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F Barkhof

Publications and source records attributed to F Barkhof.

At least 55 records · Page 3Linked to original sources
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

[New diagnostic criteria for multiple sclerosis in clinical practice].

In two women, aged 29 and 49 years respectively, and a man aged 44 years, neurological signs pointed to multiple sclerosis (MS). In 2001, an international panel of experts revised the diagnostic criteria for multiple sclerosis (MS), which had been in use since 1983. As before, the fundamental diagnostic criterion remains dissemination in time and place of neurological abnormalities suggestive of demyelination. In contrast to the old criteria, the new criteria give diagnostic rules for the diagnosis of primary progressive MS. An even more important step is the further integration of MRI results in the new diagnostic criteria. This allows neurologists to diagnose MS earlier in the disease course, as was the case in the first woman: three months after the first symptoms a new MRI scan revealed dissemination in time. Recent research has shown, that MRI scans are reliable and can be used in clinical practice. If used correctly, the reliability of the diagnosis will also improve. The male patient had word-finding problems that do not fit with MS, and there were more than 9 MRI abnormalities, including juxtacortical, but no periventricular and infratentorial abnormalities. He had a vasculopathy. The second woman had dissemination in time and place, but there was a better explanation for the symptoms: neuromyelitis optica.

Adult↗
PubMed2004

White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease.

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Arterioles↗
PubMed2004

Measuring progression of cerebral white matter lesions on MRI: visual rating and volumetrics.

OBJECTIVE: To evaluate the concordance of a volumetric method for measuring white matter lesion (WML) change with visual rating scales. METHODS: The authors selected a stratified sample of 20 elderly people (mean age 72 years, range 61 to 88 years) with an MRI examination at baseline and at 3-year follow-up from the community-based Rotterdam Scan Study (RSS). Four raters assessed WML change with four different visual rating scales: the Fazekas scale, the Scheltens scale, the RSS scale, and a new visual rating scale that was designed to measure change in WML. The authors assessed concordance with a volumetric method with scatter plots and correlations, and interobserver agreement with intraclass correlation coefficients. RESULTS: For assessment of change in WML, the Fazekas, Scheltens, and periventricular part of the RSS scale showed little correlation with volumetrics, and low interobserver agreement. The authors' new WML change scale and the subcortical part of the RSS scale showed good correlation with volumetrics. After additional training, the new WML change scale showed good interobserver agreement for measuring WML change. CONCLUSIONS: Commonly used visual rating scales are not well suited for measuring change in white matter lesion severity. The authors' new white matter lesion change scale is more accurate and precise, and may be of use in studies focusing on progression of white matter lesions.

Aged↗
PubMed2004

Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.

OBJECTIVE: The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. METHODS: The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. RESULTS: Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. CONCLUSION: Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.

Adult↗
PubMed2004

Osteopontin levels and increased disease activity in relapsing-remitting multiple sclerosis patients.

Osteopontin (OPN) has been identified as the most prominent cytokine-encoding gene expressed within multiple sclerosis (MS) lesions. Recently, we demonstrated that OPN plasma levels were elevated in active relapsing-remitting (RR) MS patients. In this longitudinal study, a trend was observed for OPN serum levels in relation to clinical exacerbations. Moreover, OPN protein levels were significantly elevated 1 month prior to increase of gadolinium (Gd)-enhancing lesion number, whereas no relation was observed between OPN levels and increase in Gd-enhancing lesion volume. Although no robust relation between OPN and disease activity was observed, these data suggest that OPN levels are elevated prior to increased disease activity in RR MS patients.

Adult↗
PubMed2004

Interindividual differences of medial temporal lobe activation during encoding in an elderly population studied by fMRI.

Functional MRI (fMRI) is used to study medial temporal lobe (MTL) activation during encoding of new information into memory. In most studies, fMRI data of different subjects are averaged in standard coordinate space. However, interindividual differences in activation can be extensive, reflecting functional heterogeneity. Further, anatomical differences in brain structure cause additional variance and loss of registration accuracy. Such differences in structural and functional MTL characteristics may interfere with the efficiency of averaging data across subjects, and may become more significant with aging and dementia. The current study concerns the analysis of individual differences in MTL activation associated with episodic encoding.Twenty-nine healthy elderly men between 60 and 70 years old performed a simple face encoding task during fMRI scanning. Individual data were analyzed in native space, and compared to the group average in standard space (Talairach and Tournoux).MTL volumes between subjects varied between 6.34 and 11.27 cm(3), and had considerable variation when mapped to standard space. Eighteen of the 29 subjects showed MTL activity and activation patterns varied both in location and size (ranging from 0.11 to 1.78 cm(3)), with the strongest activation in the left posterior part of the MTL. In standard space, no region was significantly activated on a group level at a comparable alpha level. We conclude that while the majority of elderly subjects show MTL activation during episodic encoding of faces, there is considerable structural and functional variability between subjects. Group analysis in standard space may not be appropriate for studies of a complex structure such as the MTL, particularly not in aging and dementia.

Aged↗
PubMed2004

Global and local gray matter loss in mild cognitive impairment and Alzheimer's disease.

PURPOSE: Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. MATERIALS AND METHODS: Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxel-based morphometry (VBM); VBM was optimized for template mismatch and statistical mass. RESULTS: AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 +/- 58 vs. 590 +/- 52 ml; P < 0.001). Global GM volume in the MCI group (552 +/- 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. CONCLUSION: GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.

Aged↗
PubMed2004

Polymorphisms in the genes encoding interferon-gamma and interferon-gamma receptors in multiple sclerosis.

Genome screens suggest that several genes, each contributing to a small extent, are involved in multiple sclerosis (MS) susceptibility. Simultaneous analysis of related genes may improve the power to detect such small effects. Interferon-gamma (IFN-gamma), mediating its effects through the IFN-gamma receptor, is a pleiotropic, pro-inflammatory cytokine for which a detrimental effect on the course of MS has been reported. The role of IFN-gamma receptor 1 (IFNGR1) and IFN-gamma receptor 2 (IFNGR2) gene polymorphisms has not been studied in MS, and, for the IFNG gene polymorphism there is only one previous study, which incorporates clinical, but not imaging, data. The aim of this study was to investigate whether polymorphisms in the IFNG and IFNGR1 and IFNGR2 genes are associated with susceptibility to MS, or disease characteristics, as defined by clinical and imaging criteria. Genotypes for IFNG, IFNGR1 and IFNGR2 were determined in 509 patients with MS and in 193 healthy controls. Patient files were reviewed for disease course, age at onset of disease, and rate of progression. Serial magnetic resonance imaging (MRI) data were available for 107 patients. No significant differences in the distribution of IFNG, IFNGR1 and IFNGR2 genotype and allele frequencies were found between patients and controls. A progressive, as opposed to a relapsing, onset was significantly more frequent in carriers of the IFNGR2 allele Arg64 (P = 0.028). Moreover, IFNGR2 allele Arg64 carriers had a lower black hole ratio than non-carriers (P = 0.016). No other associations with clinical parameters, such as age at onset or rate of progression, or with imaging parameters, were observed. The IFNG intron 1 gene polymorphism studied is unlikely to play a major role in MS susceptibility or disease course. The IFNGR1 and IFNGR2 gene polymorphisms studied do not exert an important influence on MS susceptibility, but allele IFNGR2*Arg64 may be associated with a progressive disease onset.

Adult↗
PubMed2004

Magnetic resonance imaging as a tool to examine the neuropathology of multiple sclerosis.

Magnetic resonance imaging (MRI) has significantly extended the understanding of multiple sclerosis (MS), owing to its ability to sensitively depict the dynamics of the disease process in vivo. The subject of this review is the use of MRI in the post-mortem setting, with emphasis on how it may be used to improve the specimen selection process at autopsy. Lesions with active demyelination are highly interesting in the study of MS pathogenesis, but are rare in a typical autopsy material of chronic MS. The yield of MS lesions in autopsy specimen selection can be increased by the use of MRI-guided tissue sampling, as a significant proportion of abnormalities detected by post-mortem MRI are not macroscopically visible/palpable. The majority of these MRI abnormalities have been found to represent either discrete areas of microglial activation with no demyelination (so-called (p)reactive lesions), or active demyelinating MS lesions by further histopathological examination. The presence and extent of MS pathology outside of the focal demyelinated lesions is more readily appreciated by MRI-guided specimen sampling, as has been shown in the study of extensive areas of partial myelin loss in the spinal cord. A further advantage of MRI-guided specimen sampling is the ability to use three-dimensional and quantitative measures. The potential of correlating these with histopathological data may be further exploited in the future. The technical procedure for MRI-guided tissue sampling at autopsy is presented, and the limitations of the technique are discussed.

Autopsy↗
PubMed2004

Alzheimer's disease--one clinical syndrome, two radiological expressions: a study on blood pressure.

BACKGROUND: Vascular risk factors could play a role in the aetiology of Alzheimer's disease, but this has not been investigated in relation to neuroimaging findings OBJECTIVE: To evaluate the distribution of blood pressure and an indicator of atherosclerosis (pulse pressure) in patients with Alzheimer's disease with and without small vessel disease. METHODS: 152 Alzheimer patients underwent 1.0T MRI scanning. Blood pressure was measured with a sphygmomanometer. Small vessel disease was assessed by the presence of lacunar infarcts and white matter lesions. The distribution of blood pressure and pulse pressure, with or without small vessel disease, was assessed by linear regression analysis. RESULTS: Patients with small vessel disease had a higher blood pressure, a wider pulse pressure, and an increased prevalence of hypertension. These findings were strongly age dependent: for patients under 65, mean systolic blood pressure was higher in the subpopulation with small vessel disease than in those without (mean (SD): 149.9 (19.3) v 135.7 (20.5) mm Hg; p = 0.02). Hypertension was more common in patients with white matter lesions than in those without (75.6% v 45.1%; p = 0.03) and the pulse pressure was higher (61.9 (14.4) v 51.7 (11.5) mm Hg; p = 0.01). There was no relation between blood pressure and the degree of (sub)cortical and hippocampal atrophy in patients without small vessel disease. CONCLUSIONS: There was heterogeneity in Alzheimer's disease patients with respect to blood pressure and pulse pressure. Alzheimer's disease encompasses a heterogeneous group of disorders which share a common cognitive profile but with distinct radiological features with respect to white matter lesions.

Age Factors↗
PubMed2004

No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis.

BACKGROUND: Whereas a number of studies suggest that the ApoE polymorphism is not associated with disease susceptibility in multiple sclerosis (MS), results with regard to disease severity, however, are conflicting. Some studies suggest an unfavourable role of the epsilon4 allele. This study was performed to assess the association of the ApoE polymorphism with both disease susceptibility and disease course in a large group of MS patients using clinical and MRI measures. In addition the data were combined with available data from the literature. METHODS: In a group of 408 patients with clinically definite MS, genotype distribution was compared with that of 144 healthy controls. Combined analysis of published data on the association of ApoE polymorphism with MS was performed. Demographic and clinical findings were recorded and related to the ApoE genotype. In a subgroup, longitudinal MRI findings were available and related to the ApoE genotype. RESULTS: No significant differences were found in the distribution of genotypes between MS patients and controls. Combined analysis of published data showed a slightly increased susceptibility for MS in epsilon2-carriers. Disease characteristics (including age at onset and onset type), disease severity (progression index, time to reach EDSS 6) and MRI findings (lesion volumes and atrophy measures) were not associated with carriership o epsilon2 or epsilon4. CONCLUSIONS: In this cohort no association of the ApoE genotype with disease susceptibility nor clinical and MRI measures could be identified. However, combined analysis of published data could not definitely exclude the possibility of a minor role for epsilon2-carriership in MS.

Adult↗
PubMed2004

Outcome measures for multiple sclerosis clinical trials: relative measurement precision of the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite.

We compared the relative measurement precision (RMP) of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) for discriminating between groups of patients known to differ in their extent of multiple sclerosis (MS). A total of 133 patients were rated with the EDSS and MSFC and had magnetic resonance imaging (MRI) scans. Patients were grouped on the basis of MRI appearances (T1- and T2-weighted lesion loads, parenchymal and ventricular fractions--T1LL, T2LL, PF, VF, respectively) and RMP was determined using the method of group differences. For each MRI parameter, the total sample was arranged in ascending order of magnitude and divided into two, three, four and five similar sized groups. For each division (two, three, four or five groups), EDSS and MSFC scores for the groups were compared using parametric (paired samples t-tests, one-way ANOVA) and nonparametric (Wilcoxon's rank-sum test, Kruskal-Wallis analysis of variance) statistical methods and RMP was estimated. The EDSS and MSFC were correlated substantially (r = -0.64). Relative to the MSFC, the EDSS had inferior measurement precision regardless of the number of groups into which the total sample was divided, or the statistical method. However, the RMP of the EDSS compared with the MSFC varied from 2% to 86%. Results suggest the MSCF is better than the EDSS for detecting differences between groups of patients, defined by these MRI markers of MS. However, the finding that both scales correlated weakly with MRI markers, indicated that they are limited as predictors of MS pathology as defined by MRI. An explanation for this well-established clinical-MRI paradox is that rating scales and MRI measure fundamentally different manifestations of MS.

Adolescent↗
PubMed2003

[Alpha]B-crystallin genotype has impact on the multiple sclerosis phenotype.

BACKGROUND: Both multiple sclerosis (MS) susceptibility and MS clinical phenotype are in part genetically determined. [Alpha]B-crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene (CRYAB): at positions -C249G, -C650G, and -A652G. METHODS: These polymorphisms were studied in sporadic cases of MS, assessing disease susceptibility, clinical phenotype, and MRI appearance. RESULTS: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS. CONCLUSION: Carriers of the rare allele CRYAB-650*C had an increased likelihood of a noninflammatory, neurodegenerative phenotype characterized by a relatively rapid, primary progressive clinical disease course.

Adult↗
PubMed2003

Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD.

OBJECTIVE: To compare frontal cortex activation in patients with early frontotemporal dementia (FTD) with that in patients with early AD. METHODS: Seven patients with FTD and seven patients with AD were studied (Clinical Dementia Rating: four patients with FTD 0.5, three patients with FTD 1, all patients with AD 1; mean Mini-Mental State Examination score: FTD 28.0 +/- 2.1, AD 23.1 +/- 2.7). Cerebral atrophy on MRI was mild, with no differences between FTD and AD. A parametric working memory task was applied to assess frontal activation as a function of working memory load. RESULTS: The activated working memory network in FTD and AD included frontal and parietal lobe and thalamus. In frontal and parietal cortex, brain activation was significantly decreased in FTD. Frontal regions in patients with FTD showed less linear activation increase with working memory load than in AD. Possibly as a compensation mechanism, the cerebellum showed a stronger increasing response in FTD. CONCLUSIONS: These data on regional functional loss in the frontal cortex in early FTD suggest that fMRI can identify FTD when results on structural MRI are normal.

Aged↗