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1.
Sabine Nick Piero Pileri Stefania Tongiani Yasushi Uematsu Ludwig Kappos Gennaro De Libero 《European journal of immunology》1995,25(2):355-363
To study the relevance of γδ T cells in multiple sclerosis (MS) we analyzed the T cell receptor (TCR) γδ repertoire and the antigen reactivity of γδ clones isolated from cerebrospinal fluid (CSF). In T cell cultures derived from CSF we found an increased percentage of Vδ1+ cells as compared to peripheral blood of the same donors. Phenotypic analysis of cells from MS CSF with Vγ- and Vγ-specific monoclonal antibodies (mAb) showed that the Vγ1 chain is most frequently associated with γ chains belonging to the VγI family. Sequence analysis of TCR genes revealed heterogeneity of junctional regions in both δ and γ genes indicating polyclonal expansion. γδ clones were established and some recognized glioblastoma, astrocytoma or monocytic cell lines. Stimulation with these targets induced serine esterase release and lymphokine expression characteristic of the TH0-like phenotype. Remarkably, these tumor-reactive γδ cells were not detected in the peripheral blood using PCR oligotyping, but were found in other CSF lines independently established from the same MS patient. Altogether, these results demonstrate that in the CSF there is a skewed TCR γδ repertoire and suggest that γδ cells reacting against brain-derived antigens might have been locally expanded. 相似文献
2.
Haselhorst R Kappos L Bilecen D Scheffler K Möri D Radü EW Seelig J 《Journal of magnetic resonance imaging : JMRI》2000,11(5):495-505
Since the pathogenesis of multiple sclerosis (MS) lesions is not yet fully understood, we investigated the potential of dynamic susceptibility contrast (DSC) magnetic resonance (MR) perfusion imaging for a better characterization of lesion pathology. Twenty-five MS patients were examined on a 1.5 T scanner. A single dose of gadolinium (Gd)-DOTA contrast agent was injected, and echoplanar images were acquired every 0.5 seconds for 1 minute. From the signal intensity-versus-time curves, the relative cerebral blood volume (rCBV) was evaluated for regions in plaques and in gray and white matter. The rCBV calculated for acute, Gd-enhancing plaques was corrected for the effects of blood-brain barrier leakage, using a new correction algorithm. Acute plaques had significantly higher blood volumes than normal-appearing white matter (P < = 0.01). Chronic plaques that appeared hypointense on T(1)-weighted images had lower rCBV than T(1)-isointense plaques (P < = 0.03). Our results indicate that the acute phase in MS is accompanied by vasodilation. In later stages of gliosis, the perfusion decreases with increasing axonal injury. Although the DSC technique is less sensitive than conventional MR imaging, the information provided is essentially different from that obtained with any other MR method. 相似文献
3.
The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion load measurement 总被引:1,自引:0,他引:1
Molyneux PD Miller DH Filippi M Yousry T Kappos L Gasperini C Adèr HJ Barkhof F 《Journal of neurology》2000,247(1):34-40
Phase III definitive treatment trials of new multiple sclerosis (MS) therapies now routinely incorporate an annual magnetic
resonance imaging protocol, with change in T2-weighted brain lesion load providing an important outcome measure. To date the
accepted strategy has been to perform a core imaging protocol on all patients in such studies. The aim of this study was to
provide power calculations based on this MRI endpoint. Serial MRI data from 128 patients with either relapsing remitting (RR)
or secondary progressive (SP) MS were used to calculate sample size requirements using a repeated measures analysis of variance
design. We provide sample size calculations based on various follow-up intervals and effect sizes. Sample sizes for the SPMS
cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients
in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation
of MRI lesion load in the RRMS and SPMS groups, respectively. Our results suggest that ongoing phase III treatment trials
are more than adequately powered to detect even subtle treatment effects, and indicate that incorporating measurements from
longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and
powerful tool for assessing effects on the radiological appearance of the disease process.
Received: 11 February 1999/Received in revised form: 28 July 1999/Accepted: 10 October 1999 相似文献
4.
Comi G Kappos L Clanet M Ebers G Fassas A Fazekas F Filippi M Hartung HP Hertenstein B Karussis D Martino G Tyndall A van der Meché FG 《Journal of neurology》2000,247(5):376-382
Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases
such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue
for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple
Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American
countries discussed the guidelines form performing HSCT in MS. This conference was organized in order to : (a) define criteria
for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity;
(c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and
safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement
was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial
for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design
of the clinical trial are summarized in this contribution.
Received: 14 May 1999, Received in revised form: 4 January 2000, Accepted: 19 January 2000 相似文献
5.
Lorscheider Johannes Benkert Pascal Lienert Carmen Hänni Peter Derfuss Tobias Kuhle Jens Kappos Ludwig Yaldizli Özgür 《Journal of neurology》2021,268(3):941-949
Journal of Neurology - Dimethyl fumarate and fingolimod are oral disease modifying treatments (DMTs) that reduce relapse activity and slow disability worsening in relapsing–remitting multiple... 相似文献
6.
Mark S. Freedman Nicola De Stefano Frederik Barkhof Chris H. Polman Giancarlo Comi Bernard M. J. Uitdehaag Florence Casset-Semanaz Brian Hennessy Lorenz Lehr Bettina Stubinski Dominic L. Jack Ludwig Kappos 《Journal of neurology》2014,261(3):490-499
The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS. 相似文献
7.
Paul W. O’Connor Fred D. Lublin Jerry S. Wolinsky Christian Confavreux Giancarlo Comi Mark S. Freedman Tomas P. Olsson Aaron E. Miller Catherine Dive-Pouletty Gaëlle Bégo-Le-Bagousse Ludwig Kappos 《Journal of neurology》2013,260(10):2472-2480
Multiple sclerosis (MS) relapses impose a substantial clinical and economic burden. Teriflunomide is a new oral disease-modifying therapy approved for the treatment of relapsing MS. We evaluated the effects of teriflunomide treatment on relapse-related neurological sequelae and healthcare resource use in a post hoc analysis of the Phase III TEMSO study. Confirmed relapses associated with neurological sequelae [defined by an increase in Expanded Disability Status Scale/Functional System (sequelae-EDSS/FS) ≥30 days post relapse or by the investigator (sequelae-investigator)] were analyzed in the modified intention-to-treat population (n = 1086). Relapses requiring hospitalization or intravenous (IV) corticosteroids, all hospitalizations, emergency medical facility visits (EMFV), and hospitalized nights for relapse were also assessed. Annualized rates were derived using a Poisson model with treatment, baseline EDSS strata, and region as covariates. Risks of sequelae and hospitalization per relapse were calculated as percentages and groups were compared with a χ2 test. Compared with placebo, teriflunomide reduced annualized rates of relapses with sequelae-EDSS/FS [7 mg by 32 % (p = 0.0019); 14 mg by 36 % (p = 0.0011)] and sequelae-investigator [25 % (p = 0.071); 53 % (p < 0.0001)], relapses leading to hospitalization [36 % (p = 0.015); 59 % (p < 0.0001)], and relapses requiring IV corticosteroids [29 % (p = 0.001); 34 % (p = 0.0003)]. Teriflunomide-treated patients spent fewer nights in hospital for relapse (p < 0.01). Teriflunomide 14 mg also decreased annualized rates of all hospitalizations (p = 0.01) and EMFV (p = 0.004). The impact of teriflunomide on relapse-related neurological sequelae and relapses requiring healthcare resources may translate into reduced healthcare costs. 相似文献
8.
Meningoradiculitis associated with giant cell arteritis 总被引:1,自引:0,他引:1
9.
A randomized,double-blind,dose-comparison study of weekly interferon beta-1a in relapsing MS 总被引:5,自引:0,他引:5
Clanet M Radue EW Kappos L Hartung HP Hohlfeld R Sandberg-Wollheim M Kooijmans-Coutinho MF Tsao EC Sandrock AW;European IFNbeta-a 《Neurology》2002,59(10):1507-1517
BACKGROUND: Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known. OBJECTIVE: To determine whether IFNbeta-1a 60 micro g IM once weekly is more effective than IFNbeta-1a 30 micro g IM once weekly in reducing disability progression in relapsing MS. METHODS: In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 micro g (n = 402) or 60 micro g (n = 400) IM once weekly for >/=36 months. The primary endpoint was disability progression, defined as time to a sustained increase of >/=1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression. RESULTS: Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60- micro g dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60- micro g group. The incidences of neutralizing antibodies (titers >/= 20) were 2.3% in the 30- micro g group and 5.8% in the 60- micro g group. CONCLUSION: There was no difference between IFNbeta-1a 30 micro g and 60 micro g IM in clinical or MRI measures. 相似文献
10.
Mader I Roser W Kappos L Hagberg G Seelig J Radue EW Steinbrich W 《AJNR. American journal of neuroradiology》2000,21(7):1220-1227
BACKGROUND AND PURPOSE: The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2 years, we compared the absolute concentrations of these metabolites between patients treated with a placebo or 15 +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or secondary-progressive MS. METHODS: Sixteen patients, recruited from a pharmacological study of DSG, and 11 healthy control subjects were investigated by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected volume initially contained a contrast-enhancing plaque, which was followed up for a period of 2 years. RESULTS: In contrast-enhancing plaques, Cho was significantly elevated and showed a significant reduction after both 3 and 12 months. The initially normal Cr significantly increased between 3 and 12 months, and was negatively correlated with plaque volume on T1-weighted MR images. NAA initially showed normal values, a significant decrease at 1 month, and a slow recovery over 2 years. Myo-inositol did not show a clear tendency. The placebo group did not differ from the treated group, nor did the relapsing-remitting group differ from the secondary-progressive group. CONCLUSION: The contradictory time courses of Cr and NAA show that an absolute quantification in proton MR spectroscopy in MS is necessary to avoid a false interpretation of reduced NAA/Cr ratios. The increase in Cr is probably due to remyelination. The initial dip and later recovery of NAA seem to be related to diminishing edema and remyelination. 相似文献