Sensitivity of the Edinburgh Criteria for Lobar Intracerebral Hemorrhage in Hereditary Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: The Edinburgh computed tomography and genetic criteria enable diagnosis of cerebral amyloid angiopathy (CAA) associated lobar intracerebral hemorrhage (ICH) but have not been validated in living patients. We assessed the sensitivity of the Edinburgh criteria in patients with acute lobar ICH due to Dutch-type hereditary CAA; a genetic and pure form of CAA. METHODS: We retrospectively analyzed computed tomography-scans from a cohort of consecutive Dutch-type hereditary CAA patients who presented with ≥1 episode(s) of acute lobar ICH at the Leiden University Medical Center. Presence of subarachnoid hemorrhage (SAH) and finger-like projections (FLP) were determined. Association of SAH and FLP with ICH volume was analyzed using multivariate linear regression. RESULTS: We included 55 Dutch-type hereditary CAA patients (mean age 56 years, 55% men) with a total of 107 episodes of acute lobar ICH. SAH was present in 82/107 (76%) and FLP in 62/107 (58%), resulting in a sensitivity of 76% for SAH and 58% for FLP. In 56 (52%), both markers were present. Nineteen (18%) lobar ICH showed no SAH extension or FLP. ICH volume was significantly associated with presence of SAH (median volume 4 versus 28 mL; P=0.001) and presence of FLP (median volume 7 versus 39 mL; P<0.001). With an ICH volume of ≥40 mL, the sensitivity of the presence of both SAH and FLP was >81% (95% CI, 70%-92%), whereas in ICH volumes <15 mL the sensitivity was <50%. CONCLUSIONS: The computed tomography-based Edinburgh criteria seem to be a sensitive diagnostic test for CAA-associated lobar ICH, although they should be used with caution in small-sized lobar ICH.

Hemorrhagic transformation after stroke: inter- and intrarater agreement.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a complication of stroke that can occur spontaneously or after treatment. We aimed to assess the inter- and intrarater reliability of HT diagnosis. METHODS: Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification of HT or of the presence (yes/no) of HT were systematically reviewed. A total of 18 raters independently examined 30 post-thrombectomy computed tomography scans selected from the Aspiration versus STEnt-Retriever (ASTER) trial. They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) (HI indicates hemorrhagic infarctions and PH indicates parenchymal hematomas) was and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement was measured with Fleiss' and Cohen's κ statistics. RESULTS: The systematic review yielded four studies involving few (≤3) raters with heterogeneous results. In our 18-rater study, agreement for the presence of HT was moderate [κ = 0.55; 95% confidence interval (CI), 0.41-0.68]. Agreement for ECASS classification was only fair for all five categories, but agreement improved to substantial (κ = 0.72; 95% CI, 0.69-0.75) after dichotomizing the ECASS classification into 0/HI1/HI2/PH1 versus PH2. The inter-rater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ = 0.70; 95% CI, 0.57-0.84). CONCLUSION: The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma.

SMASH-U versus H-ATOMIC: A Head-to-Head Comparison for the Etiologic Classification of Intracerebral Hemorrhage.

BACKGROUND: There is no agreement for the etiologic classification of patients with intracerebral hemorrhage (ICH). In a series of patients with ICH, we performed a randomized head-to-head comparison between the two recently proposed etiologic classification systems. METHODS: We evaluated patients registered in a prospective database of consecutive patients. A simplified H-ATOMIC classification defines 8 categories: hypertension, amyloid, tumor, oral anticoagulants, malformation, infrequent, cryptogenic, and combination. SMASH-U also defines 8 categories: structural, medication, amyloid, systemic, hypertension, and undetermined, and nonstroke and stroke-non-ICH. Experienced stroke neurologists applied both classification systems to a randomly assigned list of patients. The concordances between the 2 systems were analyzed. In a subset of patients, the percent of agreement and the inter-rater reliability (kappa coefficient) were calculated. RESULTS: A total of 156 patients (age 72.3 ± 13.5 years) were evaluated, and 54 of these patients were evaluated by 2 neurologists. Concordance (a patient classified in equivalent categories for both systems) was 63%. The percentage of interobserver agreement was 85.5% for SMASH-U and 87.6% for H-ATOMIC. Inter-rater reliability was similar for SMASH-U (kappa .82) and H-ATOMIC (kappa .76). The range of reliability among neurologists was .66-.93 for SMASH-U and .66-.94 for H-ATOMIC. CONCLUSIONS: The percentage agreement among investigators is remarkably high for both classification systems, and the inter-rater reliability is substantial to almost perfect for both systems. However, discrepancies between the 2 systems are frequent (in about one third of the patients) due to different categories and definitions.

Leading causes of preterm delivery as risk factors for intraventricular hemorrhage in very preterm infants: results of the EPIPAGE 2 cohort study.

BACKGROUND: Intraventricular hemorrhage is a major risk factor for neurodevelopmental disabilities in preterm infants. However, few studies have investigated how pregnancy complications responsible for preterm delivery are related to intraventricular hemorrhage. OBJECTIVE: We sought to investigate the association between the main causes of preterm delivery and intraventricular hemorrhage in very preterm infants born in France during 2011 between 22-31 weeks of gestation. STUDY DESIGN: The study included 3495 preterm infants from the national EPIPAGE 2 cohort study who were admitted to neonatal intensive care units and had at least 1 cranial ultrasound assessment. The primary outcome was grade I-IV intraventricular hemorrhage according to the Papile classification. Multinomial logistic regression models were used to study the relationship between risk of intraventricular hemorrhage and the leading causes of preterm delivery: vascular placental diseases, isolated intrauterine growth retardation, placental abruption, preterm labor, and premature rupture of membranes, with or without associated maternal inflammatory syndrome. RESULTS: The overall frequency of grade IV, III, II, and I intraventricular hemorrhage was 3.8% (95% confidence interval, 3.2-4.5), 3.3% (95% confidence interval, 2.7-3.9), 12.1% (95% confidence interval, 11.0-13.3), and 17.0% (95% confidence interval, 15.7-18.4), respectively. After adjustment for gestational age, antenatal magnesium sulfate therapy, level of care in the maternity unit, antenatal corticosteroids, and chest compressions, infants born after placental abruption had a higher risk of grade IV and III intraventricular hemorrhage compared to those born under placental vascular disease conditions, with adjusted odds ratios of 4.3 (95% confidence interval, 1.1-17.0) and 4.4 (95% confidence interval, 1.1-17.6), respectively. Similarly, preterm labor with concurrent inflammatory syndrome was associated with an increased risk of grade IV intraventricular hemorrhage (adjusted odds ratio, 3.4; 95% confidence interval, 1.1-10.2]). Premature rupture of membranes did not significantly increase the risk. CONCLUSION: Relationships between the causes of preterm birth and intraventricular hemorrhage were limited to specific and rare cases involving acute hypoxia-ischemia and/or inflammation. While the emergent nature of placental abruption would challenge any attempts to optimize management, the prenatal care offered during preterm labor could be improved.

Identification of Plasma Biomarkers of Human Intracerebral Hemorrhage Subtypes through Microarray Technology.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating form of stroke and depending on the underlying cause, primary ICH is mainly caused by hypertension (HTN-ICH) or cerebral amyloid angiopathy (CAA-ICH). Currently, neuroimaging markers are required to identify the pattern for each etiology. The discovery of new biomarkers to improve the management of this pathology is therefore needed. METHODS: A microarray analysis was carried out to analyze gene expression differences in blood samples from patients (>1.5 months since the last ICH event) who suffered a CAA-ICH and HTN-ICH, and controls. The results were replicated by quantitative polymerase chain reaction and the plasma protein level of the best candidate was measured with enzyme-linked immunosorbent assay. RESULTS: The microarray analysis and the validation study revealed an increase in Golgin A8 Family, Member A (GOLGA8A) mRNA and protein levels in ICH cases compared to controls (P < .01), although no differences were found between specific ICH etiologies. GOLGA8A plasma levels were also associated with the presence of multiple hemorrhages (P < .05). CONCLUSIONS: The GOLGA8A level was increased in the blood of patients who suffered a primary ICH. We did not, however, find any candidate biomarker that distinguished CAA-ICH from HTN-ICH. The role of GOLGA8A in this fatal disorder has yet to be determined.

Pattern and location of intracerebral hemorrhage in Enugu, South-East Nigeria: A review of 139 cases.

INTRODUCTION: The incidence rates and location of nontraumatic intracerebral hemorrhage (ICH) have been shown to vary between population and races. Knowledge of ICH patterns may give some insight into the etiology of ICH and help reduce its burden particularly among Africans where health infrastructure is poorly developed. We present a retrospective review of ICH using a modern neuroimaging technique. OBJECTIVES: To determine the pattern and location of ICH among patients presenting in a tertiary hospital in Enugu. METHODS: All the medical and computer tomography records of patients with a clinical diagnosis of hemorrhagic stroke with the location of hemorrhage clearly specified and complete patients' data were reviewed. The study duration was 11 years (January 2003 to December 2013). Relevant data were obtained, and statistical analysis was done using SPSS version 19 (IBM Corporation, New York, USA). RESULTS: A total of 139 (17.4%) out of 799 scans done over the period under review were analyzed. The frequency of lobar and deep cerebral hemorrhages (LH and DCHs) was 46.8% and 53.2%, respectively. The most common types of hemorrhage in men and women were deep cerebral (52.2% and 55.3%, respectively). Five percent (7/139) of all hemorrhages occurred in the cerebellum. Age distribution of the location of ICH shows that LHs peaked at 16-39 years while DCHs peaked at 40-49 years. There was not statistically significant difference between mean ages of occurrence of LH and hemorrhages of other locations. CONCLUSION: Frequency of LH and DCH varied with age as LH peaked before the age of 40 while deep cerebral at 40-49 years. The age distribution of different types of ICH may suggest a higher role of other factors apart from hypertension. Further studies are required to establish the risk factors of LH and DCHs in our environment.

Pathogenetical subtypes of recurrent intracerebral hemorrhage: designations by SMASH-U classification system.

BACKGROUND AND PURPOSE: Pathogenetic classification of intracerebral hemorrhage (ICH), using systems such as SMASH-U (structural vascular lesions, medication, cerebral amyloid angiopathy [CAA], systemic disease, hypertension, or undetermined), is important in predicting functional outcomes and mortality in patients with ICH. This study aimed to compare pathogenetic subtypes between the first and recurrent ICH. METHODS: This study obtained data related to 4578 consecutive acute patients with ICH from the National Taiwan University Hospital Stroke Registry during January 1995 to December 2013. Using the SMASH-U method, patients were classified into 6 subtypes. We then analyzed the outcomes of first-ever ICH cases and pathogenetic classification of recurrent ICH. RESULTS: Among 3785 patients who experienced first-ever ICH (male, 63.3%; mean age, 58.7±17.0 years), the most common cause was hypertensive angiopathy (54.9%), followed by CAA (12.2%), systemic disease (12.1%), undetermined (10.1%), structural vascular lesions (7.8%), and medication related (2.9%). In 185 cases of recurrent ICH, pathogenetic differences between the 2 ICH events were observed in 34 (18.4%) cases, most of which were CAA to hypertensive angiopathy (n=10) or vice versa (n=7). The rates of ICH recurrence were highest for systemic disease-related and CAA-related ICH at 1, 5, 10, and 15 years after the indexed ICH event. CONCLUSIONS: In approximately one fifth of the recurrent patients with ICH, pathogenetic differences were observed between initial and recurrent events, particularly among those with CAA. It is possible that some patients with ICH with concomitant hypertensive angiopathy and CAA may have been categorized as CAA by the SMASH-U method.

Oxfordshire Community Stroke Project classification improves prediction of post-thrombolysis symptomatic intracerebral hemorrhage.

BACKGROUND: The Oxfordshire Community Stroke Project (OCSP) classification is a simple stroke classification system with value in predicting clinical outcomes. We investigated whether and how the addition of OCSP classification to the Safe Implementation of Thrombolysis in Stroke (SITS) symptomatic intracerebral hemorrhage (SICH) risk score improved the predictive performance. METHODS: We constructed an extended risk score by adding an OCSP component, which assigns 3 points for total anterior circulation infarcts, 0 point for partial anterior circulation infarcts or lacunar infarcts. Patients with posterior circulation infarcts were assigned an extended risk score of zero. We analyzed prospectively collected data from 4 hospitals to compare the predictive performance between the original and the extended scores, using area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI). RESULTS: In a total of 548 patients, the rates of SICH were 7.3% per the National Institute of Neurological Diseases and Stroke (NINDS) definition, 5.3% per the European-Australasian Cooperative Acute Stroke Study (ECASS) II, and 3.5% per the SITS-Monitoring Study (SITS-MOST). Both scores effectively predicted SICH across all three definitions. The extended score had a higher AUC for SICH per NINDS (0.704 versus 0.624, P = 0.015) and per ECASS II (0.703 versus 0.612, P = 0.016) compared with the SITS SICH risk score. NRI for the extended risk score was 22.3% (P = 0.011) for SICH per NINDS, 21.2% (P = 0.018) per ECASS II, and 24.5% (P = 0.024) per SITS-MOST. CONCLUSIONS: Incorporation of the OCSP classification into the SITS SICH risk score improves risk prediction for post-thrombolysis SICH.

Damages of spinal cord in newborns after intraventricular hemorrhage.

We studied the spinal cords of 14 dead premature newborn with intraventricular hemorrhages. In all cases, grade III intraventricular hemorrhage was followed by the translocation of blood into the subarachnoid space of the cervical, dorsal, and lumbar parts of the spinal cord. Ischemic changes were found in neurons of the cervical intumescence and other parts of the spinal cord. These changes are important during thanatogenesis. Three stages in the development of intraventricular hemorrhage were distinguished. Imperfections of clinical classification of this pathology were demonstrated.

[Not Available]. / L'hémorragie cérébrale.

Intracerebral hemorrhage (ICH) is one of the most severe forms of stroke, yet several factors continue to undermine effective patient management: (1) Contrary to ischemic stroke, no dedicated ICH classification has so far been established for routine clinical use. (2) The diagnostic workup for patients presenting with acute ICH has not been standardized (3) Specific ICH treatment options remain limited. (4) Major uncertainties exist regarding preventive interventions for unruptured, hemorrhage-prone lesions such as cerebral AVMs, aneurysms, and cavernous malformations. This paper summarizes recent progress in establishing an etiology-based ICH classification, a pragmatic stepwise algorithm for the diagnostic workup of ICH, and novel treatment strategies such as rapid blood pressure-lowering therapy for acute ICH.

Obesity and the risk of intracerebral hemorrhage: the multicenter study on cerebral hemorrhage in Italy.

BACKGROUND AND PURPOSE: The effect of obesity on the risk of intracerebral hemorrhage (ICH) may depend on the pathophysiology of vessel damage. To further address this issue, we investigated and quantified the correlations between obesity and obesity-related conditions in the causal pathways leading to ICH. METHODS: A total of 777 ICH cases ≥ 55 years of age (287 lobar ICH and 490 deep ICH) were consecutively enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy and compared with 2083 control subjects by a multivariate path analysis model. Separate analyses were conducted for deep and lobar ICH. RESULTS: Obesity was not independently associated with an increased risk of lobar ICH (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-1.01) or deep ICH (OR, 1.18; 95% CI, 0.95-1.45) when compared with control subjects. The path analysis confirmed the nonsignificant total effect of obesity on the risk of lobar ICH (OR, 0.77; 95% CI, 0.58-1.02) but demonstrated a significant indirect effect on the risk of deep ICH (OR, 1.28; 95% CI, 1.03-1.57), mostly determined by hypertension (OR, 1.07; 95% CI, 1.04-1.11) and diabetes mellitus (OR, 1.04; 95% CI, 1.01-1.07). Obesity was also associated with an increased risk of deep ICH when compared with lobar ICH (OR, 1.62; 95% CI, 1.14-2.31). CONCLUSIONS: Obesity increases the risk of deep ICH, mostly through an indirect effect on hypertension and other intermediate obesity-related comorbidities, but has no major influence on the risk of lobar ICH. This supports the hypothesis of different, vessel-specific, biological mechanisms underlying the relationship between obesity and cerebral hemorrhage.

Correlation between intracerebral hemorrhage score and surgical outcome of spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) comprises 10-15% of all strokes and has a higher risk of morbidity and mortality (40-45%). A simple and widely valid clinical grading scale, the Intracerebral Hemorrhage Score (ICH score) was developed to predict to outcome of spontaneous ICH. The aim of the present study was to assess the relation between the ICH score and the surgical outcome of ICH by Glasgow Outcome Scale (GOS) at the 30th post ictus day in our perspective. This prospective study was done during the period of April 2009 to October 2010 in Department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Forty three cases were enrolled by set inclusion and exclusion criteria. Intracerebral Hemorrhage Score was calculated during admission and the surgical outcome of ICH was determined by GOS by face to face or telephone interview using structured questionnaire on their 30th post ictus day. Correlation between the ICH score and the surgical outcome of ICH was done by Pearson's correlation coefficient test. Value of r was found to be -0.635 which was statistically highly significant (p = .001) and the relation was found to be negative. Higher ICH score had unfavorable outcome As correlation between the ICH score and the surgical outcome of ICH was found statistically highly significant, it can be used widely as a grading scale in preoperative counseling. The use of ICH score could improve standardization of clinical treatment protocols and clinical research studies in ICH.

SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to provide a simple and practical clinical classification for the etiology of intracerebral hemorrhage (ICH). METHODS: We performed a retrospective chart review of consecutive patients with ICH treated at the Helsinki University Central Hospital, January 2005 to March 2010 (n=1013). We classified ICH etiology by predefined criteria as structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). Clinical and radiological features and mortality by SMASH-U (Structural lesion, Medication, Amyloid angiopathy, Systemic/other disease, Hypertension, Undetermined) etiology were analyzed. RESULTS: Structural lesions, namely cavernomas and arteriovenous malformations, caused 5% of the ICH, anticoagulation 14%, and systemic disease 5% (23 liver cirrhosis, 8 thrombocytopenia, and 17 various rare conditions). Amyloid angiopathy (20%) and hypertensive angiopathy (35%) were common, but etiology remained undetermined in 21%. Interrater agreement in classifying cases was high (κ, 0.89; 95% CI, 0.82-0.96). Patients with structural lesions had the smallest hemorrhages (median volume, 2.8 mL) and best prognosis (3-month mortality 4%), whereas anticoagulation-related ICHs were largest (13.4 mL) and most often fatal (54%). Overall, median ICH survival was 5½ years, varying strongly by etiology (P<0.001). After adjustment for baseline characteristics, patients with structural lesions had the lowest 3-month mortality rates (OR, 0.06; 95% CI, 0.01-0.37) and those with anticoagulation (OR, 1.9; 1.0-3.6) or other systemic cause (OR, 4.0; 1.6-10.1) the highest. CONCLUSIONS: In our patients, performing the SMASH-U classification was feasible and interrater agreement excellent. A plausible etiology was determined in most patients but remained elusive in one in 5. In this series, SMASH-U based etiology was strongly associated with survival.

Systemic administration of urocortin after intracerebral hemorrhage reduces neurological deficits and neuroinflammation in rats.

BACKGROUND: Intracerebral hemorrhage (ICH) remains a serious clinical problem lacking effective treatment. Urocortin (UCN), a novel anti-inflammatory neuropeptide, protects injured cardiomyocytes and dopaminergic neurons. Our preliminary studies indicate UCN alleviates ICH-induced brain injury when administered intracerebroventricularly (ICV). The present study examines the therapeutic effect of UCN on ICH-induced neurological deficits and neuroinflammation when administered by the more convenient intraperitoneal (i.p.) route. METHODS: ICH was induced in male Sprague-Dawley rats by intrastriatal infusion of bacterial collagenase VII-S or autologous blood. UCN (2.5 or 25 µg/kg) was administered i.p. at 60 minutes post-ICH. Penetration of i.p. administered fluorescently labeled UCN into the striatum was examined by fluorescence microscopy. Neurological deficits were evaluated by modified neurological severity score (mNSS). Brain edema was assessed using the dry/wet method. Blood-brain barrier (BBB) disruption was assessed using the Evans blue assay. Hemorrhagic volume and lesion volume were assessed by Drabkin's method and morphometric assay, respectively. Pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) expression was evaluated by enzyme-linked immunosorbent assay (ELISA). Microglial activation and neuronal loss were evaluated by immunohistochemistry. RESULTS: Administration of UCN reduced neurological deficits from 1 to 7 days post-ICH. Surprisingly, although a higher dose (25 µg/kg, i.p.) also reduced the functional deficits associated with ICH, it is significantly less effective than the lower dose (2.5 µg/kg, i.p.). Beneficial results with the low dose of UCN included a reduction in neurological deficits from 1 to 7 days post-ICH, as well as a reduction in brain edema, BBB disruption, lesion volume, microglial activation and neuronal loss 3 days post-ICH, and suppression of TNF-α, IL-1ß, and IL-6 production 1, 3 and 7 days post-ICH. CONCLUSION: Systemic post-ICH treatment with UCN reduces striatal injury and neurological deficits, likely via suppression of microglial activation and inflammatory cytokine production. The low dose of UCN necessary and the clinically amenable peripheral route make UCN a potential candidate for development into a clinical treatment regimen.

Validity of HAT score for predicting symptomatic intracranial hemorrhage in acute stroke patients with proximal occlusions: data from randomized trials of sonothrombolysis.

BACKGROUND: The Hemorrhage after Thrombolysis (HAT) score has recently been introduced as a practical scale for risk stratification of intracranial hemorrhage (ICH) in patients receiving intravenous tissue plasminogen activator (tPA). We aimed to externally validate and evaluate the predictive ability of the HAT score in patients with proximal arterial occlusions (PAO) enrolled into randomized clinical trials of sonothrombolysis. METHODS: The HAT score (range 0, minimum risk, to 5, maximum risk) was retrospectively calculated for each patient using clinical trial data (baseline NIHSS, extent of hypodensity on CT, history of diabetes mellitus and serum glucose). Symptomatic ICH (sICH) was defined as imaging evidence of ICH with clinical worsening (NIHSS ≥ 4) within 72 h from stroke onset. The predictive ability of the HAT score for sICH and any ICH (both asymptomatic and symptomatic) was calculated using c statistics. RESULTS: A total of 161 tPA-treated patients (mean age 68 ± 13 years, 58% men, median NIHSS 16, interquartile range 9) with PAO were randomized in TUCSON (n = 35) and CLOTBUST (n = 126). sICH occurred in 9 (5.6%) cases, and 6 had asymptomatic ICH. The rates of sICH for the corresponding HAT scores were: HAT 0-1: 3%; 2: 9%; 3: 14%; 4-5: 14%. The risk of sICH (c statistic 0.72, 95% CI: 0.58-0.86; p = 0.027) and any ICH (c statistic 0.70, 95% CI: 0.58-0.82; p = 0.011) increased with higher HAT scores. Higher HAT scores were also associated with higher likelihood of persisting occlusion (c statistic 0.63, 95% CI: 0.54-0.72; p = 0.004). CONCLUSIONS: The HAT score has reasonable external validity for predicting the risk of sICH following intravenous thrombolysis in patients with PAO. Moreover, higher HAT scores appear to be associated with higher likelihood of persisting occlusion in tPA-treated patients.

A comparative evaluation of existing grading scales in intracerebral hemorrhage.

BACKGROUND: In recent years, a multitude of clinical grading scales have been created to help identify patients at greater risk of poor outcome following ICH. We sought to validate and compare eight of the most frequently used ICH grading scales in a prospective cohort. METHODS: Eight grading scales were calculated for 67 patients with non-traumatic ICH enrolled in the prospective intracerebral hemorrhage outcomes project (ICHOP) database. Receiver operating characteristic (ROC) analysis, including area under the curve (AUC) and maximum Youden Index were used to assess the ability of each score to predict in-hospital mortality, long-term (3 months) mortality, and functional outcome at 3 months (mRS ≥ 3). RESULTS: All scales demonstrated excellent to outstanding discrimination for in-hospital and long-term mortality, with no significant differences between them after controlling for the false discovery rate. All scales demonstrated acceptable to outstanding discrimination for functional outcome at 3 months, with the new ICH score demonstrating significantly lower AUC than 6 of the 8 scores. Essen ICH score was the only score to demonstrate outstanding discrimination for each outcome measure. CONCLUSION: Though significant differences were minimal in our cohort, we showed the existing selection of ICH grading scales to be useful in stratifying patients according to risk of mortality and poor functional outcome. Continued validation and comparison in large prospective cohorts will bring the goal of a singular prognostic model for ICH closer to fruition.

Clinical characteristics by topographical distribution of brain microbleeds, with a particular emphasis on diffuse microbleeds.

From the perspective of the underlying pathogenesis of primary intracerebral hemorrhage (pICH), the topographical distribution of brain microbleeds (MBs) is divided into the lobar area and the deep brain or infratentorial areas. We investigated clinical features, including ambulatory blood pressure (ABP), of patients with MBs distributed in both areas (diffuse MBs). A total of 124 patients with first-ever acute stroke were enrolled prospectively. Gradient-echo T2∗-weighted magnetic resonance imaging (MRI) was performed using a 1.5-T scanner. Patients were classified into 4 groups: MBs-negative group (n=68), those with MBs in lobar areas (lobar group; n=6), those with MBs in deep or infratentorial areas (deep or infratentorial group; n=31), and those with MBs in both areas (diffuse group; n=19). The admission casual BP (CBP) was recorded in all patients, and ABP was measured in the ischemic stroke patients. There were significant differences in the distribution of MBs (P=.004) among the 6 stroke subtypes. All stroke subtypes except transient ischemic attack had diffuse MBs; pICH had the highest prevalence of it (35%). The severity of white matter hyperintensity (WMH) differed among the 4 groups (P < .0001), with the diffuse group having the highest prevalence of early confluent (47%) and confluent types (21%). ABP and CBP were significantly higher in the deep and diffuse groups compared with the MBs-negative group, but did not differ between the lobar group and the MBs-negative group. Our data suggest that diffuse MBs are associated with hypertensive stroke, elevated BP, and severe WMH. The pathogenesis of diffuse MBs may be related to the more severe microangiopathy involved in hypertensive arteriopathy and cerebral amyloid angiopathy.

Deep versus Superficial Spontaneous Cerebellar Hemorrhages: Separated Vascular Etiologies with Different Clinical Consequences.

BACKGROUND: Spontaneous cerebellar hemorrhage (CH) is a critical neurosurgical event. It is usually categorized as a homogenous group under the general term of deep/nonlobar intracerebral hemorrhage. However, increasing evidence suggests it is composed of 2 subgroups, separated from each other by their anatomic location (deep vs. superficial), as well as by their vascular etiology (small vessel disease vs. cerebral amyloid angiopathy). OBJECTIVE: To identify any clinically significant differences between anatomically separated subgroups of CHs: deep versus superficial. METHODS: This is a retrospective study on patients who were diagnosed with spontaneous CHs at a single tertiary center. On the basis of the radiologic location of the hematoma, patients were divided into 2 groups: deep (group 1) and superficial (group 2). Computerized medical records were extracted for multiple variables. RESULTS: A total of 69 patients fulfilled the inclusion criteria. Fifty-three (77%) were in group 1, and 16 (23%) were in group 2. Having any vascular risk factor was associated with the highest odds ratio for having a deep CH. Morbid obesity (body mass index ≥30) and the use of antiplatelets were also associated with increased odds ratios. Group 1 is also associated with high prevalence of intraventricular hemorrhage, acute hydrocephalus, and less favorable outcome. CONCLUSIONS: This study supports the notion that CH is most likely a heterogenous condition, composed of 2 subgroups, separated from each other in terms of anatomic location, vascular etiologies, and clinical consequences. Further studies on large cohort of patients are needed in order to accurately define the subgroups of this life-threatening event.

Are radiation-induced cavernomas clinically relevant findings? Results from long-term follow-up with brain magnetic resonance imaging of childhood cancer survivors.

INTRODUCTION: Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. PATIENTS AND METHODS: We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into "high" (Zabramski type I, II or V) or "low" (type III or IV) risk of hemorrhage. RESULTS: 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. CONCLUSIONS: RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.