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C H Polman

Publications and source records attributed to C H Polman.

At least 109 records · Page 6Linked to original sources
PubMed2000

Magnetization transfer ratio of the spinal cord in multiple sclerosis: relationship to atrophy and neurologic disability.

The authors compare the spinal cord magnetization transfer ratio (MTR) of multiple sclerosis (MS) patients to healthy volunteers, relate MTR to spinal cord atrophy, and relate these and other magnetic resonance (MR) imaging parameters to disability. Sixty-five patients with MS (14 relapsing remitting [RR], 34 secondary progressive [SP], and 17 primary progressive [PP] MS), and 9 healthy volunteers were studied using MR at 1.0 T. Disability of the patients was assessed using the expanded disability status scale (EDSS). Magnetic resonance parameters were upper spinal cord MTR, number of focal spinal lesions, presence of diffuse abnormalities, and spinal cord cross-sectional area (CSA). Correlations were assessed using Spearman's rank correlation coefficient (r). Magnetization transfer ratio was higher in the controls (median, 33%; range, 30%-38%) than in patients with MS (median, 30%; range, 16-36; p < 0.05). In patients with MS EDSS correlated with spinal cord MTR, albeit weakly (r = -0.25, p < 0.05). Correlation between EDSS and spinal cord CSA was better (SRCC = -0.40, p < 0.01). No correlation was found between MTR and CSA (r = 0.1, p = 0.4). Combining MTR with spinal cord CSA improved correlation with EDSS (r = -0.46, p < 0.001), suggesting an independent correlation between disability and these 2 MR parameters. Expanded disability status scale scores were higher in patients who had diffuse spinal cord abnormality regardless of focal lesions (median, 6; range, 1.5-7.5) than in patients without diffuse abnormalities (median, 3.5; range, 0-8; p < 0.01). CSA was lower in patients with diffuse spinal cord abnormality (median, 62; range, 46-89 mm2) than in patients without diffuse abnormalities (median, 73; range, 47-89 mm2; p < 0.01). MTR was slightly lower in patients with diffuse spinal cord abnormalities (median, 29; range, 21%-33%) than in patients without diffuse abnormalities (median, 31; range, 16-36; t-test, p < 0.05).

Adult↗
PubMed2000

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

OBJECTIVE: To document clinical and magnetic resonance imaging (MRI) characteristics of a large cohort of primary and transitional progressive multiple sclerosis (PP and TP MS) patients over one year. INTRODUCTION: Patients with PP or TP MS have been shown to have low brain T2 and T1 lesion loads and slow rates of new lesion formation with minimal gadolinium enhancement, despite their accumulating disability. Serial evaluation of these patients is needed to elucidate the pathological processes responsible for disease progression and to identify clinical and MRI measures which can monitor these processes in treatment trials. METHOD: Patients, recruited from six European centres, underwent two assessments on the expanded disability status scale (EDSS) and MRI of the brain and spinal cord, 1 year apart. RESULTS: Of the 167 patients studied (137 with PP MS and 30 with TP MS), 41 (25%; 35 PP and six TP) showed a one step increase in the EDSS. The mean number of new brain lesions seen was 0.88 in the PP group and 0.47 in the TP MS group. Both groups demonstrated change in T2 lesion load over the year (p< or =0.002), with median percentage changes of 7.3% in the PP group and 10. 8% in the TP MS group. The PP group also showed a significant change in T1 load (p< 0.001, median change 12.6%). The number of new cord lesions seen was small (mean of 0.14 in the PP group and no new cord lesions in the TP group). Both groups demonstrated a decrease in cord cross sectional area (p< 0.001, median changes; PP 3.8%, TP 4. 9%), but only the PP group showed evidence of significant brain atrophy (p<0.001, 0.95%). CONCLUSION: Although the monitoring of disease progression in this patient group is difficult, this study demonstrates changes in both lesion load and atrophy, which, if shown to correlate with clinical change over a longer time will facilitate therapeutic trial design.

Atrophy↗
PubMed2000

Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials.

Due to an unexpected increase in serious cardiovascular events in MS patients treated with Linomide, a synthetic immunomodulator, two phase-III multinational relapsing remitting (RR) and secondary progressive (SP) MS trials had to be discontinued. MRI results of 413 patients who participated for at least 3 months were analysed. Patients received placebo, 2.5 or 5 mg Linomide. Scans were performed at pre-enrolment, month 3 and termination. The number and volume of enhancing lesions (ELV), and the number of active scans were evaluated. At month 3, the decrease in the number of enhancing lesions in the placebo group was 11%, compared with 15% in the 2.5 mg group (P=0.027) and 23% in the 5 mg group (P=0.057). Using the percentage of active scans as outcome parameter, the odds ratio for improvement between placebo and 2.5 mg group was 1.62 (P=0.14); between placebo and 5 mg Linomide group 3.58 (P=0.003). At termination, a rebound effect was noted in the 2.5 mg group (P=0.01). Analysis of the ELV showed no significant difference between placebo and treatment groups. Although Linomide has unacceptable side effects, it seems to have a modest effect on MS disease activity, as measured by MRI. Multiple Sclerosis (2000) 6, 99 - 104

Adjuvants, Immunologic↗
PubMed2000

Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR.

In this study we evaluated the correlation between neuropsychological impairment (measured with the Brief Repeatable Battery Neuropsychological Tests) and (juxta)cortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to spin-echo MRI sequences in detecting (juxta)cortical MS lesions. A total of 39 patients with definite MS were evaluated by MRI with a conventional and fast spin echo sequence and fast FLAIR sequence, and neuropsychological tests of the Brief Repeatable Battery Neuropsychological tests were performed. The Z-score of all subtests were used to calculate a Cognitive Impairment Index. The results show that a high number of (juxta)cortical lesions is detected with thin slice FLAIR (30% of all lesions seen). This percentage was not superior to spin-echo, reflecting the thin slice thickness (3 mm) we used. The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques. While the number of non-cortical lesions correlated with the expanded disability status scale (r=0.32, P=0.045), the number of (juxta)cortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index. Our study underlines the high number of (juxta)cortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI. It also stresses the importance of (juxta)cortical lesions on determining neuropsychological impairment. Multiple Sclerosis (2000) 6 280 - 285

Adult↗
PubMed2000

Quality of life during the first 6 months of interferon-beta treatment in patients with MS.

OBJECTIVES: To determine the quality of life (QoL) of MS patients during the initial 6 months of treatment with interferon-beta (IFN-beta). Furthermore, to determine whether changes in QoL relate to disability, emotional state, therapeutic expectations or side effect profile. BACKGROUND: IFN-beta has been shown to have beneficial effects on the course of MS. Since the aim of IFN-beta treatment is not to cure but to slow down the disease it is important to know how this treatment affects QoL. Surprisingly, the impact of treatment with IFN-beta on QoL measures has not been extensively studied so far. METHODS: Case report documentation, including EDSS, SF-36 and MADRAS scores, of 51 relapsing-remitting MS patients treated with IFN-beta was obtained at baseline and at months 1, 3 and 6. Patients also filled in a form about their expectations of therapy and a questionnaire on side effects. RESULTS: During treatment there was a significant linear trend indicating improvement in the role-physical functioning (RPF) scale of the SF-36 (F(1,50)=4.9, P=0.032). A transient decrease at month 1 was found in the scale for bodily pain, indicating more experienced pain (F(1,50)=19.8, P<0.001). Subgroup analysis showed that patients with most depressive symptoms on the MADRAS at baseline contributed most to the increase in RPF scores over time (F(1,24)=5,6 P=0.026). Furthermore, we found associations between adverse event scores and several domains of QoL. CONCLUSIONS: Our findings suggest that IFN-beta therapy has an impact on QoL of MS patients in that it improves role-physical functioning and transiently worsens experienced bodily pain. QoL during treatment with IFN-beta is influenced by depressive symptoms at baseline as well as by treatment-associated side-effects. Multiple Sclerosis (2000) 6 338 - 342

Adjuvants, Immunologic↗
PubMed2000

Diagnostic criteria for primary progressive multiple sclerosis: a position paper.

The unique clinical characteristics of primary progressive multiple sclerosis (PPMS) pose particular diagnostic difficulties, both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS, which is not adequately addressed by current diagnostic criteria. This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS. (We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made.) Three levels of diagnostic certainty have been defined-definite, probable, and possible--based on clinical findings, abnormal cerebrospinal fluid, abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord, and evoked potentials. In definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required: (1) nine brain lesions, (2) two spinal cord lesions, or (3) four to eight brain lesions and one spinal cord lesion. Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS: 64% fulfilled the criteria for definite PPMS, 35% for probable PPMS, and only 1% for possible PPMS. These criteria now require prospective validation in a cohort of newly diagnosed patients and by postmortem examination.

Diagnosis, Differential↗
PubMed1999

Interferon (IFN)-beta treatment enhances CD95 and interleukin 10 expression but reduces interferon-gamma producing T cells in MS patients.

Interferon (IFN)-beta has been shown to favorably alter the disease course of relapsing-remitting multiple sclerosis (RRMS) patients. Although its mode of action is still unclear, there is ample evidence from in vitro studies that IFN-beta directly modulates the function of immune cells. We analyzed here the effects of IFN-beta treatment on immune functions in vivo in a group of 25 RRMS patients who received IFN-beta (8 MIU) on alternate days. At baseline and at 1, 3 and 6 months from the start of the treatment, parameters for differentiation and activation states of both monocytes and T lymphocytes were assessed. A transient increase was seen in plasma (p) interleukin (IL)-10 level whereas pIL-12 (p40) was not affected. A similar change was found in the ability of monocytes to secrete these cytokines in vitro. Notably, patients who in vitro readily responded to IFN-beta with enhanced IL-10 production had the highest pIL-10 levels. Concerning T-cell differentiation, flow cytometric analysis of cytokine production showed that treatment with IFN-beta moderately decreased the mean percentages of CD8pos T cells producing IL-2 and IFN-gamma and CD8neg T cells producing IL-4 (p<0.05 for all cytokines), whereas a more significant decline was seen in the mean percentage of CD8neg T cells producing IFN-gamma (p<0.01). This resulted in a significant lower ratio T(HELPER(H))1 vs. T(HELPER(H))2 type cells in the CD8pos T-cell subset (p<0.05), but not in the CD8neg T-cell subset. Finally, IFN-beta treatment resulted in an initial rise in the mean percentage of CD95pos T cells and in a gradual increase in the mean level of soluble CD95 (sCD95) in plasma (p<0.01). Additional in vitro studies showed that IFN-beta indeed rapidly (within 24 h) upregulates CD95 expression on both primed and unprimed T cells and augments the release of sCD95 in culture supernatants. Thus, we confirm here that IFN-beta treatment leads to similar changes in cytokine production of T cells and monocytes as previously described in vitro. Enhanced IL-10 secretion may downmodulate cytokine secretion by activated T cells and in this way dampen newly-induced and/or ongoing immune responses. In addition, we identified a novel effect of IFN-beta treatment, i.e., induction of CD95 expression. The augmentation of CD95 expression may directly interfere with T-cell selection, notably of autoaggressive T cells. Future studies are needed to show whether this increased CD95 expression indeed leads to increased apoptosis of immune cells.

Adjuvants, Immunologic↗
PubMed1999

Primary and transitional progressive MS: a clinical and MRI cross-sectional study.

BACKGROUND: Ten percent of patients with MS have a progressive course from onset with no history of relapses or remissions. A smaller subgroup follow a similar progressive course but have a single relapse at some point (transitional progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials. OBJECTIVE: To document the clinical and MRI characteristics of a large cohort of progressive patients, including 158 with primary progressive (PP) MS and 33 with TPMS. Data from a small reference group of 20 patients with secondary progressive (SP) MS are also presented for reference. METHODS: Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the brain and spinal cord. RESULTS: The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group. The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years). On MRI the PP group had lower mean brain T2 and T1 hypointensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015). The SP and TP cohorts had significantly more T2-weighted lesions in the spinal cord than the PP patients, and the SP cohort had the greatest degree of atrophy. There was a correlation in the PP and TP patients between EDSS score and brain and spinal cord atrophy (r = 0.3, 0.2, p < or = 0.006) but not with brain lesion load. The PP and TP patients who presented with spinal cord pathology had significantly lower brain T2 and T1 lesion loads than those with non-spinal cord presentations (p = 0.002). CONCLUSIONS: The monitoring of disease progression in PPMS is difficult, although measures of atrophy correlate with the EDSS and appear most promising. This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.

Adult↗
PubMed1999

Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis.

It has been shown that proinflammatory and antiinflammatory cytokines correlate with disease activity in multiple sclerosis (MS). To establish whether such correlations depend on the disease stage, we assessed in a longitudinal fashion the expression of interleukin (IL)-12 (p40 and p35), tumor necrosis factor-alpha, interferon-gamma, and IL-10 mRNA by competitive polymerase chain reaction in unstimulated peripheral blood mononuclear cells of relapsing-remitting (RR) and secondary progressive (SP) MS patients, in relation to monthly clinical and magnetic resonance imaging monitoring. MS patients had increased levels of IL-12p40 and decreased levels of IL-10 mRNA compared with controls; this difference was most pronounced in SP patients. Both RR and SP patients had increased levels of IL-12p40 mRNA compared with controls during the development of active lesions. Moreover, in RR MS an increase was found before relapse. IL-12p35 mRNA was decreased in both groups, and in relation to disease activity it showed a pattern different from IL-12p40 mRNA. In RR MS, IL-10 mRNA was low 4 weeks before magnetic resonance imaging activity and 6 weeks before relapse; a significant increase to normal levels was noted when active lesions became apparent. In contrast, SP patients showed low IL-10 mRNA levels constitutively, suggesting that IL-10 plays an important role in the control of disease progression.

Adult↗
PubMed1999

Neuronal damage in T1-hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy.

Hypointense T1 lesions in multiple sclerosis patients correlate with axonal loss at autopsy and biopsy. We evaluated the chemical substrate of hypointense T1 lesions by using in vivo proton magnetic resonance spectroscopy, and analyzed the spectroscopic correlate of increased T1-relaxation time measurements. Localized proton magnetic resonance spectroscopy and T1-relaxation time measurements were performed in lesions, selected on T1-weighted spin-echo magnetic resonance images according to degree of hypointensity, in normal appearing white matter (NAWM) and in normal white matter of controls. In NAWM, prolongation of T1-relaxation time and a decrease in N-acetylaspartate (NAA) were present, compared with normal white matter. Severely hypointense lesions showed a lower concentration of NAA and creatine compared with NAWM and a lower concentration of NAA compared with isointense to mildly hypointense lesions. NAA concentration correlated with degree of hypointensity of lesions and with T1-relaxation time within the spectroscopic voxel. Our results provide the first in vivo evidence of axonal damage in severely hypointense T1 lesions in multiple sclerosis patients. T1-relaxation time correlates with the concentration of NAA in both multiple sclerosis lesions and NAWM, indicating that this parameter deserves further evaluation to monitor disease progression.

Adult↗
PubMed1999

Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability.

Magnetic resonance imaging (MRI) monitoring of disease progression in multiple sclerosis is limited by the lack of correlation of abnormalities seen on T2-weighted imaging, and disability. We studied the histopathology of multiple sclerosis lesions, as depicted by MRI, in a large postmortem sample, focusing on axonal loss. Tissue samples from 17 patients were selected immediately postmortem for histopathological analysis on the basis of T2-weighted imaging, including normal appearing white matter and T1 hypointense lesions. In each region, we measured magnetization transfer ratios (MTR), T1 contrast ratio, myelin, and axonal density. T2 lesions (109 samples) were heterogeneous with regard to MRI appearance on T1 and MTR, whereas axonal density ranged from 0% (no residual axons) to 100% (normal axonal density). Of 64 T2 lesions, 17 were reactive (mild perivascular inflammation only), 21 active, 15 chronically active, and 11 chronically inactive. MTR and T1 contrast ratio correlated strongly with axonal density. Also in normal appearing white matter (24 samples), MTR correlated with axonal density. In conclusion, postmortem tissue sampling by using MRI revealed a range of pathology, illustrating the high sensitivity and low specificity of T2-weighted imaging. T1 hypointensity and MTR were strongly associated with axonal density, emphasizing their role in monitoring progression in multiple sclerosis.

Adult↗
PubMed1999

A comparison of responsiveness indices in multiple sclerosis patients.

Responsiveness was measured in a number of health-related quality of life (HRQoL) instruments among which two generic (SF-36 and COOP/WONCA Charts) and one disease-specific instrument, the Disability & Impact Profile (DIP). Subjects were 162 multiple sclerosis patients. The following responsiveness indices were used: effect size, standardised response mean and smallest real difference (SRD). The latter measure gives an indication of the magnitude of real change, i.e. change not attributable to 'noise' or 'error' and can thus be used for the interpretation of change scores in clinical practice whereby change scores larger than the SRD value indicate real change. It is assumed that low SRD values indicate high responsiveness. The results confirmed our expectation that the effect size and standardised response mean are probably less suitable for use in slowly progressive diseases, since they use the average change as the numerator. Therefore, the article focused on the SRD. Compared to scales, items measured on a visual analogue scale show high SRD values. The DIP scales generally show lower SRD values compared to scales of other questionnaires. The SRD seems to be a promising new measure to study responsiveness. More research into the interpretation of this measure is necessary.

Adult↗
PubMed1999

Factor structure of the Disability and Impact Profile in patients with multiple sclerosis.

The Disability and Impact Profile (DIP) is used for the measurement of quality of life in multiple sclerosis (MS) patients. Data from 211 persons with definite MS from Belgium, Denmark and the Netherlands were used to address three questions. To what extent do the impairment ratings and their complementary weighted scores share common variance? What is the factor structure of the weighted scores? To what extent do disease-related information and information from psychological questionnaires offer concurrent validity for the factors? Correlations between impairment ratings and the weighted item scores were high; for most items the complementary ratings of impact do not supplement information provided by impairment ratings. The DIP weighted scores can be represented to some extent by three independent dimensions: a motor (skeletal movement) or displacement ability factor, a factor relating to sensory-cognitive intactness and a psychological well-being factor. A two-factor solution provides a first factor identical to that of the three-factor solution and a second factor representing psychological well-being. The two factors correlate well with instruments measuring disability and with satisfaction versus emotional distress. Provisional scales based on the factors were constructed.

Activities of Daily Living↗
PubMed1999

Cardiovascular autonomic function in patients with relapsing remitting multiple sclerosis: a new surrogate marker of disease evolution?

Twenty patients with active relapsing remitting multiple sclerosis (MS) were examined annually for 2 years with a set of autonomic function tests (AFT) consisting of heart rate variability during deep breathing (IE), standing-up, and ratios of Valsalva manoeuvre (VR). Disease characteristics, including T2-weighted magnetic resonance imaging (MRI) of the brain and the expanded disability status scale (EDSS) score were documented each year within 1 week of the AFT. The EDSS score, MRI load lesion and VR did not change significantly over the follow-up period. The IE and initial heart-rate on standing during the first 30 s (DeltaHRMAX) showed significant worsening during follow-up. No relationship was found between deterioration of AFT and EDSS score, number of exacerbations, duration of disease, gender, age, size and number of lesions on MRI. We conclude that patients with active relapsing remitting MS show progression of autonomic dysfunction over a relatively short time. Therefore, in the absence of changes in clinical disability or brain MRI lesion load, AFT might be useful as a sensitive surrogate outcome measure for demonstrating subclinical change in MS.

Adult↗
PubMed1999

Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates.

The relative rarity of primary progressive (PP) and transitional progressive (TP) multiple sclerosis has meant that little documentation of cognitive function in such patients is currently available. The aim of this study was to investigate the cognitive skills of patients with PP and TP multiple sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters. Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same cognitive tasks as the patient group. The neuropsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of depression. Patients also underwent T1- and T2-weighted brain MRI. These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that the re were no significant differences between the mean scores of the PP and TP groups on any of the cognitive variables. The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of verbal memory, attention, verbal fluency and spatial reasoning. An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-hypointensity load (r = 0.45, P = 0.01) and cerebral volume (r = -0.35, P = 0.01). Thus, PP and TP multiple sclerosis patients demonstrate significant cognitive dysfunction when compared with matched healthy controls. The relationship between this impairment and MRI parameters is moderate, suggesting that cognitive dysfunction in PP and TP multiple sclerosis has a complex and multifactorial aetiology, which is not adequately explained by pathology as demonstrated on conventional MRI.

Adult↗