Search

IntroductionThe efficacy and safety of local intra-arterial (IA) thrombolytics during endovascular thrombectomy (EVT) for large-vessel occlusions is uncertain. We analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA thrombolytics.MethodsIn this observational study, we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry (March 2014–November 2017). The primary endpoint was favourable functional outcome, defined as an modified Rankin Scale score ≤2 at 90 days. Secondary endpoints were reperfusion status, early neurological recovery and symptomatic intracranial haemorrhage (sICH). Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were performed.ResultsOf the 2263 included patients, 95 (4.2%) received IA thrombolytics during EVT. The IA thrombolytics administered were urokinase (median dose, 250 000 IU (IQR, 1 93 750–2 50 000)) or alteplase (median dose, 20 mg (IQR, 12–20)). No association was found between IA thrombolytics and favourable functional outcome (adjusted OR (aOR), 1.16; 95% CI 0.71 to 1.90). Successful reperfusion was less often observed in those patients treated with IA thrombolytics (aOR, 0.57; 95% CI 0.36 to 0.90). The odds of sICH (aOR, 0.82; 95% CI 0.32 to 2.10) and early neurological recovery were comparable between patients treated with and without IA thrombolytics. For primary and adjuvant revascularisation attempts, IA thrombolytics were more often administered for proximal than for distal occlusions. Functional outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation attempt.ConclusionLocal IA thrombolytics were rarely used in the MR CLEAN Registry. In the relatively small study sample, no statistical difference was observed between groups in the rate of favourable functional outcome or sICH. Patients whom required and underwent IA thrombolytics were patients less likely to achieve successful reperfusion, probably due to selection bias.

Background: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT through femoral versus alternative arterial access. Methods: In this observational study, we included patients from the MR CLEAN Registry who underwent EVT for acute ischemic stroke in the anterior circulation between 2014 and 2019 in the Netherlands. Patients who underwent EVT through alternative and femoral access were matched on propensity scores in a 1:3 ratio. The primary endpoint was favorable functional outcome (modified Rankin Scale score ≤ 2) at 90 days. Secondary endpoints were early neurologic recovery, mortality, successful intracranial reperfusion and puncture related complications. Results: Of the 5197 included patients, 17 patients underwent EVT through alternative access and were matched to 48 patients who underwent EVT through femoral access. Alternative access was obtained through the common carotid artery (n = 15/17) and brachial artery (n = 2/17). Favorable functional outcome was less often observed after EVT through alternative than femoral access (18% versus 27%; aOR, 0.36; 95% CI, 0.05–2.74). The rate of successful intracranial reperfusion was higher for alternative than femoral access (88% versus 58%), although mortality (59% versus 31%) and puncture related complications (29% versus 0%) were more common after alternative access. Conclusions: EVT through alternative arterial access is rarely performed in the Netherlands and seems to be associated with worse outcomes than standard femoral access. A next step would be to compare the additional value of EVT through alternative arterial access after failure of femoral access.

Introduction: The aim of endovascular treatment (EVT) for acute ischaemic stroke is to relieve the cerebral tissue hypoxia in the area supplied by the occluded artery. Near-infrared spectroscopy (NIRS) monitoring is developed to assess regional cerebral tissue oxygen haemoglobin saturation (rSO2). We aimed to investigate whether NIRS can detect inter- and intra-hemispheric rSO2 differences during EVT. Patients and methods: In this prospective, observational study, patients undergoing EVT for a proximal intracranial occlusion of the anterior circulation between May 2019 and November 2020, were included. A four-wavelength NIRS monitor (O3® Regional Oximeter (Masimo, Irvine, CA)) was used to measure rSO2 during EVT with sensors placed over the temporal lobes in 20 patients and over the frontal lobes in 13 patients. The Wilcoxon signed-rank test was used to test for inter-hemispheric rSO2 differences after groin puncture and after recanalisation, and intra-hemispheric rSO2 changes before and after recanalisation. Results: In the temporal cohort, no inter-hemispheric rSO2 differences were observed after groin puncture (median [IQR] rSO2 affected hemisphere, 70% [67–73] and unaffected hemisphere, 70% [66–72]; p = 0.79) and after recanalisation. There were no intra-hemispheric rSO2 changes over time. In the frontal cohort, no inter- and intra-hemispheric rSO2 differences or changes were found. Discussion and conclusion: A NIRS monitor could not detect inter- and intra-hemispheric rSO2 differences or changes during EVT, irrespective of the sensor position. It is likely that even with temporal sensor application, a significant proportion of the received NIRS signal was influenced by oxygenation of surrounding tissues.

Objective To determine the association between medical knowledge relevant to radiology practice (as measured by the Dutch radiology progress test [DRPT]) and clinical productivity during radiology residency. Methods This study analyzed the results of 6 DRPTs and time period–matched clinical production points of radiology residents affiliated to a tertiary care academic medical center between 2013 and 2016. The Spearman correlation analysis was performed to determine the association between DRPT percentile scores and average daily clinical production points. Linear regression analyses were performed to determine the association of DRPT percentile scores with average daily clinical production points, adjusted for age and gender of the radiology resident, and postgraduate year. Results Eighty-four DRPTs with time period–matched clinical production points were included. These 84 DRPTs were made by 29 radiology residents (18 males and 11 females) with a median age of 31 years (range: 26–38 years). The Spearman correlation coefficient between DRPT percentile scores and average daily clinical production points was 0.550 (95% confidence interval: 0.381–0.694) (p < 0.001), indicating a significant moderate positive association. On multivariate analysis, average daily clinical production points (β coefficient of 0.035, p = 0.003), female gender of the radiology resident (β coefficient of 12.690, p = 0.001), and postgraduate year (β coefficient of 10.179, p < 0.001) were significantly associated with DRPT percentile scores. These three independent variables achieved an adjusted R2 of 0.527. Conclusion Clinical productivity is independently associated with medical knowledge relevant to radiology practice during radiology residency. These findings indicate that clinical productivity of a resident could be a potentially relevant metric in a radiology training program. Key Points • There is a significant moderate correlation between medical knowledge relevant to radiology practice and clinical productivity during radiology residency. • Medical knowledge relevant to radiology practice remains independently associated with clinical productivity during radiology residency after adjustment for postgraduate year and gender. • Clinical productivity of a resident may be regarded as a potentially relevant metric in a radiology training program.

Background The optimal volumetric threshold for determining progressive disease (PD) in recurrent glioblastoma is yet to be determined. We investigated a range of thresholds in association with overall survival (OS). Methods First recurrent glioblastoma patients treated with bevacizumab and/or lomustine were included from the phase II BELOB and phase III EORTC26101 trials. Enhancing and nonenhancing tumor volumes were measured at baseline, first (6 weeks), and second (12 weeks) follow-up. Hazard ratios (HRs) for the appearance of new lesions and several thresholds for tumor volume increase were calculated using cox regression analysis. Results were corrected in a multivariate analysis for well-established prognostic factors. Results At first and second follow-up, 138 and 94 patients respectively, were deemed eligible for analysis of enhancing volumes, while 89 patients were included in the analysis of nonenhancing volumes at first follow-up. New lesions were associated with a significantly worse OS (3.2 versus 11.2 months, HR = 7.03, P < .001). At first follow-up a threshold of enhancing volume increase of ≥20% provided the highest HR (5.55, p = .001. At second follow-up, any increase in enhancing volume (≥0%) provided the highest HR (9.00, p < .001). When measuring nonenhancing volume at first follow-up, only 6 additional patients were scored as PD with the highest HR of ≥25% increase in volume (HR=3.25, p = .008). Conclusion Early appearing new lesions were associated with poor OS. Lowering the volumetric threshold for PD at both first and second follow-up improved survival prediction. However, the additional number of patients categorized as PD by lowering the threshold was very low. The per-RANO added change in nonenhancing volumes to the analyses was of limited value.

PURPOSE: Response evaluation in patients with glioblastoma after chemoradiotherapy is challenging due to progressive, contrast-enhancing lesions on MRI that do not reflect true tumour progression. In this study, we prospectively evaluated the ability of the PET tracer 18F-fluorothymidine (FLT), a tracer reflecting proliferative activity, to discriminate between true progression and pseudoprogression in newly diagnosed glioblastoma patients treated with chemoradiotherapy.METHODS: FLT PET and MRI scans were performed before and 4 weeks after chemoradiotherapy. MRI scans were also performed after three cycles of adjuvant temozolomide. Pseudoprogression was defined as progressive disease on MRI after chemoradiotherapy with stabilisation or reduction of contrast-enhanced lesions after three cycles of temozolomide, and was compared with the disease course during long-term follow-up. Changes in maximum standardized uptake value (SUVmax) and tumour-to-normal uptake ratios were calculated for FLT and are presented as the mean SUVmax for multiple lesions.RESULTS: Between 2009 and 2012, 30 patients were included. Of 24 evaluable patients, 7 showed pseudoprogression and 7 had true progression as defined by MRI response. FLT PET parameters did not significantly differ between patients with true progression and pseudoprogression defined by MRI. The correlation between change in SUVmax and survival (p = 0.059) almost reached the standard level of statistical significance. Lower baseline FLT PET uptake was significantly correlated with improved survival (p = 0.022).CONCLUSION: Baseline FLT uptake appears to be predictive of overall survival. Furthermore, changes in SUVmax over time showed a tendency to be associated with improved survival. However, further studies are necessary to investigate the ability of FLT PET imaging to discriminate between true progression and pseudoprogression in patients with glioblastoma.

Transluminal attenuation gradient (TAG) represents the slope of intraluminal contrast that decreases along a coronary vessel during coronary computed tomography angiography (CCTA). The aim of this study was to determine the added value of TAG to qualitative CCTA assessment of significant stenosis (&gt, 50%) detecting ischemia as determined by stress myocardial blood flow (MBF) or myocardial flow reserve (MFR) measured by positron emission tomography (PET). Individual contributions of TAG, qualitative assessment and the impact of calcium score were also investigated. Methods: We studied 38 consecutive patients that were referred due to suspected or known coronary artery disease (CAD). All patients underwent a two-phase hybrid 13N-ammonia PET/CT and CCTA. Results: TAG and presence of qualitatively assessed significant stenosis, but not calcium score, were associated with stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). The area under the curves (AUC) of the linear predictor model including qualitative assessment and TAG was superior to the AUC of separate qualitative assessment or TAG for the detection of ischemia according to stress MBF (AUCs were: 88% vs. 79% and 77%, p = 0.01 and p = 0.01, respectively). Conclusions: TAG combined with qualitative CCTA assessment improved ischemia detection.

Structured reporting contributes to the completeness of radiology reports and improves quality. Both the content and the structure are essential for successful implementation of structured reporting. Contextual structured reporting is tailored to a specific scenario and can contain information retrieved from the context. Critical findings detected by imaging need urgent communication to the referring physician. According to guidelines, the occurrence of this communication should be documented in the radiology reports and should contain when, to whom and how was communicated. In free-text reporting, one or more of these required items might be omitted. We developed a contextual structured reporting template to ensure complete documentation of the communication of critical findings. The WHEN and HOW items were included automatically, and the insertion of the WHO-item was facilitated by the template. A pre- and post-implementation study demonstrated a substantial improvement in guideline adherence. The template usage improved in the long-term post-implementation study compared with the short-term results. The two most often occurring categories of critical findings are “infection / inflammation” and “oncology”, corresponding to the a large part of urgency level 2 (to be reported within 6 h) and level 3 (to be reported within 6 days), respectively. We conclude that contextual structured reporting is feasible for required elements in radiology reporting and for automated insertion of context-dependent data. Contextual structured reporting improves guideline adherence for communication of critical findings.

AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia.METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs).RESULTS: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p＜0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR.CONCLUSIONS: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence.

Myocardial Bridging (MB) refers to the band of myocardium that abnormally overlies a segment of a coronary artery. This paper quantitatively evaluates the influence of MB of the left anterior descending artery (LAD) on myocardial perfusion of the entire left ventricle. We studied 131 consecutive patients who underwent hybrid rest/stress 13N-ammonia positron emission tomography (PET) and coronary computed tomography angiography (CCTA) due to suspected myocardial ischemia. Patients with previous myocardial infarction and/or significant coronary artery disease (≥ 50% stenosis) were excluded. Myocardial perfusion measurements were compared between patients with and without LAD-MB. Additionally, we evaluated the relationship between anatomical characteristics (length and depth) of LAD-MB and myocardial perfusion measurements. 17 (13%) patients presented a single LAD-MB. Global myocardial perfusion reserve (MPR) was lower in patients with LAD-MB than in patients without LAD-MB (1.9 ± 0.5 vs. 2.3 ± 0.6, p

Background. The current method for assessing progressive disease (PD) in glioblastoma is according to the Response Assessment in Neuro-Oncology (RANO) criteria. Bevacizumab-treated patients may show pseudo-response on postcontrast T1-weighted (T1w) MRI, and a more infiltrative non-enhancing growth pattern on T2w/fluid attenuated inversion recovery (FLAIR) images. We investigated whether the RANO criteria remain the method of choice for assessing bevacizumab-treated recurrent glioblastoma when compared with various volumetric methods.Methods. Patients with assessable MRI data from the BELOB trial (n = 148) were included. Patients were treated with bevacizumab, lomustine, or both. At first and second radiological follow-up (6 and 12 wk), PD was determined using the 2D RANO criteria and various volumetric methods based on enhancing tumor only and enhancing plus non-enhancing tumor. Differences in overall survival (OS) between PD and non-PD patients were assessed with the log-rank test and a Cox model. Hazard ratios (HRs) and their 95% CIs were determined.Results. For all patients together, all methods (except subtraction of non-enhancing from enhancing volume at first follow-up) showed significant differences in OS between PD and non-PD patients (P Conclusions. In the first 12 weeks, volumetric methods did not provide significant improvement over the RANO criteria as a posttreatment prognostic marker.

Objective: Chronic kidney disease (CKD) is associated with structural brain damage and with a high prevalence of depression. We therefore investigated structural brain alterations in both gray and white matter in CKD patients, focusing on depression-related (frontal-subcortical) regions.Method: This cross-sectional MRI study in 24 CKD patients and 24 age- and sex-matched controls first tested whether CKD was associated with regionally lower gray matter (GM) volumes and more severe white matter lesions (WMLs). In exploratory subanalyses, we examined whether differences were more pronounced in CKD patients with depressive symptoms.Results: CKD patients showed lower global GM volume (P=.04) and more severe WMLs (P=.04) compared to controls. In addition, we found substantial clusters of lower GM in the bilateral orbitofrontal-cortex for CKD patients, which were however nonsignificant after proper multiple-comparison correction. In exploratory analyses for depressed CKD patients, reduced GM clusters were mainly detected within the frontal lobe. WML severity was unrelated to depression.Conclusion: CKD was characterized by differences in brain structure. Although subthreshold, lower GM volumes were observed in depression-related brain areas and were more pronounced for depressed patients. There is a need for replication in larger and longitudinal studies to investigate whether WMLs and regional GM reductions may render CKD patients more susceptible for depression. (C) 2016 Elsevier Inc. All rights reserved.

Background: In the current DTI study we compared euthymic bipolar I disorder (BD-I) patients and healthy controls (HC). We subsequently divided the total patient group into lithium-users and non-lithium-users and estimated differences across the three groups.Methods: Twenty-one euthymic BD-I patients and twenty-two HC participants were included in psychiatric interviews and MRI image acquisition (diffusion-weighted (DW) and T1-weighted scans). Fractional anisotropy (FA), radial, mean and axial diffusivity (RD, MD, AD) were estimated from the DW data, using DTI. These measures were then compared between groups using FSL Tract Based Spatial Statistics (TBSS). Correlations with age at onset, number of episodes and depression score were analyzed.Results: A difference in FA, MD, RD and AD between the whole sample of euthymic BD-I patients and healthy controls could not be detected. Amongst others, lithium-using patients demonstrated a higher FA and lower RD when compared to non-lithium-using BD-I patients in the corpus callosum and left anterior corona radiata. Widespread clusters demonstrated negative FA associations and positive RD and MD associations with minor depressive symptoms.Limitations: Patients were naturalistically treated. Although the sample size is comparable to several other DTI studies, a larger sample size would have been benificial. TBSS and DTI have their own limitations.Conclusion: Our findings support the theory that previously described DTI-based microstructural differences between HC and BD patients could be less pronounced in euthymic BD patients. Differences in FA between patients using and not using lithium suggest a counteracting effect of lithium on white matter microstructural disturbances. (C) 2016 Elsevier B.V. All rights reserved.

Transforming growth factor-beta (TGF-beta) signaling is involved in glioma development. The monoclonal antibody fresolimumab (GC1008) can neutralize all mammalian isoforms of TGF-beta, and tumor uptake can be visualized and quantified with Zr-89-fresolimumab PET in mice. The aim of this study was to investigate the fresolimumab uptake in recurrent high-grade gliomas using Zr-89-fresolimumab PET and to assess treatment outcome in patients with recurrent high-grade glioma treated with fresolimumab. Methods: Patients with recurrent glioma were eligible. After intravenous administration of 37 MBq (5 mg) of Zr-89-fresolimumab, PET scans were acquired on day 2 or day 4 after tracer injection. Thereafter, patients were treated with 5 mg of fresolimumab per kilogram intravenously every 3 wk. Zr-89-fresolimumab tumor uptake was quantified as maximum standardized uptake value (SUVmax). MR imaging for response evaluation was performed after 3 infusions or as clinically indicated. Results: Twelve patients with recurrent high-grade glioma were included: 10 glioblastomas, 1 anaplastic oligodendroglioma, and 1 anaplastic astrocytoma. All patients underwent Zr-89-fresolimumab PET 4 d after injection. In 4 patients, an additional PET scan was obtained on day 2 after injection. SUVmax on day 4 in tumor lesions was 4.6 (range, 1.5-13.9) versus a median SUVmean of 0.3 (range, 0.2-0.5) in normal brain tissue. All patients showed clinical or radiologic progression after 1-3 infusions of fresolimumab. Median progression-free survival was 61 d (range, 25-80 d), and median overall survival was 106 d (range, 37-417 d). Conclusion: Zr-89-fresolimumab penetrated recurrent high-grade gliomas very well but did not result in clinical benefit.

Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [C-11]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential focus of neuroinflammation in bipolar disorder. We aim to determine if there is increased [C-11]-(R)-PK11195binding to activated microglia in the hippocampus of patients with bipolar I disorder when compared to healthy controls.Material and methods: Fourteen patients with bipolar I disorder and eleven healthy controls were included in the analyses. Dynamic 60-min PET scans were acquired after the injection of [C-11]-(R)-PK11195. All subjects underwent psychiatric interviews as well as an MRI scan, which was used for anatomic co-registration in the data analysis. The data from the PET scans was analyzed with a twotissue-compartment model to calculate the binding potential, using the metabolite-corrected plasma and blood curve as input.: A significantly increased [C-11]-(R)-PK11195 binding potential, which is indicative of neuroinflammation, was found in the right hippocampus of the patients when compared to the healthy controls (1.66 (CI 1.45-1.91) versus 1.33 (Cl 1.16-1.53); p = 0.033, respectively). Although the same trend was observed in the left hippocampus, this difference was not statistically significant.Conclusion: This study is the first to demonstrate the presence of focal neuroinflammation in the right hippocampus in bipolar I disorder. (C) 2014 Elsevier Inc. All rights reserved.

This review summarizes the long-term consequences of the posterior reversible encephalopathy syndrome (PRES) that have been described in the obstetric literature (eclampsia and preeclampsia) and compares these with data from the nonobstetric literature. Preeclampsia is characterized by new-onset hypertension and proteinuria after the 20th week of pregnancy. Neurological symptoms include headache; visual deficits; confusion; seizures; and, in the most severe cases, intracranial hemorrhage. Eclampsia is an acute cerebral complication of preeclampsia, defined as the occurrence of tonic-clonic seizures in pregnant or recently postpartum women. With severe preeclampsia, in conjunction with neurological symptoms, or eclampsia, neuroimaging changes consistent with PRES can be seen. Posterior reversible encephalopathy syndrome is a specific clinicoradiological syndrome presenting with headaches, visual impairment, seizures, and altered mental status. Characteristic neuroimaging features are consistent with cerebral edema predominantly in the parietal and occipital lobes. In addition to preeclampsia/eclampsia, PRES has been associated with various conditions in the nonobstetric population, that is, severe hypertension, transplantation, or autoimmune disease, in combination with immunosuppressive therapy or high-dose chemotherapy for various malignant conditions. Long-term sequelae of both preeclampsia/eclampsia and other PRES-related conditions are poorly described. After eclampsia or preeclampsia, nonspecific white matter lesions may be found on magnetic resonance imaging, which may or may not be related to the PRES episode. Previously (pre)eclamptic women report cognitive failures; however, no neurocognitive impairment has been shown so far. Various nonobstetric PRES-related conditions have been described with long-term neuroimaging abnormalities as well as cognitive problems, epilepsy, or visual impairment. Although no firm conclusions can be drawn because of the heterogeneity of reported cases, some general comments can be made. Because most persistent long-term problems are present in the nonobstetric population, the main determinant for these long-term problems may be the underlying condition that gave rise to the PRES episode. In addition, most reports suggest that late diagnosis or inadequate therapy may contribute, emphasizing the need for early recognition, adequate treatment, follow-up, and support.

BACKGROUND CONTEXT: A bipartite atlas is a rare coincidental finding, and it is reported in only 0.1% of the general population. It is a congenital disorder characterized by incomplete fusion of the anterior and the posterior arches of C1, and it is important to differentiate it from a Jefferson fracture.STUDY DESIGN/SETTING: Case report and literature review.PURPOSE: To report three cases of patients with bipartition of the atlas with a focus on imaging. To review the literature on these fusion defects, the embryologic basis, and the differentiation from a Jefferson fracture.METHODS: We report three cases of patients with a bipartite atlas as a coincidental finding in a trauma setting. The bipartite atlas was assessed by multidetector computed tomography (CT). The first case, for example, describes a 36-year-old patient who was struck by a moped. The CT of the skull showed a bipartite atlas as an additional finding. The embryologic development of C1 is reviewed and also the imaging features and the management. Furthermore, a CT image of a Jefferson fracture is provided for comparison.RESULTS: The CT scans of the three patients show midline clefts of the anterior and the posterior arches of C1 with similar imaging features: smooth margins lined by cortical bone and no lateral offset. The patients had no neurological symptoms relating to the C1 abnormality, and no follow-up was performed. The clefts at level C1 are the result of the failure of three ossification centers to fuse properly. Anterior and posterior clefts are caused by hypoplasia of the hypochordal bow and lateral parts of the C1 sclerotome, respectively. Because of the risk of instability, assessing atlantoaxial stability is advised. However, patients usually have no symptoms and require no specific treatment.CONCLUSIONS: A bipartite atlas is a rare congenital abnormality, caused by a failure of anterior and lateral ossification centers to fuse. It needs to be differentiated from a Jefferson fracture in a trauma setting. It usually requires no specific treatment. (c) 2013 Elsevier Inc. All rights reserved.

Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel–Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DNA. Hemangioblastomas overexpress CXCR4, CXCL12, and VEGFA compared to normal surrounding tissue. In sporadic hemangioblastomas the mean percentage of CXCR4 positive hemangioblastoma cells was 16 %, SD 8.4, in VHL-related hemangioblastomas 8 %, SD 4.4 (P = 0.002). There was no relation between preoperative tumor size and CXCR4 or CXCL12 expression. Compared to normal surrounding tissue CXCR4, CXCL12, and VEGFA were overexpressed in hemangioblastomas. Most interestingly, sporadic hemangioblastomas overexpress CXCR4 compared to VHL-related hemangioblastoma. Electronic supplementary material The online version of this article (doi:10.1007/s10689-016-9879-3) contains supplementary material, which is available to authorized users.

While retrieving additional information from patients’ medical files for another study, it became clear that one patient who was actually using valproate and levetiracetam, was previously processed as a lithium user. Below you will find the corrected version of the subjects’ characteristics Table 1, as well as corrected results of the explorative analyses of this study where lithium use was involved and an updated version of Fig. 7, summarizing the explorative analysis results of the left hippocampus. The altered text of the concerned paragraphs are set in boldface. The cited references are as in the original report.

OBJECTIVE: Hypertensive disorders of pregnancy, like preeclampsia, are a leading cause of maternal and fetal morbidity/mortality worldwide. Preeclampsia can be complicated by the occurrence of convulsions (eclampsia). Women who experienced (pre)eclampsia more frequently report daily cognitive failures and showed increased emotional dysfunction several years later, but are not impaired on objective neurocognitive testing. In addition, women with preterm preeclampsia more often have cerebral white matter lesions (WML) on follow-up. We aimed to determine whether WML presence is related to cognitive dysfunction, anxiety, and depressive symptoms in (pre)eclamptic women.METHOD: Forty-one eclamptic, 49 preeclamptic, and 47 control women who had a normotensive pregnancy completed the Cognitive Failures Questionnaire (CFQ), the Hospital Anxiety and Depression Scale (HADS), and a broad neurocognitive test battery (visual perception and speed of information processing, motor functions, working memory, long-term memory, attention, and executive functioning). All underwent cerebral magnetic resonance imaging (MRI), and WML presence was recorded. Median elapsed time since index pregnancy was 6 years. Average age was 40 years.RESULTS: WML were more prevalent in women who had experienced preterm (pre)eclampsia (CONCLUSION: Formerly (pre)eclamptic women report cognitive dysfunction, but do not exhibit overt cognitive impairment when objectively tested on average 6 years following their pregnancy. The presence of WML is not related to objective nor to subjective cognitive impairment, anxiety, and depressive symptoms. Longitudinal studies are needed to study whether the presence of WML is a risk factor for developing objective cognitive impairment in the long term.

Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning.Materials and methods: Twenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [C-11]-(R)PK11195 neuroinflammation positron emission tomography scan.Results: In contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA) + N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr) + phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA + NAAG concentration, between alcohol use and NM + NAAG concentration, between microglial activation and the depression score and a negative relation between Cr + PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally.Conclusion: Compared to HCs, the decreased NAA + NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis. (C) 2015 Elsevier Inc. All rights reserved.

At former allergic contact dermatitis reaction sites retesting causes augmented hyper-reactivity, characterized by an accelerated onset within a few hours. This expression of ‘local skin memory’ has been ascribed to locally persisting allergen-specific effector/memory T cells. To verify this hypothesis, we investigated whether accelerated retest reactivity also occurs with cross-reactive allergens. Guinea pigs were immunized with either or both 2,4-dinitrochlorobenzene (DNCB) and 2-hydroxyethyl methacrylate (HEMA), and primary skin tests to these and cross-reactive methacrylic compounds were performed 12–21 days later. Subsequently, new skin tests were conducted 3 weeks later both at the former test (‘retest’) and contralateral, non-pretreated test (‘control’) sites, and skin test readings started 2 h later. Retest reactivity was evaluated by comparing retest and contralateral control reactions. Both contact sensitizers, HEMA and DNCB, induced strong retest reactivity, peaking at 4–6 h. Fully allergen-specific retest reactivity was observed when primary skin tests had been postponed until 21 days after immunization, most probably reflecting loss of accumulation of irrelevant allergen-primed T cells at that time. As hypothesized, retesting with various methacrylate congeners at primary HEMA, but not DNCB, skin test sites showed early hyperreactivity strengths in line with those observed earlier in conventional cross-reactivity studies. These results, therefore, support the view that local skin memory exhibits allergen specificity through residual allergen-primed T cells. Because the retesting procedure is readily applicable in clinical practice, it provides a tool not only for confirmation of doubtful contact allergic skin reactions, but also for distinguishing between true cross-reactivity and coincident multiple sensitization in man.

OBJECTIVE: Women who suffered eclampsia or preterm preeclampsia are twice as likely to demonstrate cerebral white matter lesions (WML) on magnetic resonance imaging compared with age-matched women who had normotensive pregnancies, and they report more cognitive dysfunctions in everyday life. We aimed to determine whether pregnancy in and of itself has a relationship with the presence of WML and subjective cognitive dysfunction.STUDY DESIGN: Eighty-one parous women who had a normotensive pregnancy were matched for age with 65 nulliparous women and all underwent cerebral magnetic resonance imaging. Presence of cerebral WML was rated and blood pressure was measured. Subjective cognitive functioning was assessed using the Cognitive Failures Questionnaire.RESULTS: There was no difference in the presence (22% vs 19%) of WML between parous and nulliparous women. Age was a predictor for the presence of WML, whereas the presence of current hypertension was not. Average score on the Cognitive Failures Questionnaire was not different between both groups, nor related to WML.CONCLUSION: A history of pregnancy in and of itself is not related to the presence of cerebral WML and the perception of cognitive dysfunction. Because of the relationship with preterm preeclampsia and eclampsia, future research should focus on the clinical importance and development throughout the years of such cerebral WML in young women and focus on risk factors for cardiovascular disease.

Delirium is an acute change of consciousness and cognition that is associated with poor outcome. The arsenal to treat delirium is limited due to the poor understanding of the pathophysiology of the underlying encephalopathy. Neuroimaging can be used to elucidate possible neural mechanisms. In delirium, however, neuroimaging is still in its infancy. Despite concerns about the feasibility of neuroimaging in delirious patients, several investigations have been performed. Most structural imaging studies suggest that delirium is associated with more brain atrophy and focal abnormalities, such as infarcts and white matter disruption. Functional imaging studies suggest perfusion abnormalities and altered functional connectivity. More advanced imaging techniques may provide new insight in the pathophysiology of delirium.

Item does not contain fulltext OBJECTIVE: To assess the distribution of cerebral white matter lesions in women who had eclampsia, preeclampsia, or normotensive pregnancies. The pathophysiology of these lesions, more often seen in formerly eclamptic and preeclamptic women, is unclear but may be related to a predisposition for vascular disease, the occurrence of the posterior reversible encephalopathy syndrome, or both while pregnant. Assessing the distribution of such lesions may give insight into their pathophysiology and possible consequences. METHODS: This retrospective cohort study determined the presence, severity, and location of white matter lesions on cerebral magnetic resonance imaging scans of 64 formerly eclamptic, 74 formerly preeclamptic, and 75 parous control women. RESULTS: Formerly preeclamptic and eclamptic women have white matter lesions more often (34.4% [n=47] compared with 21.3% [n=16]; P

OBJECTIVES: To study the relation between serum levels of carotenoids and white matter lesions (WMLs) on magnetic resonance imaging (MRI). DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Rotterdam Scan Study. PARTICIPANTS: Two hundred and three nondemented older persons, age 60 to 90, from the Rotterdam Scan Study. MEASUREMENTS: Serum levels of carotenoids were determined. WMLs on MRIs were rated separately into periventricular and subcortical WMLs. Odds ratios (ORs) for the presence of severe WMLs (upper decile) were calculated per standard deviation (SD) increase in serum carotenoid level and per SD increase in overall carotenoid serum level. Effect modification by smoking status was studied through stratified analyses. RESULTS: Increasing levels of all the separate carotenoids were associated with less severe periventricular WMLs, which reached statistical significance for the overall carotenoid serum level (OR 0.4 per SD; 95% confidence interval (CI) = 0.2-0.9). We found no association between carotenoid levels and the presence of severe subcortical WMLs (OR 1.2 per SD; 95% CI = 0.7-2.0). The association of carotenoid levels with severe periventricular WMLs was more marked in those who ever smoked (OR 0.1 per SD; 95% CI = 0.0-0.9) than in those who had never smoked (OR 0.9 per SD; 95% CI = 0.4-2.1). CONCLUSIONS: These findings are compatible with the view that high levels of carotenoids may protect against WMLs in the periventricular region, in particular in smokers. Longitudinal studies with repeated measurements of both carotenoids and WMLs are necessary to explore this hypothesis further.

To assess whether differences in cerebral atrophy and white matter lesions or in the presence of lactate and lipid signals can explain the observed differences in brain choline, creatine, and N-acetylaspartate levels between healthy elderly women and men.In addition to standard magnetic resonance imaging of the brain, an 8 x 8 x 2-cm3 supraventricular transverse brain volume parallel to the canthomeatal line was examined by magnetic resonance spectroscopy (automated 1H chemical shift imaging) in 540 healthy elderly persons.At P = 0.01, 0.001, and 0.0001, choline differed between women and men in 14, 9, and 5 of 36 voxels, respectively. On correction for cerebral atrophy (more frequent in men than in women), white matter lesions (more frequent in women), and lactate and lipid (more frequent in women), the differences in choline were reduced to 13, 6, and 3. Sex differences for creatine and N-acetylaspartate were similar but less numerous after correction.Elderly women and men in the general population show differences in the levels of creatine, N-acetylaspartate, and especially choline in portions of the brain. The sex-related differences in brain metabolite levels cannot be explained by differences in cerebral atrophy or other aging-related phenomena (white matter lesions, lactate, lipid).

Fanconi anemia (FA) is an autosomal recessive disorder in humans characterized by bone marrow failure, cancer predisposition, and cellular hypersensitivity to cross-linking agents such as mitomycin C and diepoxybutane. FA genes display a caretaker function essential for maintenance of genomic integrity. We have cloned the murine homolog of FANCA, the gene mutated in the major FA complementation group (FA-A). The full-length mouse Fanca cDNA consists of 4503 bp and encodes a protein with a predicted molecular weight of 161 kDa. The deduced Fanca mouse protein shares 81% amino acid sequence similarity and 66% identity with the human protein. The nuclear localization signal and partial leucine zipper consensus motifs found in the human FANCA protein were also present in the murine homolog. In spite of the species difference, the murine Fanca cDNA was capable of correcting the cross-linker sensitive phenotype of human FA-A cells, suggesting functional conservation. Based on Northern as well as Western blots, Fanca was mainly expressed in lymphoid tissues, testis, and ovary. This expression pattern correlates with some of the clinical symptoms observed in FA patients. The availability of the murine Fanca cDNA now allows the gene to be studied in experimental mouse models.

White matter lesions are often observed on cerebral magnetic resonance imaging scans of elderly people and may play a role in the pathogenesis of dementia. Cross-sectional studies have shown an association between elevated blood pressure and white matter lesions. We prospectively studied the relation between blood pressure and white matter lesions in 1,077 subjects aged 60 to 90 years who were randomly sampled from two prospective population-based studies. One study had blood pressure measurements 20 years before, the other 5 years before. Overall response for the magnetic resonance imaging study was 63%, and declined from 73% among 60- to 70-year-olds to 48% for 80- to 90-year-olds. Diastolic and systolic blood pressure levels assessed 20 years before were significantly associated with subcortical and periventricular white matter lesions. The association between 20-year change in diastolic blood pressure and subcortical white matter lesions was J-shaped (relative risk, 2.2; 95% confidence interval, 1.0-5.2; and relative risk, 3.2; 95% confidence interval, 1.4-7.4, for decrease or increase of more than 10 mm Hg, respectively). The association between concurrent diastolic blood pressure level and white matter lesions was linear in subjects without, and J-shaped in subjects with, a history of myocardial infarction. Our results indicate that the J-shape relationship of diastolic blood pressure is not restricted to cardiovascular disease, but is also manifest in cerebrovascular disease.

Schizophrenia is a chronic and disabling brain disease characterized by psychotic episodes with unknown etiology. It is suggested that neuroinflammation plays a role in the pathophysiology of schizophrenia. Neuroinflammation is characterized by the activation of microglia cells, which show an increase in the expression of the peripheral benzodiazepine receptor. The isoquinoline (R)-N-(11)C-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide ((11)C-(R)-PK11195) is a peripheral benzodiazepine receptor ligand that can be used for the imaging of activated microglia cells, and thus neuroinflammation, with PET. We hypothesized that neuroinflammation would be more profound in schizophrenic patients during psychosis, and it was therefore investigated whether neuroinflammation was present in patients within the schizophrenia spectrum who were in a psychotic phase. Methods: Seven patients within the schizophrenia spectrum who were recovering from psychosis were included. Recovering psychosis was defined by a score of 5 or more on 1 item of the positive scale of the positive and negative symptoms scale (PANSS) or a score of 4 on 2 items. The patients were compared with 8 age-matched healthy volunteers. Dynamic 60-min PET scans were acquired after the injection of (11)C-(R)-PK11195. All subjects underwent T1- and T2-weighted MRI, and the scans were visually examined for abnormalities and used for anatomic coregistration in data analysis. The PET data were analyzed with a 2-tissue-compartment model to calculate the binding potential, using the metabolite-corrected plasma curve as input. Results: A significantly higher binding potential of (11)C-(R)-PK11195, indicative of neuroinflammation, was found in the hippocampus of schizophrenic patients than in healthy volunteers (2.07 +/- 0.42 vs. 1.37 +/- 0.30; P = 0.004). A nonsignificant 30% higher (11)C-(R)-PK11195 binding potential was found in the whole-brain gray matter of schizophrenic patients. The MR images did not reveal any visual abnormalities. Conclusion: The present study suggests that focal neuroinflammation may play an important role in schizophrenia during psychosis.

OBJECTIVE: Eclampsia is thought to have no long-term neurological consequences. We aimed to delineate the neurostructural sequelae of eclampsia, in particular brain white matter lesions, utilizing high-resolution 3-Tesla magnetic resonance imaging (MRI).STUDY DESIGN: Formerly eclamptic women were matched for age and year of index pregnancy with normotensive parous controls. The presence and volume of brain white matter lesions were compared between the groups.RESULTS: MRI scans of 39 women who formerly had eclampsia and 29 control women were performed on average 6.4 +/- 5.6 years follow-ing the index pregnancy at a mean age of 38 years. Women with eclampsia demonstrated subcortical white matter lesions more than twice as often as compared with controls (41% vs 17 %; odds ratio, 3.3; 95% confidence interval, 1.05-10.61; P = .04).CONCLUSION: Cerebral white matter lesions occur more often in women who formerly had eclampsia compared with women with normotensive pregnancies. The exact pathophysiology underlying these imaging changes and their clinical relevance remain to be elucidated.

Background and Purpose— Cerebral white matter lesions (WMLs) are frequently found on magnetic resonance imaging scans in both cognitively intact and demented elderly persons. Vascular risk factors, especially hypertension, are related to their presence. However, not every person with vascular risk factors has WMLs, which suggests interaction with other determinants, eg, genetic factors. The ε4 allele of the apolipoprotein E gene (apoE) may be a candidate because this allele is associated with both the vascular risk factors and the consequences (cognitive impairment, dementia) of WMLs. Methods— We investigated apoE genotype, blood pressure levels, and their interaction in relation to subcortical and periventricular WMLs in 971 participants in the Rotterdam Scan Study. Results— ApoE ε4 carriers had a significantly higher subcortical WML volume than did apoE ε3ε3 carriers (adjusted mean difference, 0.5; 95% confidence interval, 0.2 to 0.8), irrespective of hypertension. This was not found for periventricular WMLs. Participants with both hypertension and at least 1 apoE ε4 allele had the highest degree of both types of WML; the interaction was statistically significant for subcortical WMLs ( P =0.016). Conclusions— apoE ε4 carriers are at increased risk for WMLs if they suffer from hypertension as well. This may reflect a diminished capacity for neuronal repair in apoE ε4 carriers.

The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood pressure and performed MRI in 1077 nondemented elderly (age 60-90 years). For 513 of these, we had information on a blood pressure level 20 years before. The degree of cortical atrophy was semi-quantitatively scored (range 0-15). In late life, a high (>/=90 mmHg) and low (

The prospect of declining cognitive functions is a major fear for many elderly persons. Cerebral white matter lesions, as commonly found with magnetic resonance imaging, have been associated with cognitive dysfunction in cross-sectional studies. Only a few longitudinal studies using small cohorts confirmed these findings. We examined the relation between severity of white matter lesions and cognitive decline over a nearly 10-year period in 563 elderly subjects sampled from the general nondemented Dutch population. Severity of white matter lesions was scored for periventricular and subcortical regions separately using an extensive semiquantitative scale. Cognitive function was measured by the Mini-Mental State Examination at regular time intervals during 1990 to 2000, and magnetic resonance imaging scans were made in 1995 to 1996. More severe white matter lesions were associated with more rapid cognitive decline over a mean follow-up period of 7.3 years (standard deviation, 1.5). After adjusting for age, gender, educational level, measures of depression, and brain atrophy and infarcts, subjects with severe periventricular white matter lesions experienced cognitive decline nearly three times as fast (0.28 Mini-Mental State Examination points/year [95% confidence interval, 0.20-0.36]) as the average (0.10 points/year [95% confidence interval, 0.09-0.111). There was no independent relationship between severity of subcortical white matter lesions and rate of cognitive decline.

To evaluate whether mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance (MR) imaging surpasses dual-phase spiral computed tomography (CT) in differentiating focal liver lesions.One hundred forty-five patients who had or were suspected of having focal liver lesions were included in a multicenter study and underwent dual-phase spiral CT and enhanced MR imaging. Image interpretations performed by independent experienced radiologists were compared with the final diagnosis that was based on all available clinical information (including histopathologic findings in 77 patients) and that was determined with consensus. Differences in classifications by using either enhanced MR imaging or dual-phase spiral CT were analyzed with the McNemar test, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance of enhanced MR imaging and dual-phase spiral CT.Lesion classification was correct in 108 (74%) patients with enhanced MR imaging and in 83 (57%) with dual-phase spiral CT (P =.001). Lesions were correctly classified as either malignant or benign in 123 (85%) patients with enhanced MR imaging and in 98 (68%) with dual-phase spiral CT (P =.001). Classification of lesions as either hepatocellular or nonhepatocellular was correct in 130 (90%) patients with enhanced MR imaging and in 93 (64%) with dual-phase spiral CT (P =.001). These differences remained when analyses were restricted to histopathologically confirmed diagnoses. Comparison of the ROC curves illustrated that enhanced MR imaging performance surpassed that of dual-phase spiral CT.Mn-DPDP-enhanced MR imaging is superior to dual-phase spiral CT in classification of focal liver lesions.

2009 Background: Response evaluation in glioblastoma (GBM) patients after concomitant radiotherapy and temozolomide (TMZ) is hampered by the occurrence of progressive contrast enhancing lesions on MRI that do not reflect true tumor progression. 18F-fluorothymidine (FLT) is a Positron Emission Tomography (PET) tracer that is taken up by proliferating cells. The goal of this study was to prospectively assess the value of FLT-PET in discriminating between true progression and pseudoprogression in patients with primary GBM treated with radiotherapy and TMZ (NTR3680). Methods: FLT-PET scans were performed before start and 4 weeks after radiochemotherapy. MRI scans were performed at these time points and after 3 cycles of adjuvant TMZ. Macdonald criteria were used for response evaluation on MRI. Pseudoprogression was defined as progressive disease on MRI after radiochemotherapy, with stabilization or improvement of enhancing lesions after 3 cycles of adjuvant TMZ. Changes in SUVmax and tumor to normal brain tis...

Background and Purpose —MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions. Methods —We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531 subjects in late life. Results —The presence of aortic atherosclerosis during midlife was significantly associated with the presence of periventricular white matter lesions ≈20 years later (adjusted relative risk, 2.4; 95% CI, 1.2 to 5.0); the relative risks increased linearly with the severity of aortic atherosclerosis. No association was found between midlife aortic atherosclerosis and subcortical white matter lesions (adjusted relative risk, 1.1; 95% CI, 0.5 to 2.3) or between late-life aortic atherosclerosis and white matter lesions. Conclusions —The pathogenetic process that leads to cerebral periventricular white matter lesions starts already in or before midlife. The critical period for intervention directed at prevention of white matter lesions and its cognitive consequences may be long before these lesions become clinically detectable.

Cerebral white matter lesions (wmls) have been associated with cognitive dysfunction. Whether periventricular or subcortical wmls relate differently to cognitive function is still uncertain. In addition, it is unclear whether wmls are related to specific cognitive domains such as memory or psychomotor speed. We examined the relationship between periventricular and subcortical wmls and cognitive functioning in 1,077 elderly subjects randomly sampled from the general population. Quantification of wmls was assessed by means of an extensive rating scale on 1.5-t magnetic resonance imaging scans. Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed, memory performance, and global cognitive function. When analyzed separately, both periventricular and subcortical wmls were related to all neuropsychological measures. When periventricular wmls were analyzed conditional on subcortical wmls and vice versa, the relationship between periventricular wmls and global cognitive function remained unaltered whereas the relationship with subcortical wmls disappeared. Subjects with most severe periventricular wmls performed nearly 1 sd below average on tasks involving psychomotor speed, and more than 0.5 sd below average for global cognitive function. Tasks that involve speed of cognitive processes appear to be more affected by wmls than memory tasks. Ann neurol 2000;47:145–151.

4-Hydroperoxy-cyclophosphamide (4-HPCY) is an in vitro active form of cyclphosphamide. In a previous study, using an in vivo contact sensitivity model in the guinea pig, we demonstrated that intradermal injection of small amounts (50–200 μg) of 4-HPCY at the sensitization site resulted in strong potentiation of contact hypersensitivity (Boerrigter and Scheper, 1984). It was postulated that 4-HPCY induces a local decrease of feedback control within the draining antigenically stimulated lymph nodes. The present data are in support of this view: ( i ) Lymph node hyperplasia induced by contact sensitization (to dinitrochlorobenzene or oxazolone) was further enhanced by 4-HPCY treatment. ( ii ) The paracortical area was preferentially enlarged. ( iii ) 4-HPCY-treated lymph nodes showed an augmentation of hapten-specific T effector cell function as determined in transfer experiments. ( iv ) The response of such lymph node-derived cells to the T cell mitogen PHA was enhanced. Although 4-HPCY treatment resulted simultaneously in a decrease in responsiveness of draining lymph node-derived cells to the B cell mitogen lipopolysaccharide, anti-hapten antibody production was not affected. The present study demonstrates that important similarities exist between the effects of local 4-HPCY treatment and systemic cyclophosphamide pretreatment on the immune response. As systemic treatment with a high dose of cyclophosphamide is known to have serious side effects, the present local protocol provides a new attractive and versatile strategy for T cell immunopotentiation.

New imaging sequences with increasing spatial and temporal resolution are introduced frequently in Magnetic Resonance Imaging (MRI) to perform noninvasive angiography both with and without contrast media for the enhancement of the vessels. These new sequences produce a growing amount of data to be evaluated by the radiologist to form the diagnosis. Because of the growing amount of data and thus the growing amount of slices, more and more images are reconstructed and either printed on film or viewed on a diagnostic workstation. When a diagnostic work-station is used the radiologist most frequently uses the stack or cine mode view of the slices, but other techniques like Multi Planar Reformatting (MPR), Maximum Intensity Projection (MIP), Surface Rendering (SR), and Volume Rendering (VR) are also available to process the data. When using these techniques, the radiologist needs to interact closely with the data to obtain optimal views and in some cases special purpose workstations are required to be able to use them. In this article an overview of available techniques is presented. The technique itself, its advantages and disadvantages, and the (possible) clinical applications are discussed.