Showing papers by "Franz Fazekas published in 2011"

Heterogeneity in age-related white matter changes

Abstract: White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of normal-appearing brain tissue beyond what can be expected from standard MRI scans. There is a need for additional pre- and postmortem studies in humans, including these new imaging techniques.

2001-2011: A Decade of the LADIS (Leukoaraiosis And DISability) Study: What Have We Learned about White Matter Changes and Small-Vessel Disease?

Abstract: Over the last 20 years, evidence about the clinical correlates of cerebral white matter changes (WMC; also called leukoaraiosis) has been accumulating. WMC are now listed among the neuroimaging expressions of cerebral small-vessel disease and are no longer considered an innocuous finding because they are associated, in cross-sectional surveys, with various disturbances and, in follow-up studies, with poor prognosis. The Leukoaraiosis And DISability (LADIS) study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration that was started in 2001 with the aim of assessing the independent role of WMC in predicting disability in subjects aged 65–84. The main results of the LADIS study have been released in 2009 with the demonstration that severe WMC more than double the risk of transition from an autonomous to a dependent status after 3 years of follow-up. The LADIS study has also

Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium.

Abstract: textObjective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (pdiscovery= 4.0 × 10-9; preplication= 1.3 × 10-7; pcombined= 4.0 × 10-15). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10-9), rs11869977 (p = 5.7 × 10-9), rs936393 (p = 6.8 × 10-9), rs3744017 (p = 7.3 × 10-9), and rs1055129 (p = 4.1 × 10-8). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH.

Incident lacunes influence cognitive decline: the LADIS study.

Abstract: Background: In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML. Methods: Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression. Results: After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions ( p = 0.021) and speed and motor control ( p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score ( p = 0.016). Conclusion: Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.

Determinants of brain iron in multiple sclerosis: a quantitative 3T MRI study.

Abstract: Objectives: Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to indicate brain iron accumulation in a quantitative manner. We used this technique to assess brain iron levels in different stages of MS and healthy controls (HC) and determined their relation with demographic, clinical, neuropsychological, and other imaging variables. Methods: We studied 113 consecutive patients (35 clinically isolated syndrome [CIS], 78 MS) and 35 HC with 3 T MRI and clinical and neuropsychological examination. Iron deposition in subcortical gray matter structures was assessed by automated, regional calculation of R2* rates. Results: Basal ganglia (BG) R2* levels were significantly increased in MS compared to CIS ( p p r = 0.5, p r = 0.5, p r = 0.3, p z values of mental processing speed ( r = −0.3, p p p p Conclusion: BG iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, which argues for iron deposition as an epiphenomenon. The absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS.

MRI assessment of iron deposition in multiple sclerosis

Abstract: Iron deposition in the human brain tissue occurs in the process of normal aging and in many neurodegenerative diseases. Elevated iron levels in certain brain regions are also an increasingly recognized finding in multiple sclerosis (MS). The exact mechanism(s) for this phenomenon and its implication in terms of pathophysiology and clinical significance are still largely unknown and debated. Reliable methods to exactly quantify brain iron are a first step to clarify these issues. Therefore, the aim of this review is to present currently available magnetic resonance imaging (MRI) techniques for the assessment of brain iron. These include relaxation time mapping, phase imaging, susceptibility-weighted imaging, susceptibility mapping, magnetic field correlation imaging, and direct saturation imaging. After discussing their advantages and disadvantages, existing MRI clinical correlations with brain iron concentration in MS are summarized and future research directions are shown.

Clinical Presentation, Etiology, and Long-Term Prognosis in Patients With Nontraumatic Convexal Subarachnoid Hemorrhage

Abstract: Background and Purpose— Nontraumatic subarachnoid hemorrhage at the convexity of the brain (cSAH) is an incompletely characterized subtype of nonaneurysmal subarachnoid bleeding. This study sought to systematically describe the clinical presentation, etiology, and long-term outcome in patients with cSAH. Methods— For a 6-year period, we searched our radiological database for patients with nontraumatic nonaneurysmal subarachnoid hemorrhages (n=131) seen on CT or MRI. By subsequent image review, we identified 24 patients with cSAH defined by intrasulcal bleeding restricted to the hemispheric convexities. We reviewed their medical records, analyzed the neuroimaging studies, and followed up patients by telephone or a clinical visit. Results— The 24 patients with cSAH had a mean age of 70 years (range, 37–88 years), 20 (83%) were >60 years, and 13 (54%) were women. Patients often presented with transient sensory and/or motor symptoms (n=10 [42%]) and seizures (n=5 [21%]), whereas headaches typical of subarachnoid hemorrhage were rare (n=4 [17%]). MRI provided evidence for prior bleedings in 11 patients (microbleeds in 10 and parenchymal bleeds in 5) with a bleeding pattern suggestive of cerebral amyloid angiopathy in 5 subjects. At follow-up (after a mean of 33 months), 14 patients (64%) had an unfavorable outcome (modified Rankin scale score 3–6), including 5 deaths. We did not observe recurrent cSAH. Conclusions— Our data suggest that cSAH often presents with features not typical for subarachnoid bleeding. In the elderly, cSAH is frequently associated with bleeding-prone conditions such as cerebral amyloid angiopathy. Recurrence of cSAH is rare but the condition itself is a marker of poor prognosis.

Lesion probability mapping to explain clinical deficits and cognitive performance in multiple sclerosis.

Abstract: Background: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load an...

Reorganization in cognitive networks with progression of multiple sclerosis: Insights from fMRI

Abstract: Objectives: Cognitive dysfunction (CD) is frequent in multiple sclerosis (MS) and can occur at early stages. Whereas functional reorganization with disease progression has been described for the motor system in MS using fMRI, no such studies exist for cognition. We attempted to assess the concept of functional reorganization concerning cognition using a simple “Go/No-go” fMRI paradigm. Methods: Patients with a clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS) (n = 10), or secondary progressive MS (SPMS) (n = 10), and 28 healthy controls (HC), underwent a comprehensive neuropsychological test battery, clinical examination, structural imaging, and an fMRI Go/No-go discrimination task at 3 T. Results: Patients performed worse than HC regarding memory, sustained attention and concentration, and information processing. These differences were driven by patients with SPMS. The fMRI task elicited activation in a widespread network including bilateral mesial and dorsolateral frontal, parietal, insular, basal ganglia, and cerebellar regions. Task performance was similar between phenotypes, but deviation from the activation pattern observed in HC and patients with CIS increased with disease progression. Patients with RRMS showed increased brain activation in the precuneus, both superior parietal lobes, and the right fusiform gyrus, and recruited the hippocampus with increasing demands. Patients with SPMS demonstrated the most abnormal network function, including recruitment of pre-SMA, bilateral superior and inferior parietal, dorsolateral prefrontal, right precentral, bilateral postcentral, and right temporal brain areas. Conclusion: Using a cognitive fMRI paradigm, we were able to confirm adaptive changes of neuronal activation with progressing MS and to provide strong evidence for their compensatory nature, at least partially.

Cognitive impairment in relation to MRI metrics in patients with clinically isolated syndrome.

Abstract: Background: Cognitive deficits are frequent in multiple sclerosis (MS) and have been associated with morphologic brain changes Less information exists on their extent and relation to MRI findings in clinically isolated syndrome (CIS) It is also unclear if structural changes as detected by magnetization transfer (MT) imaging may provide an additional explanation for cognitive dysfunctionObjective: To analyse the extent of cognitive deficits and their relation to MRI metrics including MT imaging in CIS compared to relapsing-remitting MS (RRMS)Methods: Forty-four CIS and 80 RRMS patients underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) and a 3 T MRI scanResults: BRB-N subtests revealed similar results in CIS and RRMS Impaired mental processing speed was most prevalent in both groups (CIS 136%; RRMS 163%) and thus served for correlation with MRI metrics Using stepwise linear regression analyses, the strongest predictor for decreased mental processing speed was normalized cor

Oxidative stress is associated with migraine and migraine-related metabolic risk in females.

Abstract: Background and purpose: Oxidative stress is discussed to be implicated in the pathophysiology of migraine. However, data are in part controversial and the possible underlying mechanisms remain elusive to date. The aim of this study was to investigate the oxidative stress status of female patients with migraine and its implications on migraine-related metabolic alterations. Methods: Oxidative stress markers malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), carbonylated proteins, parameters of associated nitric oxide stress, inflammation, lipid- and glucose-metabolism were determined in the interictal phase in female patients with migraine and controls. Results: We found significantly increased HNE levels in female migraineurs compared with controls. Logistic regression analyses of HNE revealed an odds ratio for migraine of 4.55. HNE showed significant correlations with the nitric oxide pathway, the insulin- and the lipid-metabolism. Conclusions: We show here that increased oxidative stress is associated with migraine and contributes to migraine-related metabolic risk like nitrosative stress, an atherogenic lipid profile and hyperinsulinemia. Our data suggest that oxidative stress may represent a key event in the pathophysiology of migraine and a suitable therapeutic target.

Cognitively preserved MS patients demonstrate functional differences in processing neutral and emotional faces

Abstract: The ability to recognize emotional facial expressions is crucial to adequate social behavior. Previous studies have suggested deficits in emotion recognition in multiple sclerosis (MS). These deficits were accompanied by several confounders including cognitive or visual impairments, disease duration, and depression. In our study we used functional MRI (fMRI) to test for potential early adaptive changes in only mildly disabled MS patients performing an emotion recognition task including the facial expressions of the emotions anger, fear and disgust. Fifteen relapsing-remitting MS patients with a median Expanded Disability Status Scale (EDSS) score of 2 (range: 0-3.5) and 15 healthy controls (HC) matched for age, gender, and education underwent behavioral (BERT: behavioral emotion recognition test; BRB-N: Brief Repeatable Battery for neuropsychological tests, WCST: Wisconsin Card Sorting Test) and clinical assessments (BDI: Beck Depression Inventory). Conventional MRI at 3.0T served to assess whole-brain volume, white matter, gray matter, cerebrospinal fluid, and T2-lesion load; during fMRI, participants were confronted with neutral, scrambled, angry, disgusted, and fearful faces, and houses. In the absence of differences in cognitive performance and in the ability to accurately recognize distinct emotional facial expressions, MS patients demonstrated excess fMRI activations during facial recognition compared to HC. These differences concerned the posterior cingulate cortex (PCC) and precuneus for anger and disgust contrasted to neutral faces, and the occipital fusiform gyri and the anterior CC for neutral faces versus houses. This study provides first evidence for excess activation during processing of higher order visual stimuli of emotional content in the absence of emotional, visual or cognitive behavior abnormalities already in earlier stages of MS.

MRI-detected white matter lesions: do they really matter?

Abstract: Despite extensive research over the last decades the clinical significance of white matter lesions (WMLs) is still a matter of debate. Here, we review current knowledge of the correlation between WMLs and cognitive functioning as well as their predictive value for future stroke, dementia, and functional decline in activities of daily living. There is clear evidence that age-related WMLs relate to all of these outcomes on a group level, but the inter-individual variability is high. The association between WMLs and clinical phenotypes exists particularly for early confluent to confluent changes, which are ischaemic in aetiology and progress quickly over time. One reason for the variability of the relationship between WMLs and clinic on an individual level is probably the complexity of the association. Numerous factors such as cognitive reserve, concomitant loss of brain volume, and ultrastructural changes have been identified as mediators between white matter damage and clinical findings, and need to be incorporated in the consideration of WMLs as visible markers of these detrimental processes.

Basilar artery diameter is a potential screening tool for Fabry disease in young stroke patients.

Abstract: Background: Fabry disease (FD) is a rare hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age. Enlarged basilar artery diam

Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a prospective multicenter European study of 5,024 young stroke patients aged 18-55 years.

Abstract: Background: Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports

Increased matrix metalloproteinase activity is associated with migraine and migraine‐related metabolic dysfunctions

Abstract: Objective: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are discussed to be involved in the pathophysiology of migraine. Moreover, MMPs may also be involved in migraine-related metabolic alterations like an atherogenic lipid profile and hyperinsulinemia. The aim of this study was to investigate the impact of MMPs and TIMPs on migraine with and without aura and related metabolic dysfunctions. Methods: MMP activity, six MMPs and three TIMPs, parameters of the insulin and lipid metabolism as well as anthropometric parameters were determined in 124 non-obese subjects. Results: We found highly significant increased MMP activity in migraine patients independent of aura symptoms, which was associated with migraine with an odds ratio of 7.57. Interestingly, none of the determined MMPs and TIMPs showed significant different serum levels between migraine patients and healthy controls. We found significant correlations between MMP activity and parameters of the insulin and lipid metabolism, like Homeostasis Model Assessment index (HOMA index), cholesterol, triglycerides, and oxidized LDL. Conclusion: We show here that increased MMP activity is tightly associated with migraine and migraine-related hyperinsulinemia and atherogenic lipid alterations. Our findings represent a new pathophysiological mechanism, which may be of clinical relevance, especially in regard to therapeutic approaches using MMP inhibitors.

Corpus callosum tissue loss and development of motor and global cognitive impairment: the LADIS study.

Abstract: Objective: To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly Methods: This study was based on the Leukoaraiosis and Disability (LADIS) study Assessment of cognitive and motor functions and magnetic resonance imaging (MRI) were done at baseline and at a 3-year follow-up in nondemented elderly subjects Results: 328 of 639 LADIS subjects had MRIs at baseline and at the 3-year follow-up, which allowed for assessment of CC Logistic regression revealed differential tissue loss rates in posterior CC in subjects converting to dementia, compared to nonconverters (p Conclusion: The present longitudinal study on CC supports the role of callosal tissue loss in the development of global cognitive as well as motor impairment

Self-perceived memory complaints predict progression to Alzheimer disease. The LADIS study.

Abstract: Memory complaints are frequent in the elderly but its implications in cognition over time remain a controversial issue. Our objective was to evaluate the risk of self perceived memory complaints in the evolution for future dementia. The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes (WMC) on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Dementia and subtypes of dementia were classified. Self perceived memory complaints in independent elderly were collected during the interview. MRI was performed at entry and at the end of the study. 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). At end of follow-up, 90 patients were demented (vascular dementia, 54; Alzheimer's disease (AD) and AD with vascular component, 34; frontotemporal dementia, 2). Using Cox regression analysis, we found that self perceived memory complaints were a strong predictor of AD and AD with vascular component during the follow-up (β = 2.7, p = 0.008; HR = 15.5, CI 95% [2.04, 117.6]), independently of other confounders, namely depressive symptoms, WMC severity, medial temporal lobe atrophy, and global cognition status at baseline. Self perceived memory complaints did not predict vascular dementia. In the LADIS study, self perceived memory complaints predicted AD but not vascular dementia in elderly subjects with WMC living independently. © 2011 - IOS Press and the authors. All rights reserved.

Fast bound pool fraction mapping using stimulated echoes.

Abstract: Magnetization transfer imaging advanced to an indispensible tool for investigating white matter changes. Quantitative magnetization transfer imaging methods allow the determination of the bound pool fraction (BPF), which is thought to be directly linked to myelin integrity. Long acquisition times and high specific absorption rates are still inhibiting broad in vivo utilization of currently available BPF mapping techniques. Herewith, a stimulated echoes amplitude modulation-based, single-shot echo planar imaging technique for BPF and T1 quantification is presented at 3T. It allows whole brain mapping in 10–15 min and is low in specific absorption rates. The method was validated with different concentrations of bovine serum albumin (BSA) phantoms. Intra- and inter-subject variability was assessed in vivo. Phantom measurements verified linearity between bovine serum albumin concentrations and measured BPF, which was independent of T1 variations. T1 values in the phantoms correlated well with values provided by standard T1 mapping methods. Intrasubject variability was minimal and mean regional BPFs of 10 volunteers (e.g., left frontal white matter = 0.135 ± 0.003, right frontal white matter = 0.129 ± 0.006) were in line with previously published data. Assessment of interhemispheric BPF differences revealed significantly higher BPF for the left brain hemisphere. To sum up, these results suggest the proposed method useful for cross-sectional and longitudinal studies of white matter changes in the human brain. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

Abstract: Background: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data.Objectives: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument.Methods: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20–60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire.Results: Analysis of variance and post-hoc Scheffe-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the fact...

Altered functional organization of the motor system related to ankle movements in Parkinson's disease: insights from functional MRI.

Abstract: Bradykinesia represents one of the cardinal and most incapacitating features of Parkinson’s disease (PD). In this context, investigating the cerebral control mechanisms for limb movements and defining the associated functional neuroanatomy is important for understanding the impaired motor activity in PD. So far, most studies have focused on motor control of upper limb movements in PD. Ankle movement functional MRI (fMRI) paradigms have been used to non-invasively investigate supraspinal control mechanisms relevant for lower limb movements in healthy subjects, patients with Multiple sclerosis, and stroke. Using such an active and passive paradigm in 20 PD patients off medication (mean age 66.8 ± 7.2 years) and 20 healthy controls (HC; mean age 62.3 ± 6.9 years), we here wished to probe for possible activation differences between PD and HC and define functional correlates of lower limb function in PD. Active ankle movement versus rest was associated with a robust activation pattern in expected somatotopy involving key motor areas both in PD and HC. However, contrasting activation patterns in patients versus controls revealed excess activation in the patients in frontal regions comprising pre-supplementary motor areas (pre-SMA) and SMA proper. The extent of SMA activation did not correlate with behavioural parameters related to gait or motor function, and no differences were seen with the passive paradigm. This finding might be indicative of higher demand and increased effort in PD patients to ensure adequate motor function despite existing deficits. The missing correlation with behavioural variables and lack of differences with the passive paradigm suggests that this excess activation is not exclusively compensatory and also not hard-wired.

Predicting the severity of relapsing-remitting MS: The contribution of cross-sectional and short-term follow-up MRI data:

Abstract: Background and objective: Predicting the long-term clinical course of multiple sclerosis (MS) is difficult on clinical grounds. Recent studies have suggested magnetic resonance imaging (MRI) metrics to be helpful. We wanted to confirm this.Methods: Contactable individuals (N = 84) from an initial 99 patients with relapsing–remitting MS (RRMS) who had undergone careful baseline and 2-year follow-up examinations including MRI were reassessed after a mean of 10.8 ± 2.7 years. We investigated using multivariate linear regression analyses if clinical and MRI data obtained at the prior time-points and the rates of change in morphologic variables over a mean observational period of 2.5 years could have served to predict a patient’s MS severity score (MSSS) 11 years later. Conversion to secondary progressive MS (SPMS) was a further outcome variable.Results: In univariate analyses, the ‘black hole ratio’ (BHR) at baseline (p = 0.017, beta = 0.148) and at first follow-up (p = 0.007, beta = −0.154) was the only MRI ...

Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency: The Neuroimaging Perspective

Abstract: In patients with multiple sclerosis (MS), Zamboni et al[1][1] described anomalies of venous outflow at color Doppler high-resolution examination and multiple severe extracranial stenosis at venography, affecting the internal jugular, the vertebral, and the azygous veins. The authors focused their

Relaxation time mapping in multiple sclerosis.

Abstract: Several relaxation mapping techniques have been proposed to quantitatively assess disease-related brain tissue changes in multiple sclerosis. Newer developments also account for the distribution of hydrogen protons in different tissue compartments, and therefore provide markers for myelin and macromolecular content. This article will cover the broad spectrum of the pulse sequences and analysis techniques related to this topic that are currently available. Various technical and practical limitations linked with specific approaches will be discussed. These include acquisition time, accuracy and precision, radiofrequency absorption and limited coverage of the brain. Finally, the application of these techniques in the context of multiple sclerosis will be reviewed.

Relationship between brain MRI lesion load and short-term disease evolution in non-disabling MS: a large-scale, multicentre study:

Abstract: Background and Objectives: We evaluated clinical and conventional MRI features of a large population of patients with non-disabling MS to identify potential markers of a benign disease course.Methods: In seven MAGNIMS centres we retrospectively identified 182 patients with benign (B) MS (EDSS score ≤3.0, disease duration ≥15 years) and 187 patients with non-disabling relapsing–remitting MS (NDRRMS) (Expanded Disability Status Scale score ≤3.0, disease duration between 5 and 14 years), in whom clinical data were collected within two weeks from a brain T2-weighted scan. Brain T2 lesion volume (LV) was measured in all patients. In 146 BMS and 146 NDRRMS patients, clinical data were also available after a median follow up of 29 months (range: 7–104 months).Results: Mean LV was higher in BMS than in NDRRMS patients (p < 0.001), but the mean ratio between LV and disease duration was higher in NDRRMS than in BMS patients (1.1 vs. 0.6 ml/year, p < 0.001). In BMS patients, brain LV was correlated with EDSS score i...

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register

Abstract: Background: We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non-Austrian centres as documented in the Internet-based registers Safe Implementation of Thrombolysis for Stroke – MOnitoring STudy (SITS-MOST) and – International Stroke Thrombolysis Register (SITS-ISTR). Methods: We analysed patient data entered in the registers SITS-MOST and SITS-ISTR in the period December 2002 to 15 November 2007. Results: Compared to the non-Austrian cohort (n = 15153), the Austrian cohort (n = 896) was slightly older [median, interquartile range (IQR): 70, 60–77 years vs. 69, 60–76 years, P = 0.05] and included more women (44.6% vs. 41.0%, P = 0.03). Austrian patients had a significantly shorter stroke onset-to-treatment time (OTT; median, IQR: 135, 105–160 min vs. 145, 115–170 min, P < 0.0005). Symptomatic intracerebral haemorrhages were observed in 1.6% of Austrian and 1.7% of non-Austrian patients (P = 0.82). At 3 months, 50.8% of Austrian and 53.0% of non-Austrian patients were independent (P = 0.23), but death was less frequent in Austrian patients (12.1% vs. 14.9%, P = 0.03). Multivariate analyses adjusted for demographic and baseline characteristics confirmed lower mortality at 3 months in the Austrian cohort (odds ratio 0.81, 95% confidence intervals 0.71–0.92, P = 0.001). Longer OTT was associated with increased mortality at 3 months, with a hazard ratio of 1.02 (95% CI 1.01–1.03; P = 0.005) for each 10-min increase in OTT. Conclusions: The implementation of intravenous alteplase for acute stroke has been safe and efficacious in Austrian centres. OTT and mortality were significantly lower in Austrian patients compared to non-Austrian SITS centres.

Clinical Core Symptoms of Posterior Spinal Artery Ischemia

Abstract: Introduction: Ischemia in the distribution of the posterior spinal artery is rare. Methods: Between 2004 and 2008 we observed 4 patients with posterior spinal artery ischemia (PSAI). Results: All patients had the expected loss of posterior column function but also suffered from motor deficits which were severe, and the leading symptom in 2 patients. Severe pain, bowel and bladder dysfunction were other concomitant symptoms. In 3 of 4 patients, a follow-up spinal MRI was needed to show the cord infarct together with vertebral body ischemia in 2 patients. Conclusion: An acute onset of posterior column dysfunction with a variable degree of motor deficit and dorsalgia suggests PSAI.