Biomedical subjects

F Fazekas

Publications and source records attributed to F Fazekas.

At least 19 recordsLinked to original sources

PubMed2006

Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study.

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB < or = 10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE < or = 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. CONCLUSION: 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.

Aged↗

PubMed2006

Clinical significance of corpus callosum atrophy in a mixed elderly population.

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

Age Factors↗

PubMed2006

MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.

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.

Adult↗

PubMed2006

APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers.

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 epsilon2 or epsilon4 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.

Alleles↗

PubMed2006

Lack of association of lobar intracerebral hemorrhage with apolipoprotein E genotype in an unselected population.

BACKGROUND: Both the upsilon2 and upsilon4 alleles of the apolipoprotein E gene (APOE) have been reported to be overrepresented in lobar intracerebral hemorrhage and to be associated with cerebral amyloid angiopathy (CAA). These studies were performed primarily on the North American population and investigated in partly selected patient cohorts. METHODS: 193 consecutive patients suffering from primary intracerebral hemorrhage (ICH) were included in our study. The localization of the ICH, i.e. cortico-subcortical, deep white matter, basal ganglia, brainstem and cerebellum, was put in relation to the APOE genotype and vascular risk factors. In 101 of these patients, the APOE genotype was also correlated to the presence and distribution of microbleeds and other microangiopathy-related damage, as shown by magnetic resonance imaging (MRI). RESULTS: We found neither an association of a specific APOE genotype with ICH localization nor with microangiopathy-related MRI findings. CONCLUSIONS: In our 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.

Aged↗

PubMed2006

A recommended treatment algorithm in relapsing multiple sclerosis: report of an international consensus meeting.

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.

Algorithms↗

PubMed2006

EFNS guidelines on the use of neuroimaging in the management of multiple sclerosis.

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.

Brain↗

PubMed2005

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials.

BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. METHODS: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. RESULTS: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. CONCLUSION: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials.

Adult↗

PubMed2005

Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects.

OBJECTIVES: To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, APOE epsilon4, and white matter hyperintensity (WMH) on its progression. METHODS: We assessed the brain parenchymal fraction at baseline and subsequent annual brain volume changes over 6 years for 201 participants (F/M = 96/105; 59.8 +/- 5.9 years) in the Austrian Stroke Prevention Study from 1.5-T MRI scans using SIENA (structural image evaluation using normalization of atrophy)/SIENAX (an adaptation of SIENA for cross-sectional measurement)(www.fmrib.ox.ac.uk/fsl). Hypertension, cardiac disease, diabetes mellitus, smoking, and regular alcohol intake were present in 64 (31.8%), 60 (29.9%), 5 (2.5%), 70 (39.3%), and 40 (20.7%) subjects, respectively. Plasma levels of fasting glucose (93.7 +/- 18.6 mg/dL), glycated hemoglobin A (HbA1c; 5.6 +/- 0.7%), total cholesterol (228.3 +/- 40.3 mg/dL), and triglycerides (127.0 +/- 75.2 mg/dL) were determined. WMH was rated as absent (n = 56), punctate (n = 120), early confluent (n = 14), and confluent (n = 11). RESULTS: The baseline brain parenchymal fraction of the entire cohort was 0.80 +/- 0.02 with a mean annual brain volume change of -0.40 +/- 0.29%. Univariate analysis demonstrated a higher rate of brain atrophy in older subjects (p = 0.0001), in those with higher HbA1c (p = 0.0001), higher body mass index (p = 0.02), high alcohol intake (p = 0.04), severe WMH (p = 0.03), and in APOE epsilon4 carriers (p = 0.07). Multivariate analysis suggested that baseline brain parenchymal fraction, HbA1c, and WMH score explain a major proportion of variance in the rates of brain atrophy in the cohort (corrected R2 = 0.27; p = 0.0001). CONCLUSIONS: Neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. Glycated hemoglobin A (HbA1c) was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called metabolic syndrome in subjects with high HbA1c suggests a link between this syndrome and late-life brain tissue loss.

Age Distribution↗

PubMed2005

Discrimination of white matter lesions and multiple sclerosis plaques by short echo quantitative 1H-magnetic resonance spectroscopy.

Multiple sclerosis (MS) plaques and age related white matter lesions (WML) are of similar morphological appearance on T2 weighted MRI. Therefore their differentiation is sometimes crucial. Proton magnetic resonance spectroscopy ((1)H-MRS) adds metabolic information to conventional imaging and may help to distinguish inflammatory MS plaques from vascular related WML. This study was performed to evaluate the metabolite pattern in MS plaques and WML. 15 MS patients, 14 elderly individuals with WML and 16 controls were investigated by conventional MRI and short echo quantitative (1)H-MRS (TE: 30ms, TR: 3000ms). The mean metabolite concentrations in normal control white matter (NCWM), MS plaques and WML were: t-NAA: 8.96 mmol/l (SD: 0.93) vs 6.79 mmol/l (SD: 1.99) vs 7.18 mmol/l (SD: 1.41); Cho:1.66 mmol/l (SD: 0.4) vs 1.49 mmol/l (SD: 0.45) vs 1.46 mmol/l (SD: 0.34); PCr:5.64 mmol/l (SD: 0.83) vs 4.9mmol/l (SD: 1.3) vs 4.95 mmol/l (SD: 0.86); myo-Ins: 4.57 mmol/l (SD:1.05) vs 6.34 mmol/l (SD: 2.03) vs 4.5 mmol/l (SD: 0.96). t-NAA reduction in MS plaques and WML was significant compared with controls (p <or= 0.001). MS plaques showed significantly elevated myo- Ins concentrations compared with controls (p = 0.002) and to WML (p = 0.003). In summary MS plaques and WML show a decrease in their t-NAA concentrations compared with controls. Elevated concentrations of myo-Ins in MS plaques but not in WML makes this metabolite of special interest for their differentiation.

Adult↗

PubMed2005

Relapsing acute transverse myelitis: a specific entity.

Acute transverse myelitis (ATM) not related to systemic disease may present in a relapsing manner. Data in the literature about this condition are scarce. We describe three patients suffering from relapsing myelitis in whom no association with systemic disease, i.e. infectious or connective tissue disease was found. Magnetic resonance imaging (MRI) findings were also distinctly different from multiple sclerosis and consistent with a necrotizing type of inflammation. Despite various treatment strategies, all patients became severely disabled. Relapsing ATM not related to systemic disease appears to be a specific entity which accounts for severe disability and currently lacks effective treatment.

Disability Evaluation↗

PubMed2005

Acute small subcortical infarctions on diffusion weighted MRI: clinical presentation and aetiology.

OBJECTIVE: To determine the clinical presentation and aetiology of small subcortical infarctions as found on diffusion weighted magnetic resonance imaging (DWI). DWI is both sensitive and specific in the early detection of acute ischaemic brain lesions irrespective of pre-existing vascular damage. METHODS: Ninety three patients were identified showing subcortical or brainstem DWI lesions <1.5 cm in diameter within a maximum of 7 days from the onset of stroke symptoms. The patients' clinical status on admission was reviewed according to the Oxfordshire Community Stroke Project (OCSP). The results of procedures searching for cerebrovascular risk factors, large artery disease, and potential sources of cardiac embolism were included to determine stroke aetiology. Magnetic resonance imaging scans were also reviewed for concomitant changes that could support the aetiologic classification. RESULTS: Only 41 (44.1%) patients presented clinically with a lacunar syndrome according to OCSP criteria. The nine (9.7%) patients who showed two or more DWI lesions in different vascular territories were also significantly more likely to have potential sources of cardiac embolism (5/9, 55.6% v 20/84, 23.8%). Hypertension was significantly more prevalent in the group of patients who showed a microangiopathy related imaging pattern, but this pattern did not exclude the presence of large artery disease or a possible cardioembolic source of stroke. CONCLUSION: Identification of small subcortical infarctions as the cause of stroke appears quite uncertain based on clinical characteristics only. DWI adds significant aetiologic information but does not obviate the search for other potentially causative mechanisms.

Acute Disease↗

PubMed2005

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study.

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

Aged↗

PubMed2005

MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS).

BACKGROUND: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. METHODS: A total of 318 patients (mean age 44 +/- 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. RESULTS: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the 'black hole' volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit: -0.62 -/+ 0.88% versus -0.88 +/- 0.91%; P=0.009). This difference remained statistically significant with correction for active lesions at baseline (P=0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score > or = 6 and no relapses in the two years before the study. CONCLUSION: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

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

Midbrain ischemia presenting as vertical gaze palsy: value of diffusion-weighted magnetic resonance imaging.

BACKGROUND: Conventional magnetic resonance imaging may fail to identify very small but clinically relevant acute subcortical brain infarcts. Diffusion-weighted magnetic resonance imaging (DWI) is very sensitive and specific for acute cerebral ischemia and should contribute to the early detection of such lesions. METHODS: We analyzed 6 patients who presented with acute vertical gaze palsy and in whom DWI was performed within 1-6 days from symptom onset. RESULTS: DWI accurately identified ischemia in an area supplied by the posterior thalamosubthalamic paramedian artery in all patients. T(2)-weighted and FLAIR imaging failed to identify the clinically relevant lesion in 2 and 3 patients, respectively. CONCLUSION: DWI improves the clinicoanatomical correlation in patients presenting with supranuclear oculomotor disturbances.

Acute Disease↗

PubMed2004

Acupuncture using laser needles modulates brain function: first evidence from functional transcranial Doppler sonography and functional magnetic resonance imaging.

Acupuncture using laser needles is a new totally painless stimulation method which has been described for the first time. This paper presents an experimental double-blind study in acupuncture research in healthy volunteers using a new optical stimulation method. We investigated 18 healthy volunteers (mean age +/- SD: 25.4 +/- 4.3 years; range: 21-30 years; 11 female, 7 male) in a randomized controlled cross-over trial using functional multidirectional transcranial ultrasound Doppler sonography (fTCD; n = 17) and performed functional magnetic resonance imaging (fMRI) in one volunteer. Stimulation of vision-related acupoints resulted in an increase of mean blood flow velocity in the posterior cerebral artery measured by fTCD [before stimulation (mean +/- SE): 42.2 +/- 2.5; during stimulation: 44.2 +/- 2.6; after stimulation: 42.3 +/- 2.4 cm/s, n.s.]. Mean blood flow velocity in the middle cerebral artery decreased insignificantly. Significant changes (p < 0.05) of brain activity were demonstrated in the occipital and frontal gyrus by fMRI. Optical stimulation using properly adjusted laser needles has the advantage that the stimulation cannot be felt by the patient (painless and no tactile stimulation) and the operator may also be unaware of whether the stimulation system is active. Therefore true double-blind studies in acupuncture research can be performed.

Acupuncture↗

PubMed2004

Role of magnetic resonance imaging within diagnostic criteria for multiple sclerosis.

The diagnosis of multiple sclerosis (MS) has been improved in recent decades with the incorporation of paraclinical investigations in diagnostic workup. In the last 15 years, magnetic resonance imaging (MRI) has become an especially valuable tool for supporting MS diagnosis, and specific imaging criteria became fundamental to the guidelines for the diagnosis of MS published in 2001 by an international panel (IP). The new IP criteria include MRI evidence of dissemination in space and time, making it possible to diagnose MS after a single clinical episode. This review considers current evidence concerning the reliability of the new IP criteria for the diagnosis of relapsing-onset MS, discusses strengths and weaknesses of the criteria, and outlines areas which may need modification or should be the focus of future research directed toward improving diagnostic accuracy. It also makes practical recommendations when using MRI and the IP criteria in MS diagnosis, especially in patients with clinically isolated syndromes or atypical presentations. The IP criteria are timely and concrete and introduce an important concept to MS diagnosis. Future modifications, based on emerging evidence, should further facilitate their implementation and improve their accuracy.

Humans↗