Deep Intracerebral Hemorrhage Research Articles

Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage (P5.143)

Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage (P5.143)

Abstract W P257: Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage

Objectives: Intracerebral hemorrhage (ICH) patients with CT angiography (CTA) spot sign are at increased risk of hematoma expansion and poor outcome. Since ICH is often the acute manifestation of a chronic cerebral vasculopathy, we investigated whether different clinical or imaging characteristics predict spot sign presence in patients with different underlying vasculopathies. Using ICH location as a surrogate for hypertension-related ICH and cerebral amyloid angiopathy-related ICH, we identified risk factors associated with spot sign. METHODS: We retrospectively analyzed a prospective cohort of consecutive spontaneous ICH patients with available CTA. Spot sign presence was ascertained by two independent readers blinded to clinical data. We assessed potential predictors of spot sign be performing uni- and multivariable logistic regression, analyzing deep and lobar ICH separately. RESULTS: 649 patients were eligible, 291 (45%) deep and 358 (55%) lobar ICH. Median time from symptom onset to CTA was 4.5 (IQR 5.2) and 5.7 (IQR 7.4) hours in patients with deep and lobar ICH, respectively. At least one spot sign was present in 76 (26%) deep and 103 (29%) lobar ICH patients. In mutivariable logistic regression, independent predictors of spot sign in deep ICH were warfarin (OR 2.82 [95%CI 1.06-7.57]; p=0.03), time from symptom onset to CTA (OR 0.9 [95%CI 0.81-0.97]; p=0.02), and baseline ICH volume (OR 1.27 [95%CI 1.14-1.43]; p=2.5E-5; per 10 mL increase). Predictors of spot sign in lobar ICH were preexisting dementia (OR 2.7 [95%CI 1.15-6.43]; p=0.02), warfarin (OR 4.01 [95%CI 1.78-9.29]; p=0.009), and baseline ICH volume (OR 1.27 [95%CI 1.17-1.39]; p=5.4E-8; per 10 mL increase). As expected, spot sign presence was a strong predictor of hematoma expansion in both deep (OR 3.52 [95%CI 1.72-7.2]; p=0.0005) and lobar ICH (OR 6.53 [95%CI 3.23-13.44]; p=2.2E-7). CONCLUSIONS: The most potent associations with spot sign are shared by deep and lobar ICH, suggesting that ICH caused by different vasculopathic processes share biological features. The relationship between preexisting dementia and spot sign in lobar ICH, but not deep ICH, suggests that ICH occurring in the context of more advanced cerebral amyloid angiopathy may be more likely to have prolonged bleeding.

Abstract W MP93: The STICH II Prognostic Score Predicts Outcomes in the ERICH Study

Introduction: The Surgical Trial in Lobar Intracerebral Hemorrhage (STICH II) investigators developed a pre-trial prognostic score based on Glasgow Coma Scale (GCS), age, and intracerebral hemorrhage (ICH) volume at randomization: 10 х GCS - age - 0·64 х ICH volume. The STICH II results demonstrate that lobar ICH subjects with a good prognostic score are more likely to have a good to moderate recovery. Our study implements this prognostic score in both lobar and deep supratentorial ICH in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort. Methods: ERICH subjects with a supratentorial ICH, presenting GCS, ICH volume, and 6-month mRS are included in the analysis. Exclusion criteria are primary IVH cases and withdrawal of care patients at time of hospital discharge (comfort care or hospice). Based on STICH II, a good prognostic score is >27.672. We define a good outcome as 6-month mRS <=3. Prediction of outcome is analyzed using ordinal logistic regression with a cumulative logit link and positive and negative predictive values (PPV and NPV). An odds ratio (OR) is computed to estimate the effect size. Results: A total of 584 subjects were included (mean age 60 years +/- 14.7; black 42%, Hispanic 32%, white 25%; 41% women). There were 392 (67.1%) deep ICH. The average ICH volume was 19.6 cc +/-22.8, and average GCS was 12.6 +/- 3.5. The prognostic score was predictive of mRS in both lobar (OR=5.5, p<0.0001) and deep (OR=6.3, p<0.0001) ICH (Table 1). PPV’s are lobar 71.5% and deep 68.1%; NPV’s are lobar 68.8% and deep 75.0%. Conclusions: ERICH subjects with either lobar or deep ICH and a good prognostic score are more likely to have a good to moderate outcome, define in our study as a 6-month mRS <=3. In addition, the ICH subjects with a poor prognostic score are more likely have a poor outcome. Our findings suggest that the STICH II prognostic score may be applicable in other cohorts of both lobar and deep ICH.

Abstract W P259: ICH &FUNC Scores in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study

Introduction: The Intracerebral Hemorrhage (ICH) Score and Functional Outcome (FUNC) Score are prediction scales used to estimate outcome. These scales have not yet been validated in large minority cohorts. Our goal was to evaluate the predictive ability of the ICH and FUNC Score for white, black, and Hispanic patients. Methods: ERICH is an ongoing study of genetic and environmental risk factors for spontaneous ICH. The analysis included 847 cases enrolled prior to 1/1/2013 that had chart abstraction, baseline interview, CT imaging, GCS, and 3-month follow-up data available. Spearman’s rank correlation was used to assess the correlation between each score and 3-month modified Rankin Scale (mRS) score by ethnicity. Regression models were used to determine the predictive ability of each score. Results: Patients analyzed were 42% non-Hispanic black, 34% Hispanic, and 24% non-Hispanic white. Black and Hispanic subjects were younger compared with white subjects (p<.0001) and had higher proportions of deep ICH (p=.0013). Spearman’s rank correlations for ICH Score/FUNC Score and mRS at 3 months post ICH were 0.53/0.53 for black subjects, 0.66/0.63 for Hispanics, and 0.55/0.54 for whites. Both ICH and FUNC Scores had better predictive ability for minorities compared with whites (ICH Score, B = 0.87 black, 1.02 Hispanic, 0.76 white, p<.0001; FUNC Score, B = 0.56 black, 0.65 Hispanic, 0.49 white, p<.0001). Multiple regression demonstrated independent contributions by both scores for each ethnicity. Figure 1 demonstrates distribution of mortality by score. Conclusions: Both the ICH Score and FUNC Score were independently predictive of functional outcome at 3 months. Importantly, each score exhibits higher predictive ability in minority populations compared with whites. Whether or not this difference is attributed to minority status or baseline differences in age or ICH location requires further study.

Antithrombotic medications and the etiology of intracerebral hemorrhage

To test the hypothesis that the effect of antithrombotic medications on the risk of intracerebral hemorrhage (ICH) varies according to the location of the hematoma. Consecutive patients with ICH were enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy). Multivariable logistic regression models served to examine whether risk factors for ICH and location of the hematoma (deep vs lobar) predict treatment-specific ICH subgroups (antiplatelets-related ICH and oral anticoagulants [OACs]-related ICH). A total of 870 (313 lobar ICH, 557 deep ICH) subjects were included. Of these, 223 (25.6%) were taking antiplatelets and 77 (8.8%) OACs at the time of stroke. The odds of antiplatelet-related ICH increased with aging (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.03-1.07) and hypertension (OR 1.86; 95% CI 1.22-2.85) but had no relation with the anatomical location of ICH. Conversely, lobar location of the hematoma was associated with the subgroup of OAC-related ICH (OR 1.70; 95% CI 1.03-2.81) when compared to the subgroup of patients taking no antithrombotic medications. Within the subgroup of patients taking OACs, international normalized ratio (INR) values were higher in those with lobar ICH as compared to those with deep ICH (2.8 ± 1.1 vs 2.2 ± 0.8; p = 0.011). The proportion of patients with lobar hematoma increased with increasing intensity of anticoagulation, with a ~2-fold increased odds of lobar compared to deep ICH (odds 2.17; p = 0.03) in those exposed to overanticoagulation (INR values >3.0). OACs, as opposed to antiplatelets, predispose to lobar location of brain hematomas according to a dose-response relationship.

Neuroimaging in Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is described as spontaneous extravasation of blood into the brain parenchyma. This clinical entity is present in 10% to 15% of all stroke cases1 in the Western population, with reported incidence rates higher in Asia.2–4 It is also associated with a higher mortality rate compared with either ischemic stroke (IS) or subarachnoid hemorrhage.5 ICH is classified according to its primary (80% to 85%) or secondary (15% to 20%) causes. More than 50% of primary ICH events are directly correlated with hypertension as a risk factor, whereas ≈30% are known to be associated with cerebral amyloid angiopathy (CAA). The causes of secondary ICH include hemorrhage conversion of IS, amyloid angiopathy, stimulant drugs, vascular malformations (aneurysms, arterovenous malformations, venous angioma, cavernoma, dural arteriovenous fistula), coagulopathy (hereditary, acquired, induced by anticoagulants or antiplatelets), neoplasms, trauma, vasculitis, Moyamoya disease, or sinus venous thrombosis (Table 1). View this table: Table 1. Intracerebral Hemorrhage (ICH) Classification According to Causes Currently, ICH is classified as either primary or secondary according to only causes. However, this classification does not take into account the inherent differences of underlying vascular pathologies. Hence, a more systematic stratification based on new criteria is currently being developed.1 Specifically, Meretoja et al6 have proposed the SMASH-U classification, based on the underlying diseases of ICH: Structural lesions (cavernomas and arterovenous malformations), Medication (anticoagulation), Amyloid angiopathy, Systemic diseases (liver cirrhosis, thrombocytopenia, and various rare conditions), Hypertension, and Undetermined causes. This classification has proven to be feasible and is also associated with survival prognosis.6 Another classification used in clinical practice distinguishes between deep and lobar ICHs according to location. Deep ICHs are located in the basal ganglia, thalamus, internal capsule, cerebellum, or brain stem and are generally related to hypertension. Whereas, lobar ICHs usually require more extensive diagnostic testing because …

COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy

Type IV collagen α1 and α2 chains form heterotrimers that constitute an essential component of basement membranes. Mutations in COL4A1, encoding the α1 chain, cause a multisystem disease with prominent cerebrovascular manifestations, including porencephaly, bleeding-prone cerebral small vessel disease, and intracranial aneurysms. Mutations in COL4A2 have only been reported in a few porencephaly families so far. Herein, we report on a young adult patient with recurrent intracerebral hemorrhage, leukoencephalopathy, intracranial aneurysms, nephropathy, and myopathy associated with a novel COL4A2 mutation. We extensively investigated a 29-year-old male patient with recurrent deep intracerebral hemorrhages causing mild motor and sensory hemisyndromes. Brain MRI showed deep intracerebral hemorrhages of different age, diffuse leukoencephalopathy, multiple cerebral microbleeds and small aneurysms of the carotid siphon bilaterally. Laboratory work-up revealed significant microscopic hematuria and elevation of creatine-kinase. Genetic testing found a de novo glycine mutation within the COL4A2 triple helical domain. The presented case completes the spectrum of cerebral and systemic manifestations of COL4A2 mutations that appears to be very similar to that in COL4A1 mutations. Therefore, we emphasize the importance of screening both COL4A1 and COL4A2 in patients showing recurrent intracerebral hemorrhage of unknown etiology, particularly if associated with leukoencephalopathy.

Clinical and Angiographic Features and Stroke Types in Adult Moyamoya Disease

This study was conducted to elucidate the association between clinical and angiographic characteristics and stroke types in adult Moyamoya disease that has been rarely evaluated. We analyzed the clinical and radiologic data obtained from a retrospective adult Moyamoya disease cohort with acute strokes, which were classified into 7 categories: large-artery infarct, hemodynamic infarct, perforator infarct, deep intracerebral hemorrhage, lobar intracerebral hemorrhage, intraventricular hemorrhage, and SAH. With conventional angiography, which was performed in the hemispheres with acute strokes, the Suzuki angiographic stage, intracranial aneurysm, major artery occlusion, and collateral vessel development were confirmed within 1 month of stroke onset. This study included 79 patients with acute ischemic stroke and 96 patients with acute hemorrhagic stroke. The angiographic stage had a strong tendency to be more advanced in the hemorrhagic than the ischemic patients (P = .061). Intracranial aneurysms were more frequently found in the hemorrhagic than ischemic or control hemispheres (P = .002). Occlusions of the anterior cerebral artery and development of fetal-type posterior cerebral artery were more frequently observed in the hemorrhagic than the ischemic (P = .001 and .01, respectively) or control hemispheres (P = .011 and .013, respectively). MCA occlusion (P = .039) and collateral flow development, including the ethmoidal Moyamoya vessels (P = .036) and transdural anastomosis of the external carotid artery (P = .022), occurred more often in the hemorrhagic than the ischemic hemispheres. Anterior cerebral artery occlusion occurred more frequently in patients with deep intracerebral hemorrhage or intraventricular hemorrhage than with lobar intracerebral hemorrhage (P = .009). In adult Moyamoya disease, major artery occlusion and collateral compensation occurred more often in the hemorrhagic than in the ischemic hemispheres. Thus, anterior cerebral artery occlusion with or without MCA occlusion and intracranial aneurysms may be the main contributing factors to hemorrhagic stroke in adult patients with Moyamoya disease.

Location and characteristics of warfarin associated intracranial hemorrhage.

ObjectiveIn the so-called primary intracerebral hemorrhage (ICH), lobar and deep ICH were mainly due to cerebral amyloid angiopathy and deep perforating arterial disease. Our aim was to identify specifics of warfarin associated ICH (WAICH) and to focus on differences in susceptibility to warfarin according to the underlying vasculopathies, expressed by ICH location.Materials and MethodsWe identified all subjects aged ≥ 18 years who were admitted with primary ICH between January 1, 2007 and September 30, 2012. We retrospectively collected demographic characteristics, the presence of vascular risk factors and pre-ICH medication by chart reviews. We categorized ICH into four types according to location: lobar, deep, posterior fossa, and undetermined. We investigated characteristics (including hematoma volume and expansion) of ICH according to the location of ICH.Results WAICH accounted for 35 patients (5.6%) of 622 ICH cases. In WAICH, 13 patients (37.1%) had lobar ICH and 22 patients (60.0%) had non-lobar ICH. Compared to other locations of ICH, lobar ICH showed an excess risk of WAICH (OR 2.53, 95% CI 1.03-6.21, p = 0.042). The predictors of lobar location of ICH were warfarin (OR 2.29, 95% CI 1.05-5.04, p = 0.038) and diabetes mellitus (DM) (OR 0.54, 95% CI 0.29-0.98, p = 0.044). The lobar location of ICH showed significant association with larger hematoma volume (p = 0.001) and high ratio of hematoma expansion (p = 0.037) compared with other locations of ICH.ConclusionIn our study, warfarin showed significant association with lobar ICH and it caused larger hematoma volume and more expansion of hematoma in lobar ICH.

Arterial stiffness in patients with deep and lobar intracerebral hemorrhage.

Background and PurposeIntracerebral hemorrhage (ICH) accounts for approximately 10% of stroke cases. Hypertension may play a role in the pathogenesis of ICH that occurs in the basal ganglia, thalamus, pons, and cerebellum, but not in that of lobar ICH. Hypertension contributes to decreased elasticity of arteries, thereby increasing the likelihood of rupture in response to acute elevation in intravascular pressure. This study aimed to evaluate arterial stiffness (using the arterial stiffness index [ASI]) in patients with deep (putaminal and thalamic) ICH in comparison with patients with lobar ICH.MethodsWe enrolled 64 patients (mean±SD age: 69.3±10.7 years; 47 men and 17 women) among 73 who referred consecutively to our department for intraparenchymal hemorrhage and underwent brain computed tomography (CT) and cerebral angio-CT. In all the subjects, 24-hour heart rates and blood pressures were monitored. The linear regression slope of diastolic on systolic blood pressure was assumed as a global measure of arterial compliance, and its complement (1 minus the slope), ASI, has been considered as a measure of arterial stiffness.ResultsIn the patients with deep ICH, ASI was significantly higher than in the patients with lobar ICH (0.64±0.19 vs. 0.53±0.17, P=0.04).ConclusionsOur results suggest that in deep ICH, arterial stiffening represents a possible pathogenetic factor that modifies arterial wall properties and contributes to vascular rupture in response to intravascular pressure acute elevation. Therapeutic strategies that reduce arterial stiffness may potentially lower the incidence of deep hemorrhagic stroke.

943

Introduction: The optimal anticoagulation strategy for pediatric patients receiving extracorporeal membrane oxygenation (ECMO) is the subject of significant debate. Antithrombin (AT) has become an attractive adjunct therapy to traditional heparin, but its use remains quite variable amongst institutions. Methods: A retrospective, descriptive study was designed and institutional review board exemption obtained. Data were obtained from the Pediatric Health Information System (PHIS) database, an administrative database from 43 tertiary care children's hospitals in the United States for patients admitted from 2004-2011 who were 18 years of age or younger and placed on ECMO. Results: 7,083 patients were identified as having met study criteria. AT was utilized in only 5% of patients in 2004 versus 52% in 2011 (p<0.001). There was no change in the use of fresh frozen plasma or cryoprecipitate over time. The total number of patients receiving red blood cell transfusions decreased from 88.5% in 2004 to 68.4% in 2011 (p<0.001). The average adjusted cost of an ECMO course increased from $213,681 +/- $162,250 in 2004 to $351,735 +/- $361,280 in 2011 (p<0.001). Correlations were observed between the use of AT and the diagnosis of deep vein thrombosis (p<0.001), pulmonary embolism (p=0.001), cerebral infarction (p<0.001), intracerebral hemorrhage (p=0.037) and subdural hemorrhage (p=0.002). Overall patient mortality decreased from 44.46% in 2004 to 42.81% in 2011 (p=0.0084). Conclusions: Between 2004 and 2011, there was decreased mortality but increased cost of ECMO. During this time, AT use increased significantly. However, only red blood cell transfusions were decreased. Of note, there was an association between increasing use of AT and both thrombotic and hemorrhagic complications. Further investigation is warranted to better understand the role of AT in pediatric ECMO and whether or not it contributes to patient outcomes.

Natural history and prognostic value of corticospinal tract Wallerian degeneration in intracerebral hemorrhage.

BackgroundThe purpose of this study was to define the incidence, imaging characteristics, natural history, and prognostic implication of corticospinal tract Wallerian degeneration (CST‐WD) in spontaneous intracerebral hemorrhage (ICH) using serial MR imaging.Methods and ResultsConsecutive ICH patients with supratentorial ICH prospectively underwent serial MRIs at 2, 7, 14, and 21 days. MRIs were analyzed by independent raters for the presence and topographical distribution of CST‐WD on diffusion‐weighted imaging (DWI). Baseline demographics, hematoma characteristics, ICH score, and admission National Institute of Health Stroke Score (NIHSS) were systematically recorded. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS) and the motor‐NIHSS. Twenty‐seven patients underwent 93 MRIs; 88 of these were serially obtained in the first month. In 13 patients (48%), all with deep ICH, CST‐WD changes were observed after a median of 7 days (interquartile range, 7 to 8) as reduced diffusion on DWI and progressed rostrocaudally along the CST. CST‐WD changes evolved into T2‐hyperintense areas after a median of 11 days (interquartile range, 6 to 14) and became atrophic on MRIs obtained after 3 months. In univariate analyses, the presence of CST‐WD was associated with poor functional outcome (ie, mRS 4 to 6; P=0.046) and worse motor‐NIHSS (5 versus 1, P=0.001) at 3 months.ConclusionsWallerian degeneration along the CST is common in spontaneous supratentorial ICH, particularly in deep ICH. It can be detected 1 week after ICH on DWI and progresses rostrocaudally along the CST over time. The presence of CST‐WD is associated with poor motor and functional recovery after ICH.

Predictors of Hematoma Volume in Deep and Lobar Supratentorial Intracerebral Hemorrhage

Hematoma volume is the strongest predictor of outcome in intracerebral hemorrhage (ICH). Despite known differences in the underlying biology between deep and lobar ICHs, limited data are available on location specificity of factors reported to affect hematoma volume. To evaluate whether determinants of ICH volume differ by topography, we sought to estimate location-specific effects for potential predictors of this radiological outcome. Prospective cohort study. Academic medical center. A total of 744 supratentorial primary ICH patients (388 deep and 356 lobar) aged older than 18 years admitted between January 1, 2000, and December 31, 2010. Intracerebral hemorrhage volume measured from the computed tomography scan obtained on presentation to the emergency department. Linear regression analysis, stratified by ICH location, was implemented to identify determinants of log-transformed ICH volume. Median ICH volume was larger in lobar hemorrhages (39 mL; interquartile range, 16-75 mL) than in deep hemorrhages (13 mL; interquartile range, 5-40 mL; P < .001). In multivariable linear regression, independent predictors of deep ICH volume were intensity of anticoagulation (β = 0.32; standard error [SE] = 0.08; P < .001; test for trend across 4 categories of the international normalized ratio), history of coronary artery disease (β = 0.33; SE = 0.17; P = .05), male sex (β = 0.28; SE = 0.14; P = .05), and age (β = -0.02; SE = 0.01; P = .001). Independent predictors of lobar ICH volume were intensity of anticoagulation (β = 0.14; SE = 0.06; P = .02) and antiplatelet treatment (β = 0.27; SE = 0.13; P = .03). Predictors of hematoma volume only partially overlap between deep and lobar ICHs. These findings suggest that the mechanisms that determine the extent of bleeding differ for deep and lobar ICHs. Further studies are needed to characterize the specific biological pathways that underlie the observed associations.

Prevalence of Hypertension in Deep and Lobar Intracerebral Hemorrhage in a Group of Iraqi Patients

Background: Non-traumatic Intracerebral Hemorrhage (ICH) results from rupture of blood vessels in the brain. ICH categories can also be considered as being either lobar in location or within the deep white matter. Although hypertension is a major risk factor for ICH in general[11], it is commonly considered to be associated more with patients having deep than with those having lobar haemorrhage.Objectives: We investigate the relationship between hypertension and deep versus lobar intracerebral hemorrhage (ICH).Methods: a retrospective review of records of 163 patients aged 18-89 years admitted to Al-Kadhimiya Teaching Hospital (January 2008 - October 2010) and diagnosed with ICH.Results: There was no significant relationship between hypertension in deep versus lobar intracerebral hemorrhage (p=0.814)Conclusions: Although the relation between hypertension and ICH was not found to be significant, our study suggests and recommends age-appropriate investigations for patients with ICH, as well as the need to promote patients’ education with regards to this disease and the importance of adherence to treatment of risk factors.

Nascent Lobar Microbleeds and Stroke Recurrences

Lobar microbleeds (MBs) are occasionally visible on gradient-echo T2*-weighted (T2*-w) magnetic resonance imagings (MRIs) in patients with deep intracerebral hemorrhages (ICHs). This study investigated the contribution of nascent lobar MBs to occurrences of deep ICHs. We prospectively analyzed nascent lobar MBs in patients admitted to our hospital who were treated with index strokes between April 2004 and November 2009. Numbers of nascent lobar MBs were counted on T2*-w MRI scans around 1 year after index strokes and compared with previous MRIs on admission. Deep ICH occurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. The odds ratio (OR) for deep ICH occurrence was derived from a multivariate logistic regression model using nascent lobar MBs and risk factors. We investigated MRIs (interscan interval: 14.6 ± 5.9 months) of 508 patients (207 women, 68.9 ± 11.5 years), with a follow-up period of 44.1 ± 15.4 months. Repeated T2*-w MRIs demonstrated 157 nascent lobar MBs in 62 of 508 patients. The occurrence rate of deep ICHs (1.9% per year) was significantly higher in patients with nascent lobar MBs than in those without (.5% per year, P = .012). Multivariate analyses revealed that the rate of nascent lobar MBs was significantly elevated in patients with deep ICH-type stroke recurrences (OR: 3.85, P = .020), adjusted by the presence of hypertension, diabetes mellitus, use of antithrombotic drugs, severity of white matter lesions, age, and gender. Though a cohort study limited the power of analyses, our findings suggested that lobar MBs might be associated with deep ICH.

Nascent Deep Microbleeds and Stroke Recurrences

Cerebral microbleeds (MBs) on gradient echo T2*-weighted magnetic resonance imaging (MRI) scans are associated with the severity of cerebral microangiopathies. This study investigated the contributions of nascent deep MBs to stroke recurrence. We prospectively analyzed nascent deep MBs in patients admitted to our hospital who were treated for index strokes between April 2004 and November 2009. The number of nascent deep MBs was counted on T2*-weighted MRI scans around 1 year after the index strokes, and compared to previous MRIs on admission. Stroke recurrence-free rate curves were generated using the Kaplan-Meier method using the log-rank test. The odds ratio for nascent deep MBs was derived using a multivariate logistic regression model that was based on recurrent strokes and other risk factors. We evaluated the MRIs (interval between MRIs 14.6 ± 5.9 months) of 508 patients (207 women; 68.9 ± 11.5 years), with a follow-up period of 44.1 ± 15.4 months. Repeated T2*-weighted MRI scans revealed 256 nascent deep MBs in 116 of 508 patients. The incidence of deep intracerebral hemorrhage was significantly greater in patients with nascent deep MBs than those without (2.0% vs 0.4% per year, respectively; P < .0001). Multivariate analyses revealed that the rate of nascent deep MBs was significantly elevated in patients whose stroke recurrences took the form of deep intracerebral hemorrhages (odds ratio 5.41; P = .007), when adjusted for hypertension, preexisting MBs, and other risk factors. Our findings suggested that nascent deep MBs might be associated with stroke recurrence, in particular with deep intracerebral hemorrhage.

Obesity and the Risk of Intracerebral Hemorrhage

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. 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. 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). 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.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Abstract 118: Burden of Blood Pressure-Related Alleles is Associated with Larger Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage

Purpose: Intracerebral hemorrhage (ICH) is the acute manifestation of a progressive disease of the cerebral small vessels. The severity of this disease appears to influence not only risk of ICH, but also the size of the hematoma. As the burden of high blood pressure(BP)-associated alleles is associated with hypertension-related end-organ damage, we sought to determine if this burden influences ICH admission hematoma volume (AHV). Methods: Prospective study undertaken in 441 ICH patients of European ancestry (210 deep and 231 lobar intracranial hematomas). Forty-three single-nucleotide polymorphisms (SNPs) known to be associated with high BP were genotyped in Illumina610-Quad. Single-SNP association analyses with AHV were performed using linear regression. Subsequently, a genetic risk score was calculated as the sum of the products generated by multiplying, at each of the 43 loci, the number risk alleles times the reported effect of that allele on BP. The score was utilized as the independent variable of univariate and multivariate regression models for 2 outcomes: AHV and poor clinical outcome (modified Rankin Scale 3-6). Principal components analysis was utilized to account for population structure. Results: Individually assessed, no single SNP was associated with AHV. In univariate linear regression, the genetic risk score was associated with AHV in all (deep and lobar) and deep locations (Figure 1), but not in lobar hemorrhages. In multivariate regression analyses, each additional standard deviation of the genetic risk score increased mean deep AHV by 21% (or 2.7-milliliter increase, beta=0.21, standard error=0.08, p=0.01) and risk poor clinical outcome by 55% (odds ratio=1.55, 95% confidence interval 1.05-2.28, p=0.03). No significant associations were observed when considering all (deep and lobar) and lobar hemorrhages. Conclusion: In deep ICH, increasing numbers of high BP-related alleles are associated with larger AHV and poor clinical outcome.

Abstract WP306: Determinants of Hematoma Volume Differ by Location in Intracerebral Hemorrhage

Background and purpose: Admission hematoma volume (AHV) is the strongest predictor of outcome in intracerebral hemorrhage (ICH). Mounting evidence suggests that the biological mechanisms underlying ICH occurrence differ by bleeding location. We aimed to assess if the determinants of AHV vary by bleeding topography, and to estimate location-specific effects for warfarin, a factor known to influence AHV. Methods: Retrospective analysis of 902 ICH cases (388 deep, 356 lobar and 58 cerebellar) enrolled in a single-center, prospective study of ICH. AHV was measured in the first available computed tomography using semi-automated, computer-assisted volumetric methods. Univariate and multivariate linear regression analyses, stratified by ICH location, were implemented to model natural log-transformed AHV as a function of covariates. Admission International Normalized Ratio (INR) values were utilized to establish intensity of anticoagulation. INR was categorized in &lt;1.2, 1.2-2, 2.1-3 and &gt;3. Results: AHV medians (interquartile range) for deep, lobar and cerebellar ICH were 13 (35), 39 (59) and 13 (24), respectively (p&lt;0.0001). Within these location categories, 18, 21 and 29% of subjects were on warfarin, and 36, 42 and 35% had died at 90 days, respectively. In multivariate analysis, independent predictors of deep AHV were male sex (beta[β]=0.28, standard error[SE]=0.14, p=0.05), history of coronary artery disease (β=0.33, SE=0.17, p=0.05), and degree of anticoagulation (β=0.32, SE=0.08, p=0.00005, tested for trend across INR categories); predictors of lobar AHV were antiplatelet treatment (β=0.27, SE=0.13, p=0.03) and degree of anticoagulation (β=0.14, SE=0.06, p=0.02, comparing INR &lt;1.2 to &gt;3); and predictors of cerebellar AHV were effective anticoagulation (β=0.99, SE=0.41, p=0.02, comparing INR &lt;2 vs INR &gt;2) and statin treatment (β=-1.21, SE=0.38, p=0.001). Conclusion: Determinants of AHV differ by ICH location. Anticoagulation is associated with larger AHV in all locations, but the strength and shape of the dose-response curve for this relationship varies with ICH topography. Pre-ICH treatment with antiplatelets and statins was associated with increased mean lobar AHV and decreased mean cerebellar AHV, respectively.