Poststroke neuropsychiatric symptoms: relationships with IL-17 and oxidative stress.

Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female), 19 had depressive symptoms (CES-D ≥ 16), which was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17 concentrations did not differ between subjects with and without depressive symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004). In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ = 0.518, P = 0.023) and lower IL-10 (ρ = -0.484, P = 0.036), but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.

Toward patient-tailored perfusion thresholds for prediction of stroke outcome.

BACKGROUND AND PURPOSE: Multiple patient-specific clinical and radiologic parameters impact traditional perfusion thresholds used to classify/determine tissue outcome. We sought to determine whether modified baseline perfusion thresholds calculated by integrating baseline perfusion and clinical factors better predict tissue fate and clinical outcome. MATERIALS AND METHODS: CTP within 4.5 hours of acute anterior circulation stroke onset and 5- to 7-day MR imaging were performed for 203 patients with stroke, divided into derivation (n = 114) and validation (n = 89) data bases. Affected regions were operationally classified as infarct and noninfarct according to baseline CTP and follow-up FLAIR imaging. Perfusion thresholds were derived for each of the infarct and noninfarct regions, without and with transformation by baseline clinical and radiologic variables by using a general linear mixed model. Performance of transformed and nontransformed perfusion thresholds for tissue fate and 90-day clinical outcome prediction was then tested in the derivation data base. Reproducibility of models was verified by using bootstrapping and validated in an independent cohort. RESULTS: Perfusion threshold transformation by clinical and radiologic baseline parameters significantly improved tissue fate prediction for both gray matter and white matter (P < .001). Transformed thresholds improved the 90-day outcome prediction for CBF and time-to-maximum (P < .001). Transformed relative CBF and absolute time-to-maximum values demonstrated maximal GM and WM accuracies in the derivation and validation cohorts (relative CBF GM: 91%, 86%; WM: 86%, 83%; absolute time-to-maximum 88%, 79%, and 80%, 76% respectively). CONCLUSIONS: Transformation of baseline perfusion parameters by patient-specific clinical and radiologic parameters significantly improves the accuracy of tissue fate and clinical outcome prediction.

Intracranial atherosclerotic plaque enhancement in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Inflammation of an atherosclerotic plaque is a well-known risk factor in the development of ischemic stroke and myocardial infarction. MR imaging is capable of characterizing inflammation by assessing plaque enhancement in both extracranial carotid arteries and coronary arteries. Our goal was to determine whether enhancing intracranial atherosclerotic plaque was present in the vessel supplying the territory of infarction by using high-resolution vessel wall MR imaging. MATERIALS AND METHODS: High-resolution vessel wall 3T MR imaging studies performed in 29 patients with ischemic stroke and intracranial vascular stenoses were reviewed for presence and strength of plaque enhancement. RESULTS: Sixteen patients were studied during the acute phase (<4 weeks from acute stroke), 5 patients in the subacute phase (4-12 weeks), and 8 patients in the chronic phase (>12 weeks) of the ischemic injury. In all of the acute phase patients, atherosclerotic plaque in the vessel supplying the stroke territory demonstrated strong enhancement. There was a trend of decreasing enhancement as the time of imaging relative to the ischemic event increased. CONCLUSIONS: Strong pathologic enhancement of intracranial atherosclerotic plaque was seen in all patients imaged within 4 weeks of ischemic stroke in the vessel supplying the stroke territory. The strength and presence of enhancement of the atherosclerotic plaque decreased with increasing time after the ischemic event. These findings suggest a relationship between enhancing intracranial atherosclerotic plaque and acute ischemic stroke.

Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI.

BACKGROUND: Conventional arterial imaging focuses on the vessel lumen but lacks specificity because different pathologies produce similar luminal defects. Wall imaging can characterize extracranial arterial pathology, but imaging intracranial walls has been limited by resolution and signal constraints. Higher-field scanners may improve visualization of these smaller vessels. METHODS: Three-tesla contrast-enhanced MRI was used to study the intracranial arteries from a consecutive series of patients at a tertiary stroke center. RESULTS: Multiplanar T2-weighted fast spin echo and multiplanar T1 fluid-attenuated inversion recovery precontrast and postcontrast images were acquired in 37 patients with focal neurologic deficits. Clinical diagnoses included atherosclerotic disease (13), CNS inflammatory disease (3), dissections (3), aneurysms (3), moyamoya syndrome (2), cavernous angioma (1), extracranial source of stroke (5), and no definitive clinical diagnosis (7). Twelve of 13 with atherosclerotic disease had focal, eccentric vessel wall enhancement, 10 of whom had enhancement only in the vessel supplying the area of ischemic injury. Two of 3 with inflammatory diseases had diffuse, concentric vessel wall enhancement. Three of 3 with dissection showed bright signal on T1, and 2 had irregular wall enhancement with a flap and dual lumen. CONCLUSIONS: Three-tesla contrast-enhanced MRI can be used to study the wall of intracranial blood vessels. T2 and precontrast and postcontrast T1 fluid-attenuated inversion recovery images at 3 tesla may be able to differentiate enhancement patterns of intracranial atherosclerotic plaques (eccentric), inflammation (concentric), and other wall pathologies. Prospective studies are required to determine the sensitivity and specificity of arterial wall imaging for distinguishing the range of pathologic conditions affecting cerebral vasculature.

Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline.

BACKGROUND: The anterior-medial thalamus (AMT), which is associated with memory processing, is severely affected by Alzheimer's disease pathology and, when damaged, can be the sole cause of dementia. OBJECTIVE: To assess the frequency of magnetic resonance imaging (MRI) hyperintensities affecting the AMT, and their relationship with sudden cognitive decline. METHODS: 205 consecutive participants from a university cognitive neurology clinic underwent clinical evaluation, neuropsychological testing and quantitative MRI. RESULTS: AMT hyperintensities >5 mm3 occurred in 0 of 34 normal controls but were found in 5 of 30 (17%) participants with cognitive impairment with no dementia (CIND), 9 of 109 (8%) patients with probable Alzheimer's disease, 7 of 17 (41%) with mixed disease and 8 of 15 (53%) with probable vascular dementia (VaD). AMT hyperintensities occurred more often in participants with stepwise decline than in those with slow progression (chi2 = 31.7; p<0.001). Of the 29 people with AMT hyperintensities, those with slow progression had smaller medial temporal width (p<0.001) and smaller anterior-medial thalamic hyperintensities (p<0.001). In a logistic regression model, both variables were significant, and the pattern of decline was correctly classified in 86% of the sample (Cox and Snell R2 = 0.56; p<0.001). Those with AMT hyperintensities >55 mm3 were likely to have stepwise decline in cognitive function regardless of medial temporal lobe width; in contrast, those with smaller AMT hyperintensities showed a stepwise decline only in the absence of medial temporal lobe atrophy. All patients with VaD had left-sided AMT hyperintensities, whereas those with CIND had right-sided AMT hyperintensities. CONCLUSIONS: AMT hyperintensities >55 mm3 probably result in symptomatic decline, whereas smaller lesions may go unrecognised by clinicians and radiologists. Only half of those with AMT hyperintensities had diagnoses of VaD or mixed disease; the other AMT hyperintensities occurred in patients diagnosed with Alzheimer's disease or CIND. These silent hyperintensities may nevertheless contribute to cognitive dysfunction. AMT hyperintensities may represent a major and under-recognised contributor to cognitive impairment.

Cognitive impairment in dementia: correlations with atrophy and cerebrovascular disease quantified by magnetic resonance imaging.

This project assessed the contributions of atrophy and cerebrovascular disease (CVD) to cognitive impairment in dementia. Ten individuals with clinically diagnosed pure VaD were age-, sex-, and education-matched to individuals with AD. All participants underwent neuropsychological testing and MRI which were processed to generate quantitative indices of atrophy and CVD. A linear regression, including thalamic lesion and vCSF volumes, predicted cognitive status (R2 = .74; p < .0005). Three VaD subgroups were identified: thalamic lesion (n = 4), hippocampal infarcts (n = 3), and other (n = 3). In participants without thalamic lesion, vCSF predicted general cognition (R2 = .48), hippocampal atrophy predicted memory impairment (R2 = .33), and white matter lesions predicted executive dysfunction (R2 = .48). Both atrophy and CVD burden correlated highly with cognitive impairment and should be simultaneously assessed in studies of brain-behaviour relations in dementia.

Three brain SPECT region-of-interest templates in elderly people: normative values, hemispheric asymmetries, and a comparison of single- and multihead cameras.

UNLABELLED: The purpose of this study was to generate anatomically guided region-of-interest (ROI) brain SPECT templates based on scans of elderly healthy volunteers. We describe normal tracer uptake and hemispheric asymmetries for each of 3 camera systems and compare these characteristics among systems. METHODS: 99mTc-hexamethyl propyleneamine oxime SPECT scans were acquired from 28 elderly healthy volunteers (mean age [+/-SD], 70.3 +/- 6.5 y) on a single-head rotating gamma camera (n = 15) or on dual- (n = 18) or triple-head (n = 13) cameras. The average number of counts in each ROI was calculated and referenced to counts in a cerebellar ROI, providing semiquantitative regional cerebral blood flow (rCBF) ratios. For the templates and ROI map, base images of a healthy volunteer were obtained with each camera. Data from individuals scanned with 2 cameras on the same day (n = 15) were used to evaluate rCBF differences across cameras. For each camera, averaged SPECT templates were made using automated image registration. The base volunteer's T1-weighted MR image was converted to stereotactic space with dimensions similar to those of the SPECT templates, and 79 bilateral ROIs were defined. To obtain ROI rCBF ratios, we aligned individual images to their appropriate template and then to this modified MR image. RESULTS: The ROI coefficients of variation indicated that the fit of the ROIs was acceptable (0.07-0.35). Mean rCBF ratios ranged from 0.57 to 1.0, 0.67 to 1.01, and 0.63 to 1.00 for single-, dual-, and triple-head cameras, respectively. The cuneus, occipital cortex, occipital pole, middle temporal gyrus, and posterior middle frontal gyrus showed consistent hemispheric asymmetry (right side greater than left side in 83%-100% of individuals). Mean rCBF ratios did not differ between dual- and triple-head cameras, whereas the ratios for single- and dual-head cameras differed significantly (39 ROIs differed), even after smoothing and filtering the dual-head images to the level of the single-head images. CONCLUSION: The use of SPECT templates based on elderly healthy volunteers is an important feature of this technique because most available templates have used young individuals. Another important feature is the use of MR image-based ROIs. These procedures are versatile because they use more than 1 camera. They can easily be implemented in clinical and research settings to detect camera-specific, abnormal deviations in rCBF ROI ratios and asymmetry magnitudes in diseases associated with aging, such as stroke and dementia.

Apolipoprotein E and Alzheimer's disease: a genetic, molecular and neuroimaging review.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly and an increasingly significant health concern in our aging population. In the past 10 years, our understanding of this disease has increased dramatically. While the discovery of three rare genetic mutations that can cause AD has provided much information about the causes and progression of the disease, a great deal of attention has been focused on apolipoprotein (ApoE) because of its involvement in the more common, later onset form of AD. Due to the rapid pace of recent advances, it has not been easy for health care professionals, researchers and the general public to keep abreast of these developments. This paper reviews recent research in ApoE and late-onset AD, emphasizing molecular neuropathological, genetic and neuroimaging findings and highlighting current controversies that remain to be addressed.