Search

Background: Brain volume loss occurs in patients with relapsing-remitting MS. Fingolimod reduced brain volume loss in three phase 3 studies., Objective: To evaluate whether the effect of fingolimod on disability progression was mediated by its effects on MRI lesions, relapses or brain volume loss, and the extent of this effect., Methods: Patients (992/1272; 78%) from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study were analyzed. Month-24 percentage brain volume change, month-12 MRI-active lesions and relapse were assessed. The Prentice criteria were used to test surrogate marker validity. The proportion of treatment effect on disability progression explained by each marker was calculated., Results: Two-year disability progression was associated with active T2 lesions (OR = 1.24; p = 0.001) and more relapses during year 1 (OR = 2.90; p < 0.001) and lower percentage brain volume change over two years (OR = 0.78; p < 0.001). Treatment effect on active T2 lesions, relapses and percentage brain volume change explained 46%, 60% and 23% of the fingolimod effect on disability. Multivariate analysis showed the number of relapses during year 1 (OR = 2.62; p < 0.001) and yearly percentage brain volume change over two years (OR = 0.85; p = 0.009) were independent predictors of disability progression, together explaining 73% of fingolimod effect on disability., Conclusions: The treatment effect on relapses and, to a lesser extent, brain volume loss were both predictors of treatment effect on disability; combining these predictors better explained the effect on disability than either factor alone., (© The Author(s), 2015.)

Magnetization transfer (MT) reflects the exchange of magnetization between protons bound to macromolecules, such as lipids and proteins, and protons in free liquid, and thus might be an early marker for subtle and undetermined pathologic changes in tissue. Detailed analysis of the entire MT phenomenon, however, commonly requires extensive data acquisition and scanning time, and hence is only of limited clinical interest. Therefore, in practice, magnetization transfer effects are commonly confined into a simple ratio measure, the so-called magnetization transfer ratio (MTR), calculated from a MT-weighted and a non-MT-weighted image. However, subtle physiologic and pathologic changes in tissue, invaluable for specific diagnostic imaging, may be lost since MTR-values depend not only on quantitative magnetization transfer (qMT) parameters but also on sequence parameters and relaxation properties. In order to evaluate and assess the diagnostic specificity of MTR versus qMT, high-resolution whole brain MT data was collected from twelve healthy volunteers using balanced steady-state free precession (bSSFP). In contrast to common MT imaging based on spoiled gradient echo (SPGR) sequences, whole brain qMT imaging can be performed with MT-sensitized bSSFP within a clinically feasible acquisition time. Hence, MT-sensitized bSSFP provides access to both MTR and qMT parameters within a clinical setting. The reliability and possible diagnostic value of MTR are analyzed for twelve white matter (WM) and eleven gray matter (GM) structures of the normal appearing brain. Strong correlations were found within and between longitudinal and transverse relaxation times (T1, T2) and MT parameters (ratio between macromolecular and water protons, F, and magnetization exchange rate, kf), whereas weaker correlations were observed between MTR-values and relaxation times or MT parameters. Structures with highly similar MTR-values, such as the crus cerebri and the anterior commissure in the WM, or the pallidum and the amygdala in the GM, however, were also found that showed significant differences in most quantitative parameters. This observation was confirmed from simulations revealing that the overall effect on MTR from an increase (decrease) in relaxation times may be counterbalanced with a decrease (increase) in MT parameters. These findings corroborate the expectation that qMT is superior to MTR imaging, especially for the evaluation and assessment of pathologic or physiological changes in healthy and pathologic brain tissue., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To describe the diagnosis and management of a 49-year-old woman with multiple sclerosis (MS) developing a progressive hemiparesis and expanding MRI lesion suspicious of progressive multifocal leukoencephalopathy (PML) 19 months after starting natalizumab., Results: Polyomavirus JC (JCV)-specific qPCR in CSF was repeatedly negative, but JCV-specific antibodies indicated intrathecal production. Brain biopsy tissue taken 17 weeks after natalizumab discontinuation and plasmapheresis was positive for JCV DNA with characteristic rearrangements of the noncoding control region, but histology and immunohistochemistry were not informative except for pathologic features compatible with immune reconstitution inflammatory syndrome. A total of 22 months later, the clinical status had returned close to baseline level paralleled by marked improvement of neuroradiologic abnormalities., Conclusions: This case illustrates diagnostic challenges in the context of incomplete suppression of immune surveillance and the potential of recovery of PML associated with efficient immune function restitution.

Compared to standard spoiled gradient echo (SPGR)-methods, balanced steady-state free precession (bSSFP) provides quantitative magnetization transfer (qMT) images with increased resolution and high signal-to-noise ratio (SNR) in clinically feasible acquisition times. The aim of this study was to acquire 3D high-resolution qMT-data to create standardized qMT-values of many single brain structures that might serve as a baseline for the future characterization of pathologies of the brain. QMT parameters, such as the fractional pool size (F), exchange rate (kf) and relaxation times of the free pool (T1, T2) were assessed in a total of 12 white matter (WM) and 11 grey matter (GM) structures in 12 healthy volunteers with MT-sensitized bSSFP. Our results were compared with qMT-data from previous studies obtained with SPGR-methods using MT-sensitizing preparation pulses with significantly lower resolution. In general, qMT-values were in good accordance with prior studies. As expected, higher F and kf and lower relaxation times were observed in WM as compared to GM structures. However, many significant differences were observed within WM and GM regions and also between different regions of the same structure like in the internal capsule where the posterior limb showed significant higher kf than the anterior limb. Significant differences for all parameters were observed between subjects. In contrast to previous studies, bSSFP allowed assessment of even small brain structures due to its high resolution. The observed differences from previous studies can partly be explained by the reduced partial volume effects. MT-sensitized bSSFP is an ideal candidate for qMT-analysis in the clinical routine as it provides high-resolution 3D qMT-data of even small brain structures in clinically feasible acquisition times. The present qMT-data can serve as a reference for the characterization of cerebral diseases., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objectives: In early stage psychosis research the identification of neurobiological correlates of vulnerability to schizophrenia is an important hurdle., Methods: We systematically reviewed the neuroimaging publications on high-risk subjects with subsequent transition to psychosis (HR-T) and conducted a meta-analysis calculating the effect size Cohen's d., Results: Out of 30 identified studies 25 met the inclusion criteria. Structural (s)MRI studies showed small to medium effect sizes of decreased prefrontal, cingulate, insular and cerebellar gray matter volume in HR-T compared to high-risk subjects without transition (HR-NT). Meta-analysis revealed relatively larger whole brain volumes in HR-T compared to HR-NT subjects (mean Cohen's d 0.36, 95% CI 0.27-0. 46). Compared to HR-NT, HR-T subjects showed in functional imaging studies reduced brain activation in prefrontal cortex, reduced neuronal density, and increased membrane turnover in frontal and cingulate cortex with medium to large effect sizes., Conclusions: Despite methodological differences between studies, structural and neurochemical abnormalities in prefrontal, anterior cingulate, medial temporal and cerebellar cortex might be predictive for development of psychosis within HR subjects.

Magnetic resonance imaging (MRI) is a sensitive paraclinical test for diagnosis and assessment of disease progression in multiple sclerosis (MS) and is often used to evaluate therapeutic efficacy. The formation of new T2-hyperintense MRI lesions is commonly used to measure disease activity, but lacks specificity because edema, inflammation, gliosis, and axonal loss all contribute to T2 lesion formation. As the role of neurodegeneration in the pathophysiology of MS has become more prominent, the formation and evolution of chronic or persistent Tl-hypointense lesions (black holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. Despite the use of various detection methods, including advanced imaging techniques such as magnetization transfer imaging and magnetic resonance spectroscopy, correlation of persistent black holes with clinical outcomes in patients with MS remains uncertain. Furthermore, although axonal loss and neuronal tissue destruction are known to contribute to irreversible disability in patients with MS, there are limited data on the effect of therapy on longitudinal change in Tl-hypointense lesion volume. Measurement of black holes in clinical studies may elucidate the underlying pathophysiology of MS and may be an additional method of evaluating therapeutic efficacy.

Despite a large number of neuroimaging studies in schizophrenia reporting subtle brain abnormalities, we do not know to what extent such abnormalities reflect the effects of antipsychotic treatment on brain structure. We therefore systematically reviewed cross-sectional and follow-up structural brain imaging studies of patients with schizophrenia treated with antipsychotics. 30 magnetic resonance imaging (MRI) studies were identified, 24 of them being longitudinal and six cross-sectional structural imaging studies. In patients with schizophrenia treated with antipsychotics, reduced gray matter volume was described, particularly in the frontal and temporal lobes. Structural neuroimaging studies indicate that treatment with typical as well as atypical antipsychotics may affect regional gray matter (GM) volume. In particular, typical antipsychotics led to increased gray matter volume of the basal ganglia, while atypical antipsychotics reversed this effect after switching. Atypical antipsychotics, however, seem to have no effect on basal ganglia structure.

Purpose: Magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in T 2-weighted scans contributes substantially to diagnosis. The initial lesion number or lesion volume stands for an increased probability of further accumulation of lesion burden, an earlier conversion to clinically definite MS and progression of disability in the next 5 - 15 years. This diagnostic and prognostic information gained from MRI early in the disease course lead in 2001 to a revision of the diagnostic criteria., Materials and Methods: For the first time MRI criteria were defined in addition to the clinical and paraclinical criteria using the clinical terms for dissemination with respect to space and time. In particular, the defined MRI criteria are based on lesion number and location, the appearance of new lesions and lesion enhancement using contrast agent., Results: Reliable detection and description of older and new lesions in the disease course by MRI represents subclinical disease activity which can substitute the clinical confirmation of a relapse leading to an earlier diagnosis. This places importance on the assessment of the subclinical disease activity in sequential MR scans requiring a standardized and reproducible approach to minimize variability despite different MR scanners., Conclusion: This review provides an updated proposal for the approach and management of cranial and spinal MR scans in patients with MS. We describe the influence of variables which cannot be standardized (scanner, field strength, manufacturer and software) and outline potential pitfalls of clinical MR imaging in MS resulting from a non-standardized approach. This updated proposal for slice positioning, sequences and documentation is a result of a consensus process targeting systematic and standardized use in clinical MR evaluations of MS.

Objective: To determine the time course of brain atrophy during treatment with once-weekly IM interferon beta-1a (IFNbeta-1a)., Methods: The MRI cohort (n = 386) of the European IFNbeta-1a dose comparison study in relapsing multiple sclerosis (MS) was analyzed. In addition to baseline and three annual scans, a frequent subgroup (n = 138) had two scans before treatment initiation and scans at months 4, 5, 6, 10, and 11. Brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, and volume of Gd-enhancing lesions (T1Gd) and T2 hyperintense lesions (T2LL) were evaluated., Results: BPF decrease was -0.686% (first year), -0.377% (second year), and -0.378% (third year). Analysis of the frequent subgroup showed that 68% of the first-year BPF decrease occurred during the first 4 months of treatment. This change was paralleled by a drop in T1Gd and T2LL. In the frequent subgroup, an annualized atrophy rate was determined by a regression slope for the pretreatment period and from month 4 of treatment onward. Annualized pretreatment rate (-1.06%) was significantly higher than the under-treatment rate (-0.33%)., Conclusions: In the first year of treatment with anti-inflammatory agents, atrophy measurements are possibly confounded by resolution of inflammatory edema or more remote effects of previous damage to the CNS. The atrophy rate reduction observed after treatment month 4 may reflect a beneficial but partial effect of interferon beta-1a and was sustained over the 3-year study period.

The use of syntactic structures on a sentence level is a unique human ability. Functional imaging studies have usually investigated syntax comprehension. However, language production may be performed by different neuronal resources. We have investigated syntax generation on a sentence level with functional magnetic resonance imaging (fMRI). BOLD contrast was measured while subjects articulated utterances aloud. In the active condition 'sentence generation' (SG), subjects had to produce subject verb object (SVO) sentences (e.g. "The child throws the ball") according to syntactically incomplete stimuli (e.g. "throw ball child") presented visually. In the control condition 'word reading' (WR), subjects had to read identical stimuli without completing the syntactic structure, while in a second control condition 'sentence reading' (SR), subjects had to read complete sentences. The semantic meaning of all expressions was obvious despite the syntactically incomplete structure in conditions SG and WR. In both contrasts, SG minus WR and SG minus SR, activation was mainly present in the left inferior frontal (BA 44/45) and medial frontal (BA 6) gyri, the superior parietal lobule (BA 7) and the right insula (BA 13). A region of interest analysis revealed significantly stronger left-dominant activation in BA 45 compared to BA 44. Our data illustrates the crucial involvement of the left BA 45 in syntactic encoding and is in line with more recent imaging and brain lesion data on syntax processing on a sentence level, emphasizing the involvement of a distributed left and right hemispheric network in syntax generation.

After whiplash trauma, up to one fourth of patients develop chronic symptoms including head and neck pain and cognitive disturbances. Resting perfusion single-photon-emission computed tomography (SPECT) found decreased temporoparietooccipital tracer uptake among these long-term symptomatic patients with late whiplash syndrome. As MT/MST (V5/V5a) are located in that area, this study addressed the question whether these patients show impairments in visual motion perception. We examined five symptomatic patients with late whiplash syndrome, five asymptomatic patients after whiplash trauma, and a control group of seven volunteers without the history of trauma. Tests for visual motion perception and functional magnetic resonance imaging (fMRI) measurements during visual motion stimulation were performed. Symptomatic patients showed a significant reduction in their ability to perceive coherent visual motion compared with controls, whereas the asymptomatic patients did not show this effect. fMRI activation was similar during random dot motion in all three groups, but was significantly decreased during coherent dot motion in the symptomatic patients compared with the other two groups. Reduced psychophysical motion performance and reduced fMRI responses in symptomatic patients with late whiplash syndrome both point to a functional impairment in cortical areas sensitive to coherent motion. Larger studies are needed to confirm these clinical and functional imaging results to provide a possible additional diagnostic criterion for the evaluation of patients with late whiplash syndrome.

Objective: To investigate the brain of patients with anorexia and bulimia nervosa by localized proton magnetic resonance spectroscopy (1H-MRS) and to look for metabolic alterations., Method: Twenty patients with anorexia and bulimia nervosa were investigated by magnetic resonance imaging (MRI) and 1H-MRS in three regions of the brain. Age and sex-matched healthy subjects were investigated as controls., Results: 1H-MRS revealed metabolic changes, such as a significant decrease of both myo-inositol and lipid compounds within the frontal white matter. The concentration of these compounds was further reduced with decreasing body mass index. Reduced lipid signals were also found in the occipital gray matter. In the cerebellum, the concentration of all metabolites including water, except lipids, was increased., Discussion: The metabolic changes found in this study seem to be a consequence of nutritional deficiency. It has to be further investigated whether these findings have any relevance for brain function. 1H-MRS might serve as a valuable investigative tool to observe eating disorders as anorexia and bulimia nervosa and to follow the success of therapy.

Twenty patients with anorexia or bulimia nervosa were prospectively investigated by magnetic resonance spectroscopy (MRS) of the brain. Compared to healthy controls, MRS of those with eating disorders revealed metabolic changes, which seem to be a consequence of their nutritional deficiency.

Background: Reliable prognostic factors are lacking for multiple sclerosis (MS). Gadolinium enhancement in magnetic resonance imaging (MRI) of the brain detects with high sensitivity disturbance of the blood-brain barrier, an early event in the development of inflammatory lesions in MS. To investigate the prognostic value of gadolinium-enhanced MRI, we did a meta-analysis of longitudinal MRI studies., Methods: From the members of MAGNIMS (European Magnetic Resonance Network in Multiple Sclerosis) and additional centres in the USA, we collected data from five natural-course studies and four placebo groups of clinical trials completed between 1992 and 1995. We included a total of 307 patients, 237 with relapsing disease course and 70 with secondary progressive disease course. We investigated by regression analysis the relation between initial count of gadolinium-enhancing lesions and subsequent worsening of disability or impairment as measured by the expanded disability status scale (EDSS) and relapse rate., Findings: The relapse rate in the first year was predicted with moderate ability by the mean number of gadolinium-enhancing lesions in monthly scans during the first 6 months (relative risk per five lesions 1.13, p=0.023). The predictive value of the number of gadolinium-enhancing lesions in one baseline scan was less strong. The best predictor for relapse rate was the variation (SD) of lesion counts in the first six monthly scans which allowed an estimate of relapse in the first year (relative risk 1.2, p=0.020) and in the second year (risk ratio=1.59, p=0.010). Neither the initial scan nor monthly scans over six months were predictive of change in the EDSS in the subsequent 12 months or 24 months. The mean of gadolinium-enhancing-lesion counts in the first six monthly scans was weakly predictive of EDSS change after 1 year (odds ratio=1.34, p=0.082) and 2 years (odds ratio=1.65, p=0.049)., Interpretation: Although disturbance of the blood-brain barrier as shown by gadolinium enhancement in MRI is a predictor of the occurrence of relapses, it is not a strong predictor of the development of cumulative impairment or disability. This discrepancy supports the idea that variant pathogenetic mechanisms are operative in the occurrence of relapses and in the development of long-term disability in MS.