Biomedical subjects

F Fazekas

Publications and source records attributed to F Fazekas.

At least 37 records · Page 2Linked to original sources

PubMed2004

[Health care costs of multiple sclerosis in Austria. Cross-sectional study including consideration of quality of life].

A retrospective, cross-sectional study was performed to evaluate direct and indirect costs related to multiple sclerosis (MS) in Austria in a representative cohort of patients ( n=895) with typical symptoms. Demographic, socioeconomic, and disease-related data including degree of disability and health-related quality of life as well as consumption of medical and nonmedical resources were recorded and mean total costs per patient and year were calculated (based on 1999 figures). Total direct costs borne by public sources were 15,684 euro per MS patient per year. Overall societal costs increased disproportionately with the progression of the disease, from 12,990 euro per year in patients with mild disability to 69,554 euro per year in patients with severe disability. Increasing disability was reflected by substantial deterioration of health status-related quality of life. Direct costs of MS in Austria are similar to those in other countries.

Adult↗

PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

PubMed2003

Low interleukin-10 production is associated with higher disability and MRI lesion load in secondary progressive multiple sclerosis.

Abnormalities in T-cell-derived cytokine production are a well-known phenomenon in multiple sclerosis (MS). An association between disability and the production of interferon gamma has been demonstrated recently. The present study investigated associations between disability, cytokine production in stimulated blood lymphocytes and magnetic resonance imaging data in 37 patients with the secondary progressive course in the stable phase of the disease. Patients with high interleukin-10 (IL-10) production had significantly lower disability scores (p=0.009) and lower T2 lesion load (p=0.03). Interleukin-10 might not only play a role in the pathological process of multiple sclerosis but has an impact on disease outcome as well.

Adult↗

PubMed2003

Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.

BACKGROUND AND PURPOSE: To provide further insight into the MRI assessment of age-related white matter changes (ARWMCs) with visual rating scales, 3 raters with different levels of experience tested the interrater agreement and comparability of 3 widely used rating scales in a cross-sectional and follow-up setting. Furthermore, the correlation between visual ratings and quantitative volumetric measurement was assessed. METHODS: Three raters from different sites using 3 established rating scales (Manolio, Fazekas and Schmidt, Scheltens) evaluated 74 baseline and follow-up scans from 5 European centers. One investigator also rated baseline scans in a set of 255 participants of the Austrian Stroke Prevention Study (ASPS) and measured the volume of ARWMCs. RESULTS: The interrater agreement for the baseline investigation was fair to good for all scales (kappa values, 0.59 to 0.78). On the follow-up scans, all 3 raters depicted significant ARWMC progression; however, the direct interrater agreement for this task was poor (kappa, 0.19 to 0.39). Comparison of the interrater reliability between the 3 scales revealed a statistical significant difference between the scale of Manolio and that of Fazekas and Schmidt for the baseline investigation (z value, -2.9676; P=0.003), demonstrating better interrater agreement for the Fazekas and Schmidt scale. The rating results obtained with all 3 scales were highly correlated with each other (Spearman rank correlation, 0.712 to 0.806; P< or =0.01), and there was significant agreement between all 3 visual rating scales and the quantitative volumetric measurement of ARWMC (Kendall W, 0.37, 0.48, and 0.57; P<0.001). CONCLUSIONS: Our data demonstrate that the 3 rating scales studied reflect the actual volume of ARWMCs well. The 2 scales that provide more detailed information on ARWMCs seemed preferential compared with the 1 that yields more global information. The visual assessment of ARWMC progression remains problematic and may require modifications or extensions of existing rating scales.

Adult↗

PubMed2003

[Diagnosis of multiple sclerosis].

This article prepared by members of International Panel working on new diagnostic criteria of multiple sclerosis (MS) presents and discusses these criteria, which pay special attention to MRI as a method of confirmation of dissemination in space and in time, necessary for MS diagnosis. Also main problems of MS differential diagnosis are discussed as well as significance of other laboratory methods like evoked potentials and cerebrospinal fluid studies. Nevertheless the significance of clinical signs in MS diagnosis are decisive.

Acute Disease↗

PubMed2002

Statins as immunomodulators: comparison with interferon-beta 1b in MS.

BACKGROUND: Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)beta-1b. METHODS: Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFN beta-1-treated patients with relapsing-remitting MS or from healthy donors (HD) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, simvastatin, mevastatin, IFN beta-1b, or statins plus IFN beta-1b. The authors analyzed proliferative activity of T cells and B cells, cytokine production and release, activity of matrix metalloproteinases (MMP), and surface expression of activation markers, adhesion molecules, and chemokine receptors on both T and B cells. RESULTS: All three statins inhibited proliferation of stimulated PBMC in a dose-dependent manner, with simvastatin being the most potent, followed by lovastatin and mevastatin. IFN beta-1b showed a similar effect; statins and IFN beta-1b together added their inhibitory potentials. Furthermore, statins reduced the expression of activation-induced adhesion molecules on T cells, modified the T helper 1/T helper 2 cytokine balance, reduced MMP-9, and downregulated chemokine receptors on both B and T cells. Besides strong anti-inflammatory properties, statins also exhibited some proinflammatory effects. CONCLUSIONS: Statins are effective immunomodulators in vitro that merit evaluation as treatment for MS.

Adjuvants, Immunologic↗

PubMed2002

Future aspects of the presurgical evaluation in epilepsy.

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

Brain Diseases↗

PubMed2002

CT and MRI rating of white matter changes.

The impact of white matter changes (WMC) detectable on CT or MRI on various diseases like ischemic stroke and intracerebral hemorrhage and their association with cognitive impairment was and still is under debate. To assess WMC in a qualitative and/or semiquantitative fashion rating scales have been developed. For MRI most widely used scales are the scales of Manolio, Fazekas, Schmidt, and Scheltens. Most recently a new scale extending earlier suggestions has been introduced by Wahlund et al. applicable for both CT and MRI. This article will review strengths and weaknesses of these rating scales and will discuss further requirements and future perspectives.

Aged↗

PubMed2002

Risk factors and progression of small vessel disease-related cerebral abnormalities.

A three year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate and clinical predictors of progression of small vessel disease related cerebral abnormalities including white matter changes and lacunes. White matter hyperintensity progression was found in 17.9% of individuals over the 3 year period. New lacunes occurred in 2.2% of subjects. The overall frequency of progression of small vessel disease related brain changes was 19%. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline predicted lesion progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study described that polymorphisms in the renin angiotensin system (RAS) increase the susceptibility for progression of cerebral small vessel disease. Homozygosity for the T allele of the M235T polymorphism of the angiotensinogen gene was associated with a 3.19-fold increased risk for lesion progression independently of arterial hypertension. These data suggest that drugs influencing the RAS system may allow to intervene with an unfavorable course of cerebral small vessel disease.

Aged↗

PubMed2002

Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology.

Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the best accepted risk factors for MARCD. Genes involved in blood pressure regulation, like genes encoding the proteins of the renin-angiotensin system (RAS) therefore represents good candidate genes for MARCD. Plasma angiotensinogen level is a major determinant of the RAS activity. Positive correlation between angiotensinogen gene expression and RAS activity, as well as blood pressure were observed. Common mutations described in the AGT promoter were able to alter AGT expression in cell culture. We described that 4 frequent mutations at the AGT promoter are combined in 5 haplotypes coded as A (-6:g, -20:a, -152:g, -217:g), B (-6:a, -20:c, -152:g, -217:g), C (-6:a, -20:c, -152:a, -217:g), D (-6:a, -20:a, -152:g, -217:g), and E (-6:a, -20:a, -152:g, -217:a). The B haplotype was significantly associated with MARCD in the cohort of the Austrian Stroke Prevention Study (p = 0.005). The association was independent of hypertension, which pinpointed to a possible role of the local RAS in this relationship. Investigation of the promoter activity of the AGT gene in astrocytes suggests that expression of this gene may be modulated by the haplotype.

Aged↗

PubMed2002

Can small-vessel disease-related cerebral abnormalities be used as a surrogate marker for vascular dementia trials?

Clinical scales for measuring the effectiveness of disease-modifying therapies in patients with vascular dementia are of limited sensitivity. Moreover, they cannot serve to directly probe the potential of a drug in slowing further progression of vascular damage. Assessment of morphologic abormalities that reflect ischemia-related cerebral tissue changes and have a bearing on cognitive function could serve to address both of these aspects and, if sensitive enough, could constitute an ideal surrogate for measuring progression of the disease. For drug licensing agencies a validated surrogate has to meet several requirements: First, the surrogate must predict the future clinical course. Second, the effect of treatment on the disease must be explained by the effect of the treatment on the surrogate; the treatment needs to affect clinical outcome by working through mechanisms related to the surrogate. Third, evidence must exist that treatments of various classes affect the surrogate in the same and predictable manner. Apart from these requirements, regulatory guidelines may also allow the use of even an unvalidated surrogate if it is considered reasonably likely to predict future clinical outcome or disease activity. Various morphologic measures, particularly those using conventional or more sophisticated MRI techniques have already shown a close correlation to neuropsychologic functions. If these associations can also be confirmed in longitudinal studies and following specific treatments, morphologic markers will play a major role in future clinical trials of vascular dementia.

Aged↗

PubMed2002

Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis.

Intravenous immunoglobulin (IVIG) has several effects on the immune system that could have a beneficial influence on disease processes in multiple sclerosis (MS). Four double-blind trials in relapsing-remitting MS have demonstrated that IVIG may reduce the relapse rate, progression and the number of gadolinium-enhancing lesions. However, these trials were smaller than the pivotal trials of interferon-beta and glatiramer acetate, and therefore, we performed a meta-analysis of the four trials in order to provide an overall assessment of the benefits of IVIG in relapsing-remitting multiple sclerosis in comparison with other drugs currently available for treatment of disease activity in MS. The meta-analysis showed a significant beneficial effect on the annual relapse rate (effect size -0.5; P = 0.00003), on the proportion of relapse-free patients (0.29 difference; P = 2.1 x 10(-8)), change in Expanded Disability Status Scale (EDSS) score (effect size: 0.25; P = 0.04), and a trend towards a reduction in the proportion of patients who deteriorated (P = 0.03). Each single study in the meta-analysis had its weaknesses, but all studies were positive regarding their primary end-point, and the results yield concordant evidence for reduction of relapse rate and progression. The ideal dosage of IVIG for treating MS needs still to be determined. In conclusion, IVIG may be a valuable alternative for treatment of relapsing-remitting MS, but can presently not be considered as a first-line treatment. IVIG could be considered in patients who do not tolerate or are unwilling to take the approved injectable medications, but additional studies are needed to establish the role of IVIG in the management of multiple sclerosis.

Persons with Disabilities↗

PubMed2002

[F-18 fluorodeoxyglucose positron emission tomography in neurology].

Positron emission tomography using F-18-fluorodeoxyglucose (F-18-FDG-PET) is an ideal tool for imaging regional cerebral metabolism as glucose is the most important source of energy for neurons. Under physiologic conditions the pattern of metabolism reflects the state of cerebral activation which can be modulated by various stimuli to investigate cerebral organization. Pathologic conditions usually cause a drop in metabolism because of neuronal inactivity or loss. They can, however, also be associated with an increased rate of glucose metabolism such as in case of active epileptic foci or malignant tumors. As a consequence F-18-FDG-PET has become a valuable functional imaging modality especially for the diagnostic clarification of non-contributory or negative morphologic imaging results. Dementia, pre-surgical evaluation of epilepsy and neurooncology are currently frequent indications for referral to F-18-FDG-PET in neurology.

Brain↗

PubMed2002

TACE mRNA expression in peripheral mononudear cells precedes new lesions on MRI in multiple sclerosis.

Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of multiple sclerosis (MS). It has to be released from its cell membrane-bound precursor by proteolytic cleavage. This is mainly performed by a member of the ADAM (a disintegrin and metalloproteinase) family of enzymes, TNF-alpha-converting enzyme (TACE, ADAM 17). In a longitudinal study on 11 relapsing-remitting MS patients, we qualitatively determined mRNA expression of TNF-alpha and TACE in peripheral blood mononuclear cells (PBMCs) without ex vivo stimulation. mRNA expression was related to disease activity as assessed by monthly gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI). Patients found positive for TACE mRNA in PBMCs showed a significantly higher mean number of new Gd-enhancing lesions per scan one month following PBMC sampling.

ADAM Proteins↗

PubMed2002

Quantitative magnetization transfer imaging of pre-lesional white-matter changes in multiple sclerosis.

OBJECTIVE: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. METHODS: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). RESULTS: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p<0.0001) and of kfor (F7,166=105.2; p<0.0001), and by an increase of T1free (F7,166=57.3; p<0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. CONCLUSIONS: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event

Adjuvants, Immunologic↗

PubMed2001

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Adult↗

PubMed2001

Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE).

Diffusion-weighted single-shot EPI (sshEPI) is one of the most important tools for the diagnostic assessment of stroke patients, but it suffers from well known artifacts. Therefore, sshEPI was combined with SENSitivity Encoding (SENSE) to further increase EPI's potential for stroke imaging. Eight healthy volunteers and a consecutive series of patients (N = 8) with suspected stroke were examined with diffusion-weighted SENSE-sshEPI using different reduction factors (1.0 < or = R < or = 3.0). Additionally, a high-resolution diffusion-weighted SENSE-sshEPI scan was included. All examinations were diagnostic and of better quality than conventional sshEPI. No ghostings or aliasing artifacts were discernible, and EPI-related image distortions were markedly diminished. Chemical shift artifacts and eddy current-induced image warping were still present, although to a markedly smaller extent. Measured direction-dependent diffusion-coefficients and isotropic diffusion values were comparable to previous findings but showed less fluctuation. We have demonstrated the technical feasibility and clinical applicability of diffusion-weighted SENSE-sshEPI in patients with subacute stroke. Because of the faster k-space traversal, this novel technique is able to reduce typical EPI artifacts and increase spatial resolution while simultaneously remaining insensitive to bulk motion.

Adult↗

PubMed2001

T1 maps from shifted spin echoes and stimulated echoes.

A new pulse sequence for fast multislice T1 mapping is presented. This method is based on calculating T1 from spin echo (SE) and stimulated echo (STE) images obtained with different degrees of T1 weighting, and uses the interleaved acquisition scheme of the fast phase acquisition of composite echoes (FastPACE) technique. In contrast to the FastPACE technique, the two echoes are sampled separately. Experimental comparisons confirm that the new sequence layout overcomes most of the FastPACE restrictions, such as its motion sensitivity and the need for a fully complex data set. Moreover, this method offers a higher precision for long T1 values and a further reduction of acquisition time.

Brain↗