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The trials and errors in MS therapy. 多发性硬化症治疗的试验和错误。
International MS journal Pub Date : 2008-09-01
Christoph Kleinschnitz, Sven G Meuth, Heinz Wiendl
{"title":"The trials and errors in MS therapy.","authors":"Christoph Kleinschnitz,&nbsp;Sven G Meuth,&nbsp;Heinz Wiendl","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The development programme for novel therapies in multiple sclerosis (MS) has an impressive track record which is unique in the field of neurology, and has led to the approval of several drugs during the past decade. However, therapeutic prosperities face numerous trials that either failed to show efficacy or that had to be halted because of other reasons including adverse events. Moreover, certain treatment strategies are controversial, both for reasons of practicability and for their true clinical benefit. There are serious caveats that highly immunoselective approaches such as monoclonal antibodies can only be applied at the expense of an increased risk of acute or long-term adverse effects. This review focuses on the most important clinical trials on yet unlicensed compounds in relapsing-remitting and secondary-progressive MS which failed, were halted or are associated with significant adverse effects since 2002. Furthermore, we discuss the implications these experiences have for our current view of MS pathogenesis as well as future study design. Examples include agents that target leukocyte differentiation molecules, co-stimulatory molecules, adhesion molecules and chemotaxis, as well as novel immunomodulators and anti-infective therapies.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 3","pages":"79-90"},"PeriodicalIF":0.0,"publicationDate":"2008-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27689418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wilhelm Uhthoff: a phenomenon 1853 to 1927. 威廉·乌霍夫:1853年到1927年的一个现象。
International MS journal Pub Date : 2008-09-01
P Stutzer, Jurg Kesselring
{"title":"Wilhelm Uhthoff: a phenomenon 1853 to 1927.","authors":"P Stutzer,&nbsp;Jurg Kesselring","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The name of Wilhelm Uhthoff is associated with several aspects of progress in neurology in the 19th and 20th Century but is best known for his contribution to the pathophysiology of transient visual disturbance. Uhthoff was born on 31 July 1853 in Klein Warin, Germany and died on 21 March 1927 in Breslau, Germany. This ophthalmologist described for the first time that increased body temperature from physical exertion may lead to transient impairment of vision in patients with multiple sclerosis.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 3","pages":"90-3"},"PeriodicalIF":0.0,"publicationDate":"2008-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27689980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
18th meeting of the European Neurological Society, Nice, France, 7 to 11 June 2008. 欧洲神经学会第18次会议，尼斯，法国，2008年6月7日至11日。
International MS journal Pub Date : 2008-09-01
I Milonas
{"title":"18th meeting of the European Neurological Society, Nice, France, 7 to 11 June 2008.","authors":"I Milonas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Over 3200 neurologists attended the 18th Meeting of the European Neurological Society to participate in the exciting and highly scientific programe. There was a 19% rejection of the submitted abstracts which covered all the aspects of neurology. One major symposium, 27 oral presentations and 107 posters on multiple sclerosis (MS) were presented. Additionally, there were three teaching courses and one workshop on MS.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 3","pages":"106-7"},"PeriodicalIF":0.0,"publicationDate":"2008-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27692077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spotlight on anti-CD25: daclizumab in MS. 抗cd25: daclizumab治疗多发性硬化症
International MS journal Pub Date : 2008-09-01
Dr Sven Schippling, Roland Martin
{"title":"Spotlight on anti-CD25: daclizumab in MS.","authors":"Dr Sven Schippling,&nbsp;Roland Martin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Monoclonal antibodies are a promising new class of therapeutic agents that can be employed to target specific molecules of the immune system or any tissue. They are currently being tested in a number of clinical trials in autoimmune diseases such as multiple sclerosis (MS). One of these, the humanized monoclonal anti-CD25 antibody daclizumab (Zenapax), is directed against the interleukin-2 (IL-2) receptor alpha chain (CD25) that is involved in clonal expansion of autoreactive T-cells by binding of its ligand IL- 2. Several years ago daclizumab was approved for the prevention of renal allograft rejection. Following promising observations in uveitis, daclizumab has since been tested in a number of small clinical trials in MS based on the rationale that blocking CD25 would prevent the expansion of autoreactive T-lymphocytes. Safety and efficacy data from the preliminary clinical exploration as well as findings about the mechanism of action of anti-CD25 treatment are reviewed here.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 3","pages":"94-8"},"PeriodicalIF":0.0,"publicationDate":"2008-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27689981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: current status of the assays. 视神经脊髓炎中抗水通道蛋白-4抗体的检测现状。
International MS journal Pub Date : 2008-09-01
P Waters, Angela Vincent
{"title":"Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: current status of the assays.","authors":"P Waters,&nbsp;Angela Vincent","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease that predominantly affects the optic nerve and spinal cord. Since the discovery of a specific serum marker for NMO in 2004, and its subsequent identification as an antibody to aquaporin-4 (AQP-4), various methods have been developed to test for the antibodies in patients sera.</p><p><strong>Objective: </strong>To assess the principal methods used to measure AQP-4 antibodies in patients sera, describe their contribution to neuromyelitis spectrum disease and examine their value in the early detection of disease.</p><p><strong>Methods: </strong>We compared the published data on each assay and used the relapsing NMO cohort as a uniform patient group for direct assay comparison.</p><p><strong>Results: </strong>The indirect immunofluorescence assay, a cellbased assay (CBA) and a fluorescence-based immunoprecipitation assay have broadly similar high sensitivities (86%, 91% and 83%) in the relapsing cohort, but the indirect immunofluorescence has a lower specificity (91%) compared with the other two (both 100% specific).</p><p><strong>Conclusions: </strong>The indirect immunofluorescence assay for NMO-IgG allows the detection of antibodies in routine screening, but the CBA for AQP-4 antibodies is the most sensitive. The fluoroimmunoprecipitation assay is a potentially high-throughput test for identifying positive sera and for serial estimations of antibody levels, but in its present form is slightly less sensitive. Overall, these assays are proving very useful in helping to diagnose those patients with longitudinally extensive transverse myelitis or recurrent optic neuritis who are likely to have relapsing NMO, including patients with myelopathy and Sjogrens syndrome, but it appears to be less often positive in patients with monophasic NMO.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 3","pages":"99-105"},"PeriodicalIF":0.0,"publicationDate":"2008-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27689982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional symptoms in clinically definite MS--pseudo-relapse syndrome. 临床明确的MS-伪复发综合征的功能症状。
International MS journal Pub Date : 2008-06-01
A Merwick, B J Sweeney
{"title":"Functional symptoms in clinically definite MS--pseudo-relapse syndrome.","authors":"A Merwick,&nbsp;B J Sweeney","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although the diagnostic criteria for multiple sclerosis (MS) have become more formalized and sensitive in the era of magnetic resonance imaging (MRI) scanning, the assessment of individual relapses may not always be straightforward or easily linked to a particular lesion seen on imaging. In addition, acute episodes often have to be assessed outside of normal working hours or when the individual patients usual medical team is not available. Often the emergency department physicians have little formal neurological training and are under time pressure to get patients through the system as quickly as possible. It is therefore possible to mislabel functional symptoms as being true relapses. To illustrate scenarios of possible pseudo-relapse, three clinical vignettes are described. Misclassification of functional symptoms as relapse carries a number of inherent risks. Functional symptoms can be multifactorial and may cause a burden of disease. A multidisciplinary approach may be useful in minimizing unnecessary harm and identify if there is more than meets the eye to an episode of clinical deterioration.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 2","pages":"47-51"},"PeriodicalIF":0.0,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27666691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
American Academy of Neurology (AAN) 60th Annual Meeting. 12 to 19 April 2008. 美国神经病学学会(AAN)第60届年会。2008年4月12日至19日。
International MS journal Pub Date : 2008-06-01
E Willoughby
{"title":"American Academy of Neurology (AAN) 60th Annual Meeting. 12 to 19 April 2008.","authors":"E Willoughby","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Annual Meeting of the AAN is the major meeting in the USA covering all aspects of neurology and attracts a large number of international presenters. At the 2008 meeting in Chicago, as has been the case in recent years, multiple sclerosis (MS) was the neurological disorder that attracted the most extensive contributions and interest. Aspects of MS that were most actively addressed were trials of treatment with new agents (oral immune-modulating medications and monoclonal antibodies), further assessment of established immune-modulating agents particularly head-to-head trials, Devics disease (neuromyelitis optica) and its relationship to MS, and MS in children. In addition to about 300 poster and platform presentations on MS topics, MS therapy was reviewed at a 2-hour evening meeting. Space does not allow acknowledgement of most of the individual reports of particular interest and the following is a general overview.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 2","pages":"70-1"},"PeriodicalIF":0.0,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27666695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Recurrent monofocal demyelinating disease. 复发性单灶脱髓鞘病。
International MS journal Pub Date : 2008-06-01
P Jung, M Strittmatter, H Steinmetz
{"title":"Recurrent monofocal demyelinating disease.","authors":"P Jung,&nbsp;M Strittmatter,&nbsp;H Steinmetz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We describe a patient with recurrent brainstem symptoms and migraine-like headache. Magnetic resonance imaging (MRI) showed a symptomatic hyperintense T2-weighted lesion in the middle cerebellar peduncle and the trigeminal nuclei and an asymptomatic periventricular lesion of Dawson finger shape. The findings were suspicious for a first demyelinating event, possibly representing the first manifestation of multiple sclerosis (MS). Nevertheless, this case report also illustrates several pitfalls in the differential diagnosis of MS.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 2","pages":"42-6"},"PeriodicalIF":0.0,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27666690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNA profiling of MS brain tissues. 多发性硬化症脑组织的RNA图谱。
International MS journal Pub Date : 2008-06-01
J Kinter, T Zeis, N Schaeren-Wiemers
{"title":"RNA profiling of MS brain tissues.","authors":"J Kinter,&nbsp;T Zeis,&nbsp;N Schaeren-Wiemers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recently, the introduction of RNA profiling using microarray technology has helped to elucidate gene expression changes in diseased tissue samples from postmortem human brains. Especially, in the field of multiple sclerosis (MS) research, microarray-based RNA profiling has been applied in the hope to identify disease specific alterations. The lack of good biomarkers for diagnostic as well as for prognostic purposes, but also the need for new drug targets and for a better understanding of the pathophysiology, makes this technique a valuable tool. Different RNA profiling approaches have been used, addressing distinct scientific questions. MS brain tissue samples have been proven to be an appropriate source for RNA profiling to investigate molecular pathomechanisms. This work discusses the critical parameters for RNA profiling of MS brain tissues, and reviews the results obtained by microarray studies analyzing differential gene expression in MS brain tissues.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 2","pages":"51-8"},"PeriodicalIF":0.0,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27666692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Jean-Martin Charcot. 1825 to 1893. 让-马丁·夏可1825年至1893年
International MS journal Pub Date : 2008-06-01
M Clanet
{"title":"Jean-Martin Charcot. 1825 to 1893.","authors":"M Clanet","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>During the 31 years of his working life, Jean-Martin Charcot built up an exceptional career in Salpétrière hospital, and was a pioneer in different fields. He developed an organized teaching and research centre, contributed to increase the medical knowledge with a systematic use of physiology and pathology besides a rigorous clinical analysis, he founded geriatry and neurology and finally tried to create a scientific psychological approach for hysteria.</p>","PeriodicalId":86075,"journal":{"name":"International MS journal","volume":"15 2","pages":"59-61"},"PeriodicalIF":0.0,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27666693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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