Underwent Brain Magnetic Resonance Imaging Research Articles

Lesion Topography and Microscopic White Matter Tract Damage Contribute to Cognitive Impairment in Symptomatic Carotid Artery Disease.

Purpose To investigate associations between neuroimaging markers of cerebrovascular disease, including lesion topography and extent and severity of strategic and global cerebral tissue injury, and cognition in carotid artery disease (CAD). Materials and Methods All participants gave written informed consent to undergo brain magnetic resonance imaging and the Addenbrooke's Cognitive Examination-Revised. One hundred eight patients with symptomatic CAD but no dementia were included, and a score less than 82 represented cognitive impairment. Group comparison and interrelations between global cognitive and fluency performance, lesion topography, and ultrastructural damage were assessed with voxel-based statistics. Associations between cognition, medial temporal lobe atrophy (MTA), lesion volumes, and global white matter ultrastructural damage indexed as increased mean diffusivity were tested with regression analysis by controlling for age. Diagnostic accuracy of imaging markers selected from a multivariate prediction model was tested with receiver operating characteristic analysis. Results Cognitively impaired patients (n = 53 [49.1%], classified as having probable vascular cognitive disorder) were older than nonimpaired patients (P = .027) and had more frequent MTA (P < .001), more cortical infarctions (P = .016), and larger volumes of acute (P = .028) and chronic (P = .009) subcortical ischemic lesions. Lesion volumes did not correlate with global cognitive performance (lacunar infarctions, P = .060; acute lesions, P = .088; chronic subcortical ischemic lesions, P = .085). In contrast, cognitive performance correlated with presence of chronic ischemic lesions within the interhemispheric tracts and thalamic radiation (P < .05, false discovery rate corrected). Skeleton mean diffusivity showed the closest correlation with cognition (R2 = 0.311, P < .001) and promising diagnostic accuracy for vascular cognitive disorder (area under the curve, 0.82 [95% confidence interval: 0.75, 0.90]). Findings were confirmed in subjects with a low risk of preclinical Alzheimer disease indexed by the absence of MTA (n = 85). Conclusion Subcortical white matter ischemic lesion locations and severity of ultrastructural tract damage contribute to cognitive impairment in symptomatic CAD, which suggests that subcortical disconnection within large-scale cognitive neural networks is a key mechanism of vascular cognitive disorder. Online supplemental material is available for this article.

Fine-mapping the effects of Alzheimer's disease risk loci on brain morphology

The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions. Brain regions most significantly associated with AD risk variants were the left postcentral gyrus with ABCA7 (rs4147929, p = 4.45 × 10−6), right superior frontal gyrus by ZCWPW1 (rs1476679, p = 5.12 × 10−6), and right postcentral gyrus by APOE (p = 6.91 × 10−6). Although no individual voxel passed multiple-testing correction, we found significant spatial overlap between the effects of AD risk loci on VBM and the expression of genes (MEF2C, CLU, and SLC24A4) in the Allen Brain Atlas. Results are available online on www.imagene.nl/ADSNPs/. In this single largest imaging genetics data set worldwide, we found that AD risk loci affect cortical gray matter in several brain regions known to be involved in AD, as well as regions that have not been implicated before.

White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age.

ObjectiveExamine the association of white matter hyperintensities (WMH) with risk of incident mild cognitive impairment (MCI) and rate of decline in multiple cognitive systems in community‐based older persons.MethodsParticipants (n = 354) were older persons initially free of cognitive impairment from two ongoing longitudinal epidemiologic studies of aging. All underwent brain magnetic resonance imaging (MRI) for quantification of WMH and gray matter volumes and detailed annual clinical evaluations including 17 cognitive tests. Proportional hazards models were used to examine the relationship between WMH and incident MCI, and mixed‐effects models were used to examine the relationship between WMH and decline in global cognition and five specific cognitive systems.ResultsDuring up to about 6 years of follow‐up (mean = 4.1), 106 (30% of 354) persons developed MCI. In a proportional hazards model adjusted for age, gender, and education, WMH volume was associated with a substantially increased risk of MCI (P < 0.001). Thus, a person with a high WMH volume (90th percentile) was about 2.7 times more likely to develop MCI compared to a person with a low volume (10th percentile). WMH volume also was associated with an increased rate of decline in global cognition (P < 0.001), perceptual speed, working memory, episodic memory, and semantic memory. Associations persisted after adjustment for total gray matter volume, vascular risk factors, and vascular diseases.Interpretation WMH contribute to the development of MCI and are associated with progressive decline in multiple cognitive systems in old age.

Associations Between Serum Inflammatory Markers and Hippocampal Volume in a Community Sample.

To quantify associations between inflammatory biomarkers and hippocampal volume (HV) and to examine effect modification according to sex, race, and age. Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized β-coefficients adjusted for age, sex, race, and education. Community cohorts in Jackson, Mississippi and Rochester, Minnesota. The Genetic Epidemiology Network of Arteriopathy study. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors 1 (sTNFR-1) and 2 (sTNFR-2) from peripheral blood were measured in a sample of 773 non-Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation (SD) increase in sTNFR-1 was associated with 59.1 mm(3) (95% confidence interval (CI) = -101.4 to -16.7 mm(3) ) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm(3) (95% CI = -92.2 to -5.3 mm(3) ) smaller HV. Relationships were stronger for sTNFR-2 in men (HV = -116.6 mm(3) for each SD increase, 95% CI = -201.0 to -32.1) than women (HV = -26.0 per SD increase, 95% CI = -72.4-20.5) and sTNFR-1 in non-Hispanic whites (HV = -84.7 mm(3) per SD increase, 95% CI = -142.2 to -27.1) than African Americans (HV = -14.1 mm(3) per SD increase, 95% CI = -78.3-50.1). Associations between IL-6 or CRP and HV were not supported. Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late-life cognitive impairment.

Duplication of the right vertebral artery: MRA findings and review of the literature.

IntroductionDuplication of the vertebral artery (VA) is a rare vascular variant. To the best our knowledge, only fourteen cases have been reported with angiographic findings that they have dual origin of the VA from ipsilateral subclavian artery. Herein, we present a case of duplication of right VA which was incidentally detected by magnetic resonance (MR) angiography.Case descriptionA 69-year-old female patient presented with headache for 30 days. She underwent brain MR imaging with MR angiography for evaluating possible intracranial cause. There was a dual origin of the right vertebral artery (VA) as an incidental finding without other significant abnormalities.Discussion and EvaluationDiagnosis of duplicated VA can be difficult due to its rarity and misinterpreted as the vascular dissection. In addition, a detailed knowledge of this variation is potentially important to prevent inadvertent challenges during endovascular procedure. Because duplicated VA has smaller lumen and usually enters the higher transverse foramen than those of normal side, it can be influence the choice or route of endovascular treatment.ConclusionsWe suggested that the understanding of embryologic background about VA can be helpful to identify unexpected vascular findings on imaging studies in clinical practice.

Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: A voxel-based morphometric and fMRI study of the whole brain

The primary aim of this study was to identify structural and functional abnormalities in the brains of obsessive-compulsive disorder (OCD) patients. Another aim was to assess the effect of serotonin selective reuptake inhibitors (SSRIs) on brain structure of OCD patients. All subjects underwent brain magnetic resonance imaging (MRI) and resting functional MRI (fMRI). High-resolution three-dimensional images were processed using the voxel-based morphometry (VBM) method. The final analysis included 18 OCD patients and 16 healthy controls. In the OCD patients there was a decrease in gray matter volume in the bilateral cingulate cortex and bilateral striatum. In some cortical structures including the cerebellar anterior lobe, left orbital frontal gyrus, right middle frontal gyrus, left middle temporal gyrus, precentral gyrus, and postcentral gyrus, there was an increase in gray matter volume. On fMRI the OCD patients had overactivation of the right cerebellum and right parietal lobe and reduced activation of the left cingulate gyrus, putamen, and caudate nucleus. Eleven OCD patients who improved during 12 weeks of drug treatment with sertraline hydrochloride had a significant increase in gray matter volume in several brain structures but no significant differences were found on resting fMRI. The results indicated a consistent trend between structural and functional images. Higher cortical structures showed increased gray matter volume and increased activation as did the cerebellum whereas subcortical structures showed decreased gray matter volume and decreased activation. And brain structure improvement consisted with symptom improvement after SSRIs treatment in OCD patients.

SYNERGISTIC EFFECTS OF AMYLOID AND VASCULAR CHANGES ON THE LOBAR MICROBLEEDS: A THREE-YEAR LONGITUDINAL STUDY IN PATIENTS WITH SUBCORTICAL VASCULAR MILD COGNITIVE IMPAIRMENT

We determined whether amyloid and subcortical cerebral small vessel disease (sCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI). Among 72 patients with svMCI who underwent brain magnetic resonance imaging (MRI) and a [11C] Pittsburgh compound-B positron emission topography (PiB-PET), 52 (72.2%) completed the third year of follow-up. These patients were evaluated by annual brain MRI and a follow-up PiB-PET. Both baseline and longitudinal changes in lacune numbers were associated with the increased numbers of lobar and deep microbleeds, while baseline and longitudinal changes in PiB uptake ratio were associated only with the progression of lobar microbleeds, especially in the temporal, parietal, and occipital areas. There were interactive effects between the baseline and longitudinal lacune and PiB retention changes on lobar microbleeds progression. Our findings suggest that amyloid-related pathology and sCSVD have synergistic effects on the progression of lobar microbleeds, providing new clinical insight into the interaction between amyloid burden and sCSVD with implications for developing effective prevention strategies.

Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry.

Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors.

High incidence of silent cerebral infarcts in adult patients with beta thalassemia major

ObjectivesSurvival of beta thalassemia major (TM) patients has improved significantly over the past few decades. Consequently, less commonly reported complications are now being recognized. An incidence as high as 60% of silent cerebral infarcts (SCI) has been demonstrated by brain Magnetic Resonance Imaging (MRI) studies in beta thalassemia intermedia (TI). The aim of this study was to determine whether regularly transfused TM adult patients experience less SCI, as compared to the incidence described in TI. MethodsIn this observational study, 28 transfusion dependent TM patients, >18years of age underwent brain MRI studies. ResultsFocal bright foci in the cerebral white matter were demonstrated in 17 (60.7%) patients; most of them had multiple lesions. Elevated serum ferritin (SF), primarily 5years Area Under the Curve, was found to have a significant association with the presence of SCI (p<0.031). Similar results were found when 4 patients with intact spleen and 2 patients with splenules were excluded (p=0.027). There was no significant association between number of SCI and clinical or other laboratory parameter evaluated. ConclusionsThe present study demonstrates a high rate of SCI in regularly transfused TM adult patients. Effective continuous iron chelation, preventive low dose aspirin and routine periodical brain MRI are recommended.

Age disparity in diagnostic evaluation of stroke patients: Embolic Stroke of Undetermined Source Global Registry Project.

Introduction: Incomplete evaluation of stroke patients may result in an unclear diagnosis. Our objective was to determine if older stroke patients more often undergo incomplete diagnostic evaluations versus younger patients in an international cohort. Patients and methods: The Embolic Stroke of Undetermined Source Global Registry was a retrospective cohort of consecutive stroke patients evaluated at 19 stroke centers in 19 countries. Diagnostic evaluation was considered as complete if the patient had, at a minimum, brain computed tomography or magnetic resonance imaging with evidence of infarction, extracranial and intracranial vascular imaging, electrocardiography, ≥24 h of cardiac rhythm monitoring, and echocardiography. Patients were diagnosed with Embolic Stroke of Undetermined Source if brain imaging confirmed a nonlacunar infarction and no stroke etiology was determined after complete evaluation. Completeness of evaluation was compared between patients ≥75 versus <75 years old. Results: The registry included 2132 patients with recent ischemic stroke during 2013-2014, of which 349 were diagnosed with Embolic Stroke of Undetermined Source. Embolic Stroke of Undetermined Source patients ≥75 years were less likely to undergo brain magnetic resonance imaging (74% versus 89%, p = 0.001), transesophageal echocardiography (22% versus 39%, p = 0.005), and combination transthoracic and transesophageal echocardiography (16% versus 32%, p = 0.005) compared with Embolic Stroke of Undetermined Source patients <75 years. Discussion: Our study has identified an international age disparity in fundamental diagnostic testing for older patients with stroke of unknown etiology. Some testing biases were affected by geographic location (e.g., brain MRI was less frequently used in European ESUS patients), whereas other testing was implemented less frequently in the elderly regardless of location (e.g., transesophageal echocardiogram). Conclusion: Older patients in this international cohort had less sophisticated diagnostic testing for stroke, despite advanced age being well established as an independent risk factor for recurrent stroke. This was a global problem and further investigations are warranted to explore the cause.

Current Patterns of Care for Patients with Extensive-Stage SCLC: Survey of U.S. Radiation Oncologists on Their Recommendations Regarding Prophylactic Cranial Irradiation

IntroductionConflicting data from randomized clinical trials incite the debate over the appropriate use of prophylactic cranial irradiation (PCI) for patients with extensive-stage SCLC (ES-SCLC) who achieve clinical response to systemic chemotherapy. The current pattern of practice among U.S. radiation oncologists is unknown. MethodsWe surveyed practicing U.S. radiation oncologists through a short online questionnaire. Respondents' characteristics and their self-rated knowledge base were analyzed for association with their treatment recommendations. ResultsWe received 473 responses from practicing U.S. radiation oncologists. More than half of the respondents had been practicing for more than 10 years after completing residency training, and 70% had treated more than 10 patients with lung cancer per year. Of the respondents, 90% recommended brain magnetic resonance imaging (MRI) before initiation of PCI and 98% recommended PCI for patients with ES-SCLC after systemic chemotherapy. Half of the respondents followed their patients with brain MRI after completion of PCI. One-third of the respondents prescribed memantine to patients undergoing PCI. Among the respondents, recent graduates (p = 0.004) and physicians practicing in academic centers (p = 0.005) were more likely to prescribe memantine. Self-rated knowledge base was not associated with any treatment recommendations. ConclusionsOur analysis revealed that among the respondents, there was a very high adherence to current National Comprehensive Cancer Network guidelines, which recommend providing universal PCI and obtaining brain MRI before initiation of PCI for patients with ES-SCLC with clinical response to systemic chemotherapy. These guidelines and practice patterns are not supported by clinical evidence because patients in the European Organization for Research and Treatment of Cancer trial did not undergo brain MRI before PCI and the Japanese randomized trial has shown a possible detrimental effect of PCI on overall survival when brain MRI was incorporated. A critical reevaluation of current guidelines is essential to determine the appropriate management of these patients.

Correlation between Patent Foramen Ovale, Cerebral “Lesions” and Neuropsychometric Testing in Experienced Sports Divers: Does Diving Damage the Brain?

SCUBA diving exposes divers to decompression sickness (DCS). There has been considerable debate whether divers with a Patent Foramen Ovale of the heart have a higher risk of DCS because of the possible right-to-left shunt of venous decompression bubbles into the arterial circulation. Symptomatic neurological DCS has been shown to cause permanent damage to brain and spinal cord tissue; it has been suggested that divers with PFO may be at higher risk of developing subclinical brain lesions because of repeated asymptomatic embolization of decompression-induced nitrogen bubbles. These studies however suffer from several methodological flaws, including self-selection bias. We recruited 200 volunteer divers from a recreational diving population who had never suffered from DCS; we then randomly selected 50 of those for further investigation. The selected divers underwent brain Magnetic Resonance Imaging to detect asymptomatic brain lesions, contrast trans-oesophageal echocardiography for PFO, and extensive neuro-psychometric testing. Neuro-psychometry results were compared with a control group of normal subjects and a separate control group for subjects exposed to neurotoxic solvents. Forty two divers underwent all the tests and are included in this report. Grade 2 Patent Foramen Ovale was found in 16 (38%) of the divers; brain Unidentified Bright Objects (UBO's) were found in 5 (11.9%). There was no association between PFO and the presence of UBO's (P = 0.693) or their size (p = 0.5) in divers. Neuropsychometric testing in divers was significantly worse from controls in two tests, Digit Span Backwards (DSB; p < 0.05) and Symbol-Digit-Substitution (SDS; p < 0.01). Compared to subjects exposed to neurotoxic solvents, divers scored similar on DSB and SDS tests, but significantly better on the Simple Reaction Time (REA) and Hand-Eye Coordination (EYE) tests. There was no correlation between PFO, number of UBO's and any of the neuro-psychometric tests. We conclude that for uneventful recreational diving, PFO does not appear to influence the presence of UBO's. Diving by itself seems to cause some decrease of short-term memory and higher cognitive function, including visual-motor skills; this resembles some of the effects of nitrogen narcosis and we suggest that this may be a prolonged effect of diving.

Decreased fractional anisotropy values in two clusters of white matter in patients with schizotypal personality disorder: A DTI study

ObjectiveTo find a difference in fractional anisotropy (FA) between young adult males with schizotypal personality disorder (SPD) and healthy controls (HCs). MethodsSixteen males with SPD and sixteen HCs were selected from 3500 freshmen across two universities. The 32 participants were evaluated by the Minnesota Multiphasic Personality Inventory (MMPI) (Chinese Version Sc≥70) and the Schizotypal Personality Questionnaire (SPQ). Structured diagnostic interview was carried out and all the subjects in the SPD group met DSM-IV diagnostic criteria for SPD. All participants underwent brain magnetic resonance imaging, and their diffusion tensor imaging (DTI) data was collected. DTI data was analysed using tract-based spatial statistics (TBSS), and the neurofibre connection from the hippocampus to the right entorhinal cortex was traced. Informed consent was obtained from all participants. Results(1) SPD and HCs had a significant difference in SPQ symptoms (P<0.05). (2) There was a significant difference in the fractional anisotropy of two clusters of the brain between the two groups (P<0.05). The first cluster included the right pallidum, right retro-lenticular part of the internal capsule, right inferior longitudinal fasciculus (rILF), right posterior parietal lobe, right temporal lobe and right occipital lobe. The second cluster included the right hippocampus, right fornix, and right temporal lobe. (3) FA volume in the rILF positively correlated with scores related to the “lack of friends” subscale of the SPQ. ConclusionThese results suggest reduced white matter in two brain clusters of young adult males with SPD. These findings are similar to previous reports on patients experiencing their first schizophrenic episode.

Magnetic resonance imaging arterial-spin-labelling perfusion alterations in childhood migraine with atypical aura: a case-control study.

Atypical migraine with aura can be challenging to diagnose. Arterial-spin-labelling (ASL) is able to non-invasively quantify brain perfusion. Our aim was to report cerebral blood flow (CBF) alterations using ASL, at the acute phase of atypical migraine with aura in children. Paediatric patients were retrospectively included if (1) referred for acute neurological deficit(s), (2) underwent brain magnetic resonance imaging (MRI) at presentation with ASL sequence, and (3) had subsequent diagnosis of migraine with aura. Neurological symptom-free controls were matched for age. Twenty-eight regions of interest (ROIs) were drawn on CBF maps for each participant/control. Ten patients were included (median age 13y, range 8-16y). Eight of 10 had multiple aura symptoms during the episode. For every patient, CBF was decreased in a brain region consistent with symptoms when MRI was performed less than 14 hours after onset (n=7 patients) and increased if the MRI was performed 17 hours or more after (n=4 MRIs). MRI-ASL appears to be a promising tool for the diagnostic workup and differentials exclusion in paediatric migraine with aura. Constant and time-consistent non-territorial CBF modifications were found in our sample providing additional insight to migraine with aura pathophysiology. The authors encourage implementing this sequence at the acute phase of unexplained paediatric neurological deficits, with or without accompanying headache.

MR Imaging Measures of Intracranial Atherosclerosis in a Population-based Study.

Purpose To implement a magnetic resonance (MR) imaging protocol to measure intracranial atherosclerotic disease (ICAD) in a population-based multicenter study and report examination and reader reliability of these MR imaging measurements and descriptive statistics representative of the general population. Materials and Methods This prospective study was approved by the institutional review boards and compliant with HIPAA. Atherosclerosis Risk in Communities (ARIC) study participants (n = 1980) underwent brain MR imaging from 2011 to 2013 at four ARIC sites. Imaging included three-dimensional black-blood MR imaging and time-of-flight MR angiography. One hundred two participants returned for repeat MR imaging to estimate examination and reader variability. Plaque presence according to vessel segment was recorded. Quantitative measurements included lumen size and degree of stenosis, wall and/or plaque thickness, area and volume, and normalized wall index for each vessel segment. Reliability was assessed with percentage agreement, κ statistics, and intraclass correlation coefficients. Results Of the 1980 participants, 1755 (mean age, 77.6 years; 1026 women [59%]; 1234 white [70%]) completed examinations with adequate to excellent image quality. The weighted ICAD prevalence was 34.4% (637 of 1755 participants) and was higher in men than women (38.5% [302 of 729 participants] vs 31.7% [335 of 1026 participants], respectively; P = .012) and in African Americans compared with whites (41.1% [215 of 518 participants] vs 32.4% [422 of 1234 participants], respectively; P = .002). Percentage agreement of plaque identification per participant was 87.0% (interreader estimate), 89.2% (intrareader estimate), and 89.9% (examination estimate). Examination and reader reliability ranged from fair to good (κ, 0.50-0.78) for plaque presence and from good to excellent (intraclass correlation coefficient, 0.69-0.99) for quantitative vessel wall measurements. Conclusion Vessel wall MR imaging is a reliable tool for identifying and measuring ICAD and provided insight into ICAD distribution across a U.S. community-based population. (©) RSNA, 2016 Online supplemental material is available for this article.

Assessment of enlarged perivascular spaces and their relation to target organ damage and mild cognitive impairment in patients with hypertension.

Enlarged perivascular spaces (EPVS) have been recently considered a feature of cerebral small vessel disease. They have been related to aging, hypertension and dementia but their relationship with hypertension related variables (i.e. target organ damage, treatment compliance) and mild cognitive impairment (MCI) is not fully elucidated. Our aims were to investigate the relation between basal ganglia (BG) and centrum semiovale (CSO) EPVS with vascular risk factors, hypertension related variables and MCI. In all, 733 hypertensive individuals free of stroke and dementia from the Investigating Silent Strokes in Hypertensives, a magnetic resonance imaging Study (ISSYS) underwent brain magnetic resonance imaging and cognitive testing to diagnose MCI or normal cognitive aging. The numbers of participants presenting high grade (>10) EPVS at the BG and CSO were 23.3% and 40.0%, respectively. After controlling for vascular risk factors, high grade BG EPVS were associated with age (odds ratio 1.68; 95% confidence interval 1.37, 2.06), poor antihypertensive compliance (1.49; 1.03, 2.14) and the presence of microalbuminuria (1.95; 1.16, 3.28), whereas in the CSO only age (1.38; 1.18, 1.63) and male sex were associated with EPVS (1.73; 1. 24, 2.42). MCI was diagnosed in 9.3% of the participants and it was predicted by EPVS in the BG (1.87; 1.03, 3.39) but not in the CSO. This last association was greatly attenuated after correction for lacunes and white matter hyperintensities. Basal ganglia EPVS are associated with the presence of microalbuminuria and poor adherence to antihypertensive drugs. The BG EPVS relation with MCI is not independent of the presence of other cerebral small vessel disease markers.

Neuroimaging signatures of frailty: A population-based study in community-dwelling older adults (the Atahualpa Project).

Frailty is a geriatric state of physical vulnerability that might be associated with cognitive decline in the absence of a concurrent neurodegenerative disorder. This assumes that neuroimaging studies are normal, but such examinations have rarely been considered for a frailty work-up. The present study identifies neuroimaging signatures in older adults interviewed with the Edmonton Frail Scale (EFS). Community-dwellers aged ≥60 years enrolled in the Atahualpa Project were invited to undergo brain magnetic resonance imaging. Using generalized regression models, we evaluated the association between frailty and diffuse cortical and subcortical brain damage, after adjusting for relevant confounders. Multivariate models estimated the interaction of age in the association between frailty and these neuroimaging signatures. Out of 298 participants (mean age 70 ± 8 years, 57% women), 151 (51%) had moderate-to-severe cortical atrophy and 74 (25%) had moderate-to-severe white matter hyperintensities of presumed vascular origin. Mean EFS scores were 5 ± 3 points, with 140 (47%) individuals classified as robust, 65 (22%) as pre-frail and 93 (31%) as frail. Multivariate models showed a significant association between cortical atrophy with the continuous (P = 0.002) and the categorized (P = 0.008) EFS score. The relationship between white matter hyperintensities and the EFS was marginal. According to interaction models, prefrail or frail individuals aged ≥67 years presented more prominent neuroimaging signatures of diffuse cortical or subcortical damage than their robust counterparts. Neuroimaging signatures of frailty are mainly related to age. This reinforces the importance of early frailty detection to reduce its catastrophic consequences. Geriatr Gerontol Int 2017; 17: 270-276.

Ischemic Stroke in Critically Ill Patients with Malignancy.

BackgroundCerebrovascular diseases are a frequent cause of neurological symptoms in patients with cancer. The clinical characteristics of ischemic stroke (IS) in patients with cancer have been reported in several studies; however, limited data are available regarding critically ill patients with cancer who develop IS during their stay in the intensive care unit (ICU).MethodsAll consecutive patients who underwent brain magnetic resonance imaging (MRI) for suspicion of IS with acute abnormal neurologic symptoms or who developed signs of IS while in the ICU were retrospectively evaluated. We compared the clinical characteristics and diffusion-weighted imaging (DWI) lesion patterns between patients finally diagnosed as having or not having IS.ResultsOver the study period, a total of 88 patients underwent brain MRI for suspicion of IS, with altered mental status in 55 (63%), hemiparesis in 28 (32%), and seizure in 20 (23%). A total of 43 (49%) patients were ultimately diagnosed with IS. Multiple DWI lesions (41%) were more common than single lesions (8%). The etiologies of IS were not determined in the majority of patients (n = 27, 63%). In the remaining 16 (37%) patients, the most common aetiology of IS was cardioembolism (n = 8), followed by large-vessel atherosclerosis (n = 3) and small-vessel occlusion (n = 2). However, brain metastases were newly diagnosed in only 7 (8%) patients. Univariate comparison of the baseline characteristics between patients with or without IS did not reveal any significant differences in sex, malignancy type, recent chemotherapy, vascular risk factors, or serum D-dimer levels at the time of suspicion of IS. Thrombotic events were more common in the IS group than in the non-IS group (P = 0.028). However, patients who were ultimately diagnosed with IS had more hemiparesis symptoms at the time of suspicion of IS (P = 0.001). This association was significant even after adjusting for potentially confounding factors (adjusted odds ratio 5.339; 95% confidence interval, 1.521–19.163).ConclusionsIS developed during ICU stays in critically ill patients with cancer have particular features that may be associated with cancer-related mechanism.

Epidermal growth factor receptor mutations and brain metastasis in patients with nonadenocarcinoma of the lung.

This study explored the potential association between epidermal growth.factor receptor. (EGFR) mutation status and brain metastasis in patients with nonadenocarcinoma nonsmall cell lung cancer. (NSCLC). We analyzed clinical data from 286 patients with nonadenocarcinoma NSCLC, who were tested for EGFR mutations and underwent brain magnetic resonance imaging at diagnosis. We examined the relationship between EGFR mutation and brain metastasis at initial presentation. Of the 286 patients, 20 patients (7.0%) had EGFR mutations. EGFR mutations were more frequent in younger patients (11.1% in patients =64 years vs. 3.3% in patients >64 years: P = 0.01), females (21.4% vs. 3.5% in males: P <0.001), never-smokers (25.0% vs. 3.4% in smokers: P < 0.001), and tumors with nonsquamous histology (25.0% vs. 4.1% in squamous histology: P < 0.001). At diagnosis, the frequency of EGFR mutations was significantly different in patients with metastasis to different sites (4.0% [no metastases] vs. 10.4% [extracranial metastases] vs. 40.0% [brain metastases], P < 0.001). The strong association between EGFR mutation and brain metastasis remained significant in multivariate analysis (adjusted odds ratio [OR] = 9.68, 95% confidence interval [CI] =2.32-40.45; P = 0.002). Associations were also found for EGFR mutation status with nonsquamous histology (adjusted OR = 4.46, 95% CI = 1.46-13.56; P = 0.008). This study indicates that the likelihood of nonadenocarcinoma patients having EGFR mutant tumors may differ according to brain metastasis and squamous cell histology.

Exon 12 Ceruloplasmin Gene New Nonsense Mutation Causing Aceruloplasminemia in an Italian Patient

Hereditary aceruloplasminemia is a rare disease characterized by iron overload and neurodegeneration. Aceruloplasminemia is due to the absence/deficiency of ceruloplasmin, responsible for iron overload in liver, pancreas and other organs. We report the case of an Italian patient with hyperferritinemia, diabetes and hepatic iron excess, suspected to be affected by aceruloplasminemia. Patient underwent brain magnetic resonance imaging with and without paramagnetic medium contrast, which showed a hypointesity due to iron storage. The presence of a neurological disease and iron storage in the brain has led to assume the suspect of the aceruloplasminemia disease. We confirmed this hypothesis by the identification of a new nonsense mutation in exon 12 ceruloplasmin gene at codon 748, in homozygous status. When the diagnosis of ACP was established, the patient started chelation therapy with 75 mg/Kg/day deferiprone (DFP). Two months of starting therapy with DFP, serum ferritin values decreased to 693 ng/ml; the patient well tolerated the drug, and there have been no adverse events. Although rare, aceruloplasminemia should be considered in the differential diagnosis of unexplained iron overload.