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Biomedical subjects

C H Polman

Publications and source records attributed to C H Polman.

At least 73 records · Page 4Linked to original sources
PubMed2002

Information processing characteristics in subtypes of multiple sclerosis.

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing-remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing-remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. 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.

Activities of Daily Living↗
PubMed2002

The FAS-670 polymorphism influences susceptibility to multiple sclerosis.

Several studies have reported a defective Fas function in patients with multiple sclerosis (MS). We were interested whether this could result from a genetically altered Fas regulation. We examined the FAS-670 polymorphism in 382 patients with MS and 206 controls, and found that the carriership of allele FAS-670*G was significantly less frequent in patients than in controls. We found no association between the carriership of FAS-670*G and clinical features. For a subgroup of patients, longitudinal MRI data were available. 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.

Adult↗
PubMed2002

Baseline T cell reactivity in multiple sclerosis is correlated to efficacy of interferon-beta.

BACKGROUND: Measuring proliferative responses of T lymphocytes is a simple, reproducible and widely used assay of immune competence. Evidence suggests a role of T cell reactivity in autoimmune diseases. Interferon (IFN)-beta blocks in vitro proliferation of human T cells. OBJECTIVES: To assess (i) the relation between T cell proliferation and disease characteristics of MS patients, (ii) differences in T cell proliferation between subgroups and HC, and (iii) the predictive value of T cell proliferation for efficacy of IFN-beta. METHODS: Proliferative responses were measured in phytohaemagglutinin (PHA), anti-CD2/CD28 and anti-CD3 stimulated whole blood of 189 MS patients and 249 healthy controls (HC). Forty-eight patients started treatment with IFN-beta. Based on EDSS progression, number of relapses and steroid interventions, patients were classified as either clinical responder or nonresponder to IFN-beta. RESULTS: Significant differences between MS subgroups and HC were found in T cell responses upon both PHA stimulation (RR>HC: p=0.001 and SP>HC: p=0.001) and CD2/CD28 stimulation (RR>HC, SP>HC and PP>HC: all p values <0.001). No significant differences were found between the MS subgroups. A probability of 88% (95% CI, 71-95%) for a favorable response to IFN-beta was found with increased baseline proliferative T cell responses to PHA; a probability of only 16% (95% CI, 7-33%) with decreased values. CONCLUSION: Our results suggest that the level of T cell proliferation in whole blood predicts efficacy of IFN-beta in MS.

Adult↗
PubMed2002

Chemokine receptor expression on T cells is related to new lesion development in multiple sclerosis.

The expression of chemokine receptors CCR5 and CXCR3 on CD4 and CD8 positive T cells in blood, measured by flow cytometry, was studied in 124 patients with different clinical subtypes of multiple sclerosis (MS) and 22 healthy controls. In a subgroup of patients (n=69) from whom MRI was available, chemokine receptor expression was correlated to the annualised changes in T1 and T2 lesion load. It was found that CCR5 and CXCR3 on both cell types might have impact on annualised increase in T2 lesion load, but not on T1 lesion load. 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.

Adult↗
PubMed2002

Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations.

Disease progression in multiple sclerosis occurs within the interface of glial activation and gliosis. This study aimed to investigate the relationship between biomarkers of different glial cell responses: (i) to disease dynamics and the clinical subtypes of multiple sclerosis; (ii) to disability; and (iii) to cross-validate these findings in a post-mortem study. To address the first goal, 51 patients with multiple sclerosis [20 relapsing remitting (RR), 21 secondary progressive (SP) and 10 primary progressive (PP)] and 51 neurological control patients were included. Disability was assessed using the ambulation index (AI), the Expanded Disability Status Scale score (EDSS) and the 9-hole PEG test (9HPT). Patients underwent lumbar puncture within 7 days of clinical assessment. Post-mortem brain tissue (12 multiple sclerosis and eight control patients) was classified histologically and adjacent sites were homogenized for protein analysis. S100B, ferritin and glial-fibrillary acidic protein (GFAP) were quantified in CSF and brain-tissue homogenate by ELISA (enzyme-linked immunosorbent assay) techniques developed in-house. There was a significant trend for increasing S100B levels from PP to SP to RR multiple sclerosis (P < 0.05). S100B was significantly higher in RR multiple sclerosis than in control patients (P < 0.01), whilst ferritin levels were significantly higher in SP multiple sclerosis than in control patients (P < 0.01). The S100B : ferritin ratio discriminated patients with RR multiple sclerosis from SP, PP or control patients (P < 0.05, P < 0.01 and P < 0.01, respectively). Multiple sclerosis patients with poor ambulation (AI > or =7) or severe disability (EDSS >6.5) had significantly higher CSF GFAP levels than less disabled multiple sclerosis or control patients (P < 0.01 and P < 0.001, respectively). There was a correlation between GFAP levels and ambulation in SP multiple sclerosis (r = 0.57, P < 0.01), and between S100B level and the 9HPT in PP multiple sclerosis patients (r = -0.85, P < 0.01). The post-mortem study showed significantly higher S100B levels in the acute than in the subacute plaques (P < 0.01), whilst ferritin levels were elevated in all multiple sclerosis lesion stages. Both GFAP and S100B levels were significantly higher in the cortex of multiple sclerosis than in control brain homogenate (P < 0.001 and P < 0.05, respectively). We found that S100B is a good marker for the relapsing phase of the disease (confirmed by post-mortem observation) as opposed to ferritin, which is elevated throughout the entire course. GFAP correlated with disability scales and may therefore be a marker for irreversible damage. The results of this study have broad implications for finding new and sensitive outcome measures for treatment trials that aim to delay the development of disability. They may also be considered in future classifications of multiple sclerosis patients.

Adult↗
PubMed2002

Two-year follow-up study of primary and transitional progressive multiple sclerosis.

This study documents changes in clinical and magnetic resonance imaging (MRI) characteristics in a large cohort of patients with primary and transitional progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and TPMS were recruited from six European centres and underwent clinical and MRI examination at three time points: baseline, year one and year two. Of the 190 patients recruited clinical data were available on 125 patients (66%, five centres) and MRI data were available on 113 patients (59%, four centres) at 2 years. Significant increases were seen in T2 load and T1 hypointensity, while brain and cord volume decreased. In PPMS significantly higher lesion loads were found in those who presented with non-cord syndromes when compared to cord presentation and there was a trend to greater brain atrophy in those who deteriorated clinically over the course of the study compared to those who remained stable. Significant cord atrophy was only seen in those with a cord presentation. Measurable changes in MRI parameters can be detected in PPMS patients over a relatively short period of time. MRI quantification is likely to be useful in elucidating disease mechanisms in PPMS and in the execution of clinical trials.

Adult↗
PubMed2002

Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue.

INTRODUCTION: In multiple sclerosis (MS), brain atrophy measurement on magnetic resonance imaging (MRI) reflects overall tissue loss, especially demyelination and axonal loss. We studied which factor contributes most to the development of brain atrophy extent and severity of lesions or damage of whole brain issue (WBT). METHODS: Eighty-six patients with MS [32 primary progressive (PP), 32 secondary progressive (SP)] and 22 relapsing-remitting (RR) were studied MRI included T1- and T2-weighted imaging to obtain hypointense T1 lesion volume (T1LV) and two brain volume measurements: 1) the parenchymal fraction (PF; whole brain parenchymal volume/intracranial volume) as a marker of overall brain volume, and 2) the ventricular fraction (VF; ventricular volume/intracranial volume) as a marker of central atrophy. From magnetization transfer ratio (MTR) histograms, the relative peak height (rHp) was derived as an index of damage of WBT (a lower peak height reflects damage of WBT). RESULTS: Multiple linear regression analysis revealed that damage of WBT explains most of the variance of PF (standardized coeffcient beta = 0.59, p < 0.001 for WBT and beta = -0.19, p < 0.05 for T1LV). These findings are independent of disease phase; even in RR patients, damage of WBT plays a dominant role in explaining the variance in overall brain volume. By contrast the variance in VF is explained by both T1LV and damage of WBT (standardized coefficient beta = 0.43, p < 0.001 for T1LV and beta =-0.38, p < 0.001 for WBT). CONCLUSION: This study shows that overall brain volume (PF) is best explained by damage of WBT, supporting the significance of nonfocal pathology in MS in producing tissue loss. Central atrophy (VP) is determined by both lesion volume and damage of WBT. Our results underline the importance of nonfocal pathology even in the early (RR) phase of the disease.

Adult↗
PubMed2002

Multiple sclerosis functional composite: impact of reference population and interpretation of changes.

The Multiple sclerosis functional composite (MSFC) has been recommended as a clinical outcome measure to be used in future MS trials. A specific characteristic of the MSFC is that it is defined as a measure of impairment relative to a reference population. Using different reference populations affects actual MSFC scores. If the selection of a reference population also has an effect on sensitivity to change of the MSFC, comparison of data from clinical trials will be almost impossible when different reference populations are used We studied the effect of the selection of a reference population on the outcome of a trial by simulating 343 intervention trials and comparing results obtained by using three different reference populations: two previously published MS patient populations and a healthy population. Scores of the healthy population were collected in the first part of the study. The effects of sex, age and education level on test scores of healthy subjects were studied as well. In the healthy controls, sex, age and education level had a different impact on individual test scores of MSFC components and overall MSFC score. Our study shows that, with the use of the MSFC, the selection of different reference populations does not affect the trial statistics and significance, but it does affect comparability of results between different trials, and complicates the dinical interpretation of any observed change.

Clinical Trials as Topic↗
PubMed2002

Cerebral volume changes in multiple sclerosis patients treated with high-dose intravenous methylprednisolone.

OBJECTIVE: 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. METHODS: Thirty-five MS patients participating in a clinical trial of oral interferon beta, which induded monthly MRI, were included in this study. They suffered from an acute relapse and were treated with intravenous methylprednisolone (IV-MP); 13 of the patients were treated with oral prednisolone tapering after IV-MP. The last MRI scan before and the first (and second for oral tapering patients) scan after IV-MP treatment were used for measuring parenchymal fraction (PF) and ventricular fraction (VF). Changes in PF and VF were analysed using Student's t test. RESULTS: For the total population no significant changes in PF or VF were found. However, the subgroup of patients receiving oral tapering after IV-MP showed changes, compatible with atrophy in both PF and VF, that were significant immediately after IV-MP treatment and still persisted (though not statistically significant anymore) after a mean interval of 30 days. The magnitude of these changes was about the same as the annual change in cerebral volume as reported in natural history studies. CONCLUSION: Our data indicate that short courses of intravenous steroids (restricted to three or five days) have no major impact, whereas prolonged treatment with oral tapering does significantly affect brain volume. These findings are important for longitudinal studies and clinical trials in which brain volume is used as an outcome measure.

Adult↗
PubMed2002

The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study.

Progressive axonal loss is the most likely pathologic correlate of irreversible neurologic impairment in primary progressive multiple sclerosis. 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.

Adult↗
PubMed2001

The effect of IFNbeta-1b on the evolution of enhancing lesions in secondary progressive MS.

BACKGROUND: After the resolution of contrast enhancement, the majority of new MS lesions become isointense with surrounding white matter on T1-weighted MRI. Less commonly, a hypointense T1 lesion develops, representing the development of more severe focal tissue damage. Interferon beta (IFNbeta) reduces both the number of new enhancing lesions and the duration of contrast enhancement. OBJECTIVE: To determine if IFNbeta affects the degree of tissue damage within new lesions and if its effects are related to lesion size. METHODS: One hundred twenty-five patients with secondary progressive MS from seven European sites were randomized to receive either IFNbeta-1b or placebo. Monthly, contrast-enhanced T1-weighted MR images were acquired at baseline, at months 1 to 6, and at months 19 to 24. The size of all new enhancing lesions developing between months 1 and 6 was recorded and their appearance at follow-up documented. RESULTS: In the first 6 months, fewer new enhancing lesions occurred in the IFNbeta-1b arm. This difference was greater for small (70% decrease) than for large (46% decrease) lesions. Hypointense T1 lesions were more likely to form from large (25%) than from small (9%) enhancing lesions in both treatment arms. Patients taking IFNbeta-1b developed fewer hypointense T1 lesions; however, the proportion of enhancing lesions developing into hypointense T1 lesions was similar in both arms. CONCLUSION: IFNbeta-1b reduced the number of new enhancing lesions, with a greater effect on small lesions. However, when a new enhancing lesion did become established, treatment with IFNbeta-1b did not alter its subsequent course.

Adult↗
PubMed2001

Cytokine and IL-12 receptor mRNA discriminate between different clinical subtypes in multiple sclerosis.

Little is known about the involvement of cytokines in the pathogenesis of primary progressive (PP) multiple sclerosis (MS). We evaluated in this cross-sectional study whether IL-18, IL-12p35, IL-12p40, TNF-alpha, IFN-gamma, IL-10, IL-4, TGF-beta, IL-12Rbeta1, and IL-12Rbeta2 mRNA expression in unstimulated white blood cells showed significant differences between relapsing-remitting (RR), secondary progressive (SP) and PP MS patients, and healthy controls. All clinical subtypes showed unique mRNA expression patterns as compared to the controls. Both RR and SP patients displayed increased levels of IL-12p40, IL-18, and TGF-beta mRNA compared to controls, whereas PP patients showed only increased IL-18 mRNA levels. Both in PP and SP patients, IFN-gamma and IL-10 mRNA were decreased compared to RR patients and controls. PP patients were unique in that they showed decreased IL-12Rbeta1 mRNA. In conclusion, our data show that the assessment of cytokine (receptor) mRNA profiles is useful to discriminate between the different clinical subtypes and suggest that different cytokines are involved in the pathogenesis of PP MS as compared to RR and SP MS.

Adult↗
PubMed2001

Optimizing the association between disability and biological markers in MS.

OBJECTIVE: Axonal damage is an important feature of MS pathology and the likely substrate of development of progressive disability. Brain volume measurement on MRI can be used as an overall marker of tissue damage and axonal loss. The authors studied the relation of brain volume measurements with the MS Functional Composite (MSFC) in an attempt to improve the clinico-radiologic association. METHODS: In 137 patients with MS (80 relapsing-remitting [RR], 36 secondary progressive [SP], and 21 primary progressive [PP]) and 12 healthy controls, a brain MRI scan was obtained. Patients also underwent MSFC and Expanded Disability Status Scale (EDSS) assessments. MRI analysis included determination of hypointense T1- and hyperintense T2-weighted lesion load, and two brain volume measurements: 1) the parenchymal fraction (PF): whole brain parenchyma/intracranial volume; and 2) the ventricular fraction (VF): ventricular volume/whole brain parenchyma. RESULTS: The median PF was smaller and the median VF larger in the patient group (0.81 for PF and 0.029 for VF) than in the control group (0.87 for PF, p < 0.001; and 0.013 for VF, p < 0.01). For the patient population, moderate correlations were found between brain volume measurements and MSFC (0.36 for PF and -0.40 for VF). Patients with short disease duration showed a correlation of MSFC with both brain and lesion volume measurements on MRI, whereas patients with long disease duration only showed a correlation with brain volume measurements. CONCLUSION: Brain volume measurements are correlated with disability as assessed by the MSFC. Although in the early phase of the disease the amount of focal demyelination is important, the residual brain volume seems to be more relevant in determining disability in later phases of the disease.

Adolescent↗
PubMed2001

TNFalpha production by CD4(+) T cells predicts long-term increase in lesion load on MRI in MS.

Reliable laboratory prognostic factors for MS are still lacking. The predictive value of markers of T-cell activation for long-term disease progression was investigated. Flow cytometry measurements were correlated to changes in Expanded Disability Status Scale and MR T2 lesion load over 36 months in 14 patients with secondary progressive 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).

Adult↗
PubMed2001

Active MRI lesion appearance in MS patients is preceded by fluctuations in circulating T-helper 1 and 2 cells.

BACKGROUND: The role of T cell subpopulations and their ability to produce immunoregulatory cytokines has been extensively studied in multiple sclerosis (MS). However, the exact mechanisms by which T cells and cytokines contribute to disease activity remain to be clarified. OBJECTIVES: To analyze the longitudinal relation between markers of T cell activation and differentiation and disease activity in MS patients. METHODS: During a period of 9 months, clinical disease activity was scored, monthly MRI scans were performed, and blood was taken for immune measurements in a group of 13 untreated clinically definite MS patients. RESULTS: Disease activity, as measured by the occurrence of active MRI lesions, is associated with a significant transient decrease in both T cells producing interferon-gamma (IFN-gamma) and T cells producing interleukin (IL)-4. CONCLUSIONS: Our results suggest that MRI-documented disease activity is associated with a transient decrease in circulating cytokine producing T cells, possibly due to the migration of activated T cells into the CNS.

Adult↗
PubMed2001

Comparisons of patient self-report, neurologic examination, and functional impairment in MS.

OBJECTIVE: To compare the recently developed Guy's Neurologic Disability Scale (GNDS), based on patient self-report, with both neurologist rating of neurologic examination abnormalities using the Expanded Disability Status Scale (EDSS) and observations of functional impairment on the Multiple Sclerosis Functional Composite (MSFC) in the assessment of disease impact in MS. METHODS: Two hundred ninety MS patients were recruited at an outpatient clinic. Impairment and disability were assessed using GNDS, EDSS, and MSFC. Correlations between GNDS, EDSS, MSFC, and their corresponding components were studied for the total population, MS phenotypes, and three disability strata. RESULTS: Mean scores were 4.6 (SD, 2.0) for EDSS, 0.0 (SD, 0.8) for MSFC, and 14.6 (SD, 7.9) for GNDS. Good correlations were found between GNDS and EDSS (r = 0.73), between GNDS and MSFC (r = -0.68), and between different subcategories of the GNDS and EDSS, MSFC, and their corresponding components. Remarkably good correlations were found between lower limb function and all three scales. Poor correlations were also found, especially between different measurements focusing on cognitive function. CONCLUSION: The good correlations between GNDS and both EDSS and MSFC were mainly due to the importance of spinal-cord-related neurologic functions in all three scoring systems. A marked discrepancy was found for the assessment of cognition between objective measurements and subjective complaints. Because patients' self-reporting correlates well with results of physical examination, GNDS can offer a valuable way to measure disease impact in MS. However, GNDS is not an adequate screen of cognitive dysfunction.

Adolescent↗
PubMed2001

Magnetization transfer histogram parameters reflect all dimensions of MS pathology, including atrophy.

INTRODUCTION: Magnetization transfer ratio (MTR) histogram analysis can be used as a method for quantifying overall disease burden in MS. 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. METHODS: Seventy-nine patients with MS [26 primary progressive (PP), and 53 'relapse-onset', including 26 secondary progressive (SP)], and 23 healthy individuals were studied. MR imaging included 3 mm 2D gradient-echo images with and without an off-resonance MT pulse. According to the visually determined cut-off, histogram parameters were classified as parenchymal or CSF-related variables. Clinical measurements included the Expanded Disability Status Scale (EDSS) as a measure of global impairment/disability and the Paced Auditory Serial Addition Test (PASAT) as a measure of cognition. RESULTS: SP MS patients differed from the other subgroups on many MTR variables, originating from both the lower and the higher MTR range. CSF-related low MTRs were clearly over-represented in SP patients, and showed a significant distinction between the SP and PP MS group. In the total group, as well as in the relapse-onset patients, significant correlations were found between MTR parameters and clinical parameters. No associations were found in the PP group. CONCLUSION: This explorative study suggests that MTR histogram analysis can distinguish between MS patients and controls, and best identifies the SP phenotype, partly as a result of increased CSF volume (atrophy). In addition, we show that MTR histogram analysis gives information about the level of impairment and disability in patients with a 'relapse-onset' course of MS, and therefore provides a useful tool to monitor the evolution of the disease in these patients.

Adult↗