Showing papers by "Franz Fazekas published in 2006"
TL;DR: In this article, the authors investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline.
Abstract: Background and Purpose— White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH. We investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms. Methods— We used data of 618 independently living elderly with WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline were compared with respect to WMH load measured qualitatively using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related White Matter Changes scales) and quantitatively with a semiautomated volumetric technique and an automatic lesion count. Statistical significance between groups was assessed with the χ2 and Mann-Whitney tests. In addition, the punctate and confluent lesion type with comparable WMH volume were compared wi...
306 citations
TL;DR: A series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses are defined, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.
Abstract: Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.
229 citations
TL;DR: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.
Abstract: Background: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. Objective: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. Methods: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. Results: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. Conclusions: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.
196 citations
TL;DR: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC and smoking and hypercholesterolemia provide additional risk.
Abstract: Background: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors a
182 citations
TL;DR: The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.
Abstract: Summary Background The McDonald International Panel accepted the Barkhof/Tintore criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. Methods In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment—ie, at least three out of four—of the Barkhof/Tintore criteria. We used survival analysis and 2×2 tables to assess the test characteristics of the criteria at baseline. Findings Overall conversion rate was 32·5% with a median survival time of 85·3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37–53) versus about 10% (6–16) in those with no asymptomatic lesions at baseline (p Interpretation MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintore criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.
133 citations
TL;DR: Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition, which suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.
Abstract: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB≤10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE≤25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r=−0.22, −0.25, −0.26, all p<0.001; MMSE: Spearman r=−0.11, −0.10, −0.09, all p<0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.
122 citations
TL;DR: Treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side‐effects on their current therapy are suggested.
Abstract: An International Working Group for Treatment Optimization in MS met to recommend evidence-based therapeutic options for the management of suboptimal responses or intolerable side-effects in patients treated with disease-modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side-effects on their current therapy.
101 citations
TL;DR: Investigating the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities found it seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke.
Abstract: Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.
98 citations
University of California, Berkeley1, Vanderbilt University2, University of California, San Francisco3, Duke University4, University of Cambridge5, National Research Council6, University of Palermo7, Magna Græcia University8, VU University Amsterdam9, University Hospitals of North Midlands NHS Trust10, Medical University of Graz11, Karolinska Institutet12, University of Copenhagen13, Hokkaido University14, University of Minho15, Medical University of Warsaw16, Queen's University17, University of Oxford18, Kaiser Permanente19
TL;DR: 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.
Abstract: 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 e2 or e4 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.
89 citations
TL;DR: Evidence for differential effects of CRP in different beds of the arterial brain supply is found, as well as associations between severity and progression of small vessel disease–related brain abnormalities and CRP.
Abstract: Background and Purpose— C-reactive protein (CRP) is an inflammatory marker known to be a risk factor for stroke. We examined the associations between CRP, carotid atherosclerosis, white matter lesions, and lacunes as manifestations of cerebral large- and small-vessel disease. Methods— In the community-based Austrian Stroke Prevention Study, CRP concentrations were measured by a highly sensitive assay in 700 participants at baseline. All underwent carotid duplex scanning, and a subset of 505 subjects underwent brain magnetic resonance imaging. Imaging was repeated after 3 and 6 years. We graded carotid atherosclerosis in both common and internal carotid arteries on a 5-point scale and calculated the sum of scores as an index of the severity of carotid atherosclerosis. The volume of white matter lesions and the number of lacunes were considered small vessel disease–related brain abnormalities. Results— After adjustment for vascular risk factors, the severity and progression of extracranial carotid atheroscl...
88 citations
TL;DR: In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance, and age and education remained important variables influencing test performance.
Abstract: The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) invo
TL;DR: These guidelines are intended to assist in the use of conventional MRI for the diagnosis and longitudinal monitoring of patients with MS and should provide a foundation for the development of more widespread but rational clinical applications of non‐conventional MR‐based techniques in studies of MS patients.
Abstract: Magnetic resonance (MR)-based techniques are widely used for the assessment of patients with suspected and definite multiple sclerosis (MS). However, despite the publication of several position papers, which attempted to define the utility of MR techniques in the management of MS, their application in everyday clinical practice is still suboptimal. This is probably related, not only, to the fact that the majority of published guidelines focused on the optimization of MR technology in clinical trials, but also to the continuing development of modern, quantitative MR-based techniques, that have not as yet entered the clinical arena. The present report summarizes the conclusions of the 'EFNS Expert Panel of Neuroimaging of MS' on the application of conventional and non-conventional MR techniques to the clinical management of patients with MS. These guidelines are intended to assist in the use of conventional MRI for the diagnosis and longitudinal monitoring of patients with MS. In addition, they should provide a foundation for the development of more widespread but rational clinical applications of non-conventional MR-based techniques in studies of MS patients.
TL;DR: Punctate and early confluent to confluent WMH show distinguishable differences in their spatial distribution within a normal elderly population, suggesting the pattern of punctate WMH is probably a consequence of mixed etiologies.
Abstract: White matter hyperintensities (WMH) are common on brain MRI of the elderly. Their size ranges from punctate to early confluent to confluent lesions. While this increase in extension is frequently seen as evidence for a continuum of changes, histological data and clinical follow-up suggest differences in underlying pathology and their progression. We tested this hypothesis by exploring the distributions of punctuate and confluent lesions using lesion probability maps (LPM) generated from MRI scans of 189 participants (mean age 60.8+/−6.2 years) in the Austrian Stroke Prevention Study. We dichotomised WMH according to the classification by Fazekas et al. [punctate (n=143) vs. early confluent and confluent (n=33)] to run voxel-based t-tests using permutation-based nonparametric inference. To test alternative hypotheses, we created similar LPM for age and arterial hypertension. We observed significant differences in the spatial distribution of lesions for the two WMH groups (p<0.01). Punctate lesions were more diffusely distributed throughout the cerebral white matter (peak probability ∼5%) relative to confluent lesions (peak probability 45%). Confluent lesions had greatest likelihood of being found in perfusion “watershed” regions. These differences in distribution could not be explained by differences in age or hypertension only, as both greater age and the diagnosis of hypertension were associated with WMH abutting the occipital horns. Punctate and early confluent to confluent WMH show distinguishable differences in their spatial distribution within a normal elderly population. The pattern of punctate WMH is probably a consequence of mixed etiologies. Preferential localization of the more confluent WMH with arterial watershed areas implies a stronger ischemic component in their development.
TL;DR: Anterior callosotomy is a surgical option for the treatment of generalized tonic or atonic seizures associated with drop attacks, but reliable data about tolerability and efficacy are sparse.
Abstract: Summary: Purpose: Anterior callosotomy is a surgical option for the treatment of generalized tonic or atonic seizures associated with drop attacks. Besides open surgery, a radiosurgical callosal disconnection using the gamma knife (GK) also can be performed, but reliable data about tolerability and efficacy are sparse.
Methods: Eight patients (three female, five male age range, 5 to 69 years) with severe generalized epilepsy associated with disabling drop attacks underwent GK callosotomy between 1993 and 2004. In six patients, the anterior third of the corpus callosum was radiosurgically disconnected. In one patient a second procedure with GK treatment of the middle third of the corpus callosum was added 17 months later. In two patients posterior GK callosotomy had followed partial hemispherotomy.
Results: Drop attacks (DAs) were completely abolished in three patients, and two patients had a marked DA seizure reduction of 60%. Two of four patients with additional generalized tonic–clonic seizures showed a reduction of 100%, and the remaining, a 50% and 60% decrease, respectively. Other seizure types responded less well to the radiosurgical treatment. In both patients with posterior GK callosotomy after hemispherotomy, partial seizures decreased. Beside transient headache in two patients, no immediate or long-term postradiosurgical side effects were observed.
Conclusions: Palliative radiosurgical callosotomy is an efficient and safe noninvasive alternative to the open procedure with comparable results. No signs of postradiosurgical side effects were noted within an up to 12-year posttreatment period.
TL;DR: There is first evidence from magnetization transfer imaging studies that other than in MS normal appearing white matter is not affected in cerebral small vessel disease, contrasting the hypothesis that ischemic white matter damage extends far beyond changes visible on conventional MR.
TL;DR: It is hypothesize that distinct differences in cognitive processing occur with the evolution of MS and that, at these early stages of the disease, they cannot be detected with sufficient sensitivity using only the PASAT.
TL;DR: In this study of an unselected Central European population, the APOE genotype was not confirmed as a candidate for providing additional diagnostic and potentially prognostic information in patients with ICH.
Abstract: Background: Both the υ2 and υ4 alleles of the apolipoprotein E gene (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage and to be as
TL;DR: The results on MS are far less homogenous but have gained support from morphologic and metabolic measures obtained with magnetic resonance imaging indicating a greater extent of brain destruction with the apoE epsilon4 allele.
TL;DR: Findings suggest a high frequency of depressive symptoms and a low quality of life with respect to mental health following HSE, and patients felt more impaired by affective than by physical symptoms.
TL;DR: Interestingly, GluR3 serum levels remained positive after successful surgical intervention leading to patient's seizure freedom, different from experiences in patients with RE immunomodulatory therapy by use of intravenous gammaglobulines.
Abstract: Antibodies against the glutamate receptor type 3-(GluR3) have been found in association with Rasmussen's encephalitis (RE) but were also detected in patients with non-inflammatory focal epilepsies. We report the case of an 18-year-old patient with treatment refractory left mesial temporal lobe epilepsy accompanied by high levels of GluR3 antibodies. Different from experiences in patients with RE immunomodulatory therapy by use of intravenous gammaglobulines neither altered GluR3 serum levels nor had any effect on seizure frequency in our patient. Interestingly, GluR3 serum levels remained positive after successful surgical intervention leading to patient's seizure freedom.
01 Jan 2006
TL;DR: The aim of this work was to investigate the statistical impact of six common partitioning schemes for regional analysis of the Corpus Callosum and hypothesize that conflicts among different CC studies may partially arise from hidden methodological differences.
Abstract: C. Ryberg, M. B. Stegmann, K. Sjostrand, E. Rostrup, F. Fazekas, F. Barkhof, G. Waldemar Dept. of Neurology, Memory Disorders Research Unit, Copenhagen, Denmark, Technical University of Denmark, Informatics and Mathematical Modelling, Kongens Lyngby, Denmark, Copenhagen University Hospital, Danish Reseach center for Magnetic Resonance, Copenhagen, Denmark, Dept. of Neurology, Medical University, Graz, Austria, Dept. of Radiology and Image Analysis Center, VU Medical Center, Amsterdam, Netherlands Introduction The Corpus Callosum (CC) is the main fiber tract connecting the two hemispheres in the brain. It functions to communicate e.g. cognitive and learned information between the hemispheres. The lack of evident landmarks that delimit anatomical and functionally distinct callosal regions has spawned several geometric partitioning schemes to subdivide the CC into regions where the fiber topography is expected to be different. These regions might be affected differently in development of disease and their structural parameters (such as size and shape) might correlate with cognitive and functional tests that evaluate different channels of interhemispheric communication. The aim of this work was to investigate the statistical impact of six common partitioning schemes for regional analysis of CC. We hypothesize that conflicts among different CC studies may partially arise from hidden methodological differences.
TL;DR: There is growing evidence that intravenous immunoglobulins (IVIG) are effective in some neuroimmunological disorders of childhood, and this short review summarizes the evidence-based indications and recommendations of IVIG therapy in these disorders.
Abstract: There is growing evidence that intravenous immunoglobulins (IVIG) are effective in some neuroimmunological disorders of childhood. This short review summarizes the evidence-based indications and recommendations of IVIG therapy in these disorders. Despite considerable efforts to define the role and mechanisms of IVIG, more clinical studies are needed to further explore the therapeutic potential of IVIG in childhood diseases of the nervous system and muscle.
TL;DR: Numerical simulations and in vitro measurements suggest that resonance offsets have effects that require further investigation, and a new magnetic resonance method for measuring T2 relaxation times in tissues is proposed.
Abstract: A new magnetic resonance (MR) method for measuring T2 relaxation times in tissues is proposed. The method is based on a T2 selective saturation period followed by sampling of the remaining longitudinal magnetization. Saturation of the longitudinal magnetization is accomplished by a single binomial RF pulse of zeroth order with a constant flip angle. The T2 selectivity is controlled by the RF pulse duration. A full T2 spectrum can be obtained by performing a series of measurements with varying RF pulse duration. On a conventional 1.5 T system this approach allows detection of T2 components as short as several hundred microseconds. A major limitation is the method's susceptibility to resonance offsets. At typical offsets of 0.1-0.2 ppm the sensitivity of the method is limited to a T2 range below 20 ms, which corresponds to an RF pulse duration shorter than 50 ms. The new method was used to acquire T2 spectra from the liver of pigs in vitro on a conventional 1.5 T system. We observed a short T2 component around 17 ms and an ultrashort T2 component in the range of 0.9-1.1 ms. Numerical simulations and in vitro measurements suggest that resonance offsets have effects that require further investigation.
Journal Article•
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TL;DR: The automated method described may provide reliable atrophy measures of the hippocampus with reduced operator time and as a result may be useful in studies where analysis of many scan-pairs is required.
Abstract: (manual segmentation of baseline hippocampi only). Template-derived regions were not devised to be accurate but rather aimed to identify the region approximately. Results: Atrophy rates (mm loss year) are shown in the table and figure. The automated method was a significant predictor of disease (p 0.001) and gave similar group discrimination compared with semi-automated and manual methods, although there was a suggestion that a combination of the manual and semi-automated or fully-automated methods may improve group discrimination (p 0.03). Manual and semiautomated rates were also calculated on a relative scale, as a percentage of baseline hippocampal volume (see table). Automated atrophy rates were not calculated relatively owing to the low accuracy of the template-based segmentation method; mean (SD) similarity of overlap (intersection/union) of template segmentation with manual, was 0.49 (0.05) in controls and 0.43 (0.07) in AD. Adjusting for the absolute rate, there was no evidence that the manual relative rate added predictive information (p 0.12). There was borderline evidence that relative rates added predictive information, adjusting for absolute rates, using semi-automated methods (p 0.051). Automated hippocampal analysis in this study took 20 minutes per hippocampal pair on a 3.4 GHz Intel Xeon server, whereas manual delineation of each hippocampal pair took 90 minutes of operator-intensive labor. Conclusions: The automated method we describe may provide reliable atrophy measures of the hippocampus with reduced operator time and as a result may be useful in studies where analysis of many scan-pairs is required.