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Bernard M J Uitdehaag

Publications and source records attributed to Bernard M J Uitdehaag.

At least 19 recordsLinked to original sources
PubMed2006

Interobserver agreement on the radiological criteria of the International Panel on the diagnosis of multiple sclerosis.

We assessed the interobserver agreement on the radiological part of the International Panel (IP) criteria for the diagnosis of multiple sclerosis (MS), comprising the assessment of dissemination in space (DIS) and time (DIT) based exclusively on MRI. Four radiologists trained and four radiologists naive in the application of the IP criteria scored the fulfillment for DIS (i.e., > or =3 periventricular, > or =1 infratentorial, > or =1 juxtacortical, > or = 1 enhancing lesion or a total of > or =9 T2-weighted lesions) and DIT (presence of new or enhancing lesions at follow-up) in baseline and two follow-up scans from 20 patients suspected for having MS. The IP-trained radiologists agreed at least moderately on all assessments (kappa>0.40), whereas the IP-naive radiologists showed fair agreement (kappa<0.40) on five of 16 assessments. In the final conclusion on DIS and DIT, the IP-trained radiologists agreed substantially on both items (kappa=0.62 and kappa=0.60, respectively) compared with a fair agreement on DIS (kappa=0.29) and moderate agreement on DIT (kappa=0.52) among the IP-naive radiologists. Given the poor interobserver agreement among IP-naive observers, the new IP criteria for MS require additional training and should perhaps be simplified.

Adolescent↗
PubMed2006

Analysing the effect of candidate genes on complex traits: an application in multiple sclerosis.

The conventional approach of candidate gene studies in complex diseases is to look at the effect of one gene at a time. However, as the outcome of chronic diseases is influenced by a large number of alleles, simultaneous analysis is needed. We demonstrate the application of multivariate regression and cluster analysis to a multiple sclerosis (MS) dataset with genotypes for 489 patients at 11 candidate genes selected on their involvement in the immune response. Using multivariate regression, we observed that different sets of genes were associated with different disease characteristics that reflect different aspects of disease. Out of 15 polymorphisms, we identified one that contributed to the severity of disease. In addition, the set of 15 polymorphisms was predictive for yearly increase in lesion volume as seen on T1-weighted MRI (p=0.044). From this set, no individual polymorphisms could be identified after adjustment for multiple hypotheses testing. By means of a cluster analysis, we aimed to identify subgroups of patients with different pathogenic subtypes of MS on the basis of their genetic profile. We constructed genetic profiles from the genotypes at the 11 candidate genes. The approach proved to be feasible. We observed three clusters in the sample of patients. In this study, we observed no significant differences in the usual clinical and MRI outcome measures between the different clusters. However, a number of consistent trends indicated that this clustering might be related to the course of disease. With a larger number of genes regulating the course of disease, we may be able to identify clinically relevant clusters. The analyses are easily implemented and will be applicable to candidate gene studies of complex traits in general.

Adult↗
PubMed2006

MR spectroscopic evidence for thalamic and hippocampal, but not cortical, damage in multiple sclerosis.

Gray matter (GM) damage is an important pathophysiological feature in Multiple Sclerosis (MS), and may be related to clinical, including cognitive, deficits. Quantitative single-voxel (1)H-Magnetic Resonance Spectroscopy (TR/TE 6000/20 ms) was performed in 33 MS patients (11 per disease subtype; mean age 48 years, 16 females) and 10 healthy controls (mean age 43 years, 7 females). No overall spectroscopic changes were found in MS cortex. In MS thalamus, a 9% decrease of N-acetyl aspartate (NAA; P=0.005) and a 31% increase of myo-inositol (Ins; P=0.002) were found. A 21% Ins increase was observed (P=0.02) in MS hippocampus. Reduced NAA and increased Ins concentrations are thought to reflect neuro-axonal damage or loss and gliosis, respectively. Significant correlations between Ins concentrations and total-brain T(2) lesion load were found for MS thalamus (r=0.65, P<0.001) and hippocampus (r=0.57, P=0.001). MS thalamic and hippocampal Ins concentrations also correlated with each other (r=0.68; P<0.001). Cortical Gln correlated with thalamic NAA (r=-0.38; P=0.03) in MS. Thalamic and hippocampal Ins increases were most prominent in secondary-progressive (SP) patients (37% and 34%, respectively), whereas the largest thalamic NAA decrease (14%) was found in primary-progressive (PP) patients. In conclusion, thalamic and hippocampal GM pathology are important features of (progressive) MS.

Adult↗
PubMed2006

Accessory nerve to suprascapular nerve transfer to restore shoulder exorotation in otherwise spontaneously recovered obstetric brachial plexus lesions.

OBJECTIVE: A systematic follow-up of infants with an obstetric brachial plexus lesion of C5 and C6 or the superior trunk showing satisfactory spontaneous recovery of shoulder and arm function except for voluntary shoulder exorotation, who underwent an accessory to suprascapular nerve transfer to improve active shoulder exorotation, to evaluate for functional recovery, and to understand why other superior trunk functions spontaneously recover in contrast with exorotation. METHODS: In 54 children, an accessory to suprascapular nerve transfer was performed as a separate procedure at a mean age of 21.7 months. Follow-up examinations were conducted before and at 4, 8, 12, 24, and 36 months after operation and included scoring of shoulder exorotation and abduction. Intraoperative reactivity of spinatus muscles and additional needle electromyographic responses were registered after electrostimulation of suprascapular nerves. Histological examination of suprascapular nerves was performed. Trophy of spinatus muscles was followed by magnetic resonance imaging scanning. The influence of perinatal variables and results of ancillary investigations on outcome were evaluated. RESULTS: Exorotation improved from 70 degrees to functional levels exceeding 0 degrees, except in two patients. Abduction improved in 27 patients, with results of 90 degrees or more in 49 patients. Electromyography at 4 months did not show signs of denervation in 39 out of 40 patients. Intraoperative electrostimulation of suprascapular nerves elicited spinatus muscle reaction in 44 out of 48 patients. Histology of suprascapular nerves was normal. Preoperative magnetic resonance imaging scans showed only minor wasting of spinatus muscles in contrast with major wasting after successful operations. CONCLUSION: An accessory to suprascapular nerve transfer is effective to restore active exorotation when performed as the primary or a separate secondary procedure in children older than 10 months of age. Contradictory spontaneous recovery of other superior trunk functions and integrity of suprascapular nerves, as well as absence of spinatus muscle wasting direct to central nervous changes are possible main causes for the lack of exorotation.

Accessory Nerve↗
PubMed2005

Overdiagnosis of multiple sclerosis and magnetic resonance imaging criteria.

Retrospectively, we assessed the specificity of two proposed magnetic resonance imaging (MRI) criteria for multiple sclerosis (MS) in patients suspected to have MS but who ultimately receive another diagnosis. Brain MRIs of 28 patients mixed with 28 MRIs of MS patients from the same cohort of 377 consecutively referred patients were scored by a neuroradiologist masked to the final diagnosis. The criteria for dissemination in space incorporated in the McDonald International Panel showed good specificity (89%). However, the more sensitive criteria proposed by a Subcommittee of the American Academy of Neurology resulted in a lower specificity (29%), indicating an increased risk of a false-positive diagnosis.

Adult↗
PubMed2005

Expression of adhesion molecules on peripheral lymphocytes predicts future lesion development in MS.

The expression of adhesion molecules (alpha4beta1-integrin, LFA-1, ICAM-1) on T cells, measured by flow cytometry, was compared in different subtypes of multiple sclerosis (MS) and related to future lesion development as seen as delta T1 and T2 lesion load per year on magnetic resonance imaging (MRI). LFA-1 and alpha4beta1-integrin showed higher expression on CD4 and CD8 T lymphocytes in the secondary progressive compared to the relapsing-remitting (CD4: p<0.01, p=ns, p<0.05; CD8: p<0.001, p<0.001, p<0.001, respectively) and primary progressive MS phase (CD4: p<0.001, p<0.01, p<0.05; CD8: p<0.01, p<0.01, p<0.001, respectively). The adhesion molecule expression of alpha4- (r=0.31; p<0.05) and beta1-integrin (r=0.38; p<0.01) on CD4+ cells and of LFA-1beta on both CD4+ and CD8+ (r=0.28, p<0.05) and r=0.29; p<0.05, respectively) cells was significantly related to increase in T2 lesion load. Our study provides further evidence for the involvement of integrins in lesion development, shown as T2 lesions on MRI in MS.

Adult↗
PubMed2005

The impact of glucocorticoid receptor gene polymorphisms on glucocorticoid sensitivity is outweighted in patients with multiple sclerosis.

Glucocorticoid (GC) sensitivity varies considerably in healthy controls as well as in patients with chronic inflammatory diseases like multiple sclerosis (MS). We investigated whether polymorphisms in the glucocorticoid receptor (N363S, ER22/23EK, and the BclI) were responsible for altered GC sensitivity. In healthy controls we found an association between the N363S allele of the GR and a reduced peripheral GC sensitivity. In MS patients neither the variant N363S, the BclI RFLP nor the ER22/23EK allele were found to be associated with GC sensitivity. GC sensitivity is probably in part genetically influenced in healthy controls, but in MS patients other factors seem to have more impact on GC sensitivity.

Analysis of Variance↗
PubMed2005

Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging.

PURPOSE: To prospectively compare the depiction of intracortical lesions by using multislab three-dimensional (3D) double inversion-recovery (DIR), multislab 3D fluid-attenuated inversion-recovery (FLAIR), and T2-weighted spin-echo (SE) magnetic resonance (MR) imaging in patients with multiple sclerosis. MATERIALS AND METHODS: Local ethics review board approval and informed consent were obtained. Conventional T2-weighted SE and multislab 3D FLAIR and DIR images were acquired in 10 patients with multiple sclerosis (five women, five men) and 11 age-matched healthy control subjects (seven women, four men). Mean age was 40 years (range, 25-54 years) in patients and 34 years (range, 24-55 years) in control subjects. Lesions were classified according to seven anatomic regions: intracortical, mixed white matter-gray matter, juxtacortical, deep gray matter, periventricular white matter, deep white matter, and infratentorial lesions. The numbers of lesions per category were compared between techniques (Dunnett-corrected analysis of variance). Gain or loss (with 95% confidence intervals [CIs]) of numbers of lesions detected at 3D DIR imaging was calculated in comparison with those detected at T2-weighted SE and 3D FLAIR imaging. RESULTS: Total number of lesions did not differ between 3D DIR and 3D FLAIR sequences, but the 3D DIR sequence showed a gain of 21% (95% CI: 4%, 41%) in comparison with the T2-weighted SE sequence. Because of high gray matter-white matter contrast, DIR images depicted more intracortical lesions (80 lesions in 10 patients) than both SE (10 lesions) and FLAIR (31 lesions) images; gains with DIR were 538% (95% CI: 191%, 1297%) and 152% (95% CI: 15%, 453%) compared with SE and FLAIR, respectively. Only four intracortical lesions were detected in control subjects. Also, DIR imaging enabled a better definition of mixed white matter-gray matter lesions because of greater contrast between the lesion and its surroundings. CONCLUSION: MR imaging with 3D DIR enables increased intracortical lesion detection in the multiple sclerosis brain, as well as improved distinction between juxtacortical and white matter-gray matter lesions.

Adult↗
PubMed2005

Discrepancies in the interpretation of clinical symptoms and signs in the diagnosis of multiple sclerosis. A proposal for standardization.

The new McDonald diagnostic criteria for multiple sclerosis (MS) incorporate detailed criteria for the interpretation and classification of magnetic resonance imaging (MRI) findings, but, in contrast, provide no instructions for the interpretation of clinical findings. Because MS according to the McDonald criteria is one of the primary endpoints in a large trial enrolling patients after the first manifestation suggestive for a demyelinating disease (BENEFIT study), it was decided to organize a centralized eligibility assessment for this trial. During this eligibility assessment it was observed that there were marked inconsistencies in the decisions of participating neurologists with respect to the classification of clinical symptoms as being caused by one or more lesions provoking discussions in about one in every five patients. This paper describes these inconsistencies and their sources, and recommends a systematic approach that attempts to reduce the variability in interpreting clinical findings.

Adolescent↗
PubMed2005

Correlating nerve conduction studies and clinical outcome measures on carpal tunnel syndrome: lessons from a randomized controlled trial.

The reported relationships between nerve conduction studies (NCS) and outcome measures in carpal tunnel syndrome (CTS) are weak to moderate. However, selection of patients may have confounded nonrandomized studies. NCS have potentially great value in selecting patients for a specific treatment and in objectively assessing the efficacy of treatments in CTS, especially if they correlate significantly with clinical outcome measures. To investigate the relationship between clinical outcome measures for the severity of complaints and NCS in patients treated for CTS, data were obtained from a multicenter randomized controlled trial on the efficacy of splinting versus surgery for CTS. At baseline and 12 months after randomization, clinical outcome measures were assessed and NCS were performed. In total, 138 patients completed the questionnaires and underwent repeated NCS. Relationships were analyzed with Spearman rank correlation coefficients and Pearson correlation coefficients. All NCS parameters showed highly significant improvement compared with baseline (P < 0.001). Modest correlations (< 0.4) were found between the neurophysiologic and clinical outcome measures after 12 months, and between the changes in these different categories of outcome measures. This study confirms that the parameters of NCS improve significantly after treatment for CTS, but the modest correlations between neurophysiologic and clinical outcome measures do not support that NCS are routinely performed in clinical practice to evaluate treatment effects. However, studies investigating the effects of treatment for CTS should incorporate both clinical outcome measures and NCS, because they are complementary. Furthermore, NCS can provide additional information to the clinician when treatment effects are unsatisfactory.

Adult↗
PubMed2004

Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis.

Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients and appeared to be negatively associated with acute inflammation. Exogenous GC are frequently used to treat relapses in MS, but the response to this treatment differs among patients, suggesting differences in sensitivity to GC. Previous, relatively small studies investigating GC sensitivity have yielded conflicting results. In the present study, we have investigated GC sensitivity in peripheral blood cells of MS patients (n = 117) and healthy controls (n = 45). GC sensitivity was measured by the in vitro suppressive effect of GC on lipopolysaccharide-stimulated TNF-alpha production. Blood cells of MS patients, especially relapsing remitting MS patients, were less sensitive to GC compared with blood cells of healthy controls. This turned out to be unrelated to previous treatment with exogenous GC expressed as frequency of courses of iv steroids or interval since last course. The use of interferon beta was found to be associated with a lower GC sensitivity. However, after correction for the use of interferon beta, relapsing remitting MS patients remained less sensitive to GC.

Adult↗
PubMed2004

Relation between objective and subjective measures of bladder dysfunction in multiple sclerosis.

The authors studied 297 patients with multiple sclerosis (MS), correlating urinary symptoms (bowel/bladder Functional System [FS] score of the Expanded Disability Status Scale [EDSS] and bladder dysfunction score of the Guy's Neurological Disability Scale [GNDS[) vs objective measurement of bladder dysfunction (postmicturition residual volume). EDSS and GNDS were of no value for predicting the presence of a clinically relevant postvoiding volume. Therefore, the authors recommend ultrasound scanning of residual volume in every patient with MS, even in the absence of subjective urinary symptoms.

Adult↗
PubMed2004

Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis.

BACKGROUND: The number and volume of abnormalities on baseline brain magnetic resonance images in patients with initial findings suggestive of multiple sclerosis are known to predict outcome in terms of disability. However, no long-term data exist on specific locations or types of lesions. OBJECTIVE: To assess the long-term predictive value of baseline magnetic resonance imaging parameters, including location of lesions and gadolinium-enhancing and hypointense lesions in patients with initial findings suggestive of multiple sclerosis for the occurrence of clinically relevant disability as defined by an Expanded Disability Status Scale score of 3. PATIENTS: After a median follow-up period of 8.7 years, the medical records of 42 patients were reviewed and assessed for time until patients received an Expanded Disability Status Scale score of 3. Magnetic resonance imaging parameters were dichotomized according to maximum accuracy and then used to calculate hazard ratios using the Cox model for proportional hazard ratios. RESULTS: Conversion to clinically definite multiple sclerosis was observed in 26 patients (62%), of whom 14 (54%) progressed to an Expanded Disability Status Scale score of 3. Two or more infratentorial lesions best predicted long-term disability (hazard ratio, 6.3). Gadolinium-enhancing and hypointense T1-weighted lesions did not show prognostic value. CONCLUSION: Infratentorial lesions are related to long-term prognosis for patients with initial findings suggestive of multiple sclerosis and thus may help to identify patients at high risk for earlier occurrence of clinically relevant disability.

Adolescent↗
PubMed2004

Quantitative 1H-MRS of healthy human cortex, hippocampus, and thalamus: metabolite concentrations, quantification precision, and reproducibility.

PURPOSE: To evaluate metabolite concentrations in cortical gray matter, hippocampus, and thalamus of healthy adults, and to investigate precision and reproducibility of quantitative proton magnetic resonance spectroscopy (1H-MRS) in these gray matter regions. MATERIALS AND METHODS: Quantitative single-voxel short echo-time spectra were obtained from healthy human cortex, hippocampus, and thalamus. Subjects were examined twice. Metabolite concentrations, quantification precision, and reproducibility were determined. RESULTS: There were no significant differences between test and retest measurements. Regional differences were observed with respect to metabolite concentrations, quantification precision, and reproducibility. Quantification precision and reproducibility of N-acetylaspartate and N-acetyl aspartylglutamate (tNAA), creatine and phosphocreatine (tCr), choline-containing compounds (Cho), and myo-inositol (myo-Ins), were better than those of glutamate (Glu) and glutamine (Gln). Generally, precision and reproducibility were better in cortex than in hippocampus or thalamus. The quantification precision was shown to correlate both with reproducibility and spectral linewidth. CONCLUSION: The reliability of quantitative MRS depends on the metabolite concerned, its concentration, and on the brain area studied. Moreover, the quantification precision of a metabolite in a single spectrum appears to be a reliable measure for its reproducibility in a longitudinal study.

Adult↗
PubMed2004

Clinical, electrodiagnostic, and sonographic studies in ulnar neuropathy at the elbow.

The aim of this study was to determine possible correlations between the clinical characteristics, electrophysiological features, and sonographic ulnar-nerve diameter in patients with ulnar neuropathy at the elbow (UNE). We prospectively performed clinical, electrodiagnostic, and sonographic studies in 102 patients having either purely sensory signs (35%) or sensorimotor signs (65%) of UNE. Nerve conduction studies had a sensitivity of 78%, and the addition of sonography increased this to 98%. The diagnostic value of both tests was not different among cases with and without motor deficit. Motor studies with recording from the abductor digiti minimi and first dorsal interosseous muscles were equally sensitive for the detection of conduction block or velocity slowing across the elbow, but the combination yielded more positive cases than when only one study was performed. There were modest negative correlations between the electrodiagnostic parameters and the sonographic ulnar-nerve diameter. Electrodiagnostically and sonographically, there were no significant differences between clinically pure sensory and mixed sensorimotor cases of UNE, except for electrodiagnostic findings suggesting loss of motor axons in cases with motor signs. Almost half the patients with only sensory signs had electromyographic evidence of motor axonal loss. We conclude that, although UNE is clinically heterogeneous, the electrophysiological and sonographic findings are fairly consistent despite the clinical manifestations.

Action Potentials↗
PubMed2004

Gender-related association between the TGFB1+869 polymorphism and multiple sclerosis.

Our objective was to investigate whether polymorphisms and haplotypes in the TGFB1 gene are associated with susceptibility or disease characteristics of multiple sclerosis (MS). In 247 MS patients and 194 controls, single nucleotide polymorphisms (SNPs) at position +869 (Leu10Pro) and position +915 (Arg25Pro) in the signaling sequence of the TGFB1 gene were determined, and the distribution of alleles, genotypes, and haplotypes was related to clinical data. In addition, magnetic resonance imaging (MRI) data were studied in a subgroup of patients (n = 96). The allele distribution of the two polymorphisms studied was in Hardy-Weinberg equilibrium in patients and in controls. No association was found with any of the three haplotypes found in the Dutch population, denoted as haplotype 1 (TGFB1+869T-TGFB1+915G), haplotype 2 (TGFB1+869C-TGFB1+915G), and haplotype 3 (TGFB1+869C-TGFB1+915C). However, the TGFB1+869 genotype CC was significantly more frequent in patients (p = 0.031, chi2 test). The highest frequency of the TGFB1+869 genotype CC was observed in male patients (25.2% vs. 10.0% in controls, p = 0.004, chi2 test), and carriership of TGFB1+869 allele C was correspondingly increased in male patients (74.8% vs. 56.7%, p = 0.008, chi2 test, OR 2.27, 95% CI 1.23-4.17). Although there was no association with clinical markers of disease progression, patients homozygous for TGFB1+869 allele C showed a significantly higher annual increase in two MRI parameters: ventricular fraction (central atrophy) and T1-hypointense lesion load (matrix destruction). The TGFB1 T+869C (Leu10Pro) gene polymorphism is associated with MS susceptibility, especially in males, and with a more destructive course of the disease as illustrated by MRI.

Adult↗
PubMed2004

Cannabinoids in multiple sclerosis: do they have a therapeutic role?

This is an exciting time for cannabinoid research. Evidence suggests that cannabis (marijuana) can alleviate symptoms like muscle spasticity and pain in patients with multiple sclerosis (MS). Interest in the field of cannabinoids has been strengthened by the identification and cloning of cannabinoid receptors located in the central nervous system and the peripheral immune organs, and by the discovery of the endogenous cannabinoid ligands. Cannabinoids are also efficacious in animal models of MS. However, there have been only ten published clinical reports on the use of cannabis in MS, involving 78 individuals worldwide, and the results have been equivocal. Researchers encounter a number of difficulties in designing clinical studies that use cannabinoids. From the studies reporting the use of cannabinoids in MS patients with spasticity, the somewhat better designed studies failed to demonstrate objective improvement. Therefore, convincing evidence that cannabinoids are effective in MS is still lacking.

Animals↗