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C H Polman

Publications and source records attributed to C H Polman.

At least 127 records · Page 7Linked to original sources
PubMed1999

A health-related quality of life questionnaire for multiple sclerosis patients.

OBJECTIVE: The construction of a brief, valid and reliable HRQoL questionnaire for use in multiple sclerosis patients based on generic and disease-specific HRQoL measures. MATERIAL AND METHODS: The Medical Outcomes Study 36-item Short Form Health Survey (SF-36), COOP/ WONCA Charts, and Disability & Impact Profile (DIP) were used in a longitudinal study in 162 patients with multiple sclerosis. RESULTS: Factor analyses identified 2 underlying dimensions of HRQoL, relating to "physical functioning" and "psychological functioning". Selection of the 3 highest loading reliable scales on each factor resulted in a final questionnaire consisting of 3 scales of the SF-36 and 3 scales of the DIP. In total 40 items were selected; completion time is about 10 min. CONCLUSION: The final questionnaire adequately measured 2 dimensions of HRQoL. The length of the questionnaire is acceptable for patients with MS in view of respondent burden.

Adult↗
PubMed1999

Association of interleukin-1beta and interleukin-1 receptor antagonist genes with disease severity in MS.

OBJECTIVE: To investigate whether polymorphisms in the interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1RA) genes are associated with both susceptibility to and clinical characteristics of MS. BACKGROUND: Genetic susceptibility to MS is determined by many partially identified genes. The genes encoding various cytokines are logical candidates for MS susceptibility and phenotype. METHODS: Genotypes were determined from 148 patients with clinically definite MS and 98 healthy controls. All the patients were unrelated, Dutch, and white. Patient files were reviewed for disease type, initial symptoms, age at onset of disease, and rate of disease progression. RESULTS: No significant differences in genotypes, allele frequencies, or carrier frequencies were found between MS patients and healthy controls. Stratification for disease type (relapsing-remitting, primary progressive, or secondary progressive) did not provide significant differences between patients and controls. However, a specific IL-1RA/IL-1beta combination was associated with disease severity. MS patients with the IL-1RA allele 2+/IL-1beta allele 2- combination had a higher rate of progression on the Expanded Disability Status Scale when compared with the other possible combinations (p = 0.007). CONCLUSIONS: IL-1RA and IL-1beta are disease severity genes rather than disease susceptibility genes. Furthermore, these gene polymorphisms may define subgroups of patients with a worse prognosis.

Adult↗
PubMed1998

Longitudinal follow-up of cardiovascular reflex tests in multiple sclerosis.

Several studies have shown various degrees of autonomic dysfunction in patients with multiple sclerosis. Longitudinal follow-up studies are remarkably scarce up to now. We assessed autonomic dysfunction twice with an interval of 1 year in 20 relapsing remitting and 26 secondary progressive MS-patients. Autonomic function was assessed by the heart rate response during deep breathing, standing up and Valsalva manoeuvre. Only the maximum change in heart rate after standing up (in ms and beats/min) and the Max/Min ratio after standing up showed significant worsening over 1 year. The changes in EDSS scores also documented gradual deterioration of the neurological condition over the study period. We conclude that there is progression of autonomic dysfunction in MS over 1 year and that this could correlate with progression in clinical disability.

Adult↗
PubMed1998

Increased production of tumor necrosis factor alpha, and not of interferon gamma, preceding disease activity in patients with multiple sclerosis.

OBJECTIVE: To study whether tumor necrosis factor (TNF) alpha or interferon (IFN) gamma production by stimulated white blood cells precedes or accompanies clinical and magnetic resonance imaging signs of disease activity in patients with multiple sclerosis. DESIGN: Prospective study with a follow-up of 9 months. SETTING: Patients visiting an outpatient university clinic. PATIENTS: The 30 Amsterdam-based patients (28 completing all evaluations) participating in a multicenter, randomized, placebo-controlled, double-blind trial of a chimeric anti-CD4 antibody in the treatment of active relapsing-remitting and secondary progressive multiple sclerosis. Patients in both treatment arms were included, because for these patients anti-CD4 treatment in this study did not affect TNF-alpha and IFN-gamma production and did not reduce signs of disease activity on magnetic resonance imaging. MAIN OUTCOME MEASURE: Distribution of classes of TNF-alpha and IFN-gamma production (expressed as z scores) in patients with or without clinical or magnetic resonance imaging signs of disease activity. RESULTS: One month preceding exacerbations of multiple sclerosis, there was a shift toward higher z scores of TNF-alpha production (P<.05), but not of IFN-gamma production. There was no statistically significant relationship between IFN-gamma and TNF-alpha production and magnetic resonance imaging markers of multiple sclerosis activity. CONCLUSION: The production of TNF-alpha, and not of IFN-gamma, is significantly higher in patients with multiple sclerosis before exacerbations than in patients with stable disease. Although present, this relationship is too weak to use TNF-alpha production as a surrogate marker of disease activity in multiple sclerosis.

Adult↗
PubMed1998

Ophthalmoplegic and lower cranial nerve variants merge into each other and into classical Guillain-Barré syndrome.

We delineated the place of cranial nerve variants within the concept of clinically defined Guillain-Barre syndrome (GBS). In the ophthalmoplegic variant (n = 7) the oculomotor nerves were early involved. In a lower cranial nerve variant (n = 9) the cranial nerves IX, X, and XI were early involved. During progression considerable overlap occurred between these two variants, but also with the classically ascending variant of clinically defined GBS. These findings indicate common immune mechanisms in all GBS variants.

Adolescent↗
PubMed1998

Functional correlates of callosal atrophy in relapsing-remitting multiple sclerosis patients. A preliminary MRI study.

In multiple sclerosis (MS), periventricular lesions produce atrophy of the corpus callosum (CC), as evidenced by magnetic resonance imaging (MRI). We investigated whether CC atrophy in relapsing-remitting MS patients is related to functional deficits. We compared 14 mildly disabled (mean Expanded Disability Status Scale score 2.7) relapsing-remitting MS patients with 14 age- und sex-matched controls. CC size was determined using sagittal T1-weighted MRI. The function of the CC was studied using a neuropsychological battery and neurophysiological evaluation based on visual stimulation using a divided visual field paradigm. The total area of the CC in patients (mean 5.3 cm2) was significantly (P = 0.002) smaller than in controls (mean 6.6 cm2). Patients showed left ear extinction using the dichotic listening test and impaired name learning, which was correlated with atrophy of the splenium. There were no differences in interhemispheric transfer time between patients and controls. Marked atrophy of the CC can be encountered in relapsing-remitting MS patients. The associated cerebral disconnection correlated with atrophy of expected regions of the CC, thus supporting topographical organization.

Adult↗
PubMed1998

Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis.

Postmortem unfixed whole brains from five multiple sclerosis (MS) patients were examined by MRI using a T2- and T1-weighted spin-echo (SE) sequence and histology to investigate the histopathologic characteristics of hypointense lesions on T1-weighted SE MR images. The degree of hypointensity was scored semiquantitatively by two blinded observers in reference to normal-appearing white matter. Signal intensities of the lesions and the normal-appearing white matter were measured to obtain contrast ratios. Hematoxylin-eosin stain was used to assess degree of matrix destruction (decrease of density of the neuropil) and cellularity of a lesion, Klüver-Barrera stain for degree of demyelination, Bodian stain for axonal density, and immunostaining of glial fibrillary acid protein for reactive astrocytes and fibrillary gliosis. Nineteen lesions were selected for analysis. Nearly all lesions were compatible with the chronic MS plaque: hypocellularity, absence of myelinated axons, in the presence of reactive astrocytes. Contrast ratios of the lesions were highly correlated (R = -0.90; p < 0.01), with degree of hypointensity scored semiquantitatively. Degree of hypointensity on T1-weighted SE images did not correlate with degree of demyelination or number of reactive astrocytes, but was associated with axonal density (R = -0.71; p = 0.001). A trend was found with degree of matrix destruction (R = 0.45; p = 0.052). We conclude that, in our limited sample, hypointense lesions seen on T1-weighted SE MR images are associated histopathologically with severe tissue destruction, including axonal loss. Our results need to be substantiated in a larger study on more varied patient material to evaluate the use of hypointense lesions as a surrogate marker of persistent deficit in MS patients.

Adult↗
PubMed1998

Choosing drug therapy for multiple sclerosis. An update.

Multiple sclerosis (MS) is an immunologically mediated disorder in which inflammation and demyelination of the central nervous system white matter are prominent features, resulting in various neurological signs and symptoms. In most patients, the course of the disease is initially characterised by relapses and remissions. In patients with chronic disease there is a tendency towards a gradually progressive disease course. MS relapses can best be treated with a course of high dose intravenous methylprednisolone. In ambulatory patients with relapsing remitting MS, partial prevention of relapses can be achieved by the use of interferon-beta-1a or -1b, whereas there is (as yet less convincing) evidence that glatiramer acetate (copolymer-1) might also be effective. At this time, there is no proof that these drugs are effective in patients with progressive MS, although trial results are expected to be available soon. In patients with rapidly progressive disease, it might be worth considering the effect of methotrexate. Future treatment options include new strategies to interfere with disease-relevant, specific or nonspecific immune mechanisms as well as drugs that might promote remyelination. In spite of the advances that have been made over the past few years, symptomatic treatment, including a multidisciplinary rehabilitation approach, remains the mainstay of treatment of the majority of MS patients.

Anti-Inflammatory Agents↗
PubMed1998

Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR.

PURPOSE: We evaluated the appearance of enhancing multiple sclerosis (MS) lesions on unenhanced T1-weighted MR images and the natural course of enhancing MS lesions on serial unenhanced T1-weighted and magnetization transfer (MT) MR images. METHODS: One hundred twenty-six enhancing lesions were followed up monthly for 6 to 12 months to determine their signal intensity on unenhanced T1-weighted and MT MR images. At the time of initial enhancement, the size of the lesion and the contrast ratio of enhancement were calculated for each enhancing lesion. During follow-up, the contrast ratio on the corresponding unenhanced T1-weighted image was measured, and an MT ratio (MTR) was calculated. RESULTS: Twenty-five enhancing lesions (20%) appeared isointense and 101 lesions (80%) appeared hypointense relative to normal-appearing white matter on unenhanced T1-weighted images. During 6 months of follow-up, four MR patterns of active lesions were detected: initially isointense lesions remained isointense (15%); initially isointense lesions became hypointense (5%, most of which reenhanced); initially hypointense lesions became isointense (44%); and initially hypointense lesions remained hypointense (36%). MTR was significantly lower for hypointense lesions as compared with isointense lesions at the time of initial enhancement. For lesions that changed from hypointense to isointense, MTR increased significantly during 6 months of follow-up. Multiple regression analysis showed that strongly decreased MTR at the time of initial enhancement and enhancement duration of more than one scan were predictive of a hypointense appearance on unenhanced T1-weighted images at 6 months' follow-up. Ring enhancement was found to be the only (weak) predictor of persistently hypointense signal intensity. CONCLUSION: Most enhancing lesions appear slightly to significantly hypointense on unenhanced T1-weighted images. Although most hypointensities are reversible, only those lesions that fail to recover on unenhanced T1-weighted and MT images may have considerable irreversible structural changes.

Adolescent↗
PubMed1997

Treatment with depleting CD4 monoclonal antibody results in a preferential loss of circulating naive T cells but does not affect IFN-gamma secreting TH1 cells in humans.

CD4(pos) TH1 T cells are considered to play a central role in a number of human autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis. Experimental treatment protocols aimed at selectively eliminating CD4(pos) T cells thus far have yielded disappointing clinical results. Here we analyzed phenotype and function of circulating T cells in multiple sclerosis patients treated with the chimeric CD4 mAb cM-T412 in a randomized, double-blind, placebo-controlled, magnetic resonance imaging-monitored phase II trial. Treatment resulted in a long-lasting depletion of CD4(pos) T cells but did not affect CD8(pos) T cell numbers. Analysis of CD4(pos) subpopulations showed that unprimed, CD45RA(pos)/R0(neg) lymphocytes were approximately three times more sensitive to the mAb than primed, CD45RA(neg)/R0(pos) T cells. Notably, within the CD45RA(pos) subset, T cells with phenotypic evidence of prior activation, i.e., expressing Fas, were relatively insensitive to cM-T412, compared with Fas(neg) cells. Remarkably, while a decrease in the number of IL-4-producing T helper 2 (TH2)-type cells in the anti-CD4 treated group was observed, numbers of IFN-gamma-producing T helper 1 (TH1)-type cells remained stable, resulting in a significant increase in the TH1/TH2 ratio. Our data show that treatment with depleting CD4 mAb does not eliminate the cells most strongly involved in the disease process, i.e., primed, IFN-gamma-producing TH1-type cells, and may therefore give an explanation for the lack of beneficial clinical effects of depleting CD4 mAb in human chronic autoimmune disease.

Adult↗
PubMed1997

TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients.

TNF-alpha production in whole blood cultures upon stimulation with LPS was determined in 179 individuals from 61 families in order to characterise the magnitude of inherited differences in TNF-alpha production. The three families characterised by highest TNF production showed 7.1 +/- 0.3 ng TNF/ml upon culture with 10 ng LPS and 10.2 +/- 0.2 ng TNF/ml upon culture with 1000 ng LPS. in contrast to the three families characterised by the lowest TNF production that showed a production of 1.6 +/- 0.1 ng TNF upon culture with 10 ng and 2.5 +/- 0.2 ng/ml upon culture with 1000 ng LPS/ml. This difference could not be attributed to the promoter polymorphisms -308 G to A. -238 G to A or -376 G to A, although the -238 GA donors produced 2.1 +/- 0.9 ng TNF upon culture with 10 ng endotoxin compared to 3.2 +/- 2.2 ng TNF for the -238 GG donors. In line with these results the frequency of the -238 GG genotype was increased in hospitalized MS patients in a nursing home (100% 238GG, n = 57) compared to MS patients in an outpatient's clinic (94% 238GG, n = 98) or Dutch controls (90% 238GG, n = 180). These results suggest that the -238 GG genotype is differently distributed in hospitalized MS patients in a nursing home.

Disease Susceptibility↗
PubMed1997

Comparison of four potential MR parameters for severe tissue destruction in multiple sclerosis lesions.

The purpose of this study was, first, to evaluate correlations between four potential magnetic resonance (MR) parameters for severe tissue destruction in multiple sclerosis (MS) lesions. Second, to evaluate the effect of incidental magnetization transfer (MT) effect on hypointense lesions in multislice T1 spin echo (SE) imaging. In 49 lesions, from 10 MS patients, MT ratio (MTR), T1 relaxation time, signal intensity (SI) on T1-weighted SE images normalized to normal-appearing white matter (NAWM), and SI normalized to cerebrospinal fluid (CSF) were measured. Differences in contrast of hypointense lesions were measured between single slice and multislice imaging. MTR correlated significantly (p < .001) with longitudinal relaxation rates (1/T1) (r = 0.84), SI normalized to NAWM (r = 0.78), and SI normalized to CSF (r = 0.75). The degree of reduction in contrast, caused by multislice imaging, correlated significantly with MTR of lesions (r = 0.60, p < .001), leading to reduction of hypointense lesion load (p < .01). We conclude that all four MR markers for severe tissue destruction are highly correlated when applied to selected hypointense lesions on T1-weighted SE images. Due to "incidental" off-resonance excitation, contrast and hypointense lesion load will be reduced in multislice T1-weighted SE images.

Adult↗
PubMed1997

Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis.

We compared MRI criteria used to predict conversion of suspected multiple sclerosis to clinically definite multiple sclerosis. Seventy-four patients with clinically isolated neurological symptoms suggestive of multiple sclerosis were studied with MRI. Logistic regression analysis was used to remove redundant information, and a diagnostic model was built after each MRI parameter was dichotomized according to maximum accuracy using receiver operating characteristic analysis. Clinically definite multiple sclerosis developed in 33 patients (prevalence 45%). The optimum cut-off point (number of lesions) was one for most MRI criteria (including gadolinium-enhancement and juxta-cortical lesions), but three for periventricular lesions, and nine for the total number of T2-lesions. Only gadolinium-enhancement and juxta-cortical lesions provided independent information. A final model which, in addition, included infratentorial and periventricular lesions, had an accuracy of 80%, and having more abnormal criteria, predicted conversion to clinically definite multiple sclerosis strongly. The model performed better than the criteria of Paty et al. (Neurology 1988; 38: 180-5) and of Fazekas et al. (Neurology 1988; 38: 1822-5). We concluded that a four-parameter dichotomized MRI model including gadolinium-enhancement, juxtacortical, infratentorial and periventricular lesions best predicts conversion to clinically definite multiple sclerosis.

False Negative Reactions↗
PubMed1997

Primary progressive multiple sclerosis.

Patients with multiple sclerosis who develop progressive disability from onset without relapses or remissions pose difficulties in diagnosis, monitoring of disease activity and treatment. There is a need to define the diagnostic criteria for this group more precisely and, in particular, to describe a comprehensive battery of investigations to exclude other conditions. The mechanisms underlying the development of disability and the role of MRI in monitoring disease activity in this clinical subgroup require elucidation, particularly in view of the lack of change on conventional imaging in the presence of continuing clinical deterioration. The prognosis is poor and there are currently no treatment trials for this form of the disease.

Disease Progression↗
PubMed1997

Specific power calculations for magnetic resonance imaging (MRI) in monitoring active relapsing-remitting multiple sclerosis (MS): implications for phase II therapeutic trials.

Inhomogeneous patient samples have been used in previous studies to determine the power of magnetic resonance imaging (MRI) for trial monitoring in multiple sclerosis (MS). These power-calculations might not be applicable to the active relapsing-remitting patient who is preferably included in trials. In order to reevaluate the power-calculations for MRI in the monitoring of treatment in strictly relapsing-remitting MS and to compare the power of different trial designs we studied 12 relapsing-remitting MS patients prospectively for a median period of 12 months using monthly clinical assessments and gadolinium-enhanced MRI. A median number of two clinical relapses/patient occurred of which a median of one was treated with steroids. A median of 1.59 new lesions/scan/patient was detected (range 0-8). The total number of new active lesions correlated significantly with study period relapses (SRCC = 0.72, P = 0.023). Computer simulations using the bootstrap technique yielded mostly lower power values for a parallel groups design than in previous studies except for short follow-periods in larger samples. In this-sample the open cross-over design was found to be between 20 and 40% more powerful. Results of power-calculations are clearly sample dependent implying that for treatment trial monitoring using MRI in relapsing-remitting MS conservative sample size estimates are to be used. In an active patient group open cross-over trial designs could be a very powerful alternative to parallel groups design.

Adult↗