Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis.

BACKGROUND AND PURPOSE: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. METHODS: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. RESULTS: We found significant difference in total plaque volume between men and women (ß=22.9 mm3 [95% CI, 15.4-30.5]; mean volume in men 1399±425 mm3, in women 1011±242 mm3). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3-6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2-4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2-7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1-5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2-8.6]). CONCLUSIONS: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01208025.

Causality assessment between reported fatal cerebral haemorrhage and suspected drugs: developing a new algorithm based on the analysis of the Japanese Adverse Event Report (JADER) database and literature review.

PURPOSE: Cerebral haemorrhage is a life-threatening event with various causes including adverse drug reactions (ADRs). Several methods have been proposed for the causality assessment of ADRs, but none specific for cerebral haemorrhage. The purpose of this study was to develop an algorithm for causality assessment between drugs and fatal cerebral haemorrhage, based on the analysis of data from the Japanese Adverse Drug Event Report (JADER) database and literature review. METHODS: All fatal ADRs reported in the JADER database between April 2004 and March 2020 were searched, and literature on drug-related cerebral haemorrhage or general causality assessment was reviewed to summarise the information on causality between cerebral haemorrhage and ADRs. RESULTS: Of the 50,095 cases identified in the JADER database, cerebral haemorrhage was the fifth most reported cause of fatal ADRs, but the causality of >80% of the events was published as 'Unassessable'. The literature review identified articles on drug-related cerebral haemorrhage and causality assessment methods in general. Based on these articles, information on five categories (temporal relationship, previous knowledge about the relationship between drug action and ADRs, alternative aetiological candidate, appropriateness of drug use, and the relationship between death and ADRs) was determined for causality assessment between a suspected drug and fatal cerebral haemorrhage; a new algorithm was created using this information. CONCLUSION: In this study, the information considered necessary for causality assessment between drugs and fatal cerebral haemorrhage was reviewed and an assessment algorithm was developed. Future studies are needed to validate the usefulness of this method.

Epidemiological characteristics of 561 cases of intracerebral hemorrhage in Chengdu, China.

ABSTRACT: To explore the epidemiology of patients with spontaneous intracerebral hemorrhage (sICH) in Chengdu, China, we retrieved the data of patients with spontaneous cerebral hemorrhage admitted to the First Affiliated Hospital of Chengdu Medical College from January 2017 to December 2019. We performed a comprehensive analysis of the location of hemorrhage, demographics, factors of hemorrhage, condition of body, severity of disturbance of consciousness, treatment, length of stay (days), inpatient costs, prognosis, and mortality rate in patients with sICH. In total, data of 561 in patients with sICH were included. The hemorrhage site was primarily located in the basal ganglia and thalamus (64.71%). The mean patient age was 63.2 ±â€Š12.4 years (64.17% men, 35.83% women). Male patients (mean age 62.3 ±â€Š12.5 year) were younger than female patients (mean age 64.9 ±â€Š12.1 year). The age of sICH onset in our sample was between 40 and 79 years; this occurred in 87.70% of the included cases. There were more males than females, which may be related to more daily smoking, longer drinking years, and overweight in males than in females. Cases occurred most frequently during the winter and spring months, and the relationship between sICH visits and hospitalizations appeared as a U-shape. The median time from illness onset to hospital admission was 3.0 hours. According to the Glasgow Coma Scale (GCS) score at admission, 20.50% of sICH cases were of mild intensity, 39.93% were moderate, and 39.57% were severe. Moderate disorder is the most common sICH severity. Factors influencing the disturbance of consciousness were blood glucose level at the time of admission as well as the number of years with hypertension. The lower the degree of disturbance of consciousness and the more they smoked per day indicated they had a higher likelihood of receiving surgical treatment while in hospital. The median hospital stay was 13.0 days, while the median inpatient cost was USD 3609. The 30-day mortality rate was 18.36%. sICH is an important public health problem in Chengdu, China. A governmental initiative is urgently needed to establish a sICH monitoring system that covers the Chengdu region to develop more effective and targeted measures for sICH prevention, treatment, and rehabilitation.

Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy.

Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aß deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.

Assessment of Incidence and Risk Factors of Intracerebral Hemorrhage Among Participants in the Framingham Heart Study Between 1948 and 2016.

Importance: Intracerebral hemorrhage (ICH) has the highest mortality of all stroke types and is the most serious complication of anticoagulation. Data regarding trends in ICH incidence and location-specific risk factors on the population level are conflicting. Objective: To assess long-term population-based trends in the incidence of ICH, examine incidence rates stratified by deep and lobar locations, and characterize location-specific risk factors. Design, Setting, and Participants: This longitudinal prospective community-based cohort study comprised 10 333 original participants (n = 5209; age range, 28-62 years) and offspring participants (n = 5124; age range, 5-70 years) from the Framingham Heart Study who were followed up from January 1, 1948, to December 31, 2016. Original and offspring patient cohorts were confirmed to have experienced a spontaneous ICH event through imaging or pathologic testing. A total of 129 participants were identified with a primary incident of ICH. After exclusions, the remaining 99 patients were divided into 2 nested case-control samples, which were created by stratifying the first incident of ICH by brain region (lobar ICH or deep ICH), with 55 patients included in the lobar ICH sample and 44 patients included in the deep ICH sample. Patients were matched by age and sex (1:4 ratio) with 396 individuals without any stroke event (the control group). No participant in the patient samples was excluded or approached for consent, as their initial consent to participate in the Framingham Heart Study included consent to follow-up of cardiovascular outcomes. Data were analyzed in October 2019. Main Outcomes and Measures: The unadjusted and age-adjusted ICH incidence rates, assessed in 3 periods (period 1, from 1948-1986; period 2, from 1987-1999; and period 3, from 2000-2016) to study incidence trends. Nested case-control samples were used to examine baseline risk factors and medication exposures with the incidence of ICH events located in the lobar and deep brain regions within the 10 years before participants experienced a stroke event. Results: Of 10 333 original and offspring participants in the Framingham Heart Study, 129 patients (72 women [55.8%]; mean [SD] age, 77 [11] years) experienced a primary ICH incident during a follow-up period of 68 years (301 282 person-years), with an incidence rate of 43 cases per 100 000 person-years. The unadjusted incidence rate increased over time, but the age-adjusted incidence rate decreased slightly between periods 2 and 3. An age-stratified analysis indicated a continued increase in ICH incidence among patients 75 years and older, reaching 176 cases per 100 000 person-years in period 3. A concurrent 3-fold increase in the use of anticoagulant medications was observed, from 4.4% in period 2 to 13.9% in period 3. The incidence rate increased substantially with age for both lobar and deep ICH. Higher systolic and diastolic blood pressure and statin medication use (odds ratio [OR], 4.07; 95% CI, 1.16-14.21; P = .03) were associated with the incidence of deep ICH. Higher systolic blood pressure and apolipoprotein E ε4 allele homozygosity (OR, 3.66; 95% CI, 1.28-10.43; P = .02) were associated with the incidence of lobar ICH. Conclusions and Relevance: This study found that the incidence of ICH increased in the oldest patients. Hypertension is a treatable risk factor for both deep and lobar ICH, while the use of statin medications is associated with the risk of a deep ICH event.

Cerebral amyloid angiopathy mimicking central nervous system metastases: a case report.

BACKGROUND: This case describes an unusual presentation of an intracranial hemorrhage first thought to be metastatic disease on computed tomography and magnetic resonance imaging. The healthcare team completed an exhaustive search for a primary malignancy that was negative. Final diagnosis on brain biopsy showed intercranial hemorrhage secondary to cerebral amyloid angiopathy. With an increasing number of elderly patients and the rising cost of health care, this case can serve as a reminder to clinicians about their own responsibilities in limiting the cost of health care. CASE PRESENTATION: This is a case report about a 72-year-old white woman with an intracranial hemorrhage secondary to cerebral amyloid angiopathy. The brain lesions on computed tomography/magnetic resonance imaging mimicked a metastatic process until a brain biopsy could give a definitive diagnosis that was completely unexpected. Cerebral amyloid angiopathy is a rare cause of intracerebral hemorrhage and this diagnosis is important to consider in older patients on anticoagulation. CONCLUSIONS: Cerebral amyloid angiopathy is a rare diagnosis but should be considered in elderly patients on anticoagulation presenting with imaging findings consistent with intracerebral hemorrhage. While metastatic disease is a more common cause of intracerebral hemorrhage, cerebral amyloid angiopathy should remain in the differential diagnosis. This case report serves as a teaching point to clinicians in cases involving an older patient on anticoagulation.

The Cerebral Haemorrhage Anatomical RaTing inStrument (CHARTS): Development and assessment of reliability.

PURPOSE: The causes, risk factors and prognosis of spontaneous intracerebral haemorrhage (ICH) are partly determined by anatomical location (specifically, lobar vs. non-lobar (deep and infratentorial) regions). We systematically developed a rating instrument to reliably classify ICH location. METHODS: We used a two-stage iterative Delphi-style method for instrument development. The resultant Cerebral Haemorrhage Anatomical RaTing inStrument (CHARTS) was validated on CT and MRI scans from a cohort of consecutive patients with acute spontaneous symptomatic ICH by three independent raters. We tested interrater and intrarater reliability using kappa statistics. RESULTS: Our validation cohort included 227 patients (58% male; median age: 72.4 (IQR: 67.1-74.6)). The interrater reliability for the main analyses (i.e. including any lobar ICH; all deep and infratentorial anatomical categories (lentiform, caudate thalamus; brainstem; cerebellum); and uncertain location) was excellent (all kappa values>0.80) both in pair-wise between-rater comparisons and across all raters. The intrarater reliability was substantial to almost perfect (k=0.83; 95%CI: 0.77-0.88 and k=0.95; 95%CI: 0.92-0.96 respectively). All kappa statistics remained consistent for individual cerebral lobar regions. CONCLUSIONS: The CHARTS instrument can be used to reliably and comprehensively map the anatomical location of spontaneous ICH, and may be helpful for studying important questions regarding causes, risk factors, prognosis, and for stratification in clinical trials.

Quantitative assessment and correlation analysis of cerebral microbleed distribution and leukoaraiosis in stroke outpatients.

OBJECTIVE: Cerebral microbleeds (CMBs) are bleeding events associated with cerebral small vessel disease (SVD). Strictly lobar CMBs and strictly deep CMBs are likely caused by cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy, respectively. Leukoaraiosis (LA) reflects an ischaemic change in SVD, and LA severity has been correlated with CMBs. However, whether different locations (aetiologies) of CMBs correlate with LA is unknown. METHODS: Patients receiving brain MRI and tbl2*-weighted gradient-recalled echo scans in a stroke outpatient department were screened for CMBs. The MRI results of the patients with CMBs were sent to investigators for further review and were evaluated using the Microbleed Anatomical Rating Scale. Cerebral microbleed severity was graded using a numerical scale. Leukoaraiosis severity was assessed using the Fazekas scale. RESULTS: Cerebral microbleeds were observed in 14.6% of the 1289 screened patients. The CMB incidence increased with age (in years, < 50: 1.3%; 50-59: 10.7%; 60-69: 17.6% and ≥ 70: 23.6%; P = 0.000). The CMB locations were distributed as follows: 23.4% strictly lobar, 12.2% strictly deep, 6.4% strictly infratentorial and 58.0% mixed. Cerebral microbleed severity correlated with the total Fazekas scale score. The numbers of lobar, deep and infratentorial CMBs correlated with the total Fazekas scale score. The mixed CMB group displayed a significantly higher Fazekas scale score than the strictly lobar CMB group (P = 0.000). DISCUSSION: Cerebral microbleed incidence increased with age. Mixed CMB type displayed the highest incidence. The severity and number of CMBs at any location correlated with LA severity. These results suggested interactions between hypertension and CAA during LA progression.

Should DWI MRI be the primary screening test for stroke?

Patients presenting with focal neurological symptoms may suffer from ischemic stroke, intracerebral hemorrhage, or stroke mimics. Such patients are usually screened with a noncontrast-enhanced computed tomography to rule out hemorrhage and to detect early signs of ischemia. However, the sensitivity of noncontrast-enhanced computed tomography for acute stroke is far inferior to that of diffusion-weighted magnetic resonance imaging and the latter is also very sensitive for identifying acute intracerebral hemorrhage. Most centers perform a magnetic resonance imaging stroke protocol that takes long to accomplish and may therefore delay therapy. Herein, we propose that a short diffusion-weighted imaging-only magnetic resonance imaging protocol can effectively differentiate ischemic stroke from intracerebral hemorrhage and stroke mimics and could therefore be used as the first line screening test for stroke. Adopting such a screening strategy will result in increased diagnostic accuracy and avoidance of unnecessary treatment of stroke mimics with thrombolysis but may come at the increased cost of performing a magnetic resonance imaging at the emergency department. Whether such a strategy will be cost effective or not remains to be tested in future studies.

Detection of microhemorrhage in posterior reversible encephalopathy syndrome using susceptibility-weighted imaging.

BACKGROUND AND PURPOSE: PRES-related vasogenic edema is potentially reversible while hemorrhage occurs in only 15.2%-17.3% of patients. However, the true incidence of hemorrhage could be higher when SWI is considered. Thus, we set out to determine the incidence of MH, SAH, and IPH in PRES by using SWI and to particularly evaluate whether such MHs are reversible. MATERIALS AND METHODS: Thirty-one patients with PRES and SWI were included, 17 having follow-up SWI. Two neuroradiologists reviewed SWI, FLAIR, DWI, and CE-T1WI. The presence and number of MHs (<5 mm) on SWI, SAH, and IPH (>5 mm) were recorded at presentation and follow-up. We evaluated associations between the presence of MH on SWI and DWI lesions, SAH, IPH, contrast enhancement, and MR imaging severity. RESULTS: Hemorrhage was present in 20/31 patients (64.5%), with MHs on SWI in 18/31 (58.1%) at presentation and in 11/17 (64.7%) at follow-up. SAH was present in 3/31 on SWI and 4/31 on FLAIR, while 2/31 had IPH. At follow-up, no patients had acquired new MHs; 2/5 MHs in 1 patient resolved. Four patients with available SWI before PRES developed MHs after PRES onset. No association was found between the presence of MHs on SWI and DWI, SAH, IPH, enhancement, and MR imaging severity (all P > .05). CONCLUSIONS: SWI showed a higher rate of MH than previously described, underscoring the potential of SWI in evaluating PRES. Such MHs typically persist and may develop after PRES onset. However, the clinical relevance of MHs in PRES is yet to be determined. We propose that MHs in PRES relate to endothelial cell dysfunction.

Evaluation of intraventricular hemorrhage assessment methods for predicting outcome following intracerebral hemorrhage.

OBJECT: Intraventricular hemorrhage (IVH) associated with intracerebral hemorrhage (ICH) is an independent predictor of poor outcome. Clinical methods for evaluating IVH, however, are not well established. This study sought to determine the best IVH grading scale by evaluating the predictive accuracies of IVH, Graeb, and LeRoux scores in an independent cohort of ICH patients with IVH. Subacute IVH dynamics as well as the impact of external ventricular drain (EVD) placement on IVH and outcome were also investigated. METHODS: A consecutive cohort of 142 primary ICH patients with IVH was admitted to Columbia University Medical Center between February 2009 and February 2011. Baseline demographics, clinical presentation, and hospital course were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Intraventricular hemorrhage was categorized according to IVH, Graeb, and LeRoux scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge were assessed using the modified Rankin Scale (mRS). Receiver operating characteristic analysis was used to determine the predictive accuracies of the grading scales for poor outcome (mRS score ≥ 3). RESULTS: Seventy-three primary ICH patients (51%) had IVH. Median admission IVH, Graeb, and LeRoux scores were 13, 6, and 8, respectively. Median IVH, Graeb and LeRoux scores decreased to 9 (p = 0.005), 4 (p = 0.002), and 4 (p = 0.003), respectively, within 6 days of ictus. Poor outcome was noted in 55 patients (75%). Areas under the receiver operating characteristic curve were similar among the IVH, Graeb, and LeRoux scores (0.745, 0.743, and 0.744, respectively) and within 6 days postictus (0.765, 0.722, 0.723, respectively). Moreover, the IVH, Graeb, and LeRoux scores had similar maximum Youden Indices both at admission (0.515 vs 0.477 vs 0.440, respectively) and within 6 days postictus (0.515 vs 0.339 vs 0.365, respectively). Patients who received EVDs had higher mean IVH volumes (23 ± 26 ml vs 9 ± 11 ml, p = 0.003) and increased incidence of Glasgow Coma Scale scores < 8 (67% vs 38%, p = 0.015) and hydrocephalus (82% vs 50%, p = 0.004) at admission but had similar outcome as those who did not receive an EVD. CONCLUSIONS: The IVH, Graeb, and LeRoux scores predict outcome well with similarly good accuracy in ICH patients with IVH when assessed at admission and within 6 days after hemorrhage. Therefore, any of one of the scores would be equally useful for assessing IVH severity and risk-stratifying ICH patients with regard to outcome. These results suggest that EVD placement may be beneficial for patients with severe IVH, who have particularly poor prognosis at admission, but a randomized clinical trial is needed to conclusively demonstrate its therapeutic value.

Semi-automatic volumetric assessment of perihemorrhagic edema with computed tomography.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) shows perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH) with high contrast, but the procedure is often difficult or not available for clinical use. The aim of the present study was to establish and validate an observer independent method for quantification of PHE on computed tomography (CT) by comparing with simultaneously performed MRI. METHODS: Patients with spontaneous supratentorial ICH were included. Twenty-two patients received coregistered MRI and CT on day 1, and 27 patients on day 5 after admission. Volumes for PHE and ICH were measured (i) manually on CT, (ii) manually on MRI (fluid-attenuated inversion recovery sequence), and (iii) threshold based on CT. To identify optimal threshold values (Hounsfield units) for best correlation of CT with MRI, upper and lower thresholds were adjusted gradually until the PHE volume on CT best fitted the PHE volume on MRI. The established threshold range was prospectively validated in another 15 patients. RESULTS: A threshold range 5-33 Hounsfield units (HU) resulted in best correlation both on days 1 and 5. Using these thresholds in the validation group, PHE volumes on CT and MRI were highly comparable (31 ± 26 ml vs. 30 ± 27 ml) with good correlation (R(2) = 0.96, P < 0.01) and high inter- (0.96) and intraobserver (0.96) reliability. Manually traced PHE on CT was significantly larger (37.3 ± 37 ml vs. 30 ± 27 ml, P < 0.01) with worse inter- (0.89) and intraobserver (0.90) reliability. CONCLUSIONS: Threshold-based CT volumetry of PHE with a threshold range 5-33 HU is a reliable and observer independent method for quantification of PHE after spontaneous ICH.

Use of MRI in the assessment of patients with stroke.

Multimodal neuroimaging is assuming an increasingly important role in the initial evaluation and management of acute stroke patients in parallel with the expansion of therapeutic options. Multimodal MRI can identify the type of stroke (ischemia or hemorrhage), severity and location of the lesion, the patency of the intracranial vessels, the degree of cerebral perfusion, and the presence and size of the ischemic penumbra. This information can be used to guide both acute and long-term treatment decisions for stroke patients.

Asymptomatic hemorrhagic transformation of infarction and its relationship with functional outcome and stroke subtype: assessment from the Tinzaparin in Acute Ischaemic Stroke Trial.

BACKGROUND AND PURPOSE: Asymptomatic hemorrhagic transformation of infarction (AHTI) is common, but its risk factors and relationship with functional outcome are poorly defined. METHODS: The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial, a randomized controlled trial assessing tinzaparin (low molecular weight heparin) versus aspirin in 1484 patients with acute ischemic stroke. CT head scans (baseline, day 10) were adjudicated for the presence of hemorrhagic transformation. Stroke subtype was classified according to modified Trial of Org 10172 in Acute Stroke Treatment (small vessel, large vessel, cardioembolic) and the Oxfordshire Community Stroke Project (total anterior, partial anterior, lacunar, and posterior circulatory syndromes). Modified Rankin scale and Barthel Index were measured at 3 and 6 months. Analyses were adjusted for age, sex, severity, blood pressure, infarct volume, and treatment. Symptomatic hemorrhage was excluded. RESULTS: At day 10, AHTI did not differ between aspirin (300 mg; 32.8%) and medium-dose (100 IU/kg; 36.0%) and high-dose (175 IU/kg; 31.4%) tinzaparin groups (P = 0.44). Relative to lacunar stroke, AHTI on follow-up CT was significantly increased in total anterior circulation syndrome (odds ratio, 11.5; 95% CI, 7.1 to 18.7) and partial anterior circulation syndrome (odds ratio, 7.2; 95% CI, 4.5 to 11.4) stroke. Similarly, relative to small vessel disease, AHTI was increased in large vessel (odds ratio, 15.1; 95% CI, 9.4 to 24.3) and cardioembolic (odds ratio, 14.1; 95% CI, 8.5 to 23.5) stroke. After adjustment for infarct volume, the presence of AHTI was not associated with outcome at 3 or 6 months as measured by the modified Rankin Scale and Barthel Index. CONCLUSIONS: AHTI is increased in ischemic stroke with cortical syndromes and of large vessel or cardioembolic etiology. Heparin does not increase AHTI. AHTI is not associated with functional outcome.

Cerebral microhemorrhage and iron deposition in mild cognitive impairment: susceptibility-weighted MR imaging assessment.

PURPOSE: To test whether susceptibility-weighted magnetic resonance imaging at baseline may help predict cognitive decline. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. Thirty-five healthy control subjects and 69 patients with mild cognitive impairment were included. Patients with mild cognitive impairment underwent neuropsychologic follow-up after 1 year (40 patients with stable mild cognitive impairment, 27 with progressive mild cognitive impairment, and two lost to follow-up). Cerebral microhemorrhages were visually analyzed by two experienced neuroradiologists in consensus. Iron deposition in deep gray matter was assessed with voxel-wise and region-of-interest analysis after nonlinear spatial registration. In addition, individual classification of mild cognitive impairment was analyzed by using a support vector machine (SVM). RESULTS: At baseline, the number of cerebral microhemorrhages was significantly higher in the mild cognitive impairment group than in the control group (P < .01) but did not differ between the patients with stable and those with progressive mild cognitive impairment. Compared with the control group, patients with mild cognitive impairment had increased iron concentration in the right pallidum (P < .01) and right substantia nigra (P < .01) but decreased concentration in the right red nucleus (P < .05). The classification based on the SVM successfully helped discriminate patients with mild cognitive impairment from the healthy control subjects (accuracy, 84%; sensitivity, 89%; specificity, 85%) and those with stable from those with progressive mild cognitive impairment (accuracy, 85%; sensitivity, 84%; specificity, 83%). CONCLUSION: The findings reveal an accumulation of cerebral microhemorrhage in patients with mild cognitive impairment that is present at baseline, independent of subsequent cognitive decline, as well as an altered iron distribution in subcortical nuclei between the healthy control subjects and patients with mild cognitive impairment. Analysis of iron deposition at baseline performed with an SVM might help identify individual patients with mild cognitive impairment at risk for cognitive decline. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100612/-/DC1.

Value of cerebral microhemorrhages detected with susceptibility-weighted MR Imaging for prediction of long-term outcome in children with nonaccidental trauma.

PURPOSE: To determine the prevalence of parenchymal brain microhemorrhages (MHs) in infants with nonaccidental trauma (NAT) by using susceptibility-weighted (SW) magnetic resonance (MR) imaging and to assess whether the presence of MH results in improved prediction of the long-term neurologic outcome. MATERIALS AND METHODS: A retrospective case-control analysis of the data for 101 children aged 1-32 months with forensic pediatric specialist-confirmed NAT was performed with institutional review board approval. Sixty-two patients were boys (mean age, 8.4 months +/- 7.4 [standard deviation]), and 39 were girls (mean age, 7.4 months +/- 7.8). The imaging findings and clinical data of the children who were examined with SW imaging were collected. Exclusion criteria included pre-existing cognitive delays, central nervous system malformations, previous brain injuries, and/or birth before 30 weeks gestation. Dichotomized long-term neurologic outcomes (good [normal, mild disability, or moderate disability] versus poor [severe disability, vegetative state, or death]) at greater than or equal to 6 months (mean, 33 months; range 6-95 months) were available for 53 patients (36 boys [mean age, 7.3 months +/- 5.9]; 17 girls [mean age, 7.4 months +/- 7.9]; overall range, 2-32 months). Logistic regression was used to determine whether the presence of SW imaging-depicted MH, as compared with other radiologic findings, resulted in improved prediction of long-term neurologic outcome. RESULTS: Imaging findings showed that of the 101 patients, 29 (29%) had MH at SW imaging, 66 (65%) had extraaxial hemorrhages, 52 (51%) had retinal hemorrhages, and 35 (35%) had evidence of acute ischemic injury. A significantly larger number of children with poor outcomes than children with good outcomes had brain MH (nine of 14 vs seven of 39; P = .001) and ischemic injury (13 of 14 vs 17 of 39; P = .006). Logistic regression analysis revealed presence of MH at SW imaging-followed by acute ischemic injury, initial Glasgow Coma Scale score, and age-to be the most significant single variable in the final model, with an overall predictive accuracy of 92.5%. CONCLUSION: Presence of intraparenchymal brain MH in children with NAT, as detected on SW images, correlates with significantly poor long-term neurologic outcome, improves outcome prediction compared with the predictions made by using other tested clinical and imaging findings, and is most predictive when combined with presence of ischemic injury.

Cost-effectiveness of patient selection using penumbral-based MRI for intravenous thrombolysis.

BACKGROUND AND PURPOSE: Better selection of patients for intravenous recombinant tissue plasminogen activator (IV tPA) treatment may improve clinical outcomes. We examined the cost-effectiveness of adding penumbral-based MRI to usual computed tomography (CT)-based methods to identify patients for IV tPA treatment. METHODS: A decision-analytic model estimated the lifetime costs and outcomes associated with penumbral-based MRI selection in a patient population similar to that enrolled in the IV tPA clinical trials. Inputs were obtained from published literature, clinical trial data, claims databases, and expert opinion. Outcomes included cost per life-year saved and cost per quality-adjusted life-year (QALY) gained. Costs and outcomes were discounted at 3% annually. Sensitivity analyses were conducted. RESULTS: The addition of penumbral-based MRI selection increased total cost by $103 over the patient's remaining lifetime. Penumbral-based MRI selection resulted in favorable outcomes (modified Rankin Scale

[Silent microhemorrhages in patients with symptomatic cerebrovascular disease]. / Microsangrados silentes en pacientes con enfermedad cerebrovascular sintomática.

INTRODUCTION: T2*-weighted gradient echo MRI sequences (T2*-MRI) have made it possible to detect cerebral microhemorrhages (MH) that have been considered as subclinical but whose clinical significance is largely unknown. OBJECTIVE: To establish the frequency of MH in a sample of consecutive symptomatic cerebrovascular disease (SCD) patients, analyzing its associations with different vascular risk factors (VRF) and its clinical significance. METHODS: A total of 198 patients with SCD were consecutively examined using T2*-MRI. Preferential location of MH and associations between MH presence and MH number with VRF, previous antithrombotic treatment and SCD subtypes were analyzed. RESULTS: A total of 52.5% of our patients had MH. The highest frequency of MH was found in hemorrhagic strokes (72.2%), Transitory ischemic attack (TIA) (42.9%) being the group with the lowest frequency. According to the bivariate analysis, the factors associated with the presence of MH were elderly age (72.4+/-10.5 vs 67.7+/-12.7; p 0.004), hypertension (65.4 vs 51.1%; p 0.041), diabetes (35.6 vs 22.3 %; p 0.041) and being under antithrombotic treatment (45.2 vs 28.7 %; p 0.017). According to the multivariate analysis, elderly age (p 0.019; OR: 1.03 [1.01- 1.06]), hypertension (p 0.032; OR: 1.97 [1.06-3.65]), use of antithrombotic treatment (p 0.038; OR: 1.95 [1.04-3.65]) and having a hemorrhagic stroke (p 0.028; OR: 3.63 [1.15- 11.46]) were predictors of MH presence. CONCLUSIONS: The presence of MH is frequent among patients with SCD, this being especially elevated in patients with hemorrhagic stroke. Cerebral MHs are classically associated with VRF classically related with small vessel disease and previously taking antithrombotic treatment.

Temporal MRI assessment of intracerebral hemorrhage in rats.

BACKGROUND AND PURPOSE: MRI was used to evaluate the effects of experimental intracerebral hemorrhage (ICH) on brain tissue injury and recovery. METHODS: Primary ICH was induced in rats (n=6) by direct infusion of autologous blood into the striatum. The evolution of ICH damage was assessed by MRI estimates of T(2) and T(1sat) relaxation times, cerebral blood flow, vascular permeability, and susceptibility-weighted imaging before surgery (baseline) and at 2 hours and 1, 7, and 14 days post-ICH. Behavioral testing was done before and at 1, 7, and 14 days post-ICH. Animals were euthanized for histology at 14 days. RESULTS: The MRI appearance of the hemorrhage and surrounding regions changed in a consistent manner over time. Two primary regions of interest were identified based on T(2) values. These included a core, corresponding to the bulk of the hemorrhage, and an adjacent rim; both varied with time. The core was associated with significantly lower cerebral blood flow values at all post-ICH time points, whereas cerebral blood flow varied in the rim. Increases in vascular permeability were noted at 1, 7, and 14 days. Changes in T(1sat) were similar to those of T(2). MRI and histological estimates of tissue loss were well correlated and showed approximately 9% hemispheric tissue loss. CONCLUSIONS: Although the cerebral blood flow changes observed with this ICH model may not exactly mimic the clinical situation, our results suggest that the evolution of ICH injury can be accurately characterized with MRI. These methods may be useful to evaluate therapeutic interventions after experimental ICH and eventually in humans.