Lobar Hemorrhage Research Articles

Large APP locus duplication in a sporadic case of cerebral haemorrhage

We report a 54-year-old man who was admitted to the hospital because of acute neurological symptoms due to a cerebral haemorrhage. Postmortem brain examination revealed a lobar haemorrhage and advanced AD neuropathologic changes associated with severe cerebral amyloid angiopathy. Genetic study evidenced the presence of a large APP locus duplication (APPdup) in the patient and a PSEN1 p.E318G polymorphism in him and his older asymptomatic sibling. The APPdup spanned 14.5 Mb and blocks of segmental duplications were detected in the breakpoints. We propose the replication-based mechanism of Fork Stalling Template Switching (FoSTeS) to explain this APPdup rearrangement.

Management of spontaneous intracerebral hemorrhage - a review

Spontaneous intracerebral hemorrhage (SICH) is defined as a bleeding into the brain parenchyma which occurs in the absence of trauma or surgery. Medical and surgical management of SICH is complex. Medical management comprises of: treatment of arterial hypertension, treatment of increased intracranial pressure, anticonvulsant agents (recommended in supratentorial SICH). Many randomized studies have been conducted to compare surgical and medical management of SICH and the conclusions were not favourable to surgery. Still, early surgical intervention remains an option in some cases. Surgery should be considered in patients with moderate to large lobar or basal ganglia hemorrhages and those with progressive neurological deterioration. Patients with cerebellar hemorrhages larger than 3 cm, with brainstem compression and hydrocephalus and those exhibiting neurological deterioration should undergo surgical evacuation of the clot. Contraindications for surgery are: brainstem hemorrhages, small hemorrhages, elderly patients with Glasgow Coma Scale score less than 5. Evidence-based recommendations regarding the role of surgery in SICH are needed.

Cerebrovascular Complications in a Patient with Hereditary Hemorrhagic Telangiectasia (HHT, Rendu–Osler Disease)

the patient developed new symptoms of vertigo and a rightsided scotoma within 5 days due to an infarction of the left peripheral posterial cerebral artery (PCA) territory. Shortly after her release from the hospital, the patient was readmitted with paresis of the left arm. Both computed tomography (CT) and MRI showed a recurrent abscess and an infarction of the left PCA territory (Fig. 2). After subsequent resurgery and intravenous antibiosis, the paresis of the left arm improved. However, 2 weeks later, the patient presented with seizure and sensory aphasia. Besides a residual abscess in the resection cavity, MRI showed a new hemorrhagic infarction in the left temporal lobe and subarachnoidal hemorrhage, as well as thrombosis of the left Labbe vein and the left transverse and sigmoid sinus (Fig. 3). CT of the thorax revealed a 3.5-cm-measuring AVM in the left upper lobe as well as various smaller AVMs in both lungs. As the most probable origin of embolization, the AVM was occluded using an Amplatzer vascular plug (AVP) and coils in subsequent catheter angiography (Fig. 4). MRI of the brain 2 weeks later showed regressive edema in the region of surgery and around the hemorrhagic infarction. With mild aphasia, impaired short-term memory, scotoma, and a decrease in fine motor skills, but no paresis, the patient was released into rehabilitation in an otherwise good general condition.

Abstract W P246: Diagnostic Value of Lobar Hemorrhages for Cerebral Amyloid Angiopathy in Hospital and Community-based Individuals: A Pathological Correlation Study

Objectives: To determine and compare the accuracy of the Boston criteria for the diagnosis of cerebral amyloid angiopathy (CAA) applied to: 1) a large hospital-based cohort; 2) a cohort of community-dwelling individuals. Methods: Among patients seen at a single academic medical center and participants enrolled in the Framingham Heart Study (FHS) we identified all individuals having had brain MRI (including hemosiderin-specific sequences) and pathological assessment of CAA at age ≥55. CAA was defined as Vonsattel degree ≥2, except in non-autopsy studies, where any vascular amloyid deposition was considered diagnostic of CAA. We excluded cases with: 1) non-lobar ICH; 2) alternative clinical diagnosis for the lobar hemorrhage/es; 3) CAA-negative studies based on small brain biopsy samples (greater diameter <1 cm) or clot evacuations with none or rare vessels identified; 4) autopsy studies not grading CAA. We determined sensitivity and specificity of “possible CAA” (1 lobar hemorrhage) and “probable CAA” (>1 strictly lobar hemorrhage) in both cohorts. Results: The study included 143 cases: 96 from the hospital cohort (mean age at time of MRI 74.1±8.2 years, 47.9% women, 47.9% autopsy studies, 54.2% cases with any lobar microbleed, 44.8% with any lobar ICH) and 47 from FHS (mean age at time of MRI 83.4±10.9 years, 48.9% women, 100% autopsy studies, 17% cases with any lobar microbleed, no lobar ICH cases). Hospital cohort: CAA prevalence was 72.6%. Specificity/sensitivity of “possible CAA” and “probable CAA” were 78.2%/33.3% and 92%/57.7%. Community cohort: CAA prevalence was 47%. Specificity/sensitivity of “probable CAA” were 88%/3%. Discussion: Specificity of detection of multiple lobar hemorrhages on MRI (“probable CAA”) for moderate-severe CAA is similarly high in both hospital and community cohorts. This increases the opportunity to identify individuals with CAA for observational studies and emerging anti-amyloid therapeutic trials. In view of its poor sensitivity, “probable CAA” diagnosis represents an inadequate screening tool for exclusion of CAA in both populations.

Abstract 179: Racial-ethnic Blood Pressure Differences in Acute Intracerebral Hemorrhage.

Background: Intracerebral hemorrhage (ICH) incidence and hypertension prevalence vary among racial-ethnic groups. Elevated blood pressure (BP) is common following ICH, but there are few racial/ethnic comparisons of acute BP. This study assessed the BP response to acute ICH in a multi-ethnic population. Methods: We examined BP in the field (EMS), emergency department (ED) and at 24 hours after ICH in subjects enrolled in the Ethnic Racial Variations of Intracerebral Hemorrhage (ERICH) study. ERICH is a multi-center prospective case-control study of ICH in non-Hispanic whites (whites), non-Hispanic blacks (blacks) and Hispanics. Baseline characteristics and BP recordings by EMS, in the ED and at 24 hours were analyzed for group differences. Results: Of 1052 subjects enrolled, BP recordings were available by EMS in 370, ED in 1041 and at 24 hours in 1014 cases of which 24% were white, 42% black and 34% Hispanic. Whites were significantly older 68± 14 years than blacks (58±13 years) and Hispanics (59± 15 years) (p≤0.0001) and had more lobar hemorrhages (39% vs. 23% blacks and 26% Hispanics; p≤0.0001). Baseline differences included larger hematoma volumes, in whites, and more frequent hypertension history and substance use, including cocaine use and smoking, in blacks. Blacks and Hispanics had significantly higher EMS (p=0.0001) and ED (p=0.0001) systolic BPs compared to whites (blacks: 198± 39, 195± 37; Hispanics: 191± 41, 191± 39; whites: 173± 37, 176± 37 mmHg). At 24 hours blacks had a higher systolic BP (144± 25 mmHg; p=0.0014) than Hispanics and whites (139± 21 and 138± 22 mmHg). These differences remained significant after adjustment for baseline group differences, including lobar and deep location. In multivariate analysis, low GCS and being black were associated with a systolic BP> 140mmHg at 24h. Blacks were more likely to receive BP treatment in the ER when compared to whites and Hispanics (76% vs. 52% and 68%). Conclusion: We found significant differences in the acute BP response to ICH, with blacks and Hispanics having a higher systolic BP at acute presentation. At 24 hours systolic BP remained elevated in blacks. These findings contribute to our understanding of racial-ethnic differences in BP and identify groups at risk for continued BP elevation.

Assessment of the usefulness of magnetic resonance brain imaging in patients presenting with acute seizures

Magnetic Resonance Imaging (MRI) is increasingly available as a tool for assessment of patients presenting to acute services with seizures. We set out to prospectively determine the usefulness of early MRI brain in a cohort of patients presenting with acute seizures. We examined the MR imaging studies performed in patients admitted solely because of acute seizures to Cork University Hospital over a 12-month period. The main aim of the study was to determine if the MRI established the proximate cause for the patient's recent seizure. We identified 91 patients who underwent MRI brain within 48 h of admission for seizures. Of the 91 studies, 51 were normal (56 %). The remaining 40 studies were abnormal as follows: microvascular disease (usually moderate/severe) (n = 19), post-traumatic gliosis (n = 7), remote symptomatic lesion (n = 6), primary brain tumour (n = 5), venous sinus thrombosis (n = 3), developmental lesion (n = 3), post-surgical gliosis (n = 3) and single cases of demyelination, unilateral hippocampal sclerosis, lobar haemorrhage and metastatic malignant melanoma. Abnormalities in diffusion-weighted sequences that were attributable to prolonged ictal activity were seen in nine patients, all of who had significant ongoing clinical deficits, most commonly delirium. Of the 40 patients with abnormal MRI studies, seven patients had unremarkable CT brain. MR brain imaging revealed the underlying cause for acute seizures in 44 % of patients. CT brain imaging failed to detect the cause of the acute seizures in 19 % of patients in whom subsequent MRI established the cause. This study emphasises the importance of obtaining optimal imaging in people admitted with acute seizures.

Should oral anticoagulants be restarted after warfarin-associated cerebral haemorrhage in patients with atrial fibrillation?

Intracranial haemorrhage (ICH), which affects up to 1% of patients on oral anticoagulation per year, is the most feared and devastating complication of this treatment. After such an event, it is unclear whether anticoagulant therapy should be resumed. Such a decision hinges upon the assessment of the competing risks of haematoma growth or recurrent ICH and thromboembolic events. ICH location and the risk for ischaemic cerebrovascular event seem to be the key factors that lead to risk/benefit balance of restarting anticoagulation after ICH. Patients with lobar haemorrhage or cerebral amyloid angiopathy remain at higher risk for anticoagulant-related ICH recurrence than thromboembolic events and, therefore would be best managed without anticoagulants. Patients with deep hemispheric ICH and a baseline risk of ischemic stroke >6.5% per year, that corresponds to CHADS2≥ 4 or CHA2DS2-VASc ≥ 5, may receive net benefit from restarting anticoagulation. To date, a reasonable recommendation regarding time to resumption of anticoagulation therapy would be after 10 weeks. Available data regarding the role of magnetic resonance imaging in assessing the risks of both ICH and warfarin-related ICH do not support the use of this test for excluding anticoagulation in patients with atrial fibrillation.

Neuropathologic analysis of hematomas evacuated from patients with spontaneous intracerebral hemorrhage

Spontaneous intracerebral hemorrhage (ICH) is a devastating cause of morbidity and mortality. Intraparenchymal hematomas are often surgically evacuated. This generates fragments of perihematoma brain tissue that may elucidate their etiology. The goal of this study is to analyze the value of these specimens in providing a possible etiology for spontaneous ICH as well as the utility of using immunohistochemical markers to identify amyloid angiopathy. Surgically resected hematomas from 20 individuals with spontaneous ICH were examined with light microscopy. Hemorrhage locations included 11 lobar and nine basal ganglia hemorrhages. Aβ immunohistochemistry and Congo red stains were used to confirm the presence of amyloid angiopathy, when this was suspected. Evidence of cerebral amyloid angiopathy (CAA) was observed in eight of the 20 specimens, each of which came from lobar locations. Immunohistochemistry confirmed CAA in the brain fragments from these eight individuals. Patients with immunohistochemically confirmed CAA were older than patients without CAA, and more likely to have lobar hemorrhages (OR 3.0 and 3.7, respectively). Evidence of CAA was not found in any of the basal ganglia specimens. One specimen showed evidence of CAA-associated angiitis, with formation of a microaneurysm in an inflamed segment of a CAA-affected arteriole, surrounded by acute hemorrhage. In another specimen, Aβ immunohistochemistry showed the presence of senile plaques suggesting concomitant Alzheimer's disease (AD) changes. Surgically evacuated hematomas from patients with spontaneous ICH should be carefully examined, paying special attention to any fragments of included brain parenchyma. These fragments can provide evidence of the etiology of the hemorrhage. Markers such as Aβ 1-40 can help to identify underlying CAA, and should be utilized when microangiopathy is suspected. Given the association of (Aβ) CAA with AD, careful examination of entrapped brain fragments may also provide evidence of AD in a given patient.

Neuromonitoring of Neonatal Extracorporeal Membrane Oxygenation Patients Using Serial Cranial Ultrasounds*

Neuromonitoring of Neonatal Extracorporeal Membrane Oxygenation Patients Using Serial Cranial Ultrasounds*

Cerebral microbleeds and the risk of mortality in the general population

Presence of cerebral microbleeds indicates underlying vascular brain disease and has been implicated in lobar hemorrhages and dementia. However, it remains unknown whether microbleeds also reflect more systemic vascular burden. We investigated the association of microbleeds with all-cause and cardiovascular related mortality in the general population. We rated the brain magnetic resonance imaging scans of 3979 Rotterdam Scan Study participants to determine presence, number, and location of microbleeds. Cox proportional hazards models, adjusted for age, sex, subcohort, vascular risk factors, and other MRI markers of cerebral vascular disease, were applied to quantify the association of microbleeds with mortality. After a mean follow up of 5.2 (±1.1) years, 172 (4.3%) people had died. Presence of microbleeds, and particularly deep or infratentorial microbleeds, was significantly associated with an increased risk of all-cause mortality [sex-, age-, subcohort adjusted hazard ratio (HR) 2.27; CI 1.50-3.45], independent of vascular risk factors (HR 1.87; 95% CI 1.20-2.92). The presence of deep or infratentorial microbleeds strongly associated with the risk of cardiovascular related mortality (HR 4.08; CI 1.78-9.39). Mortality risk increased with increasing number of microbleeds. The presence of microbleeds, particularly multiple microbleeds and those in deep or infratentorial regions, indicates an increased risk of mortality, independent of other MRI markers of cerebral vascular disease. Our data suggest that microbleeds may mark severe underlying vascular pathology associated with poorer survival.

Plasma brain natriuretic peptide is elevated in the acute phase of intracerebral hemorrhage

Previous reports have shown that plasma brain natriuretic peptide (BNP) levels are increased in patients with subarachnoid hemorrhage and ischemic stroke. We examined BNP in patients with intracerebral hemorrhage (ICH). Between June 2006 and February 2010, we prospectively enrolled consecutive patients with acute ICH within 24hours of onset. The plasma BNP level was measured twice, on admission and 4weeks after onset or at discharge. We investigated whether plasma BNP was elevated in the acute phase of ICH and associated factors. The mean±standard deviation (SD) plasma BNP level of all patients was 71.1±104.1pg/mL. The log BNP level positively correlated with the cardio–thoracic ratio (r=0.240, p=0.0001). Moreover, BNP was significantly associated with intraventricular extension (p=0.0039) and hydrocephalus (p=0.0046). The mean±SD BNP level of patients with cerebellar hemorrhage was the highest (130.2±152.0pg/mL), followed by brainstem (84.5±170.6pg/mL), lobar (72.4±148.1pg/mL), thalamus (64.8±72.1pg/mL), and putamen (59.9±62.6pg/mL) hemorrhages. In 185 patients, BNP was measured in the subacute phase of ICH. The BNP level in the acute phase of ICH was significantly higher than that in the subacute phase of ICH (69.3±108.1 versus 21.7±23.5pg/mL, p<0.0001). In conclusion, plasma BNP appears to be elevated in the acute phase of ICH, particularly in those with cerebellar lesions.

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.

Stroke and Cancer: Misfortunes Never Come Singularly

Cancer patients exhibit an elevated stroke risk (1–5). In a case-control study examining the epidemiology of cancer in stroke patients and their clinical course, we identified 72 active cancer and 72 control patients from the 1493 stroke admissions to Princess Margaret Hospital, Hong Kong in 2009. The prevalence of cancer among stroke patients was 4·8% (Table 1), and stroke was the first symptom of their cancer in nine patients. The proportions of ischemic stroke (IS) (79·2%) and haemorrhagic stroke (HS) (20·8%) in cancer group were comparable with noncancer group, and vascular risk factors (hypertension, diabetes mellitus, and hyperlipidemia) were less prevalent. The cancers we identified followed the local cancer epidemiology, with lung and colorectal cancer being the two most common types. In HS, both groups had similar proportions of deep parenchymal and lobar haemorrhages, but multiple haemorrhages were only seen in the three cancer patients. Except for the two acute promyelocytic leukaemia patients who bled, the distributions of other cancers among HS patients were similar to those with IS. Among IS, the proportions of patients in the four Oxfordshire-classified syndromes were comparable in the two groups. The etiology of IS was undetermined in half of the cancer patients compared with only 28·3% of the noncancer patients. There was no difference in the severity of neurological impairment [National Institutes of Health Stroke Scale (NIHSS) 10·7 (cancer) and 11·8 (noncancer)], but cancer patients had a higher hospital-acquired pneumonia (11·1% vs. 4·2%) and hospital mortality (31·9% vs. 12·5%) rates. At three-months poststroke, cancer remained the most important independent predictor of mortality [odds ratio 12·4 (3·0–51·4)], and more cancer patients were disabled. We concluded that stroke and cancer, when coinciding, carried a high morbidity and mortality rate. Often, the occurrence of stroke in cancer patients could not be sufficiently explained by conventional etiology, implicating the role of cancer-related factors in their stroke pathophysiology.

Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy

We investigated the prevalence and clinical-radiologic associations of cortical superficial siderosis (cSS) in patients with probable cerebral amyloid angiopathy (CAA) compared to those with intracerebral hemorrhage (ICH) not attributed to CAA. We conducted a retrospective multicenter cohort study of 120 patients with probable CAA and 2 comparison groups: 67 patients with either single lobar ICH or mixed (deep and lobar) hemorrhages; and 22 patients with strictly deep hemorrhages. We rated cSS, ICH, white matter changes, and cerebral microbleeds. cSS was detected in 48 of 120 (40%; 95% confidence interval [CI]: 31.2%-49.3%) patients with probable CAA, 10 of 67 (14.9%; 95% CI: 7.4%-25.7%) with single lobar ICH or mixed hemorrhages, and 1 of 22 (4.6%; 95% CI: 0.1%-22.8%) patients with strictly deep hemorrhages (p < 0.001 for trend). Disseminated cSS was present in 29 of 120 (24%; 95% CI: 16.8%-32.8%) patients with probable CAA, but none of the other patients with ICH (p < 0.001). In probable CAA, age (odds ratio [OR]: 1.09; 95% CI: 1.03-1.15; p = 0.002), chronic lobar ICH (OR: 3.94; 95% CI: 1.54-10.08; p = 0.004), and a history of transient focal neurologic episodes (OR: 11.08; 95% CI: 3.49-35.19; p < 0.001) were independently associated with cSS. However, cSS occurred in 17 of 48 patients with probable CAA (35.4%; 95% CI: 22.2%-50.5%) without chronic lobar ICH. cSS (particularly if disseminated) is a common and characteristic feature of CAA. Chronic lobar ICH is an independent risk factor for cSS, but the causal direction and mechanism of association are uncertain. Hemorrhage into the subarachnoid space, independent of previous (chronic) lobar ICH, must also contribute to cSS in CAA. Transient focal neurologic episodes are the strongest clinical marker of cSS.

Cerebral microbleeds and the risk of mortality in the general population

Presence of cerebral microbleeds indicates underlying vascular brain disease and has been implicated in lobar hemorrhages and dementia. However, it remains unknown whether microbleeds also reflect more systemic vascular burden. We investigated the association of microbleeds with all-cause and cardiovascular related mortality in the general population. We rated the brain magnetic resonance imaging scans of 3979 Rotterdam Scan Study participants to determine presence, number, and location of microbleeds. Cox proportional hazards models, adjusted for age, sex, subcohort, vascular risk factors, and other MRI markers of cerebral vascular disease, were applied to quantify the association of microbleeds with mortality. After a mean follow up of 5.2 (±1.1) years, 172 (4.3 %) people had died. Presence of microbleeds, and particularly deep or infratentorial microbleeds, was significantly associated with an increased risk of all-cause mortality [sex-, age-, subcohort adjusted hazard ratio (HR) 2.27; CI 1.50-3.45], independent of vascular risk factors (HR 1.87; 95 % CI 1.20-2.92). The presence of deep or infratentorial microbleeds strongly associated with the risk of cardiovascular related mortality (HR 4.08; CI 1.78-9.39). Mortality risk increased with increasing number of microbleeds. The presence of microbleeds, particularly multiple microbleeds and those in deep or infratentorial regions, indicates an increased risk of mortality, independent of other MRI markers of cerebral vascular disease. Our data suggest that microbleeds may mark severe underlying vascular pathology associated with poorer survival.

Epidemiological and clinical characteristics of 266 cases of intracerebral hemorrhage in Hangzhou, China

Ethnicity and socioeconomic factors can influence disease susceptibility, clinical presentation, and outcome. We investigated the clinical characteristics (age, sex, seasonal variation, lesion site, symptoms, complications, prognosis, and sequelae) and risk factors for intracerebral hemorrhage (ICH) in 266 cases treated at our hospital in Hangzhou City, China, from January 2011 to December 2011. Risk of ICH increased dramatically with age; only 4.3% of cases were <30 years old, while 44.4% were >60 years of age. Men outnumbered women by 2:1 (67.3% vs. 32.7%). Single hemorrhage was most often located in the cerebral lobes (37.2% of cases), basal ganglia (34.2%), thalamus (8.3%), cerebellum (6.8%), ventricle (1.5%), and brainstem (1.1%), while 10.9% of cases exhibited hemorrhages at multiple sites. Hypertension was also a major risk factor for ICH, as 47% of all patients were hypertensive and the percentage increased with age. In hypertensive patients, the most common hemorrhage site was the basal ganglia and ICH was often associated with thrombopenia. In patients with leukemia (all forms), most hemorrhages were lobar. Warfarin- and encephalic operation-associated ICHs were all lobar. Headache was the major symptom of occipital, temporal, and frontal lobe hemorrhage. Dizziness, nausea, and vomiting were the major symptoms of cerebellum hemorrhage. Limb dysfunction was the major symptom of thalamic and basal ganglia hemorrhage. Disturbed level of consciousness was the major symptom in multisite, ventricular, parietal lobe, and brainstem hemorrhage. Hyperspasmia occurred most often in lobar hemorrhage and blurred vision in occipital lobe hemorrhage. Hospital mortality was 24.4% (n=65) with a mean delay from presentation to death of (10.5±18.5) d. The majority of fatalities were cerebral hernia cases (58.5%) and these patients also had the shortest time to death [(2.9±3.5) d]. Mortality was 100% in brainstem ICH and hemorrhagic conversion of cerebral infarct. Thrombopenia-associated ICH also had a high mortality rate (81.0%), while patients with cerebrovascular malformations and cerebral aneurysms demonstrated a much better prognosis (46.2% recovery).

Magnetic Resonance Imaging Profile of Blood–Brain Barrier Injury in Patients With Acute Intracerebral Hemorrhage

BackgroundSpontaneous intracerebral hemorrhage (ICH) is associated with blood–brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage.Methods and ResultsTwenty‐five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (Ktrans) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror–image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher Ktrans values than small hematomas (P<0.005). Ktrans values of lobar hemorrhages were significantly higher than the Ktrans values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher Ktrans values were associated with larger edema volumes.ConclusionsBBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes.

Abstract P215: Trends in Hemorrhagic Stroke in Japan, from 1986 to 2010: Circulatory Risk in Communities Study (CIRCS).

Background: The incidence of hemorrhagic stroke has substantially decreased nearly to a quarter over years from 1960s to 1980s in Japan. However, there is little evidence on the trends after 1980, or whether subtypes of hemorrhagic stroke have decreased. We examined trends in the incidence of hemorrhagic stroke and its subtypes. Hypothesis: Hemorrhagic stroke have decreased after 1980s. For intraparenchymal hemorrhage (IPH), lobar and cerebellar intraparenchymal hemorrhage has not decreased. Methods: All residents aged 30 to 84 years in two communities (Akita and Osaka, census population: 18,998 in 2000) in Japan was surveyed. The incidence of IPH and subarachnoid hemorrhage (SAH) from 1986 to 2010 was ascertained by systematic surveillance of hospital records and confirmed by physicians with CT or MRI images. The implementation rate of CT or MRI has not changed materially over years (78.9~97.4%). IPH was further categorized to lobar and cerebellar IPH, and deep IPH (thalamus, basal ganglia or brainstem). The respective age-adjusted incidence rates per 100,000 person-years were calculated by each 5 years of time periods: 1986-1990, 1991-1995, 1996-2000, 2001-2005, and 2006-2010. Results: Age-adjusted incidence of SAH has decreased in 1996-2000 but increased after 2000. Respective age-adjusted incidence rates (per 100,000 person-years) of SAH for 5 time periods were 46.2, 46.5, 14.5, 23.0, and 23.7 (p for trend=0.23). Age-adjusted incidence of all IPH has decreased from 1986-1990 to 2006-2010. Respective incidence rates of IPH were 56.8, 53.7, 48.7, 29.0, and 26.5 (p for trend=0.01). For the subtypes of IPH, incidence of lobar and cerebellar IPH has not decreased from 1986-1990 to 2006-2010, while it have decreased for deep IPH. Respective incidence rates for lobar and cerebellar IPH were 13.1, 7.6, 16.6, 10.9, and 10.3 (p for trend=0.85) and those of deep IPH were 52.0, 53.1, 49.8, 40.8, and 29.5 (p for trend=0.03). Conclusion: The age-adjusted incidence of IPH after 1980s has decreased over years, although such trend was not clear for SAH. Among IPH, the incidence of lobar and cerebellar IPH has not decreased, while the incidence of deep IPH has decreased.

Clinical analysis of related factors of delayed intracranial hemorrhage after craniectomy

Objective To study secondary surgery for DTICH after the evacuation of traumatic intracranial hematoma mainly about risk factors,predilection sites,prejudging,observations,and treatments.Methods There were 227 cases of DTICH from 2008 Feb.to 2012 Apr.which had 103 cases with secondary surgery.A retrospective and risk factors analysis was conducted with clinical materials using multivariate logistic regression.Results In line with the GOS score:there were 23 cases of good recovery,21 cases of moderate disability,23 cases of severe disability,12 cases of vegetative state,and 24 cases of deaths.Multivariate Logistic regression showed that the major risk factors were multi-site skull fractures,patients with hypertension,abnormal coagulations and brain contusions (OR =4.290,3.662,2.557,1.893).Delayed hematoma mainly occurred in the temporal lobe and frontal hemorrhage,its sources were:contuse brain tissues 51.5％,bone sewings 31.1％,small arterieson dural surface 8.7％,and sinuses 8.7％.Conclusion Pre-judgment for all patients with risk factors,attention to the mechanism of injury,changes in vital signs,surgical intervention as early as possible,and preventing complications were all keys to decreasing the mortality and disable rate. Key words: Traumatic brain injury; Postoperative hemorrhage; Delayed traumatic intracranial hematoma; Risk factors

Subarachnoid Extension of Primary Intracerebral Hemorrhage is Associated With Poor Outcomes

Extension of hemorrhage into the subarachnoid space is observed in primary intracerebral hemorrhage (ICH), yet the phenomenon has undergone limited study and is of unknown significance. The objective of this study is to evaluate the incidence, characteristics, and clinical consequences of subarachnoid hemorrhage extension (SAHE) in ICH on functional outcomes. Patients with primary ICH were enrolled into a prospective registry between December 2006 and June 2012. Patients were managed and serial neuroimaging was obtained per a structured protocol. Presence of any subarachnoid blood on imaging was identified as SAHE by expert reviewers blinded to outcomes. Regression models were developed to test whether the occurrence of SAHE was an independent predictor of functional outcomes as measured with the modified Rankin Scale. Of 234 patients with ICH, 93 (39.7%) had SAHE. Interrater agreement for SAHE was excellent (kappa=0.991). SAHE was associated with lobar hemorrhage location (65% of SAHE vs 19% of non-SAHE cases; P<0.001) and larger hematoma volumes (median 23.8 vs 6.7; P<0.001). Fever (69.9% vs 51.1%; P=0.005) and seizures (8.6% vs 2.8%; P=0.07) were more common in patients with SAHE. SAHE was a predictor of death by day 14 (odds ratio, 4.45; 95% confidence interval, 1.88-10.53; P=0.001) and of higher (worse) modified Rankin Scale scores at 28 days (odds ratio, 1.76 per mRS point; 95% confidence interval, 1.01-3.05; P=0.012) after adjustment for ICH score. SAHE is associated with worse modified Rankin Scale independent of traditional ICH severity measures. Underlying mechanisms and potential treatments of SAHE require further study.