C H Polman

..In patients who are doing poorly clinically, therapy should be switched irrespective of NAb or MxA bioactivity...

..Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed...

..g. partners) may replace self-ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient-proxy agreement on possible changes in disease impact of MS...

..This may be of interest in situations when patients suffer from limitations that interfere with reliable self-assessment, such as cognitive impairment...

..Here we assess the predictive value of clinically defined dissemination in space at first presentation for time to clinically definite MS (CDMS)...

..Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis...

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..The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity...

..The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients...

..The BENEFIT study examined interferon beta (IFNB)-1b treatment in patients with clinically isolated syndrome (CIS) and > or = 2 clinically silent brain MRI lesions...

..g., contrast acuity), at replacing the PASAT by a cognition test that has better measurement characteristics, and at developing methods to better understand the clinical relevance of changes in MSFC scores...

..Existing data from uncontrolled studies are contradictory and do not differentiate between autoimmune dysfunction, which is frequent in patients with multiple sclerosis (MS), and untoward drug effects...

..To investigate the relationship between neutralizing antibodies (NAB) and disease progression, relapses, and MR measures of MS...

..These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use...

..The purpose of this study was to evaluate safety, tolerability, and efficacy on MRI lesions of two different doses of laquinimod compared with placebo in patients with relapsing MS...

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..Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes...

..Clinical determinants of T1 lesions may differ between subgroups of patients with MS and subsequently may have implications for the selection of patients for clinical trials...

..To determine if myxovirus resistance protein A (MxA) mRNA is related to clinical disease activity in multiple sclerosis (MS)...

..g. 15%) and is therefore preferable for the assessment of disease progression. No satisfactory cut-off point for the PASAT could be determined...

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..The aim of this study was to investigate whether adding MRI parameters to a model with only clinical parameters could improve these associations...

..Alpha]B-crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G...

..In the subgroup of patients with high adverse event scores, we found an increase in plasma IL-12p40 (p=0.002). The results suggest pro-inflammatory disease-modifying potential of cannabinoids in MS...

..Until now, these studies are relatively sparse and, therefore, the predictive value of MRI parameters for clinical disability remains largely unknown...

..To evaluate markers of axonal damage in CSF and serum of patients with different subtypes of MS in relation to measures of disease progression on MRI...

..The IFNGR1 and IFNGR2 gene polymorphisms studied do not exert an important influence on MS susceptibility, but allele IFNGR2*Arg64 may be associated with a progressive disease onset...

..The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS...

..However, the exact mechanisms by which T cells and cytokines contribute to disease activity remain to be clarified...

..Disease course in PPMS shows less fluctuation than in relapsing remitting (RR) MS...

..In patients with SP multiple sclerosis, IFNbeta-1b treatment reduces the development of hypointense T(1) lesions, suggesting that reduced axonal damage in lesions may play a part in the beneficial effect that is observed clinically...

..We investigated the influence of these polymorphisms on clinical and MRI parameters. The ER22/23EK polymorphism was associated with a more aggressive MS phenotype, measured both clinically and on MRI...

..Analysis of rs6897932 (the most strongly MS-associated single nucleotide polymorphism (SNP)), showed effects of genotype on the relative expression of membrane-bound to total amount of IL7R mRNA...

..Hypothesizing that symptomatology may partly be determined by lesion location, this retrospective study explored relations between lesion location and disability using voxelwise analyses in standard space...

..The authors studied the relation of brain volume measurements with the MS Functional Composite (MSFC) in an attempt to improve the clinico-radiologic association...

..Multiple sclerosis (MS) is characterized, besides focal lesions, by brain atrophy. The determinants of atrophy rates in individual patients are poorly understood...

..Since MS is characterized by cognitive slowing rather than impaired accuracy, we used the Amsterdam Neuropsychological Tasks (ANT) program, a computerized test proven to be very sensitive to cognitive slowing in MS patients...

..Our results suggest that chemokines may play a more important role in the development of new lesions in MS than in the long-term outcome of those lesions...

..It is unclear whether the same applies to the evolution of lesions on T1-weighted MRI...

..Homocysteine levels may be elevated in patients with multiple sclerosis (MS) but large studies are lacking and the relation with disease progression remains to be determined...

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..Furthermore, we found very good correlation between the extent of abnormalities shown by histopathology and the SI changes on proton-density MRIs, mainly relating to demyelination revealed histopathologically...

..Recovery of lesion MTR is a feasible outcome measure for future multicentre clinical trials measuring the effect of remyelinating agents...

..In these situations proxies may provide valuable information, provided we can be certain that proxies and patients give consistent ratings...

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..The immune system is influenced by different factors including hormones and seasonal fluctuations (vitamin D). This overview will highlight the gender differences in MS, with emphasis on the cytokines and vitamin D...

..In conclusion, cognitive impairment in MS is moderately dependent on amount (and distribution) of structural brain damage, especially in the more physically impaired patients group...

..We conclude that disease-induced MTR changes were small in MS NAWM and NAGM, but did correlate with clinical decline, lesion volume and overall cerebral atrophy...

..The second purpose was to determine the Minimally Important Change (MIC) in absolute gait speed using the MFWC and Expanded Disability Status Scale (EDSS) as external criteria...

..We aimed to investigate the relationship of NAWM changes to the distance to the lesions...

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..While clinical subtypes differ by magnetic resonance imaging (MRI) signature on a group level, a classification of individual MS patients based purely on MRI characteristics has not been presented so far...

..Unclear is how to apply IFN beta bioactivity measurements (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical practice...

..We studied correlations between MTR histogram and clinical parameters in MS subgroups. Contrary to earlier studies we placed special emphasis on the lower MTR range, to explore the effect of partial volume averaging effects with CSF...

..The two factors correlate well with instruments measuring disability and with satisfaction versus emotional distress. Provisional scales based on the factors were constructed...

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..We hypothesized that spatial distribution may be partially driven by genetic predisposition, and we aimed to explore relations among candidate genes and the spatial distribution of white matter brain lesions in MS...

..A correlation was found between the percentage of tumor necrosis factor-alpha-producing CD4(+) T cells at baseline and the change in T2 lesion load during 3-year follow-up (r = 0.79, adjusted r(2) = 0.59, p = 0.001)...

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..Whereas RRMS patients generally performed better than the progressive subtypes, they showed relatively poor verbal fluency. CONCLUSION: MS patients with different disease courses have different cognitive profiles...

..In addition the data were combined with available data from the literature...

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..In conclusion, the data presented indicate that cytokine production and sex differences in cytokine production might differ between disease phases, probably related to underlying disease mechanisms...

..In these situations proxy respondents, such as close relatives or healthcare providers, may provide valuable information. To examine the accuracy and value of healthcare providers and close relatives to assess disease impact of MS...

..In sum, in the early stages of multiple sclerosis the most useful evaluative outcome measures for research are the SF36pf (physical functioning) and the RAPocc (social functioning)...

..Evidence suggests a role of T cell reactivity in autoimmune diseases. Interferon (IFN)-beta blocks in vitro proliferation of human T cells...

..We observed no effects of the polymorphisms on brain and lesion volumes. These data suggest that the polymorphisms under investigation do not affect the risk of developing MS and have no influence on the course of disease...

..We observed similar brain and lesion volumes in carriers and noncarriers of FAS-670*G. These data suggest that FAS-670*G decreases the risk of developing MS, but does not affect the course of disease...

..The results suggest the existence of a partial glucocorticoid resistance, in a subgroup of multiple sclerosis patients, which may have implications for treatment efficacy...

..In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS...

..It is obvious from this study that such a treatment can have a differential effect on measurements of functional impairment, rating of neurologic examination and patient self-report...

..Therefore, we conclude that although MRP8/14 expression is a good histopathological marker for monocyte activation, serum levels of these proteins do not correlate with disease activity in RR MS...

..Moreover, the quantification precision of a metabolite in a single spectrum appears to be a reliable measure for its reproducibility in a longitudinal study...

..On the other hand, it is exciting to witness how increased insight in the pathophysiology of the disease and its symptoms has led to a series of new, innovative treatment modalities...

..Although absent IFNbeta bioactivity is associated with NAb and NAb are associated with reduced drug efficacy, the direct relationship between IFNbeta bioactivity and clinical disease activity is largely unknown...

..This study aimed to characterize DAWM in vivo by using 4 quantitative MR imaging measures and to explore differences between MS disease types...

..037). These findings suggest a role for IRF5 gene variation in the pharmacological and clinical outcome of IFN? therapy that might have relevance as biomarker to predict the response to IFN? in multiple sclerosis...

..Recently, a clinical classification system was described to determine whether symptoms and signs of patients presenting with a first episode suggestive of multiple sclerosis (MS) indicate the presence of monofocal or multifocal disease...

..Underlying pathologic and MRI characteristics of DAWM are largely unknown...

..This study aimed to formulate consensus recommendations for scoring cortical lesions in patients with MS, using DIR images acquired in 6 European centers according to local protocols...

..To determine the value of health-related quality of life (HRQoL) to predict change in disability status in patients with multiple sclerosis (MS)...

..Criteria for PPMS were also revised. Current research is concentrating on the definition of uniform clinical terms, to allow a more standardized diagnosis, and aims to simplify the criteria while improving diagnostic accuracy...

..In an attempt to analyze whether MEP can serve as a valid measure for evaluating neurological dysfunction in multiple sclerosis (MS), we related MEP to clinical and MRI measures...

..He had a vasculopathy. The second woman had dissemination in time and place, but there was a better explanation for the symptoms: neuromyelitis optica...

..Patients in the non-relapse onset group have progressive neurological symptoms that are accompanied by progressive limitations in physical functioning, but not by progressive limitations in the other domains...

..In such cases proxies may provide valuable information. However, before using any questionnaires in a proxy sample, the questionnaire should be evaluated for proxy use...

..We studied which factor contributes most to the development of brain atrophy extent and severity of lesions or damage of whole brain issue (WBT)...

..Multiple sderosis (MS) patients develop varying degrees of cerebral atrophy, which may already begin at disease onset The purpose of this study is to examine the effect of steroid treatment on cerebral volume in MS patients...

..Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps...

..To determine the degree of axonal damage in relationship to signal abnormalities on T2-weighted high-resolution MRI in spinal cord tissue of patients with MS...

..In a run-in versus treatment trial, we show that the neuroprotective agent riluzole seems to reduce the rate of cervical cord atrophy and the development of hypointense T1 brain lesions on magnetic resonance imaging...

..However, it is also not possible to conclude definitely that cannabinoids are ineffective; still, this is no basis for official stimulation of their use...

..The occurrence of MS several months after starting a cannabinoid receptor antagonist suggests that the cannabinoid system might indeed be relevant to disease pathogenesis in MS...

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..The increased levels of GAP-43 in remyelinated or nondemyelinated white matter close to MS lesions may reflect regenerative attempts by damaged axons...

..We report, after 7 years, on the diagnoses made in a cohort of patients with suspected though unconfirmed MS...

..We conclude that MRI-guided sampling of brain tissue increases the yield of active multiple sclerosis lesions, including active demyelinating and (p)reactive lesions...