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Background: Several controlled studies provide evidence that treatment with interferon beta in patients with a first event suggestive of multiple sclerosis (MS) delays conversion to clinically definite MS (CDMS). Our aim was to determine whether early initiation of treatment with interferon beta prevents development of confirmed disability in MS.Methods: In the initial placebo-controlled phase of the double-blinded BENEFIT study, patients with a first event suggestive of MS and a minimum of two clinically silent lesions in MRI were randomised to receive either interferon beta-1b 250 microg (n=292) or placebo (n=176) subcutaneously every other day for 2 years, or until diagnosis of CDMS. Patients were then eligible to enter the follow-up phase with open-label interferon beta-1b. In the current prospectively planned analysis 3 years after randomisation, the effects of early interferon beta-1b treatment were compared with those of delayed treatment initiated after diagnosis of CDMS or after 2 years on the study. The primary outcomes of this ITT analysis were time to diagnosis of CDMS, time to confirmed expanded disability status scale (EDSS) progression, and score on a patient-reported functional assessment scale (FAMS-TOI). This trial is registered with ClinicalTrials.gov, number NCT00185211.Findings: Of the 468 patients originally randomised, 418 (89%) entered the follow-up phase; 392 (84%) completed 3 years' post-randomisation follow-up. After 3 years, 99 (37%) patients in the early group developed CDMS compared with 85 (51%) patients in the delayed treatment group. Early treatment reduced the risk of CDMS by 41% (hazard ratio 0.59, 95% CI 0.44-0.80; p=0.0011; absolute risk reduction 14%) compared with delayed treatment. Over 3 years, 42 (16%) patients in the early group and 40 (24%) in the delayed group had confirmed EDSS progression; early treatment reduced the risk for progression of disability by 40% compared with delayed treatment (0.60, 0.39-0.92; p=0.022; absolute risk reduction 8%). The FAMS-TOI score was high and stable in both groups over the 3-year period (p=0.31).Interpretation: Our data suggest that early initiation of treatment with interferon beta-1b prevents the development of confirmed disability, supporting its use after the first manifestation of relapsing-remitting MS. [ABSTRACT FROM AUTHOR]

Background: There is a lack of studies on the association between obesity and conversion from a clinically isolated syndrome (CIS) to multiple sclerosis (MS)., Objective: The aim of this study was to determine whether obesity predicts disease activity and prognosis in patients with CIS., Methods: Body mass index (BMI) at baseline was available for 464 patients with CIS in BENEFIT. Obesity was defined as BMI ⩾ 30 kg/m 2 and normal weight as 18.5 ⩽ BMI < 25. Patients were followed up for 5 years clinically and by magnetic resonance imaging. Hazard of conversion to clinically definite (CDMS) or to 2001 McDonald criteria (MDMS) MS, annual rate of relapse, sustained progression on Expanded Disability Status Scale (EDSS), change in brain and lesion volume, and development of new brain lesions were evaluated., Results: Obese individuals were 39% more likely to convert to MDMS (95% CI: 1.02-1.91, p  = 0.04) and had a 59% (95% CI: 1.01-2.31, p  = 0.03) higher rate of relapse than individuals with normal weight. No associations were observed between obesity and conversion to CDMS, sustained progression on EDSS or magnetic resonance imaging (MRI) outcomes, except for a larger reduction of brain volume in obese smokers as compared to normal weight smokers (-0.82%; 95% CI: -1.51 to -0.12, p  = 0.02)., Conclusion: Obesity was associated with faster conversion to MS (MDMS) and a higher relapse rate.

Interindividual variation in neurovascular reserve and its relationship with cognitive performance is not well understood in imaging in neurodegeneration. We assessed the neurovascular reserve in amnestic mild cognitive impairment (aMCI) and Alzheimer's dementia (AD). Twenty-eight healthy controls (HC), 15 aMCI, and 20 AD patients underwent blood oxygen level-dependent imaging for 9 minutes, breathing alternatively air and 7% carbon dioxide mixture. The data were parcellated into 88 anatomic regions, and carbon dioxide regressors accounting for different washin and washout velocities were fitted to regional average blood oxygen level-dependent signals. Velocity of cerebrovascular reactivity (CVR) was analyzed and correlated with cognitive scores. aMCI and AD patients had significantly slower response than HC (mean time to reach 90% of peak: HC 33 seconds, aMCI and AD 59 seconds). CVR velocity correlated with Mini Mental State Examination in 35 of 88 brain regions (p = 0.019, corrected for multiple comparisons), including 10 regions of the default-mode network, an effect modulated by age. This easily applicable protocol yielded a practical assessment of CVR in cognitive decline., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: We sought to investigate the clinical relevance of neuroforaminal patency and facet degeneration one year after anterior cervical discectomy and fusion (ACDF). Previous studies were characterized by imprecise techniques and fragmentary measurements, and most lacked reliable clinical data and correlation analyses., Methods: Patients with cervical mono- or bi-level degenerative pathology were prospectively included. Neuroforaminal size and segmental height were determined quantitatively, and the degree of facet degeneration was assessed qualitatively before and one year after the operation, by computed tomography. Clinical data, such as the severity of neck and arm pain, were assessed on a visual analogue scale (VAS) from 0 to 10, and neck disability index (NDI) was recorded before and one year after the operation. Their correlation with radiological data was investigated., Results: Seventy-nine patients aged 53.3 ± 11.3 years were included. One year after surgery, median VAS pain intensity was still significantly improved (neck, from 5 to 1; right arm, from 2 to 1; left arm, from 4 to 1) as was NDI (from 40 to 20). Neuroforaminal size showed a reduction on both sides (left, 0.0289 ± 0.09 cm(2); right, 0.0149 ± 0.08 cm(2)). One year after the operation, segmental height decreased and facet degeneration increased from measures taken before the operation. No correlations were found between neuroforaminal stenosis or the degree of facet degeneration and various clinical outcome parameters., Conclusions: The decrease in segmental height one year after ACDF leads in turn to secondary neuroforaminal stenosis and progressive facet degeneration. Of the various neuroforaminal variables used, none revealed a threshold value indicative of the presence or severity of radicular arm pain. This absence of correlation between imaging and clinical information is important and should be considered when allocating patients for surgical interventions.

Background: Depletion of B lymphocytes is associated with suppression of inflammatory activity in multiple sclerosis. We aimed to assess the safety and efficacy of atacicept, a recombinant fusion protein that suppresses B-cell function and antibody production., Methods: In this placebo-controlled, double-blind, 36-week, phase 2 trial (ATAMS) in Australia, Canada, Europe, and the USA, patients aged 18-60 years with relapsing multiple sclerosis were randomly assigned via an interactive voice response system in a 1:1:1:1 ratio, stratified by geographical region, to receive weekly subcutaneous injections with atacicept (25, 75, or 150 mg) or placebo. Both patients and study personnel were masked to treatment assignment. The primary endpoint was the change in mean number of gadolinium-enhancing lesions on T1-weighted MRI per patient per scan between weeks 12 and 36. Efficacy endpoints were analysed in the intention-to-treat population. Patients who completed week 36 were eligible to participate in a long-term extension study (ATAMS EXT), consisting of a double-blind phase followed by an open-label phase, for a total study time of up to 5 years. The study was terminated early after the independent data and safety monitoring board noted an increased annualised relapse rate with atacicept. The protocol was subsequently amended to include a 60-week safety follow-up, to allow treatment with approved multiple sclerosis drugs, and to change the primary endpoint to gadolinium-enhancing T1 lesions per scan during the entire double-blind period of ATAMS. Both the trial and the extension are registered with ClinicalTrials.gov, numbers NCT00642902 (ATAMS) and NCT00853762 (ATAMS EXT)., Findings: Between April 23, 2008, and early study termination on Sept 11, 2009, 255 patients were randomly assigned: 63 to placebo, 63 to atacicept 25 mg, 64 to 75 mg, and 65 to 150 mg. 90 (35%) patients completed the week 36 treatment visit, 26 (10%) discontinued before study termination (including one who dropped out before receiving study treatment), and 139 (55%) discontinued because of study termination. During the double-blind period of ATAMS, annualised relapse rates were higher in the atacicept groups than in the placebo group (atacicept 25 mg, 0·86, 95% CI 0·43-1·74; 75 mg, 0·79, 0·40-1·58; 150 mg, 0·98, 0·52-1·81; placebo, 0·38, 0·17-0·87). Mean numbers of gadolinium-enhancing T1 lesions per scan were similar in all groups (25 mg, 2·26, 0·97-5·27; 75 mg, 2·30, 1·08-4·92; 150 mg, 2·49, 1·18-5·27; placebo, 3·07, 1·40-6·77). Seven patients (one taking placebo and six atacicept) discontinued treatment because of adverse events. One death occurred in the placebo group. During the safety follow-up, immunoglobulin concentrations and B-cell counts returned towards predose values and annualised relapse rates in the atacicept groups decreased until they were similar to that of the placebo group, Interpretation: Increased clinical disease activity associated with atacicept suggests that the role of B cells and humoral immunity in multiple sclerosis is complex. For studies that explore therapeutic immunomodulation in multiple sclerosis, rigorous monitoring for negative effects on clinical and MRI outcomes is warranted., Funding: Merck Serono (Merck KGaA) and EMD Serono (Merck KGaA)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The objective of this paper is to investigate the relationship between total and regional corpus callosum (CC) atrophy, neuropsychological test performance and fatigue in multiple sclerosis (MS) patients., Methods: We conducted a cross-sectional study in 113 MS patients: mean age 48 ± 11 years, 75/113 women, 84/113 relapsing-remitting MS, mean disease duration 21 ± 9 years, mean Expanded Disability Status Scale (EDSS) score 3.2 ± 1.7. All patients underwent brain magnetic resonance imaging, standardised neurological assessment and comprehensive cognitive testing including assessments for fatigue and depression. Total and regional CC atrophy was assessed using the corpus callosum index (CCI)., Results: CCI correlated more strongly with T2- and T1-lesion volume and whole brain volume than with disease duration or EDSS score. CCI correlated strongly with the verbal fluency test (VFT), Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT). Multivariate regression analysis revealed that atrophy of the posterior CC segment was significantly associated with poor outcome in the PASAT, VFT and SDMT. In contrast, atrophy of the anterior CC segment was significantly associated with fatigue severity and poor outcome in the long-term memory test., Conclusions: Atrophy of the CC is associated with cognitive impairment and fatigue. Regional CCI results indicate that these associations are partially spatially segregated.

Importance: It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes., Objectives: To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome)., Design, Setting, and Participants: The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6- and 12-month (seasonally asynchronous) measurements. Patients were followed up for 5 years clinically and by magnetic resonance imaging., Main Outcomes and Measures: New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score)., Results: Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P < .001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion volume (P < .001), and 0.41% lower yearly loss in brain volume (P = .07) from months 12 to 60. Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60. In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004) during the subsequent 4 years., Conclusions and Relevance: Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.

Background: We have conducted various studies in Basel with the aim of improving the methods for the early detection of psychosis (Früherkennung von Psychosen, FePsy)., Methods: From 1.3.2000 to 29.2.2004 234 individuals were screened using the Basel Screening Instrument for Psychosis (BSIP). 106 patients were identified as at risk for psychosis; out of these 53 remained in follow-up for up to 7 years (mean 5.4 years). The assessments were done with a specifically developed instrument for history taking, various scales for the psychopathology, assessments of neuropsychology and fine motor functioning, clinical and quantitative EEG, MRI of the brain, laboratory etc., Results: Based on the BSIP alone, a relatively reliable prediction was possible: 21 (39.6%) of the individuals identified as at risk developed psychosis within the follow-up time. Post-hoc prediction could be improved to 81% by weighting psychopathology and including neuropsychology. Including the other domains obviously allows further improvements of prediction., Conclusions: The risk for psychosis should be assessed in a stepwise procedure. In a first step, a clinically oriented screening should be conducted. If an at-risk status is found, further assessments in various domains should be done in a specialised centre., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Neuroanatomical abnormalities, including cingulate cortex volume abnormalities, are a common feature in psychosis. However, the extent to which these are related to a vulnerability to psychosis, as opposed to the disorder per se, is less certain. AIM UND HYPOTHESES: The aim of the present study is to compare cingulate gray matter volumes in different stages of psychosis. We reviewed previous studies of subjects in a prodromal stage of psychosis and tested cingulate volume changes during the transition to psychosis., Methods: A cross-sectional MRI study of manually traced cingulate gray-matter volumes in 37 individuals with an at risk mental state (ARMS) for psychosis, 23 individuals with a first-episode psychosis (FEP), and 22 healthy controls (HC) was performed using a 1.5 T MRI-scanner. 16 of 37 ARMS individuals (43 %) developed psychosis during follow up (ARMS-T), whereas 21 did not (ARMS-NT). The mean duration of follow up in ARMS was 25.1 months. 8 cingulate subregions were analysed in a region-of-interest analysis., Results: Compared to HC, subjects with an ARMS had significantly reduced left caudal anterior cingulate cortex volume (p < 0.027). This finding was also evident at a trend level (p: 0.069) in FEP patients. Within ARMS, the ARMS-T group showed a significantly reduced whole right cingulate cortex (p: 0.036), right subgenual cingulate cortex (p: 0.036) and right posterior cingulate cortex (p: 0.012) compared to ARMS-NT., Discussion: These results suggest that the at risk mental state is associated with cingulate volume reductions, in particular in the left caudal anterior cingulate cortex (CACC). These abnormalities do not only seem to occur with transition to psychosis, but may be a correlate of an increased vulnerability to psychosis.

As attention, processing speed, and working memory seem to be fundamental for a broad range of cognitive performance, the present study on patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains. To explore subtle neuropsychological changes in either the clinical or fMRI domain, we applied a multistep experimental design with increasing task complexity to investigate global brain activity, functional adaptation, and behavioral responses to typical cognitive processes related to attention and working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9 females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50 years, 6 women) participated. After a comprehensive neuropsychological assessment, participants performed different fMRI experiments testing attention and working memory. In the neuropsychological assessment, patients showed only subtle reduction in learning and memory abilities. In the fMRI experiments, both groups activated the brain areas typically involved in attention and working memory. HC showed a linear in- or decrease in activation paralleling the changing task complexity. Patients showed stronger activation change at the level of the simple tasks and a subsequent saturation effect of (de-)activation at the highest task load. These group/task interaction differences were found in the right parahippocampal cortex and in the middle and medial frontal regions. Our results indicate that, in MS, functional adaptation patterns can be found which precede clinical evidence of apparent cognitive decline., (Copyright © 2010 Wiley-Liss, Inc.)

Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy. In this Review, we revisit and update previous recommendations on natalizumab for treatment of patients with RRMS, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Morphologic abnormalities of the pituitary gland volume (PV) have been reported in schizophrenia, but at what point in time they occur remains unclear. This study determines PV across different stages of emerging psychotic disorders compared to healthy controls., Methods: We compared PV of 36 individuals with an at-risk mental state (ARMS) for psychosis, 23 patients with a first episode psychosis (FEP) and 20 healthy controls (HC). Transition to psychosis was monitored using the BPRS transition criteria according to Yung et al. (Yung, A.R. et al., 1998. Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br. J. Psychiatry Suppl. 172 (33), 14-20). Applying these transition criteria, 16 of the 36 ARMS individuals made the transition to psychosis (ARMS-T) and 20 did not (ARMS-NT). We traced PV manually on 1mm slices of magnetic resonance images in three dimensions (coronal, sagittal and axial) blind to group status. We used univariate analysis of covariance (ANCOVA) with PV as dependent variable, group and sex as between-subject factors and whole brain volume as covariate., Results: PV increased from HC to ARMS-NT to ARMS-T/FEP. ANCOVA revealed a significant effect of group (F(3,78)=3.0; p=.036) and a sex × group interaction (F(3,78)=6.5; p=.001). Over all groups, women had considerably larger PV than men (F(1,78)=9.8; p=.003)., Conclusions: Our findings provide further evidence that PV is increased in emerging psychotic disorders, and suggest that this is due to a stress-associated activation of the pituitary gland., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression., Methods: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment allocation throughout the study. Primary endpoints were time to CDMS, time to confirmed disability progression measured with the expanded disability status scale, and the functional assessment of multiple sclerosis trial outcomes index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211., Findings: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment reduced the risk of CDMS by 37% (hazard ratio [HR] 0.63, 95% CI 0.48-0.83; p=0.003) compared with delayed treatment. The risk for confirmed disability progression was not significantly lower in the early treatment group (0.76, 0.52-1.11; p=0.177). At 5 years, median FAMS-TOI scores were 125 in both groups. No significant differences in other disability related outcomes were recorded. Frequency and severity of adverse events remained within the established safety and tolerability profile of interferon beta-1b., Interpretation: Effects on the rate of conversion to CDMS and the favourable long-term safety and tolerability profile support early initiation of treatment with interferon beta-1b, although a delay in treatment by up to 2 years did not affect long-term disability outcomes., Funding: Bayer Schering Pharma.

Different mechanisms have been hypothesized as contributing to abduction deficit in high myopia: the size of the eye within the orbit, tightness of the medial rectus muscles, decompensation of longstanding esotropia, and inferior displacement of the lateral rectus muscle. Using oculodynamic magnetic resonance imaging, enhanced by computer-aided visualization, we demonstrate globe restriction by the medial orbital wall on abduction in a patient with high myopia.

Objective: Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy., Methods: This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored., Results: With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed., Conclusion: This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.

Introduction: Blood-flow patterns and wall shear stress (WSS) are considered to play a major role in the development and rupture of cerebral aneurysms. These hemodynamic aspects have been extensively studied in vitro using geometric realistic aneurysm models. The purpose of this study was to evaluate the feasibility of in vivo flow-sensitized 4-D MR imaging for analysis of intraaneurysmal hemodynamics., Methods: Five cerebral aneurysms were examined using ECG-gated, flow-sensitized 4-D MR imaging at 3 T in three patients. Postprocessing included quantification of flow velocities, visualization of time-resolved 2-D vector graphs and 3-D particle traces, vortical flow analysis, and estimation of WSS. Flow patterns were analyzed in relation to aneurysm geometry and aspect ratio., Results: Magnitude, spatial and temporal evolution of vortical flow differed markedly among the aneurysms. Particularly unstable vortical flow was demonstrated in a wide-necked parophthalmic ICA aneurysm (high aspect ratio). Relatively stable vortical flow was observed in aneurysms with a lower aspect ratio. Except for a wide-necked cavernous ICA aneurysm (low aspect ratio), WSS was reduced in all aneurysms and showed a high spatial variation., Conclusion: In vivo flow-sensitized 4-D MR imaging can be applied to analyze complex patterns of intraaneurysmal flow. Flow patterns, distribution of flow velocities, and WSS seem to be determined by the vascular geometry of the aneurysm. Temporal and spatial averaging effects are drawbacks of the MR-based analysis of flow patterns as well as the estimation of WSS, particularly in small aneurysms. Further studies are needed to establish a direct link between definitive flow patterns and different aneurysm geometries.

Background: Time-resolved (TR) contrast-enhanced 3D MR angiography has recently received considerable attention for the workup of cerebrovascular diseases, foremost dural arteriovenous fistula and arteriovenous malformation, and potentially for the evaluation of dural sinus thrombosis. Thereby, the dynamic visualization of cerebral vessels is enabled similar to the principle of digital subtraction angiography. Yet, its voxel size is relatively large due to an inherent trade-off between the desired spatial and temporal resolutions. The goal of this study was to evaluate whether the limited spatial resolution of TR MR venography (MRV) is sufficient to visualize dural venous sinuses., Methods: The prospective study included 20 patients without compromise of cerebral venous outflow. Two neuroradiologists independently graded the quality of visualization of 11 predefined dural venous sinuses on images of fast TR contrast-enhanced MRV (1.5 s/dataset; voxel size, 2 x 2 x 2.2 mm; acquisition time, 37.5 s) in comparison to time-of-flight (TOF) MRV (voxel size, 0.8 x 0.8 x 4 mm; acquisition time, 3 min 51 s) and steady-state contrast-enhanced 3D (VIBE) MRV (voxel size, 1.1 x 0.9 x 1.5 mm; acquisition time, 2 min 46 s)., Results: The torcular Herophili (p < 0.001), left (p < 0.001) and right (p < 0.01) transverse sinus, and right jugular bulb (p < 0.05) were visualized better at TR MRV than at TOF MRV. For visualization of the small inferior sagittal sinus, TR MRV was inferior to VIBE (p < 0.001) and TOF (p < 0.05) sequences. The visibility of all other dural sinuses was equal., Conclusion: Despite the inferior spatial resolution, TR MRV depicted some large dural sinuses more clearly than TOF MRV. To overcome the visualization of smaller venous structures, TR MRV can be applied complementarily with high-resolution steady-state contrast-enhanced MRV.

Gorlin-Goltz syndrome is a rare inherited genodermatosis with an autosomal dominant trait. We hereby present a case of a 69 year old patient with known Gorlin-Goltz syndrome to emphasize the peculiar syndrome manifestations in the elderly.

Background: Individuals with an At Risk Mental State (ARMS) have a very high risk of developing a psychotic disorder but the basis of this risk is unclear. We addressed this issue by studying gray matter volume in this group with magnetic resonance imaging (MRI)., Methods: Thirty-five individuals with an ARMS, 25 patients with first episode schizophrenia, and 22 healthy volunteers were studied using a 1.5T MRI scanner. Twelve (34%) of the ARMS group developed schizophrenia in the 2 years subsequent to scanning., Results: There were significant volumetric differences between the three groups in the left insula, superior temporal gyrus, cingulate gyrus and precuneus. In these regions, the volume in the ARMS group was smaller than in volunteers but not significantly different from that in the first episode (FE) group. Direct comparison of the ARMS and control groups revealed additional areas of reduced volume in the left medial temporal cortex. Within the ARMS group, those subjects who later developed psychosis had less gray matter than subjects who did not in the right insula, inferior frontal and superior temporal gyrus., Conclusions: The ARMS was associated with reductions in gray matter volume in areas that are also reduced in schizophrenia, suggesting that these are a correlate of an increased vulnerability to psychosis. Volumetric differences within the ARMS group may be related to the subsequent onset of schizophrenia in a subset of those at high risk.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system whose pathological mechanisms are still not completely understood. Physical as well as cognitive deterioration are consequences within the disease process that have an extensive impact on the patient's quality of life. Therefore, understanding the functional background of spontaneous as well as induced remission is of high relevance. Studies on visualization of therapeutic effects of pharmacological or cognitive treatment by functional magnetic resonance imaging (fMRI) are still rare. From fMRI studies on focal brain lesions hypotheses on mechanisms of brain reorganization can be derived. This contribution will first give an overview of the existing studies using fMRI in MS, on cognitive decline, on cognitive treatment studies and its therapeutic effects on behavioural readouts in MS, and on therapy-induced brain plasticity and its possible visualization by fMRI. Results of a study on correlating the effects of cognitive training with changes in brain organization in patients with mild to severe cognitive impairment will be reported.

Glatiramer acetate (GA) treatment for relapsing remitting multiple sclerosis (RRMS) leads to decreased GA-specific proliferative responses and a Th2 cytokine shift. To study a possible correlation between immunological and clinical responses to GA therapy, we prospectively followed RRMS patients clinically, by magnetic resonance imaging and by primary immunological assays. Fluctuation of GA-specific proliferative responses was significantly lower in treatment responders than in untreated patients, and GA-specific proliferative responses were increased during relapses. These associations suggest a possible causal relationship between immunological and clinical responses to GA therapy. Primary proliferation assays may thus be a useful marker for treatment response.

The aim of our study was to determine whether T2-weighted (T2w) MRI of the brain could be performed immediately after the administration of gadopentetate dimeglumine (gadolinium DTPA) in patients with multiple sclerosis (MS) without a loss in image quality or diagnostic reliability. Sixteen patients with clinically diagnosed MS were included in the study. Twenty-four patients with various cerebral pathologies (14 patients with multiple lacunar lesions) were examined in order to exclude masking of T2 hyperintense lesions other than MS lesions. Images of 10 patients without pathological changes served as a control condition for the qualitative analysis. In these 50 patients, T1w and T2w MRI was performed before and after the administration of gadolinium DTPA. Signal intensities were measured within T2 hyperintense cerebral lesions, in T1-enhancing lesions and in normal appearing brain tissue on T2w turbo spin-echo (TSE) sequences. Both quantitative and qualitative analysis did not show significant differences between T2w pre- and postcontrast series. T2w MRI performed prior to and after the administration of gadolinium DTPA provides similar information in patients with MS. With a TR of 3.2 s, not a single lesion was obscured on T2w postcontrast series. Acquisition of T2w MR images immediately after the administration of gadolinium DTPA allows for shorter examination time and assures sufficient time for contrast enhancement in cerebral lesions with a disrupted blood-brain barrier.

A patient showing "prodromal symptoms" of suspected psychosis was referred to our clinic specialized in early recognition of schizophrenia where an MRI brain scan showed a chronic subdural hemorrhage. Based on this case, it will be shown that organic brain disease, in addition to incipient schizophrenia, needs to be considered in patients with marked personality changes, social withdrawal, aggressiveness, and suspiciousness. Diagnosis of the first episode and prodromal stage of schizophrenia should include-apart from the case history as well as the psychopathological and physiological findings-certain obligatory medical examinations (EEG, cCT, or MRI) in order to identify possible organic causes and avoid misdiagnoses.

More than 50 % of patients with multiple sclerosis (MS) suffer from cognitive deficits. Attention is one of the most frequently affected cognitive functions. It has been shown that MS patients suffer from a specific but not necessarily from a generalized decrease in performance and that different severity grades of impaired attentional processing can be distinguished. Little is known about patterns of brain activation in MS patients with different grades of attentional deficits. The objective was to examine if different severity grades in attentional impairment are reflected by altered patterns of brain activation in specific attention tasks. In the present study cerebral activation induced by three attention tasks of different complexity was assessed in 14 MS patients and seven healthy controls by functional MRI (fMRI). Based on their performance on the tests recorded off-line with a computerized test battery and during the fMRI investigation, patients were classified as mildly and severely impaired. MS patients with mild impairment showed increased and additional activation of brain areas which were in part not activated in normal subjects. Those were located mainly in the frontal cortex and posterior parietal cortex. This effect decreased with increasing task complexity and was strongest for the alertness task. In MS patients with severe impairment no additional activation was found in prefrontal structures and activation in the premotor cortex was not significantly different from controls. These findings suggest that compensation in MS patients is in part achieved by functional integration of frontal and parietal association areas. The extent of compensation seems to depend on the brain's capacity to access additional brain structures. Exhaustion of this capacity may finally lead to severe cognitive impairment.

Unlabelled: Locoregional administration may yield higher tumor drug concentrations compared with intravenous injection and may reduce the risk of systemic adverse effect. Furthermore, in the case of brain tumors, it may circumvent limited drug delivery imposed by the blood-brain barrier. We used PET to study the retention and spatial distribution of iododeoxyuridine (IUdR), which has been used as a DNA-targeting radiosensitizing drug and which can be charged with therapeutic nuclides., Methods: Locoregional (resection cavity, tumor) instillation of 5-19 MBq (124)I-IUdR was achieved in 7 postoperative patients with malignant gliomas through a reservoir implanted in the skull. Patients were scanned with PET during the first hour and at 2, 24, and 48 h after (124)I-IUdR instillation. (124)I-IUdR metabolism was measured in the reservoir fluid in the presence or absence of a degradation inhibitor (5'-butyryl-IUdR [butyryl-IUdR]). Region-of-interest analysis was applied to calculate intratumoral retention (K(local)) of (124)I-IUdR from the PET images after a 24-h washout phase using an autoradiographic method., Results: At 24 h, radioactivity concentration in the reservoir was approximately 1% of the concentration 5 min after tracer instillation. The major metabolite of (124)I-IUdR in the reservoir was (124)I-iodouracil. (124)I-IUdR degradation could be partially inhibited by butyryl-IUdR. In the plasma, radioactivity peaked between 2 and 6 h. The area of tissue radioactivity increased with time up to 3-fold compared with the initial distribution. Tumor (124)I-IUdR retention (K(local)) ranged from 0.006 to 0.017 micro L/g/min, which is substantially lower compared with the IUdR-DNA incorporation reported recently after intravenous injection of (124)I-IUdR (K(i), 3.9 +/- 2.3 micro L/g/min, where K(i) is the DNA incorporation rate of (124)I-IUdR after intravenous tracer injection)., Conclusion: Although a single injection of (124)I-IUdR resulted in radioactivity distribution over the tumor, retention at 24 h was substantially lower compared with intravenous injection of (124)I-IUdR. Slow diffusion after locoregional administration, in contrast to fast delivery via tumor capillaries after intravenous injection, may account for our findings, resulting in a low amount of drug incorporation into DNA before degradation and washout from tissue.

Purpose: To examine whether an internal carotid artery (ICA) steno-occlusive disease leads to a reduced blood oxygenation level dependent (BOLD)-signal change due to a decreased vasodilatory reserve capacity., Materials and Methods: Patients suffering from unilateral ICA stenosis or occlusion were examined using functional magnetic resonance imaging (fMRI) of the auditory cortex with a bilateral stimulation applying a pulsed 1000 Hz sine-tone., Results: Compared to control subjects, who showed symmetric bilateral BOLD-responses within the auditory cortex, the ICA patients revealed either a normal bilateral cortical activation pattern or a reduced cortical activation on the steno-occluded side. This latter decrease of BOLD-signal change might indicate a depressed vasomotor reserve capacity. The observed coincidence between this asymmetric reduction in BOLD-signal and ischemic borderzone lesions on the affected side in this subgroup of patients strongly supports this assumption., Conclusion: This study shows that fMRI of the auditory cortex appears to have clinical merit in the workup of cerebrovascular conditions., (Copyright 2002 Wiley-Liss, Inc.)

We report a case of a prenatally diagnosed infratentorial subdural hemorrhage. The hematoma located in the posterior cerebral fossa was detected by conventional ultrasound at 24 weeks of gestation. Intrauterine magnetic resonance imaging confirmed the diagnosis. Autopsy of the fetus revealed a well-circumscribed subdural hematoma. The prenatal findings of intracranial bleeding located in the posterior fossa and the prognosis of such cases are discussed.

We report the case of a 45-year-old man with a long history of chondrocalcinosis and recurrent painless suprapatellar swelling. Over the 3 months before his admission, the swelling had become persistent and extended 10 cm proximal to the patella on the anterior aspect of the thigh. Magnetic resonance imaging revealed an enlarged suprapatellar pouch that was completely separated from the knee joint cavity by a suprapatellar membrane. Arthroscopic treatment consisted of complete removal of the membrane, creating a passage to the articular cavity, and debridement of the synovial calcifications. The patient was followed-up postoperatively for 2 years and no recurrence of the swelling was reported during this period of time. Two potential mechanisms might have been responsible for the persistent swelling: (1) chondrocalcinosis led to effusion of a suprapatellar pouch that was originally isolated from the knee joint cavity, or (2) the suprapatellar pouch was separated from the knee joint cavity as a result of an incomplete involuted suprapatellar plica that became adherent during recurrent inflammation due to chondrocalcinosis.