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Biomedical subjects

F Fazekas

Publications and source records attributed to F Fazekas.

At least 55 records · Page 3Linked to original sources

Improved interobserver agreement for visual detection of active T2 lesions on serial MR scans in multiple sclerosis using image registration.

The aim of this study was to analyse the effect of image registration on interobserver agreement in the visual detection of active multiple sclerosis (MS) lesions from serial magnetic resonance (MR) scans. T2W spin-echo MR scans (3-mm slices) of 16 MS patients participating in a treatment trial were selected. For each patient, two pairs of scans were used: an original (i. e., non-registered) and a registered pair. For the original pair, baseline and month 6 were used, and for the registered pair month 3 and 9. For registration an automatic matching algorithm based on Mutual Information was used. Six observers identified active lesions on both original and registered scans. Kappa values were calculated to assess interobserver agreement. Reslicing caused a slight blurring of the images, but near perfect registration. The kappa value of 0.35 +/- 0.07 for new lesions on original images improved to 0.62 (+/- 0.06) by registration (p = 0.004). For enlarging lesions on original images it was extremely poor (kappa 0.11 +/- 0.05), and did not benefit much by registration (kappa 0.20 +/- 0.11). Thus, image registration improved interobserver agreement for visual detection of new lesions. For enlarging lesions, registration improved agreement but still not to a satisfactory level.

Adult↗

A survey of neuroimaging research in European neurological departments.

In the international neurological literature, neuroimaging research plays an important role. Neuroimaging techniques are also of steadily increasing importance for clinical diagnosis and treatment monitoring. Therefore, neuroimaging research activities were surveyed by a questionnaire, which was completed by 100 neurological centres across Europe. It showed that most groups use magnetic resonance imaging (MRI), fMRI, computerized tomography (CT) and single photon emission computerized tomography (SPECT). Positron emission tomography (PET) and ultrasound are also employed by nearly half of the centres. Neuroimaging research involves co-operation amongst typically five to 10 disciplines. Cerebrovascular disease, dementia, cognitive disorders, epilepsy, movement disorders, brain tumours and multiple sclerosis are frequently being studied. Many groups rely on small budgets, have few full-time scientists and limited access to expensive resources. There is little exchange of scientists amongst laboratories. It was felt that funding and co-operation needed improvement in order to maintain a high standard in neuroimaging research.

Data Collection↗

Angiotensinogen polymorphism M235T, carotid atherosclerosis, and small-vessel disease-related cerebral abnormalities.

The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. We studied the role of this polymorphism as a risk factor for carotid atherosclerosis and small-vessel disease-related brain abnormalities. A total of 431 randomly selected community-dwelling subjects without clinical evidence for strokes underwent angiotensinogen genotyping and carotid Duplex scanning; 1.5-T brain magnetic resonance imaging (MRI) was done in 396 individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5-point scale. Small-vessel disease-related brain abnormalities were deep or subcortical white matter lesions or lacunes. Progression of carotid atherosclerosis and MRI findings was rated by direct imaging comparison by 3 independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%, and 18.1% of subjects, respectively. The M235T polymorphism was neither associated with baseline carotid findings nor with progression of carotid atherosclerosis. There was a trend toward more frequent small-vessel disease-related MRI abnormalities in the T/T than in the other genotypes at the baseline examination. Progression of brain lesions occurred significantly more commonly in T/T than in M/M and M/T carriers (P<0.001). Logistic regression analysis identified the T/T genotype (odds ratio, 3.19; P=0.002) and arterial hypertension (odds ratio, 3.06; P=0.03) as significant independent predictors of lesion progression. These data suggest that the angiotensinogen T/T genotype at position 235 is a genetic marker for brain lesions from and progression of small vessel disease but not for extracranial carotid atherosclerosis.

Angiotensinogen↗

Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage: results of the Austrian Stroke Prevention Study.

BACKGROUND AND PURPOSE: 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 most important risk factors. We assessed the association between MARCD and sequence alterations in the promoter region of the angiotensinogen (AGT) gene. METHODS: We studied 410 randomly selected community-dwelling individuals aged 50 to 75 years. MARCD was defined as early confluent or confluent white matter hyperintensities or lacunes on a 1.5-T MRI. The AGT promoter was analyzed by temporal temperature gradient gel electrophoresis and automated sequencing. RESULTS: We detected 4 polymorphic sites, at positions -6, -20, -153, and -218. They created 5 haplotypes, which we coded as A (-6:g, -20:a, -153:g, -218g), B (-6:a, -20:c, -153:g, -218:g), C (-6:a, -20:c, -153:a, -218:g), D (-6:a, -20:a, -153:g, -218:g), and E (-6:a, -20:a, -153:g, -218:a). MARCD was seen in 7 subjects (63.6%) carrying 2 copies of the B haplotype (B/B), in 12 subjects (38.7%) carrying 1 copy of the B haplotype in the absence of the A haplotype (B+/A-), but in only 70 subjects (19.0%) in the remaining cohort (P:<0.001). The odds ratios for the B/B and the B+/A- genotypes were 8.0 (95% CI, 2.1 to 31.1; P:=0.003) and 1.8 (95% CI, 0.8 to 4.2; P:=0.14) after adjustment for possible confounders. CONCLUSIONS: The B haplotype of the AGT promoter in the absence of the wild-type A haplotype might represent a genetic susceptibility factor for MARCD.

Age Distribution↗

A new rating scale for age-related white matter changes applicable to MRI and CT.

BACKGROUND AND PURPOSE: MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. METHODS: Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using kappa statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. RESULTS: Interrater reliability was good for MRI (kappa=0.67) and moderate for CT (kappa=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. CONCLUSIONS: We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.

Aging↗

Clinical predominance of proximal upper limb weakness in CMT1A syndrome.

We report an Austrian family with proximal muscle weakness and wasting predominantly of the shoulder girdle musculature, normal or slightly reduced distal muscle power, mild foot deformity, absent or reduced tendon reflexes in the lower limbs, and normal or slightly diminished sensation. Electrophysiologically, motor nerve conduction velocities were slowed to less than 33 m/s, distal latencies were prolonged, and compound motor action potentials were low. Sensory nerve conduction velocities were extremely reduced or no sensory potentials were recordable. Genetic testing in three affected individuals revealed a duplication of the chromosomal region 17p11.2. In addition, genetic testing for facioscapulohumeral muscular dystrophy (FSHD) revealed a 33 kb EcoRI fragment on chromosome 4q35 in one affected individual and in the clinically normal parent, whereas in a second affected person normal DNA-sizes were observed. These clinical findings define a new phenotypic variant associated with the Charcot-Marie-Tooth 1A duplication. This may be due to a mutation in another gene contained in the 1.5 Mb duplication although mutations in the peripheral myelin protein 22 gene have been excluded. Alternatively, the genetic background of other genes in the family may modify the phenotypic expression, as found in other inherited diseases. The unusual phenotype cannot be explained by the concomitant presence of FSHD despite some evidence for coexistance in one individual.

Adult↗

Estimation of magnetization transfer rates from PACE experiments with pulsed RF saturation.

A new imaging method has been developed for estimating the magnetization transfer rate (MTR) in a biologic two-pool system such as the brain tissue. The transfer rate is calculated from the ratio of the MTR to T(1sat), where T(1sat) is the apparent longitudinal relaxation time under complete saturation of the macromolecular pool. MTR and T(1sat) maps were obtained with a phase acquisition of composite echo (PACE) technique combined with pulsed radiofrequency (RF) saturation. The influences of RF saturation power and frequency offset on quantitative results were investigated with phantom and in vivo measurements. In white matter of seven healthy volunteers we found a mean transfer rate of 1.5 sec(-1), where the highest transfer rate was found in the genu of the corpus callosum (k(f) = 1. 9 sec(-1)). It could be shown that conditions near to complete saturation can also be reached under common restrictions by the specific absorption rate.

Brain↗

Magnetic resonance diffusion tensor imaging for characterizing diffuse and focal white matter abnormalities in multiple sclerosis.

High-resolution diffusion tensor imaging (DTI) was performed in 14 patients with clinically definite multiple sclerosis (MS) and the trace of the diffusion tensor ( ) and the fractional anisotropy (FA) were determined in normal appearing white matter (NAWM) and in different types of focal MS lesions. A small but significant increase of the in NAWM compared to control white matter ((840 +/- 85) x 10(-6) mm(2)/sec vs. (812 +/- 59) x 10(-6) mm(2)/sec; P < 0.01) was found. In addition, there was a significant decrease in the FA of normal-appearing regions containing well-defined white matter tracts, such as the genu of the internal capsule. In non-acute lesions, the of T(1)-hypointense areas was significantly higher than that of T(1)-isointense lesions ((1198 +/- 248) x 10(-6) mm(2)/sec vs. (1006 +/- 142) x 10(-6) mm(2)/sec; P < 0. 001), and there was a corresponding inverse relation of FA. Diffusion characteristics of active lesions with different enhancement patterns were also significantly different. DTI with a phase navigated interleaved echo planar imaging technique may be used to detect abnormalities of isotropic and anisotropic diffusion in the NAWM and selected fiber tracts of patients with MS throughout the entire brain, and it demonstrates substantial differences between various types of focal lesions.

Adult↗

Longitudinal change of white matter abnormalities.

A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity in elderly individuals without neuropsychiatric disease. Lesion progression was found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) and early confluent or confluent white matter hyperintensities at baseline (odds ratio 2.62) were the only significant predictors of white matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period.

Aged↗

Genetic aspects of microangiopathy-related cerebral damage.

Microangiopathy related cerebral damage (MARCD) includes early confluent and confluent white matter hyperintensities (WMH) and lacunar lesions. It is expected to be the result of interactions between multiple genetic and environmental factors. The estimated proportion of genetic factors contributing to the interindividual variation seen in WMH volume is 73%. This estimate points to a significant genetic component in WMH development. In the setting of the Austrian Stroke Prevention Study we search for genes being associated with the presence, severity and progression of MARCD using the candidate gene approach. Defining susceptibility genes may allow to better identify individuals at high risk for MARCD and to target preventive measures.

Apolipoprotein E2↗

Vascular risk factors in dementia.

This review describes differing profiles of vascular risk factors in different types of dementia. Although vascular risk factors are related to various types of strokes, their independent effect on the occurrence of poststroke dementia appears to be small. Various risk factors have been identified for microangiopathy-related cerebral abnormalities, such as white matter changes and lacunae, which are the core lesions for the development of a vascular dementia syndrome without stroke symptoms. Most consistently, arterial hypertension and diabetes mellitus have been found to be associated with such brain abnormalities. Diastolic blood pressure seems to be of particular importance as recent investigations demonstrate that this factor is related to the course of multiple lacunar strokes and the progression of white matter disease. Epidemiological studies report that various vascular risk factors including arterial hypertension, diabetes mellitus, and atrial fibrillation may also be associated with Alzheimer's disease. There is also evidence of a direct relationship between Alzheimer's disease and general atherosclerosis. Further investigations are needed to determine whether these associations are due to the weakness of diagnostic criteria, or whether vascular risk factors indeed modulate the clinical expression of primary degenerative dementia. Common susceptibility genes leading to shared risk factors may be one of the reasons for a higher coincidence of Alzheimer's disease and vascular dementia than can be expected by chance. A modulatory effect of vascular risk factors in the development of primary degenerative dementia may extend treatment options.

Aged↗

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Blood Transfusion, Autologous↗

Magnetic resonance imaging of cerebral microbleeds.

Magnetic resonance imaging of patients with primary intracerebral haemorrhage has drawn attention to focal areas of signal loss, which were suggested to indicate hemosiderin deposition from earlier bleeds. Correlative histopathologic data have recently confirmed this assumption and support a strong association between the occurrence of microbleeds and various types of small vessel disease, such as hypertensive lipofibrohyalinosis and cerebral amyloid angiopathy. Therefore, microbleeds that are detectable by magnetic resonance imaging could be viewed as markers for vessel wall disorders with a higher tendency for intracerebral bleeding. This finding appears to be of diagnostic importance, but could also help to predict a patient's risk for spontaneous rebleeding or bleeding complications after anticoagulation.

Cerebral Hemorrhage↗

Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis.

OBJECTIVES: Clinical reports have speculated on a more severe course of multiple sclerosis in patients with the apolipoprotein E (apoE) epsilon4 allele. As this could be reflected by differences in the severity of tissue damage MRI was used to obtain further support for a disease modifying effect of the apoE genotype. METHODS: Brain MR scans of 83 patients (mean age 35.5 (SD 9.5 years) who participated in a cross sectional study on the distribution of genotype patterns in multiple sclerosis. The total lesion load on proton density weighted (T2-LL) and T1 weighted scans (T1-LL) obtained with conventional spin echo sequences at 1.5 T was measured. A "black hole" ratio ((T1-LL/T2-LL)x100) was also calculated. This indicates the proportion of multiple sclerosis lesions with more severe tissue damage and may reflect disease aggressiveness or quality of repair. RESULTS: Patients with the apoE-epsilon3/epsilon4 genotype (n=19) showed a non-significantly greater T2-LL (16.0 (SD 14.0) cm(3)) than patients with the epsilon2/epsilon3 (n=11; 13.3 (9.5) cm(3)) or the epsilon3/epsilon3 genotype (n=49; 9.4 (SD 9.2) cm(3)). Both the T1-LL (2.6 (SD 3.3) v 1.6 (SD 2.4) and 1.2 (SD 3.0) cm(3); p=0.04) and the black hole ratio (14.3 SD 11.9) v 7.4 (SD 9.3) and 8.4 (SD 13.3)%; p=0.02), however, were significantly higher in epsilon3/epsilon4 patients. Similar differences were seen when comparing patients with at least one epsilon4 allele with the remainder of the group. CONCLUSIONS: These data support speculations on a modulation of multiple sclerosis severity by the apoE genotype which can be attributed to more extensive tissue destruction or less efficient repair in carriers of the epsilon4 allele.

Adolescent↗

MRI cerebral white matter lesions and paraoxonase PON1 polymorphisms : three-year follow-up of the austrian stroke prevention study.

White matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of older persons are thought to be caused by cerebral small-vessel disease. As they progress, these brain abnormalities frequently result in cognitive decline and gait disturbances, and their predictors are incompletely understood. Genetic risk factors have been implicated but remain undetermined so far. We examined whether 2 common polymorphisms of the paraoxonase (PON1) gene leading to a methionine (M allele)-leucine (L allele) interchange at position 54 and an arginine (B allele)-glutamine (A allele) interchange at position 191 are associated with the presence and progression of WMLs. We studied 264 community-dwelling subjects without neuropsychiatric disease (ages 44 to 75 years). All underwent vascular risk factor assessment, brain MRI, and PON1 genotyping. MRI scanning was repeated after 3 years. The extent and number of WMLs were recorded by 3 independent readers. Progression of WMLs was assessed by direct scan comparison. The final rating relied on the majority judgment of the 3 readers. The LL, LM, and MM genotypes were noted in 111 (42.0%), 118 (44.7%), and 35 (13.3%) subjects, respectively; the AA, AB, and BB genotypes occurred in 146 (55.3%), 98 (37.1%), and 20 (7.8%) individuals, respectively. Carriers of the LL genotype showed a nonsignificant trend toward more extensive WMLs and more frequently demonstrated lesion progression over the 3-year observation period (P=0.03). The polymorphism at position 191 had no effect. Logistic regression analysis yielded age (odds ratio, 1.08/y), diastolic blood pressure (odds ratio, 1.05/mm Hg), and LL paraoxonase genotype (odds ratio, 2. 65) to be significant predictors of WML progression. These data suggest that the LL PON1 genotype at position 54 influences the extent and progression of WMLs in elderly subjects.

Adult↗

Frequency and location of microbleeds in patients with primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: MRI is known to detect clinically silent microbleeds (MBs) in patients with primary intracerebral hemorrhage (pICH), but the frequency and diagnostic and clinical significance of this finding are still debated. Therefore, we investigated a consecutive series of pICH patients and analyzed the patterns of MB distribution in the context of clinical variables and location of the symptomatic hematoma. METHODS: The study population consisted of 109 patients with pICH. There were 59 women and 50 men aged 22 to 91 years (mean 64.6 years). MRI was obtained on a 1.5-T system with use of a gradient-echo T2*-weighted sequence. A cohort of 280 community-dwelling asymptomatic elderly individuals who underwent the same imaging protocol served for comparison. RESULTS: MBs were seen in 59 (54%) patients and ranged in number from 1 to 90 lesions (mean 14, median 6). In the majority of patients, MBs were located simultaneously in various parts of the brain, with a preference for cortical-subcortical regions (39%) and the basal ganglia/thalami (38%). There was some tendency toward a regional association between MB location and the site of the symptomatic hematoma, but we could not discern specific patterns of MB distribution. Logistic regression analysis identified MBs, periventricular hyperintensity grades, and lacunes but not risk factors as independent variables contributing to a correct classification of pICH and control individuals. CONCLUSIONS: MBs can be detected in more than half of the patients with pICH and appear to be quite general markers of various types of bleeding-prone microangiopathy.

Adult↗

Diffusion-weighted MR imaging of the spinal cord.

Diffusion-weighted MR imaging may increase the sensitivity and specificity of MR imaging for certain pathologic conditions of the spinal cord but is rarely performed because of several technical issues. We therefore tested a novel phase-navigated spin-echo diffusion-weighted interleaved echo-planar imaging sequence in seven healthy volunteers and six patients with intramedullary lesions. We performed diffusion-weighted MR imaging of the spinal cord with high spatial resolution. Different patterns of diffusion abnormalities observed in patient studies support the possible diagnostic impact of diffusion-weighted MR imaging for diseases of the spinal cord.

Adult↗

Diffusion-weighted imaging of patients with subacute cerebral ischemia: comparison with conventional and contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: The importance of diffusion-weighted imaging (DWI) for delineating acute ischemic lesions has been investigated extensively; however, few studies have investigated the role of DWI in the subacute stage of stroke. Because these lesions tend to appear bright throughout the first days of ischemia, owing to restricted diffusion, we speculated that DWI could also improve the detection of subacute infarcts as compared with conventional and contrast-enhanced MR imaging. METHODS: Interleaved echo-planar DWI with phase navigation was performed on a 1.5-T MR unit in a consecutive series of 53 patients (mean age, 66 +/- 14 years) with suspected recent cerebral ischemia. The interval between onset of clinical symptoms and MR imaging ranged from 1 to 14 days (mean, 6 +/- 4 days). Contrast material was given to 28 patients in a dose of 0.1 mmol/kg. RESULTS: DWI clearly delineated recent ischemic damage in 39 patients (74%) as compared with 33 (62%) in whom lesions were identified or suspected on conventional T2-weighted images. DWI provided information not accessible with T2-weighted imaging in 17 patients when evidence of lesion multiplicity or detection of clinically unrelated recent lesions was included for comparison. Subacute ischemic lesions were also seen more frequently on DWI sequences than on contrast-enhanced images (20 versus 13 patients). DWI was more likely to make a diagnostic contribution in the first week of stroke and in patients with small lesions or preexisting ischemic cerebral damage than was conventional MR imaging. CONCLUSION: Recent ischemic damage is better shown on DWI sequences than on conventional and contrast-enhanced MR images throughout the first days after stroke and may provide further information about the origin of clinical symptoms. Adding DWI to imaging protocols for patients with subacute cerebral ischemia is recommended.

Adult↗