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Background and purpose: The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. Methods: A steering committee of MS neurologists developed case‐ and practice‐based questions for two sequential surveys distributed to MS neurologists throughout Europe. Results: Respondents generally favoured changing rather than stopping disease‐modifying treatment (DMT) in patients transitioning from relapsing−remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium‐enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice‐based questions and management are summarized. Conclusions: Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence‐based recommendations and/or guidelines. [ABSTRACT FROM AUTHOR]

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Background and purpose Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis ( MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. Methods A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome ( RIS), clinically isolated syndrome ( CIS), relapsing−remitting MS ( RRMS) and RRMS with breakthrough disease. Results Multiple sclerosis neurologists from 11 European countries responded to survey 1 ( n = 233) and survey 2 ( n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Conclusions Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The objective of this study is to comprehensively define the genetic basis of early onset myasthenia gravis (EOMG).Methods: We have carried out a 2-stage genome-wide association study on a total of 649 North European EOMG patients. Cases were matched 1:4 with controls of European ancestry. We performed imputation and conditional analyses across the major histocompatibility complex, as well as in the top regions of association outside the human leukocyte antigen (HLA) region.Results: We observed the strongest association in the HLA class I region at rs7750641 (p = 1.2 × 10(-92) ; odds ratio [OR], 6.25). By imputation and conditional analyses, HLA-B*08 proves to be the major associated allele (p = 2.87 × 10(-113) ; OR, 6.41). In addition to the expected association with PTPN22 (rs2476601; OR, 1.71; p = 8.2 × 10(-10) ), an imputed coding variant (rs2233290) at position 151 (Pro→Ala) in the TNFAIP3-interacting protein 1, TNIP1, confers even stronger risk than PTPN22 (OR, 1.91; p = 3.2 × 10(-10) ).Interpretation: The association at TNIP1 in EOMG implies disease mechanisms involving ubiquitin-dependent dysregulation of NF-κB signaling. The localization of the major HLA signal to the HLA-B*08 allele suggests that CD8(+) T cells may play a key role in disease initiation or pathogenesis. [ABSTRACT FROM AUTHOR]

Background and purpose: The cause of Tourette syndrome (TS) is not precisely known, although several lines of evidence point at an involvement of the immune system in its pathogenesis. Results: Here, we report the results of a pilot study investigating frequently analysed lymphocyte surface markers in 20 adult patients with TS (16 males; 37.3 ± 15.8 years) and 20 matched controls (16 males; 37.5 ± 15.3 years). Statistical analysis revealed significant differences for the investigated lymphocyte surface markers. The difference in CD69+/CD22+-B cells (23.0 ± 10.5% vs. 13.1 ± 6.1%; P = 0.001) and in CD95+/CD4+-T cells (41.5 ± 12.1% vs. 24.6 ± 10.0%; P = 0.0001) was still significant after Bonferroni–Holm correction. Conclusion: Our preliminary data indicate that TS may be associated with an increased peripheral immune activity. [ABSTRACT FROM AUTHOR]

In myasthenia gravis (MG), humoral and cellular immune mechanisms are involved in the autoimmune pathogenesis. In this study, we investigated the role of the CD45 molecule in MG, having recently reported an association in multiple sclerosis. CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells. Our aims were to determine (a) the prevalence of a functional mutation in the CD45 gene (exon 4 77C→G; prevalence analysis), and (b) the distribution of memory (CD45RO+) and naïve (CD45RA+) T cells in the peripheral blood (subset analysis). T cells from 78 patients with generalised MG were stained with monoclonal antibodies against CD45RO, CD45RA, CD4 and CD8 and quantified by four-colour flow cytometry. The control panel for the prevalence analysis (a) consisted of 303 healthy individuals. (b) From those, 67 age- and sex-matched probands were randomly selected as controls for the subset analysis. Patients were stratified according to their MG onset age, thymic pathology and immunosuppressive treatment. Statistical analysis was performed by Fisher's exact test, asymptotic χ 2 test, the two-sided Mann-Whitney test and Spearman's correlation coefficient. As a result, the 77C→G mutation in exon 4 of the CD45 gene was found in 1 of 78 patients versus none of the 303 controls. Thus, no association was detected with this single nucleotide polymorphism in MG patients overall. Surprisingly, however, ratios of CD45RO+ to CD45RA+ T cells were lower among CD8+ T cells from patients with late-onset MG ( P =0.023). Thymoma patients also showed a similar trend among CD4+ and CD8+ T-cells, as expected. These differences were not related to immunosuppressive drug treatment or thymectomy (in the 67 informative patients). Since there is no other evidence for increased thymopoiesis in late-onset MG, we propose an altered subset balance in the circulation. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is caused by autoantibodies against proteins at the neuromuscular junction. This autoimmune process leads to abnormal fatiguability and weakness of striated muscle. Ptosis and diplopia are among the most common manifestations of MG. The term ‘ocular MG’ (OMG) as opposed to ‘generalised MG’ (GMG) is used to define the clinical subtype of MG with isolated eye muscle weakness. Although OMG may appear to cause only moderate disability, it can significantly impair the patient's activities of daily living and progress to generalised myasthenia. Therefore, a clear management plan should be installed early in these patients. Since prospective treatment trials have not been performed, basic management strategies for OMG have to be deduced from retrospective studies, trials in GMG, and generally accepted clinical experience. Cholinesterase inhibitors are used in all types of MG, but are often less helpful in OMG. In the absence of thymoma, thymectomy is usually not considered in OMG, although a few studies have described histological abnormalities in thymuses from patients with OMG. Corticosteroids are of great short term benefit in most patients with OMG but potential adverse effects limit their long term use. Azathioprine is needed to reduce long term corticosteroid adverse effects, but this agent requires about 6 months to be effective. In summary, OMG has a good prognosis in most patients, with corticosteroids and azathioprine being the major treatment options. The challenges for the clinician are to recognise the condition despite the large number of differential diagnoses, to minimise the patient's symptoms using the therapies available and to carefully limit potentially hazardous therapeutic efforts, especially in mild or even uncertain cases. [ABSTRACT FROM AUTHOR]