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Previously, the tyrosine kinase inhibitor sunitinib failed to show clinical benefit in patients with recurrent glioblastoma. Low intratumoural sunitinib accumulation in glioblastoma patients was reported as a possible explanation for the lack of therapeutic benefit. We designed a randomized phase II/III trial to evaluate whether a high-dose intermittent sunitinib schedule, aimed to increase intratumoural drug concentrations, would result in improved clinical benefit compared to standard treatment with lomustine. Patients with recurrent glioblastoma were randomized 1:1 to high-dose intermittent sunitinib 300 mg once weekly (Q1W, part 1) or 700 mg once every two weeks (Q2W, part 2) or lomustine. The primary end-point was progression-free survival. Based on the pre-planned interim analysis, the trial was terminated for futility after including 26 and 29 patients in parts 1 and 2. Median progression-free survival of sunitinib 300 mg Q1W was 1.5 months (95% CI 1.4-1.7) compared to 1.5 months (95% CI 1.4-1.6) in the lomustine arm (P = 0.59). Median progression-free survival of sunitinib 700 mg Q2W was 1.4 months (95% CI 1.2-1.6) versus 1.6 months (95% CI 1.3-1.8) for lomustine (P = 0.70). Adverse events (≥grade 3) were observed in 25%, 21% and 31% of patients treated with sunitinib 300 mg Q1W, sunitinib 700 mg Q2W and lomustine, respectively (P = 0.92). To conclude, high-dose intermittent sunitinib treatment failed to improve the outcome of patients with recurrent glioblastoma when compared to standard lomustine therapy. Since lomustine remains a poor standard treatment strategy for glioblastoma, innovative treatment strategies are urgently needed.
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To investigate the impact of frontal macro-structural lesions on intrinsic network measures, we examined brain network function during resting-state fMRI in patients with frontal lesions in the subacute phase after mild to moderate traumatic brain injury. Additionally, network function was related to neuropsychological performances. 17 patients with frontal lesions, identified on admission CT after mild to moderate trauma, were compared to 30 traumatic brain injury patients without frontal lesions and 20 healthy controls. Three months post-injury, we acquired fMRI scans and neuropsychological assessments (measuring frontal executive functions and information processing speed). Using independent component analysis, the activity of and connectivity between network components (largely located in the prefrontal cortex) and relations with neuropsychological measures were examined and compared across groups. The analysis yielded five predominantly frontal components: anterior and posterior part of the default mode network, left and right frontoparietal network and salience network. No significant differences concerning fMRI measures were found across groups. However, the frontal lesions group performed significantly worse on neuropsychological tests than the other two groups. Additionally, the frontal lesions group showed a significant positive association of stronger default mode network-salience network connectivity with better executive performances. Our findings suggest that, on fMRI level, frontal network measures are not largely affected by frontal lesions following a mild to moderate traumatic brain injury. Yet, patients with damage to the frontal structures did show poorer executive abilities which might to some degree be related to altered frontal network connectivity between the default mode network and salience network.
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Lesões Encefálicas Traumáticas , Rede Nervosa , Humanos , Lesões Encefálicas Traumáticas/patologia , Córtex Pré-Frontal/diagnóstico por imagem , Função Executiva , Cognição , Imageamento por Ressonância Magnética , Mapeamento Encefálico , EncéfaloRESUMO
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.
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INTRODUCTION: The 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. METHODS: In 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. RESULTS: Of 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. CONCLUSION: Local 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.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Fibrinolíticos/efeitos adversos , Trombectomia/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Sistema de RegistrosRESUMO
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.
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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.
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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 (ß coefficient of 0.035, p = 0.003), female gender of the radiology resident (ß coefficient of 12.690, p = 0.001), and postgraduate year (ß 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.
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Internato e Residência , Radiologia , Adulto , Benchmarking , Avaliação Educacional , Feminino , Humanos , Masculino , Radiologia/educaçãoRESUMO
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 (>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.
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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.
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Sistemas de Informação em Radiologia , Radiologia , Comunicação , Documentação , Humanos , RadiografiaRESUMO
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%, pï¼0.001). 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.
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Cálcio/metabolismo , Disfunção Cognitiva/etiologia , Doença da Artéria Coronariana/complicações , Vasos Coronários/metabolismo , Demência/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Demência/metabolismo , Demência/patologia , Humanos , PrognósticoRESUMO
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.
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Didesoxinucleosídeos , Progressão da Doença , Glioblastoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Proliferação de Células , Quimiorradioterapia , Diagnóstico Diferencial , Feminino , Seguimentos , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem MultimodalRESUMO
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 < .001). The largest risk increase for death in case of PD at both first and second follow-up was found with the RANO criteria: HR = 2.81 (95% CI, 1.92-4.10) and HR = 2.80 (95% CI, 1.75-4.49), respectively. In the bevacizumab-treated patients, all methods assessed showed significant differences in OS between PD and non-PD patients. There were no significant differences between methods. Conclusions: In the first 12 weeks, volumetric methods did not provide significant improvement over the RANO criteria as a posttreatment prognostic marker.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/patologia , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Meios de Contraste , Glioblastoma/tratamento farmacológico , Humanos , Lomustina/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
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.
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Transtorno Bipolar/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Depressão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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.
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Depressão/patologia , Substância Cinzenta/patologia , Insuficiência Renal Crônica/patologia , Substância Branca/patologia , Adulto , Idoso , Estudos Transversais , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/fisiopatologia , Substância Branca/diagnóstico por imagemRESUMO
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 (<37 weeks; 40%) than in controls (21%, p = .03). In (pre)eclamptic women, CFQ and HADS scores were higher than those in controls (44 ± 16.1 vs. 36 ± 11.0, p < .001, and 11 ± 6.3 vs. 8 ± 5.5, p < .001). There was no difference in objective cognitive performance as measured by neurocognitive tests. Subjective and objective cognitive functioning, anxiety, and depressive symptoms were not related to WML presence. 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.
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Córtex Cerebral/patologia , Transtornos Cognitivos/etiologia , Hipertensão/complicações , Transtornos da Memória/etiologia , Reconhecimento Psicológico/fisiologia , Substância Branca/patologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Depressão , Eclampsia , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico por imagem , Pessoa de Meia-Idade , Testes Neuropsicológicos , Pré-Eclâmpsia/fisiopatologia , Gravidez , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Estatísticas não Paramétricas , Inquéritos e Questionários , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologiaRESUMO
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 [(11)C]-(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 NAA+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.
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Transtorno Bipolar/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Microglia/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Transtorno Bipolar/imunologia , Transtorno Bipolar/metabolismo , Transtorno Bipolar/patologia , Radioisótopos de Carbono/metabolismo , Feminino , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Inflamação/metabolismo , Isoquinolinas/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Adulto JovemRESUMO
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.
Assuntos
Eclampsia , Epilepsia/epidemiologia , Síndrome da Leucoencefalopatia Posterior/complicações , Pré-Eclâmpsia , Transtornos Cognitivos/epidemiologia , Eclampsia/epidemiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Fatores de Tempo , Tomografia Computadorizada por Raios X , Transtornos da Visão/epidemiologiaRESUMO
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 [(11)C]-(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 [(11)C]-(R)-PK11195 binding 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 [(11)C]-(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 two-tissue-compartment model to calculate the binding potential, using the metabolite-corrected plasma and blood curve as input. RESULTS: A significantly increased [(11)C]-(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 (CI 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.
Assuntos
Transtorno Bipolar/imunologia , Encefalite/imunologia , Hipocampo/imunologia , Adulto , Idoso , Transtorno Bipolar/diagnóstico por imagem , Radioisótopos de Carbono , Encefalite/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Isoquinolinas , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Adulto JovemRESUMO
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.