigenic determinant in myasthenia gravis.

Intratumorous expression of a 153-kd protein (p153), which contains an acetylcholine receptor-like epitope, is the only tumor marker described to date that significantly associates with thymoma in paraneoplastic myasthenia gravis (MG). Here, we report that p153 is identical to the midsize neurofilament, as verified by immunohistochemistry, immunofluorescence, and western blot analysis. Furthermore, the acetylcholine receptor-like epitope of the midsize neurofilament (NF-M) was identified by peptide epitope mapping. We also show, using T-cell proliferation assays, a significantly increased response of intratumorous T cells to a recombinant midsize neurofilament fragment in thymoma patients with MG compared with MG patients with thymic follicular hyperplasia or thymoma patients without MG. The T cells of thymic follicular hyperplasia and thymoma patients without MG seem to be unresponsive to NF-M. In contrast, we found increased T-cell responses to recombinant acetylcholine receptor fragments in MG patients in general compared with non-MG patients. Increased T-cell responses to NF-M in patients with paraneoplastic MG might be the result of an abnormal positive selection of immature T cells within thymomas, caused by the expression of NF-M in neoplastic thymic epithelial cells. Our results offer further evidence that NF-M expression in thymomas is an autoantigenic determinant in MG.

Epitopes↗
PubMed1999

Variation in diagnostic strategy of the EMG examination--a multicentre study.

OBJECTIVES: In order to improve the universal quality of the EMG examination, knowledge about the variation among physicians is needed. METHODS: The variation among physicians in diagnostic strategy or criteria for diagnosing was analysed from a multicentre database with 940 EMG examinations sampled by seven physicians from six laboratories in Europe. RESULTS: For the whole group of patients as well as for the subgroup of patients with polyneuropathy, variation among physicians in examination techniques, number of examined structures per patient and number of abnormal structures per patient required for a diagnosis was found. Some of the variation may be explained by use of different techniques, which showed differences in sensitivity, while some of the variation may be due to differences in diagnostic strategy and criteria for diagnosing. CONCLUSIONS: The study indicates a need for development and revision of international guidelines for EMG practice although implementation of standards requires caution.

Decision Making↗
PubMed1998

Can medical audit change electromyographic practice?

Considerable variation in EMG practice has been described previously. Since 1992, 7 clinical neurophysiologists from 6 European countries prospectively collected electromyographic (EMG) examinations. The aim of this study was to examine whether several years of mutual influence among physicians using medical audit resulted in a more uniform EMG practice. We studied whether there was a change in the number of examinations per patient and the techniques used from the first 12 to the last 12 EMG examinations on patients with polyneuropathy. For F-wave studies and motor nerve studies, there was a clear change towards a more uniform practice. For sensory nerve conduction studies and muscle studies, there were only minor changes. With regard to examination techniques, there was a reduction in the use of more time-consuming examination techniques (near-nerve sensory studies and quantitative muscle studies). It seems possible to change the EMG practice of individual physicians by international collaboration and medical audit. However, until now most changes have been minor and large differences in European EMG practices persist. The diversity of practices suggests a need for studies on the optimal application of existing examination techniques.

Electromyography↗
PubMed1998

Empowering patients.

Explore the source record for details and available documents.

Community-Institutional Relations↗
PubMed1997

Electromyography in myopathy.

Electromyography (EMG) is the most common procedure for screening patients with myopathies and remains the most important technique for assessing the course of the disease over time. Fibrillation potentials, positive sharp waves, myotonic or complex repetitive discharge, as well as polyphasic potentials are non specific and can occur in both myopathic and neurogenic lesions. The most sensitive and specific parameter for myopathy in conventional EMG is the decreased duration of motor unit potentials (MUP), but this can also be seen in disorders of the terminal motor fibers or the neuromuscular junction. More advanced techniques such as single fiber EMG, macro EMG, scanning EMG and turns/amplitude analysis have opened additional possibilities for analysis of the motor unit and the interference pattern, by which both the sensitivity to early changes and specificity for myopathic alterations is increased. The importance of combining different techniques to improve diagnostic yield and specificity is stressed.

Electromyography↗
PubMed1996

Expression of neurofilaments and of a titin epitope in thymic epithelial tumors. Implications for the pathogenesis of myasthenia gravis.

Autoantibodies against both striated muscle proteins, particularly titin, and the acetylcholine receptor are a hallmark of thymoma-associated myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable in these tumors. This study reports that in thymomas with cortical differentiation many of the neoplastic epithelial cells expressed low and medium molecular weight neurofilaments detected with several antibodies (on selections and blots) and at the RNA level (by reverse transcriptase polymerase chain reaction). Moreover, higher molecular weight forms sharing at least one epitope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, in medullary and mixed thymomas, and especially in the normal thymus, immunoreactivity with anti-neurofilament antibodies was rare. This aberrant overexpression of a titin epitope by epithelial cells with antigen-presenting phenotype in an inappropriate cortical microenvironment suggests that they might autosensitize maturing T cells there and so initiate anti-titin autoimmunity in these patients.

Adolescent↗
PubMed1995

Variation in performance of the EMG examination at six European laboratories.

The quality of the EMG examination might be improved by standardization. However, knowledge about interlaboratory differences in the performance of the EMG examination is a prerequisite for standardization. The aim of this study was to describe differences in EMG techniques used and number of muscles and nerves examined per patient at 6 European EMG laboratories. The EMG results of 595 patients were prospectively sampled. The average number of muscles examined per patient in different disorders varied from laboratory to laboratory, for example from 3.0 to 10.8 muscles in anterior horn cell disorders and from 2.0 to 5.5 muscles in myopathies. The average number of muscles examined by quantitative EMG varied from 0 to 4.3 in anterior horn cell disorders and from 0.0 to 4.5 in myopathies. Also the average number of nerve segments examined per patient varied from laboratory for example from 2.7 to 17.7 for motor segments and from 3.1 to 9.0 for sensory segments in polyneuropathies. The laboratories that used needle electrodes for nerve conduction studies and quantitative analysis of individual motor unit potentials examined a smaller number of muscles and nerves than laboratories using surface electrodes for nerve conduction studies and qualitative EMG studies. The results of this study may have impact on guidelines and examination protocols as well as on quality assurance.

Electromyography↗
PubMed1995

Inter- and intraobserver variation in the interpretation of electromyographic tests.

This study was undertaken with the aim of evaluating inter- and intraobserver variation on the pathophysiological interpretation of individual electromyographic (EMG) tests on muscles and nerve segments. Seven physicians from 6 European EMG laboratories independently interpreted 81 EMG studies comprising 735 muscle tests and 726 tests on nerve segments. Pathophysiological conclusions were inferred from findings of these tests without considering clinical information. For most combinations of findings, both the inter- and intraobserver variations on the interpretation were low, suggesting that common criteria for pathophysiological interpretations were used and that these were used consistently. For some combinations of findings, however, there was disagreement on whether these indicated specific or unspecific pathophysiological changes. In particular disagreement on whether findings indicated demyelination may be of clinical significance. A large part of the intraobserver variation may be explained by a change towards more cautious interpretations during the study for most of the physicians. It is concluded that there is a need to seek for consensus on the pathophysiological interpretation of individual findings and for incentives to ensure consistency in interpretations. The fact that experienced physicians changed their ways to interpret findings during the study suggests that agreement may be improved globally.

Data Interpretation, Statistical↗
PubMed1995

Quality assurance in clinical neurophysiology: the ESTEEM project example.

This paper describes the current status of the utilisation of clinical practice guidelines (protocols) in the ESTEEM project as one form of the clinical quality assurance procedures considered in the project. The performance of electrodiagnostic studies, in terms of which types of conclusions need to be inferred during the examination plan, is briefly described. The main focus of the paper is a description of an European multicentre clinical audit in the field of Clinical Neurophysiology, using a common data-entry protocol for prospective EMG case collection and assessment with the ultimate objective of building up a multicentre reference database of EMG cases.

Computer Communication Networks↗
PubMed1994

Differences in the handling of the EMG examination at seven European laboratories.

This study was undertaken to analyse epidemiological and methodological differences in referral pattern, examination techniques and distribution of diagnoses among different European EMG laboratories. Seven European EMG laboratories filled in questionnaires and sampled 700 cases retrospectively. The use of needle or surface electrodes for nerve studies and the selection of quantitative techniques for muscle studies exhibited considerable variation. The pattern of referral varied with respect to the type of referral source and the neurological expertise of the referring physician. The proportion of patients without any neurophysiological abnormality ranged from 16 to 33%. The 3 most common diagnostic groups were mononeuropathies, polyneuropathies and radiculopathies although a great inter-laboratory variation was found. The proportion of patients with multiple diagnoses varied from 0 to 23% and most of these diagnoses were from a few known combinations. The presence of an inter-laboratory variation suggests that the quality of the EMG examination may be improved by focussing on the use of techniques, strategies and diagnostic criteria.

Electromyography↗
PubMed1992

A striational muscle antigen and myasthenia gravis-associated thymomas share an acetylcholine-receptor epitope.

The coincidence of autoantibodies against the acetylcholine receptor (AChR) and muscle striational antigens (SA) is a characteristic finding in thymoma-associated myasthenia gravis (MG), but their origins are still unresolved. Some common muscle antigens that were shown to be targets of anti-SA autoantibodies in thymoma-associated MG have also been detected in normal or neoplastic thymic epithelial cells, suggesting that the release of (eventually altered) antigens from the thymic tumors could elicit SA autoimmunity. In contrast to this model, we report here that titin, which is a recently reported target of SA autoimmunity, is not expressed in thymomas. In addition, we show that skeletal muscle type-II fibers exhibit a striational immunoreactivity with monoclonal antibody mAb155, which was previously identified to label a very immunogenic cytoplasmic epitope of the AChR and neoplastic epithelial cells of MG-associated thymomas. We conclude from these findings that titin autoimmunity in thymoma-associated MG is either due to a molecular mimicry mechanism involving tumor antigens (other than titin) or is a secondary phenomenon following release of titin from muscle. Based on the common immunoreactivity of the AChR, a striational antigen and thymoma, we suggest as the pathogenetic mechanism of thymoma-associated MGa "circulus vitiosus" in which SA autoimmunity could help maintain the AChR autoimmunity that is primarily elicited by the thymomas.

Adult↗
PubMed1991

The anal sphincter in patients with myotonic muscular dystrophy.

The objective of this prospective study was to determine anal sphincter function and thickness of the anal musculature in patients with myotonic muscular dystrophy. Manometric studies were performed in 16 patients with myotonic dystrophy and in 16 healthy controls. Patients had significantly lower basal and squeeze pressures than control subjects (P less than 0.01). The results of ultrasonographic studies of the anal canal in 7 patients and 7 control subjects suggest that this decrease in muscle strength is partly explained by muscular atrophy. In addition, patients with myotonic dystrophy showed exaggerated rebound contractions following and sphincter relaxation that was induced by rectal distention. The pattern of this response and the results of electromyographic studies in 6 patients with myotonic dystrophy suggest that such abnormalities are explained by a neurogenic defect rather than a myotonic response of the anal musculature. It is concluded that patients with myotonic dystrophy show a multitude of defects in the anal sphincter that are an expression of myopathy, muscular atrophy, and neural abnormalities.

Adult↗