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Chris Polman

Publications and source records attributed to Chris Polman.

12 recordsLinked to original sources
PubMed2007

Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis.

BACKGROUND: Histopathologic studies have shown that subpial cortical demyelination is extensive in chronic multiple sclerosis (MS). OBJECTIVE: To study whether subpial cortical demyelination in MS is associated with focal or diffuse white matter (WM) pathologic features on magnetic resonance imaging (MR imaging). DESIGN: Comparison of postmortem MR imaging findings with histopathologic findings. SETTING: Brain donations from a general community. PATIENTS: Three patients with MS with extensive cortical demyelination and 3 patients with minor cortical demyelination were selected from an MS autopsy data set. The postmortem MR imaging and histopathologic data of the patients were compared. MAIN OUTCOME MEASURES: Two observers blinded to the results of each other assessed the presence, extent, and distribution of focal and diffuse pathologic changes in WM by MR imaging and by histopathology. RESULTS: Extensive subpial demyelination was not associated with a significant increase in the area of focal and diffuse WM pathologic changes as assessed by Luxol fast blue histochemistry or by MR imaging or with the presence or extent of juxtacortical abnormalities on MR imaging. CONCLUSIONS: The lack of association of MS gray matter demyelination with diffuse or focal WM changes indicates that gray matter demyelination in MS occurs largely independent of WM pathologic changes. The extent or distribution of WM abnormalities cannot be used to identify extensive cortical demyelination in the clinical setting.

Aged↗
PubMed2006

MRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study.

BACKGROUND: The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. METHODS: In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment--ie, at least three out of four--of the Barkhof/Tintoré criteria. We used survival analysis and 2x2 tables to assess the test characteristics of the criteria at baseline. FINDINGS: Overall conversion rate was 32.5% with a median survival time of 85.3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37-53) versus about 10% (6-16) in those with no asymptomatic lesions at baseline (p<0.0001). For patients with a follow-up of at least 2 years, the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for predicting conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the criteria (odds ratio 3.7, 95% CI 2.3-5.9; p<0.0001). Cox proportional hazards regression analysis accorded with this increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or centre. Age at baseline did have a small but significant effect as predictor (hazard ratio 0.97, 0.95-0.99; p=0.002), but did not affect the prognostic value of the MRI criteria. INTERPRETATION: MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.

Adolescent↗
PubMed2006

MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation".

Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.

Brain Diseases↗
PubMed2005

The distribution of magnetic resonance imaging response to interferonbeta-1b in multiple sclerosis.

Whereas the effect of interferons (IFNs) on magnetic resonance imaging (MRI) outcome measures in patients with multiple sclerosis (MS) has been convincingly shown, little work has been done to define the between-patient heterogeneity of treatment response. Our aim was to assess the distribution of the effect of IFNbeta-1b in terms of reduction of active T2 lesions in patients with MS. Using a fixed and a random effects model, we investigated the distribution of active T2 lesions reduction over a three-year follow up in response to treatment with 250 mcg IFNbeta-1b every other day in 695 patients with a complete MRI data-set of the 718 (97 %) enrolled in the European, multicenter, randomised, double-blind, placebo-controlled trial of secondary progressive MS. The two statistical models consistently showed that the between-patient response to IFNbeta-1b, in terms of reduction of active T2 lesions, is highly heterogeneous. Whereas treated patients have a high probability (more than 65%) of showing an active T2 lesion reduction equal to or greater than 60%, there is also a 7% probability for treated patients not to show any reduction of MRI-detected disease activity during the course of the trial or even to have an increase of T2 active lesions. This study might be regarded as a first step toward the definition of markers potentially useful to identify IFNbeta treatment responders and non-responders with regard to T2 lesion activity.

Case-Control Studies↗
PubMed2005

Pain in Parkinson's disease and multiple sclerosis: its relation to the medial and lateral pain systems.

Although pain is one of the major clinical symptoms of Parkinson's disease (PD) and multiple sclerosis (MS), it is often neglected and therefore undertreated. The question why the perception of pain in stages without cognitive impairment is not affected by the neuropathology has not been addressed so far. Furthermore, changes in the experience of pain as a result of cognitive impairment have not been clinically studied in PD and MS. These issues which are very relevant for pain assessment and treatment, will be addressed by discussing the neuropathology in the medial and lateral pain systems in cognitively intact versus cognitively impaired patients with PD and MS. Since there are no clinical studies that specifically address pain in cognitively impaired PD and MS patients, hypotheses will be generated about the impact of cognitive impairment on pain experience in these patients. These hypotheses should be a challenge for new research in this important but neglected area.

Brain↗
PubMed2005

Biological markers in CSF and blood for axonal degeneration in multiple sclerosis.

Biomarkers in body fluids could help to predict and monitor neurological decline in people with multiple sclerosis (MS). We discuss markers for axonal damage in body fluids in people with MS. The most promising axonal marker for discriminating patients with MS from those with other neurological diseases is the neurofilament light chain in CSF. Antibodies against the heavy-chain isoform are associated with disease progression. Other studies have shown altered CSF concentrations of tau proteins, actin, tubulin, and 14-3-3 protein. Interestingly, the concentration of 24S-hydroxycholesterol was decreased in serum of patients with MS. No clear changes have been shown for the markers apolipoprotein E and neurospecific enolase. We describe three types of markers for axonal damage: markers that reflect processes in the CNS, those that reflect extraneural processes, and those that reflect whole-body changes. These concepts may be helpful for biomarker research in various neurodegenerative diseases.

14-3-3 Proteins↗
PubMed2004

The spinal cord in multiple sclerosis: relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results.

PURPOSE: To correlate quantitative magnetic resonance (MR) imaging data (ie, relaxation times and magnetization transfer ratios [MTRs]) with histopathologic findings of demyelination and axonal disease in cervical spinal cord specimens from patients with multiple sclerosis (MS) and control subjects. MATERIALS AND METHODS: Formaldehyde-fixed cervical spinal cord specimens from 11 patients with MS-three men and eight women (mean age at death, 66 years +/- 11.3 [standard deviation])-and two female control subjects without neurologic disease (83 and 41 years of age at death) were examined at 4.7 T. Relaxation time measurements and MTR mapping were performed. Analyses included the whole cord area and region-of-interest measurements. Histopathologic analyses included semiquantitative myelin and quantitative axonal analysis. RESULTS: Compared with control specimens (P < .001, analysis of variance), specimens from patients with MS had smaller cord areas (mean area, 59.0 mm(2) +/- 12.5 vs 72.7 mm(2) +/- 10.0), significant prolongation of T1 (mean prolongation, 30%) and T2 (mean prolongation, 13%), and decreased MTRs (mean, 10.5%). Within MS specimens, 58% of the white matter area displayed signal intensity abnormalities on intermediate-weighted MR images. The number of axons in normal-appearing white matter in MS specimens was, on average, 46% lower than the number of axons in white matter in control specimens. All quantitative MR parameters correlated well with demyelination; the correlation with T2 relaxation time was the strongest (r = 0.77, Spearman and Kendall nonparametric correlations). By contrast, quantitative MR parameters correlated less well with axonal density; the correlation with T2 relaxation time was the strongest (r = -0.44, Spearman and Kendall nonparametric correlations). Multilevel analysis, corrected for age and MS phenotype, could not result in a model explaining axonal density on the basis of quantitative MR parameters when myelin density was included as a predictor. CONCLUSION: Changes in quantitative MR imaging parameters in the cervical spinal cord in MS are mainly determined by demyelination and do not reflect axonal disease well.

Adult↗
PubMed2003

1H-NMR spectroscopy combined with pattern recognition analysis reveals characteristic chemical patterns in urines of MS patients and non-human primates with MS-like disease.

Proton nuclear magnetic resonance (1H-NMR) spectroscopy in combination with pattern recognition techniques were used to investigate the composition of organic compounds in urines from patients with multiple sclerosis (MS), patients with other neurological diseases (OND) and healthy controls (H). Using a valid animal model of MS, namely the common marmoset (Callithrix jacchus) model of experimental autoimmune encephalomyelitis (EAE), the relation of disease progression and alteration of the urine composition was investigated. Urine samples were collected during different stages of EAE, either induced with whole human myelin or with the myelin protein MOG in complete adjuvant. The urine samples were analysed with 1H-NMR spectroscopy allowing simultaneous detection of an array of compounds. Spectral differences between urines from EAE-affected and healthy monkeys were assessed with multivariate analysis. Evidence is provided that development of EAE is associated with changes in the chemical composition of the urine, in particular of compounds with NMR peaks in the region of the spectrum between 0.5 and 3.50 ppm. In addition, we found preliminary evidence for differences between urines from MS, OND and H groups.

Animals↗
PubMed2003

Interferons in relapsing remitting multiple sclerosis: a systematic review.

BACKGROUND: Recombinant interferons have been approved by many national regulatory agencies for treatment of relapsing remitting multiple sclerosis, but widespread discussion continues about their true effectiveness, benefits, side-effects, and costs. METHODS: With the Cochrane Collaboration methodology, we reviewed all published, randomised, placebo-controlled trials of recombinant interferons undertaken in patients with relapsing remitting multiple sclerosis between 1993 and 2002. Our primary aim was to find out whether recombinant interferons reduced the number of patients who had clinical exacerbations and disease progression, compared with placebo. FINDINGS: The seven trials that met our criteria included 1215 randomised patients: data from 667 (55%) were available for analysis at 1 year's and from 919 (76%) at 2 years' follow-up. Interferon seemed to reduce the number of patients who had exacerbations during the first year of treatment (relative risk 0.73, 95% CI 0.54-0.99), but results at 2 years' follow-up were not robust and were difficult to interpret because of the many dropouts. Although the number of patients who had exacerbations (0.81, 0.74-0.89) or progressed (0.70, 0.55-0.88) during the first 2 years fell significantly in the protocol analysis, results were inconclusive after sensitivity analyses for exacerbations (1.11, 0.73-1.68) and disease progression (1.31, 0.60-2.89). Data were insufficient to establish whether steroid use and admissions to hospital were reduced in the interferon group. Similarly, MRI outcome data could not be analysed quantitatively. Side-effects were common, and acute toxic effects adversely affected quality of life. INTERPRETATION: Recombinant interferons slightly reduce the number of patients who have exacerbations during first year of treatment. Their clinical effect beyond 1 year is uncertain and new trials are needed to assess their long-term effectiveness and side-effects.

Adult↗
PubMed2003

Spinal-cord MRI in multiple sclerosis.

The potential of MRI of the spinal cord as a diagnostic tool in MS has recently gained much interest. Dual echo spin echo MRI is most sensitive for the detection of spinal-cord abnormalities, which range from multiple focal lesions to confluent areas of high signal intensity. In some patients, commonly those with primary progressive disease, diffuse areas of slightly increased signal intensity are found. Disappointingly, the relation between MRI findings and clinical disability is weak. Studies relating MRI findings with histopathology have revealed substantial axonal loss in the spinal cords of patients with MS, whether focal lesions are present of not. Further, diffuse cord atrophy is found in advanced MS, which may reflect axonal loss. In the diagnostic setting, spinal-cord imaging is valuable. First, asymptomatic spinal-cord lesions are very rare in disorders other than MS. For example, in a patient with equivocal brain findings such as an elderly patient with vascular-ischaemic lesions, a normal spinal-cord examination can help rule out MS. Second, presence of asymptomatic spinal lesions may help confirm a diagnosis of MS when few or no brain lesions are present.

Adult↗