PubMed Health⌕ Search

Biomedical subjects

B M J Uitdehaag

Publications and source records attributed to B M J Uitdehaag.

At least 19 recordsLinked to original sources
PubMed2006

The usefulness of evaluative outcome measures in patients with multiple sclerosis.

To select the most useful evaluative outcome measures for early multiple sclerosis, we included 156 recently diagnosed patients in a 3-year follow-up study, and assessed them on 23 outcome measures in the domains of disease-specific outcomes, physical functioning, mental health, social functioning and general health. A global rating scale (GRS) and the Expanded Disability Status Scale (EDSS) were used as external criteria to determine the minimally important change (MIC) for each outcome measure. Subsequently, we determined whether the outcome measures could detect their MIC reliably. From these, per domain the outcome measure that was found to be most sensitive to changes (responsive) was identified. At group level, 11 outcomes of the domains of physical functioning, mental health, social functioning and general health could reliably detect the MIC. Of these 11, the most responsive measures per domain were the Medical Outcome Study 36 Short Form sub-scale physical functioning (SF36pf), the Disability and Impact Profile (DIP) sub-scale psychological, the Rehabilitation Activities Profile sub-scale occupation (RAPocc) and the SF36 sub-scale health, respectively. Overall, the most responsive measures were the SF36pf and the RAPocc. In individual patients, none of the measures could reliably detect the MIC. 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).

Activities of Daily Living↗
PubMed2006

Proxy measurements in multiple sclerosis: agreement between patients and their partners on the impact of multiple sclerosis in daily life.

BACKGROUND: The use of self-report measurements in clinical settings has increased. The underlying assumption for self-report measurements is that the patient understands the questions fully and is able to give a reliable assessment of his or her own health status. This might be problematic in patients with limitations that interfere with reliable self-assessment such as cognitive impairment or serious mood disturbances, as may be the case in multiple sclerosis. In these situations proxies may provide valuable information, provided we can be certain that proxies and patients give consistent ratings. OBJECTIVE: To examine whether patients with multiple sclerosis and their partners agree on the impact of multiple sclerosis on the daily life of the patient by using the Multiple Sclerosis Impact Scale (MSIS-29). METHODS: 59 patients with multiple sclerosis and their partners completed the MSIS-29. Agreement was examined, comprehensively at scale score levels and item functioning, using both traditional and less conventional psychometric methods (Rasch analysis). RESULTS: Agreement between patients and partners was good for the physical scale, and slightly less but still adequate for the psychological scale. Mean directional differences did not show considerable systematic bias between patients and proxies. Intraclass correlation coefficients (ICCs) satisfied the requirements for agreement, but were higher for the physical scale (0.81) than for the psychological scale (0.72). These findings were supported by Rasch analyses. CONCLUSION: In this sample, albeit small, partners provided accurate estimates of the impact of multiple sclerosis. This supports the value of self-rating scales and indicates that partners might be useful sources of information when assessing the impact of multiple sclerosis on the daily life of patients.

Adult↗
PubMed2006

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

BACKGROUND: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. METHODS: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. RESULTS: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of epsilon2 or epsilon4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96-1.34 and OR 0.89, 95% CI 0.78-1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative (p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. CONCLUSION: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.

Alleles↗
PubMed2006

Classification of multiple sclerosis patients by latent class analysis of magnetic resonance imaging characteristics.

BACKGROUND: Disease heterogeneity is a major issue in multiple sclerosis (MS). Classification of MS patients is usually based on clinical characteristics. More recently, a pathological classification has been presented. 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. OBJECTIVES: To investigate whether a restricted classification of MS patients can be made based on a combination of quantitative and qualitative MRI characteristics and to test whether the resulting subgroups are associated with clinical and laboratory characteristics. METHODS: MRI examinations of the brain and spinal cord of 50 patients were scored for 21 quantitative and qualitative characteristics. Using latent class analysis, subgroups were identified, for whom disease characteristics and laboratory measures were compared. RESULTS: Latent class analysis revealed two subgroups that mainly differed in the extent of lesion confluency and MRI correlates of neuronal loss in the brain. Demographics and disease characteristics were comparable except for cognitive deficits. No correlations with laboratory measures were found. CONCLUSIONS: Latent class analysis offers a feasible approach for classifying subgroups of MS patients based on the presence of MRI characteristics. The reproducibility, longitudinal evolution and further clinical or prognostic relevance of the observed classification will have to be explored in a larger and independent sample of patients.

Adult↗
PubMed2006

Clinical impact of 20% worsening on Timed 25-foot Walk and 9-hole Peg Test in multiple sclerosis.

INTRODUCTION: Quantitative tests of motor function, like the Timed 25-foot Walk (T25FW) and 9-hole Peg Test (9HPT), are increasingly being applied as outcome measures in multiple sclerosis (MS) clinical trials. The quantitative nature of the data has a favorable impact on responsiveness, but the clinical impact of the changes is uncertain. The goal of this study was to assess whether a change on T25FW and 9HPT does indeed have a clinical meaning. This was accomplished by comparing 20% changes on these quantitative measurements to concomitant changes on the Guy's Neurological Disability Scale (GNDS), a scale which measures patient-perceived daily life disability. METHODS: From a longitudinal database, we selected patients with at least two measurements of T25FW, 9HPT and GNDS with a minimal time interval of 350 days. In those patients who experienced at least a 20% change on T25FW or 9HPT, GNDS score changes were examined more closely. RESULTS: Of 527 patients, 143 experienced a >20% worsening on their T25FW and 71 on their 9HPT, respectively. Patients with a 20% increase in T25FW or 9HPT had more GNDS worsening than patients without such an increase. GNDS worsening associated with an increase in T25FW was mainly due to an increase in perceived disability related to lower extremity function and fatigue; GNDS worsening associated with an increase in 9HPT was more diffuse with respect to domains involved. CONCLUSION: Worsening on T25FW or 9HPT has a clinical impact on disability, as perceived by MS patients during daily life functioning.

Adult↗
PubMed2006

The new global multiple sclerosis severity score (MSSS) correlates with axonal but not glial biomarkers.

This study investigated whether the new Global Multiple Sclerosis Severity Scale (MSSS) correlated with cerebrospinal fluid biomarkers for axonal and glial pathology. The MSSS correlated with the phosphorylated neurofilament heavy chain (NfH-SM135, R=0.44, P=0.016). The degree of neurofilament phosphorylation (ratio NfH-SM134 to NfH-SM135) was 8-fold higher in severely (median MSSS 6.5) versus mildly (MSSS 3.2) disabled patients (7.3 versus 0.9, P = 0.03). The MSSS may provide a statistically powerful tool for comparing overall disease severity and be useful for validating the biomarker concept in MS.

Adult↗
PubMed2005

Lack of association between VEGF polymorphisms and ALS in a Dutch population.

Sequence alterations in the promoter region of the vascular endothelial growth factor (VEGF) gene have been implicated in increasing the risk of developing ALS. VEGF promoter haplotypes were determined in 373 patients with sporadic ALS and 615 matched healthy controls in The Netherlands. No significant association between the previously reported at-risk haplotypes and ALS was found. Pooling our results with the previously studied population still showed a significant association with the AAG haplotype.

Adult↗
PubMed2005

Patterns of enhancing lesion evolution in multiple sclerosis are uniform within patients.

BACKGROUND: Histopathologic studies suggest that lesion development differs between patients with multiple sclerosis (MS), but that all lesions appear similar within patients. It is unclear whether the same applies to the evolution of lesions on T1-weighted MRI. OBJECTIVE: To evaluate lesion evolution on MRI, comparing variance within and between patients, as well as the relationship between MRI lesion development and clinical characteristics. METHODS: In 48 patients, signal intensity at baseline and at follow-up on T1-weighted MRI of 789 newly enhancing lesions was studied in relationship with clinical data. Patients were included on the basis of showing at least five enhancing lesions that could be followed on monthly scans for 6 months. Variance component analysis and multilevel analysis were used to compare within-patient and between-patient variability. RESULTS: Although various types of lesion evolution could be observed within a single patient, between-patient variance was considerably larger than within-patient variance for MRI parameters used to describe lesion evolution, indicating that lesion evolution is a patient-specific phenomenon. Evolution of lesions in patients with secondary progressive disease more frequently followed a hypointense-hypointense pattern than in patients with relapsing-remitting disease (odds ratio 4.2). Patients with a benign disease course had more persistent isointense lesions at follow-up, whereas patients with aggressive disease had more hypointense lesions. CONCLUSION: Lesion evolution on MRI appears to be a patient-specific phenomenon, although the outcome seems to vary according to the phase and severity of the disease.

Central Nervous System↗
PubMed2005

Exercise therapy for multiple sclerosis.

BACKGROUND: No intervention has proven effective in modifying long-term disease prognosis in Multiple Sclerosis (MS) but exercise therapy is considered to be an important part of symptomatic and supportive treatment for these patients. OBJECTIVES: To assess the effectiveness of exercise therapy for patients with MS in terms of activities of daily living and health-related quality of life. SEARCH STRATEGY: We searched the Cochrane MS Group Specialised Register (searched: March 2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (from 1966 to March 2004), EMBASE (from 1988 to March 2004 ), CINAHL (from 1982 to March 2004), PEDro (from 1999 to March 2004) . Manual search in the journal 'Multiple Sclerosis' and screening of the reference lists of identified studies and reviews. We also searched abstracts published in proceedings of conferences. SELECTION CRITERIA: Randomised Controlled Trials (RCTs) that reported on exercise therapy for adults with MS, not presently experiencing an exacerbation; outcomes that include measures of activity limitation or health-related quality of life or both. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and methodological quality of the included trials. Disagreements were resolved by discussion. The results were analysed using a best-evidence synthesis based on methodological quality. MAIN RESULTS: Nine high-methodological-quality RCTs(260 participants) met the inclusion criteria. Six trials focussed on comparison of exercise therapy versus no exercise therapy, whereas three trials compared two interventions that both met our definition of exercise therapy. Best evidence synthesis showed strong evidence in favour of exercise therapy compared to no exercise therapy in terms of muscle power function, exercise tolerance functions and mobility-related activities. Moderate evidence was found for improving mood. No evidence was observed for exercise therapy on fatigue and perception of handicap when compared to no exercise therapy. Finally, no evidence was found that specific exercise therapy programmes were more successful in improving activities and participation than other exercise treatments. No evidence of deleterious effects of exercise therapy was described in included studies. AUTHORS' CONCLUSIONS: The results of the present review suggest that exercise therapy can be beneficial for patients with MS not experiencing an exacerbation. There is an urgent need for consensus on a core set of outcome measures to be used in exercise trials. In addition, these studies should experimentally control for 'dose' of treatment, type of MS and should include sufficient contrast between experimental and control groups.

Exercise Therapy↗
PubMed2005

MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter.

Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetyl-aspartate), while the concentration of NAAG (N-acetyl-aspartyl-glutamate) was slightly-but significantly-elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. In conclusion, MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers (increase of Ins and tCr) without evidence of axonal dysfunction (normal NAA). Further studies should elucidate the mechanism underlying increased NAAG in MS NAWM.

Adolescent↗
PubMed2005

Axonal damage accumulates in the progressive phase of multiple sclerosis: three year follow up study.

BACKGROUND: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information. METHOD: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfH(SMI35), NfH(SMI34)) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfH(SMI34):NfH(SMI35) ratio), and changes in NfH levels between baseline and follow up (Delta NfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability. RESULTS: A significantly higher proportion (59%) of patients with SP/PPMS experienced an increase in NfH(SMI35) levels between baseline and follow up compared with those with RRMS (14%, p<0.05). CSF NfH(SMI34) levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, p<0.05) and NfH(SMI35) levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (p<0.05). NfH(SMI35) correlated with the EDSS (r(s) = 0.54, p<0.01), the AI (r(s) = 0.42, p<0.05), and the 9HPT (r(s) = 0.59, p<0.01) at follow up. CONCLUSION: The increase in NfH during the progressive phase of the disease together with the correlation of NfH(SMI35) with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfH(SMI35) levels are a poor prognostic sign.

Adolescent↗
PubMed2005

Psychometric evaluation of the multiple sclerosis impact scale (MSIS-29) for proxy use.

BACKGROUND: There may be difficulties in the use of self report measurements in patients with cognitive impairment or serious mood disturbances which interfere with reliable self assessment, as may be the case in multiple sclerosis (MS). 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. OBJECTIVE: To evaluate the psychometric properties of the 29 item Multiple Sclerosis Impact Scale (MSIS-29) when used by proxies of MS patients. METHODS: A sample of 62 partners of MS patients completed the MSIS-29. The data were evaluated for the psychometric criteria of the MSIS-29, including data quality, scaling assumptions, acceptability, reliability, validity, and responsiveness. RESULTS: Psychometric evaluation was satisfactory; data quality was high, and scaling assumptions and acceptability were good. Reliability was high (alpha>0.80). Findings were consistent with results of a psychometric evaluation in a patient sample. CONCLUSIONS: The MSIS-29 can be used reliably in proxies of patients with MS. As a next step the relation between data obtained from patients and proxies needs to be studied, focusing on factors that may affect agreement and discrepancies.

Adult↗
PubMed2005

Sex differences in proinflammatory cytokine profiles of progressive patients in multiple sclerosis.

The objective of this article is to evaluate the presence of sex differences in expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients. The predominance of females in MS and other autoimmune diseases may be related to their differential responses in many immunological settings. Recent data show beneficial effect of sex hormones on proinflammatory cytokine levels and on magnetic resonance imaging in MS. Better understanding of gender differences is warranted. In this study 124 MS subjects (M:F; 56:68) and 34 healthy controls (M:F; 12:22) were included. Stimulated peripheral blood-derived CD4+ and CD8+ T cells were analysed for interferon-gamma, interleukin (IL)-2, tumour necrosis factor alpha, IL-4, IL- 10 and IL- 13 production. There were no significant differences for these cytokines between male and female MS subjects in the whole group. Compared to males, female patients had higher proinflammatory cytokine levels in the progressive phase of the disease. 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.

Adult↗
PubMed2005

Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis.

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system, with lesions widespread through the brain and spinal cord. An important manifestation is cognitive impairment, which, though difficult to measure, may have a major social impact. To better understand the relationship between structural tissue damage and cognitive impairment, we examined the extent and spatial distribution of brain lesions, as measured by magnetic resonance imaging (MRI), in relation to abnormal cognitive performance as measured by the Brief Repeatable Battery (BRB) in 82 MS patients. Possible confounders, like fatigue, pain and depression were also assessed. Brain MR image analysis included hyperintense T2 and hypointense T1 lesion load in the whole brain and the four lobes separately, as well as whole brain volume measurements. Cognitive impairment (defined as more than two abnormal tests) was found in 67% of the patients. Moderately strong correlations were found between the subtests of the BRB and the lesion loads in the brain regions hypothesized to be associated with that cognitive test, although these correlations were in general not much stronger than those between the subtests and the overall lesion load (due to strong interrelationships). The Spatial Recall Test correlated best with parietal lesion load; the Symbol Digit Modalities Test, the Paced Auditory Serial Addition Task (PASAT) and the Word List Generation best with frontal, parietal and temporal lesion load; while the Verbal List Generation Test Index correlated only with atrophy. Atrophy and lesion load were the main factors determining the test scores, explaining 10-25% of the variance in the test results, and were more important than fatigue, pain and depression; only depression had a minor, but significant, additional effect on the PASAT. 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.

Adult↗
PubMed2004

Value of health-related quality of life to predict disability course in multiple sclerosis.

OBJECTIVE: To determine the value of health-related quality of life (HRQoL) to predict change in disability status in patients with multiple sclerosis (MS). METHODS: Over a 5-year period, data were collected on HRQoL (Medical Outcomes Study Short Form-36 Health Survey) and disability status (Expanded Disability Status Scale) from a heterogeneous group of 81 Dutch-speaking patients with MS. RESULTS: Multivariate logistic regression analysis showed that HRQoL in the domains of Physical Functioning and Role-Physical Functioning is a significant predictor of change in disability status. CONCLUSIONS: A patient's subjectively perceived health-related quality of life may not be only a clinically and psychosocially meaningful outcome per se but may also be a predictor of objective outcomes such as change in disability status over a substantial period of time.

Adult↗
PubMed2004

CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis.

OBJECTIVE: To investigate the relationship of CSF and the serum nitric oxide metabolites nitrite and nitrate (NOx) to disease activity and progression in patients with multiple sclerosis (MS). METHODS: The study was divided into cross-sectional and follow-up. In the cross-sectional study, 20 patients with relapsing-remitting (RR), 21 with secondary progressive (SP), and 10 with primary progressive (PP) MS and 14 control subjects were included. Patients were assessed on clinical (Expanded Disability Status Scale [EDSS], Ambulation Index [AI], 9-Hole Peg Test [9-HPT]) and MRI measurements. In the follow-up study, 34 MS patients from the cross-sectional study agreed to be assessed again after an average of 3.0 +/- 0.5 years. NOx was measured using a vanadium-based assay. RESULTS: In the cross-sectional study, CSF NOx was raised in patients with RR-MS (p = 0.001) and PP-MS (p = 0.02) vs controls. Higher CSF NOx levels were found in patients with mild disability (AI < or = 6.0; EDSS < or = 4.0; Multiple Sclerosis Severity Score [MSSS] < or = 4.8) vs patients with advanced disease (AI > 6.0 [p = 0.002]; EDSS > 4.0 [p = 0.02]; MSSS > 4.8 [p = 0.01]). In the subgroup of patients having Gd-enhancing MRI lesions (n = 11), correlation between the volume of enhancement and CSF NOx was found (r = 0.74, p = 0.01). In the follow-up study, patients with disability progression had higher baseline CSF NOx levels than those who were stable on EDSS (p = 0.02) or AI (p = 0.03). A positive correlation was found between baseline CSF NOx and the change in MR T2-weighted lesion load (r = 0.4, p = 0.03). CONCLUSIONS: CSF nitrite and nitrate levels were increased in mildly disabled patients with MS and found to correlate with the volume of Gd-enhanced lesions on MRI. Raised baseline CSF NOx was associated with clinical and MRI progression in MS patients over 3-year follow-up.

Adult↗
PubMed2004

Surgical treatment options for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome is a common disorder, for which several surgical treatment options are available. OBJECTIVES: To compare the efficacy of the various surgical techniques in relieving symptoms and promoting return to work and/or activities of daily living and to compare the occurrence of side-effects and complications, in patients suffering from carpal tunnel syndrome. SEARCH STRATEGY: We updated the searches in 2003. We conducted computer-aided searches of the trials register of the Cochrane Neuromuscular Disease Group (searched in July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (January 1966 to August 2003), EMBASE (January 1980 to August 2003) and tracked references in bibliographies. SELECTION CRITERIA: Randomised controlled trials comparing various surgical techniques for the treatment of carpal tunnel syndrome. DATA COLLECTION AND ANALYSIS: Two reviewers performed study selection, assessment of methodological quality and data abstraction independently of each other. MAIN RESULTS: Twenty-three studies were included in the review. The methodological quality of the trials was fair to good. However, the application of allocation concealment was mentioned explicitly in only one trial. Many studies failed to present the results in sufficient detail to enable statistical pooling. Pooling was also impeded by the vast variety of outcome measures that were applied in the various studies. None of the existing alternatives to standard open carpal tunnel release seem to offer better relief from symptoms in the short- or long-term. There was conflicting evidence about whether endoscopic carpal tunnel release resulted in earlier return to work and/or activities of daily living than open carpal tunnel release. REVIEWERS' CONCLUSIONS: There is no strong evidence supporting the need for replacement of standard open carpal tunnel release by existing alternative surgical procedures for the treatment of carpal tunnel syndrome.

Carpal Tunnel Syndrome↗