Stroke outcome studies often combine cases of intracerebral hemorrhage (ICH) and ischemic stroke (IS). These studies of mixed stroke typically ignore computed tomography (CT) findings for ICH cases, though the impact of omitting these traditional predictors of ICH mortality is unknown. We investigated the incremental impact of ICH CT findings on mortality prediction model performance.
Cases of ICH and IS (2000–2003) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Base models predicting 30-day mortality included demographics, stroke type, and clinical findings (National Institutes of Health Stroke Scale (NIHSS) +/− Glasgow coma scale (GCS)). The impact of adding CT data (volume, intraventricular hemorrhage, infratentorial location) was assessed with the area under the curve (AUC), unweighted sum of squared residuals (Ŝ), and integrated discrimination improvement (IDI). The model assessment was performed first for the mixed case of IS and ICH, and then repeated for ICH cases alone to determine whether any lack of improvement in model performance with CT data for mixed stroke type was due to IS cases naturally forming a larger proportion of the total sample than ICH.
A total of 1,256 cases were included (86% IS, 14% ICH). Thirty-day mortality was 16% overall (11% for IS; 43% for ICH). When both clinical scales (NIHSS and GCS) were included, none of the model performance measures showed improvement with the addition of CT findings whether considering IS and ICH together (ΔAUC: 0.002, 95% CI −0.01, 0.02; ΔŜ: −3.0, 95% CI −9.1, 2.6; IDI: 0.017, 95% CI −0.004, 0.05) or considering ICH cases alone (ΔAUC: 0.02, 95% CI −0.02, 0.08; Δ Ŝ: −2.0, 95% CI −9.7, 3.4); IDI 0.065, 95% CI −0.03, 0.21). If NIHSS was the only clinical scale included, there was still no improvement in AUC or Ŝ when CT findings were added for the sample with IS/ICH combined (ΔAUC: 0.005, 95%CI −0.01, 0.02; ΔŜ: −5.0, 95%CI −11.6, 1.0) or for ICH cases alone (ΔAUC: 0.05, 95% CI −0.002, 0.11; ΔŜ: −4.2, 95%CI −11.5, 2.3). However, IDI was improved when NIHSS was the only clinical scale for IS/ICH combined (IDI: 0.029, 95%CI 0.002, 0.065) and ICH alone (IDI: 0.12, 95%CI 0.005, 0.26).
Excluding ICH CT findings had only minimal impact on mortality prediction model performance whether examining ICH and IS together or ICH alone. These findings have important implications for the design of clinical studies involving ICH patients.
epidemiology; cerebral infarction; prediction of outcome; intracerebral hemorrhage
There have been many reports about the prognosis and risk factors of stroke recurrence following brain infarction (BI). However, little is known about the stroke recurrence after primary intracerebral hemorrhage (PICH). Therefore, we explored the recurrent stroke patients after initial PICH retrospectively, to reveal the critical factors of stroke recurrence. Acute BI (n=4013) and acute PICH patients (n=1067) admitted to the hospital between April 2000 and March 2009 were consecutively screened. PICH patients with a history of ICH and BI patients with a history of ICH were then classified into the ICH-ICH group (n=64, age 70.8±9.5 years) and ICH-BI group (n=52, age 72.8±9.7years), respectively. ICH lesions were categorized into ganglionic and lober types according to the brain magnetic resonance imaging. Subtypes of BI were classified into cardioembolism, large-artery atherosclerosis, small-artery occlusion and others. There was no difference in incidence of risk factors between ICH-ICH and ICH-BI groups. Distribution of initial PICH lesions was significantly abundant in the lobar type in the ICH-ICH group (P<0.01) and in ganglionic type in the ICH-BI group (P<0.02). Age of onset was significantly older in recurrent lobar ICH compared with recurrent ganglionic ICH (P<0.01: 73.6±10.0 and 59.1±9.0 years, respectively). In conclusion, ganglionic ICH patients may have a chance of recurrent stroke in both brain infarction and ganglionic ICH, suggesting the participation of atherosclerosis in intracranial arteries. Lobar ICH patients were older and prone to recurrent lobar ICH, suggesting the participation of cerebral amyloid angiopathy as a risk of stroke recurrence.
stroke; brain infarction; intracerebral hemorrhage; stroke prevention.
Patients on warfarin or clopidogrel are considered at increased risk for traumatic intracranial hemorrhage (tICH) following blunt head trauma. The prevalence of immediate tICH and the cumulative incidence of delayed tICH in these patients, however, are unknown.
A prospective, observational study at two trauma centers and four community hospitals enrolled emergency department (ED) patients with blunt head trauma and pre-injury warfarin or clopidogrel use from April 2009 through January 2011. Patients were followed for two weeks. The prevalence of immediate tICH and the cumulative incidence of delayed tICH were calculated from patients who received an initial cranial computed tomography (CT) in the ED. Delayed tICH was defined as tICH within two weeks following an initially normal CT scan and in the absence of repeat head trauma.
A total of 1,064 patients were enrolled (768 warfarin patients [72.2%] and 296 clopidogrel patients [27.8%]). There were 364 patients [34.2%] from Level 1 or 2 trauma centers and 700 patients [65.8%] from community hospitals. One thousand patients received a cranial CT scan in the ED. Both warfarin and clopidogrel groups had similar demographic and clinical characteristics although concomitant aspirin use was more prevalent among patients on clopidogrel. The prevalence of immediate tICH was higher in patients on clopidogrel (33/276, 12.0%; 95% confidence interval [CI] 8.4-16.4%) than patients on warfarin (37/724, 5.1%; 95%CI 3.6-7.0%), relative risk 2.31 (95%CI 1.48-3.63). Delayed tICH was identified in 4/687 (0.6%; 95%CI 0.2-1.5%) patients on warfarin and 0/243 (0%; 95%CI 0-1.5%) patients on clopidogrel.
While there may be unmeasured confounders that limit intergroup comparison, patients on clopidogrel have a significantly higher prevalence of immediate tICH compared to patients on warfarin. Delayed tICH is rare and occurred only in patients on warfarin. Discharging patients on anticoagulant or antiplatelet medications from the ED after a normal cranial CT scan is reasonable but appropriate instructions are required as delayed tICH may occur.
Background and Purpose:
Intracerebral hemorrhage (ICH) constitutes now 52% of all strokes. Despite of its deadly pattern, locally there is no clinical grading scale for ICH-related mortality prediction. The first objective of this study was to develop a risk stratification scale (Kinshasa ICH score) by assessing the strength of independent predictors and their association with in-hospital 30-day mortality. The second objective of the study was to create a specific local and African model for ICH prognosis.
Materials and Methods:
Age, sex, hypertension, type 2 diabetes mellitus (T2DM), smoking, alcohol intake, and neuroimaging data from CT scan (ICH volume, Midline shift) of patients admitted with primary ICH and follow-upped in 33 hospitals of Kinshasa, DR Congo, from 2005 to 2008, were analyzed using logistic regression models.
A total of 185 adults and known hypertensive patients (140 men and 45 women) were examined. 30-day mortality rate was 35% (n=65). ICH volume>25 mL (OR=8 95% CI: 3.1-20.2; P<0.0001), presence of coma (OR=6.8 95% CI 2.6-17.4; P<0.0001) and left hemispheric site of ICH (OR 2.6 95% CI: 1.1-6; P=0.027) were identified as significant and independent predictors of 30-day mortality. Midline shift > 7 mm, a consequence of ICH volume, was also a significant predictor of mortality. The Kinshasa ICH score was the sum of individual points assigned as follows: Presence of coma coded 2 (2 × 2 = 4), absence of coma coded 1 (1 × 2 = 2), ICH volume>25 mL coded 2 (2 × 2=4), ICH volume of ≤25 mL coded 1(1 × 2=2), left hemispheric site of ICH coded 2 (2 × 1=2), and right hemispheric site of hemorrhage coded 1(1 × 1 = 1). All patients with Kinshasa ICH score ≤7 survived and the patients with a score >7 died. In considering sex influence (Model 3), points were allowed as follows: Presence of coma (2 × 3 = 6), absence of coma (1 × 3 = 3), men (2 × 2 = 4), women (1 × 2 = 2), midline shift ≤7 mm (1 × 3 = 3), and midline shift >7 mm (2 × 3 = 6). Patients who died had the Kinshasa ICH score ≥16.
In this study, the Kinshasa ICH score seems to be an accurate method for distinguishing those ICH patients who need continuous and special management. It needs to be validated among large African hypertensive populations with a high rate of 30-day in–hospital mortality.
Clinical and neuroimaging data; intracerebral hemorrhage; predictors of mortality; sub-Saharan Africa
Emergency department (ED) management of mild traumatic brain injury (TBI) patients with any form of traumatic intracranial hemorrhage (ICH) is variable. Since 2000, our center’s standard practice has been to obtain a repeat head computed tomography (CT) at least 6 hours after initial imaging. Patients are eligible for discharge if clinical and CT findings are stable. Whether this practice is safe is unknown. This study characterized clinical outcomes in mild TBI patients with acute traumatic ICH seen on initial ED neuroimaging.
This retrospective cohort study included patients presenting to the ED with blunt mild TBI with Glasgow Coma Scale (GCS) scores of 14 or 15 and stable vital signs, during the period from January 2001 to January 2010. Patients with any ICH on initial head CT and repeat head CT within 24 hours were eligible. Cases were excluded for initial GCS < 14, injury > 24 hours old, pregnancy, concomitant nonminor injuries, and coagulopathy. A single investigator abstracted data from records using a standardized case report form and data dictionary. Primary endpoints included death, neurosurgical procedures, and for discharged patients, return to the ED within 7 days. Differences in proportions were computed with 95% confidence intervals (CIs).
Of 1,011 patients who presented to the ED and had two head CTs within 24 hours, 323 (32%) met inclusion criteria. The median time between CT scans was 6 hours (interquartile range = 5 to 7 hours). A total of 153 (47%) patients had subarachnoid hemorrhage, 132 (41%) patients had subdural hemorrhage, 11 (3%) patients had epidural hemorrhage, 78 (24%) patients had cerebral contusions, and 59 (18%) patients had intraparenchymal hemorrhage. Four of 323 (1.2%, 95% CI = 0.3% to 3.2%) patients died within 2 weeks of injury. Three of the patients who died had been admitted from the ED on their initial visits, and one had been discharged home. There were 206 patients (64%) discharged from the ED, 28 (13.6%) of whom returned to the ED within 1 week. Of the 92 who were hospitalized, three (0.9%, 95% CI = 0.2% to 2.7%) required neurosurgical intervention.
Discharge after a repeat head CT and brief period of observation in the ED allowed early discharge of a cohort of mild TBI patients with traumatic ICH without delayed adverse outcomes. Whether this justifies the cost and radiation exposure involved with this pattern of practice requires further study.
Intracranial/intracerebral hemorrhage (ICH) is a leading cause of death and disability in people with traumatic brain injury (TBI) and stroke. No proven drug is available for ICH. Panax notoginseng (total saponin extraction, PNS) is one of the most valuable herb medicines for stroke and cerebralvascular disorders in China. We searched for randomized controlled clinical trials (RCTs) involving PNS injection to treat cerebral hemorrhage for meta-analysis from various databases including the Chinese Stroke Trials Register, the trials register of the Cochrane Complementary Medicine Field, the Cochrane Central Register of Controlled Trials, MEDLINE, Chinese BioMedical disk, and China Doctorate/Master Dissertations Databases. The quality of the eligible trials was assessed by Jadad’s scale. Twenty (20) of the 24 identified randomized controlled trials matched the inclusive criteria including 984 ICH patients with PNS injection and 907 ICH patients with current treatment (CT). Compared to the CT groups, PNS-treated patients showed better outcomes in the effectiveness rate (ER), neurological deficit score, intracranial hematoma volume, intracerebral edema volume, Barthel index, the number of patients died, and incidence of adverse events. Conclusion: PNS injection is superior to CT for acute ICH. A review of the literature shows that PNS may exert multiple protective mechanisms against ICH-induced brain damage including hemostasis, anti-coagulation, anti-thromboembolism, cerebral vasodilation, invigorated blood dynamics, anti-inflammation, antioxidation, and anti-hyperglycemic effects. Since vitamin C and other brain cell activators (BCA) that are not considered common practice were also used as parts of the CT in several trials, potential PNS and BCA interactions could exist that may have made the effect of PNS therapy less or more impressive than by PNS therapy alone. Future PNS trials with and without the inclusion of such controversial BCAs as part of the CT could clarify the situation. As PNS has a long clinical track record in Asia, it could potentially become a therapy option to treat ICH in the US and Europe. Further clinical trials with better experimental design could determine the long-term effects of PNS treatment for TBI and stroke.
notoginsenosides; botanical medicine; nutraceuticals; TBI and stroke recovery; randomized controlled clinical trials; hemostasis; anti-coagulation; pharmacological mechanisms
Background and Purpose
Treatment with atorvastatin (80 mg) in stroke secondary prevention for patients with prior intracranial hemorrhage (ICH) has been associated with a higher frequency of ICH. The aim of this study was to determine whether 20 mg/day atorvastatin is linked to stroke recurrence in Chinese ischemic stroke patients with prior ICH.
A single-center retrospective cohort study was conducted, involving 354 cases from 395 Chinese in-patients who had ischemic stroke with prior ICH history in Beijing Chaoyang hospital from May 1, 2005 to October 31, 2010. Survivors were followed by telephone interviews for 12-60 months. Cox regression and Kaplan-Meier plot analysis were used to evaluate the effect of 20 mg/day atorvastatin on cerebral infarction and ICH recurrence.
The overall rate of stroke recurrence was lower in the 20 mg/day atorvastatin group (χ2=6.687, p=0.022) than in the control group. The incidence of cerebral hemorrhage was increased by 20 mg/day atorvastatin for ischemic stroke cases with a history of ICH compared to those not receiving the drug, but the difference was not significant [hazard ratio (HR)=1.097, 95% confidence interval (CI)=0.800-1.243, p=0.980]. The incidence of ischemic stroke recurrence was significantly reduced in subjects receiving atorvastatin (HR=0.723, 95% CI=0.578-0.862, p=0.028), and the mean duration of all stroke recurrences was significantly prolonged, compared with those not exposed to the drug (χ2=5.351, p=0.021). The mean duration of ICH recurrence appeared to have shortened with atorvastatin, but the difference was not significant (χ2=0.680, p=0.480), and the mean duration of cerebral infarction recurrence was significantly prolonged (χ2=8.312, p=0.004).
Medication with 20 mg/day atorvastatin may be beneficial in reducing ischemic stroke recurrence in ischemic stroke patients with a history of ICH and is not associated with an increased risk of ICH recurrence.
ischemic stroke; intracranial hemorrhage history; atorvastatin; stroke recurrence
The natural history and triggers of perihaematomal oedema (PHO) remain poorly understood. Cerebral amyloid angiopathy (a common cause of lobar haemorrhage) has localised anticoagulant and thrombolytic properties, which may influence PHO. We hypothesised that early (within 24 hours) oedema to haematoma volume ratios are smaller in patients with lobar intracerebral haemorrhage (ICH) than in patients with deep ICH.
Haematoma and PHO volumes were measured in consecutive patients admitted to an acute stroke unit with a diagnosis of spontaneous supratentorial ICH proven by computed tomography. The oedema to haematoma volume ratios were calculated and compared in patients with lobar ICH and deep ICH.
In total, 44 patients with ICH were studied: 19 patients had deep ICH, median haematoma volume 8.4 ml (interquartile range (IQR) 4.8 to 20.8), median PHO 8.2 ml (2.8 to 16), and 25 had lobar ICHs, median haematoma volume 17.6 ml (6.6 to 33.1) and median oedema volume 10.2 ml (3.4 to 24.2). Patients with lobar ICH were older than those with deep ICH (65.7 v 57.4 years, p = 0.009) but ICH location did not differ by sex or race. There was no evidence that haematoma or oedema volumes were related to type of ICH (p = 0.23, p = 0.39 respectively). The median oedema to haematoma volume ratios were similar in patients with lobar and deep ICH (0.67 v 0.58, p = 0.71). Controlling for age, sex, and race made little difference to these comparisons.
There are no major location specific differences in PHO volumes within 24 hours of ICH onset. Deep and lobar ICH may have common therapeutic targets to reduce early PHO.
Intracerebral haemorrhage; perihaematomal oedema
Background and Purpose
Intracerebral 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.
We 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.
In 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).
Our 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.
Hemorrhagic stroke; Intracerebral hemorrhage; Deep cerebral hemorrhage; Lobar cerebral hemorrhage; Arterial stiffness; Arterial hypertension
In recent years, intracranial hemorrhage (ICH) with parenchymal involvement has been diagnosed more often in full-term neonates due to improved neuroimaging techniques. The aim of this study is to describe clinical and neuroimaging data in the neonatal period and relate imaging findings to outcome in a hospital-based population admitted to a level 3 neonatal intensive care unit (NICU).
From our neuroimaging database, we retrospectively retrieved records and images of 53 term infants (1991–2008) in whom an imaging diagnosis of ICH with parenchymal involvement was made. Clinical data, including mode of delivery, clinical manifestations, neurological symptoms, extent and site of hemorrhage, neurosurgical intervention, and neurodevelopmental outcomes, were recorded.
Seventeen of the 53 term infants had infratentorial ICH, 20 had supratentorial ICH, and 16 had a combination of the two. Seizures were the most common presenting symptom (71.7%), another ten infants (18.9%) presented with apneic seizures, and five infants had no clinical signs but were admitted to our NICU because of perinatal asphyxia (n = 2), respiratory distress (n = 2), and development of posthemorrhagic ventricular dilatation (n = 1). Continuous amplitude-integrated electroencephalography recordings were performed in all infants. Clinical or subclinical seizures were seen in 48/53 (90.6%) infants; all received anti-epileptic drugs. Thirteen of all 53 (24.5%) infants died. The lowest mortality rate was seen in infants with supratentorial ICH (10%). Three infants with a midline shift required craniotomy, six infants needed a subcutaneous reservoir due to outflow obstruction, and three subsequently required a ventriculoperitoneal shunt. The group with poor outcome (death or developmental quotient (DQ) <85) had a significantly lower 5-min Apgar score (p = .006). Follow-up data were available for 37/40 survivors aged at least 15 months. Patients were assessed with the Griffiths Mental Developmental Scales, and the mean DQ of all survivors was 97 (SD = 12). Six infants (17%) had a DQ below 85 [two of them had cerebral palsy (CP)]. Three infants developed CP (8.6%); one had cerebellar ataxia, and two had hemiplegia.
ICH with parenchymal involvement carries a risk of adverse neurological sequelae with a mortality of 24.5% and development of CP in 8.6%. The high mortality rate could partly be explained by associated perinatal asphyxia. Infants with supratentorial ICH had a lower, although not significant, mortality rate compared with infants with infratentorial ICH and infants with a combination of supratentorial ICH and infratentorial ICH. In spite of often large intraparenchymal lesions, 30 of the 34 survivors without CP (88.2%) had normal neurodevelopmental outcome at 15 months.
Intracranial hemorrhage; Intraparenchymal hemorrhage; Subdural hemorrhage; Full-term newborns
Background and Purpose
To describe features of children with intracerebral hemorrhage (ICH) and to determine predictors of short-term outcome in a single-center prospective cohort study.
Single-center prospective consecutive cohort study of spontaneous ICH in children age 1-18 years from January 2006 to June 2008. Exclusion criteria were inciting trauma; intracranial tumor; isolated epidural, subdural, intraventricular, or subarachnoid hemorrhage; hemorrhagic transformation of ischemic stroke; and cerebral sinovenous thrombosis. Hospitalization records were abstracted. Follow-up assessments included outcome scores using the Pediatric Stroke Outcome Measure (PSOM) and King's Outcome Scale for Childhood Head Injury (KOSCHI). ICH volumes and total brain volumes (TBV) were measured by manual tracing.
Twenty-two patients, median age of 10.3 years (range 4.2-16.6 years), had presenting symptoms of headache in 77%, focal deficits 50%, altered mental status 50%, and seizures 41%. Vascular malformations caused hemorrhage in 91%. Surgical treatment (hematoma evacuation, lesion embolization or excision) was performed during acute hospitalization in 50%. One patient died acutely. At median follow-up of 3.5 months (range 0.3-7.5 months), 71% of survivors had neurological deficits; 55% had clinically significant disability. Outcome based on PSOM and KOSCHI scores was worse in patients with ICH volume >2% of TBV (p=0.023) and altered mental status at presentation (p = 0.005).
Spontaneous childhood ICH was due mostly to vascular malformations. Acute surgical intervention was commonly performed. Although death was rare, 71% of survivors had persisting neurological deficits. Larger ICH volume and altered mental status predicted clinically significant disability.
intracerebral hemorrhage; outcome; childhood; vascular malformation
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), recently received FDA approval for recurrent glioblastoma. Additionally, several VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have entered trials for recurrent glioma. Phase II studies of bevacizumab for recurrent GBM have reported incidents of ischemic stroke (IS) and intracranial hemorrhage (ICH); however, their clinical features and outcomes were not described in detail. We conducted a retrospective study of recurrent malignant glioma patients with radiographically-confirmed IS or ICH while on anti-angiogenic therapy. The study population included patients treated between 2005 and 2010 at the National Cancer Institute on four different phase I and II trials of antiangiogenic agents for recurrent malignant glioma, as well as patients receiving bevacizumab off clinical trial during this same period. Eight patients developed IS (50% lacunar) and 14 experienced ICH (79% intratumoral) while on antiangiogenic therapy for malignant glioma recurrence. The median age was 53 years, 17 patients (77%) were men, and 59% had glioblastoma. The frequencies of IS and ICH were 1.9% and 1.9% in bevacizumab trials. None of the patients on VEGFR TKI trials developed IS, while 3.8% experienced ICH. Patients with IS were treated with anti-angiogenic agents longer than those with ICH (median, 16.2 vs. 2.6 months, P = 0.001). Median survival was 7.8 months after IS and 2.6 months after ICH. The most common IS subtype was lacunar, while most ICHs were asymptomatic and intratumoral. Overall, IS seems to be a complication of prolonged antiangiogenic therapy, while intratumoral bleeds often occur in the setting of tumor progression.
Glioma; Glioblastoma; Antiangiogenic agents; Bevacizumab; stroke; CNS hemorrhage
Background and Purpose
Lobar microbleeds suggestive of cerebral amyloid angiopathy (CAA) are often identified on MRI in the absence of lobar intracerebral hemorrhage (ICH). We compared the baseline characteristics and risk of subsequent ICH among such patients to those presenting with CAA-related lobar ICH.
Clinical data (demographics, risk factors), apolipoprotein E genotype, neuroimaging markers of CAA severity (microbleed counts, leukoaraiosis volume), and clinical outcomes (incidence rates of ICH and death during a mean follow-up of 5.3±3.8 years) were compared between 63 patients enrolled because of incidentally found microbleeds and 316 with CAA-related ICH, in our prospectively enrolled cohort. Predictors of incident ICH were explored in the microbleed-only patients using multivariable Cox regression models.
Microbleed-only patients shared similar demographic, apolipoprotein E, and vascular risk profiles with lobar ICH patients, but had more lobar microbleeds (median, 10 versus 2; P<0.001) and higher leukoaraiosis volumes (median, 31 versus 23 mL; P=0.02). Microbleed-only patients had a nontrivial incidence rate of ICH, not different from patients presenting with ICH (5 versus 8.9 per 100 person-years; adjusted hazard ratio, 0.58; 95% confidence interval, 0.31–1.06; P=0.08). Microbleed-only patients had a higher mortality rate (hazard ratio, 1.67; 95% confidence interval, 1.1–2.6) compared with ICH survivors. Warfarin use and increasing age were independent predictors of future ICH among microbleed-only patients after correction for other covariates.
Patients presenting with isolated lobar microbleeds on MRI have a genetic, neuroimaging, and hemorrhagic risk profile suggestive of severe CAA pathology. They have a substantial risk of incident ICH, potentially affecting decisions regarding anticoagulation in clinical situations.
cerebral amyloid angiopathy; cerebral hemorrhage; cerebral microbleeds; magnetic resonance imaging
In 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 Methods
We 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.
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.
In our study, warfarin showed significant association with lobar ICH and it caused larger hematoma volume and more expansion of hematoma in lobar ICH.
Warfarin; Cerebral amyloid angiopathy; Intracerebral hemorrhage
Background and Purpose
Although intracerebral hemorrhage (ICH) volume and location are important predictors of outcome in adults, few data exist in children.
A consecutive cohort of children, including full-term newborns to those younger than 18 years of age with nontraumatic, acute ICH and head CT available for analysis were studied. Clinical information was abstracted via chart review. Hemorrhage volume was expressed as percentage of total brain volume (TBV) with large hemorrhage defined as ≥4% of TBV. Hemorrhages were manually traced on each head CT slice and volumes were calculated by multiplying by slice thickness. Location was classified as supratentorial or infratentorial. Logistic regression was used to identify predictors of poor neurological outcome, defined as a Glasgow outcome scale ≤2 (death or persistent vegetative state).
Thirty children were included, median age 6 years. Median ICH volume was 20.4 cm3 and median ICH size as a percentage of TBV was 1.9%. Only 4 of 22 children with ICH ≥4% of TBV had poor outcomes, vs 5 of 8 children with ICH ≥4% of TBV (P=0.03). In multivariate analysis, hemorrhage ≥4% of TBV (OR, 22.5; 95% CI, 1.4–354; P=0.03) independently predicted poor outcome 30 days after ICH. In this small sample, infratentorial hemorrhage location and the presence of intraventricular hemorrhage did not predict poor outcome.
ICH volume predicts neurological outcome at 30 days in children, with worst outcome when hemorrhage is ≥4% of TBV. Location and ICH etiology may also be important. These findings identify children with ICH who are candidates for aggressive management and may influence counseling regarding prognosis.
child; intracerebral hemorrhage; stroke
Objective: The purpose of this study was to differentiate between cerebral amyloid angiopathy (CAA) and hypertension (HTN) based on hemorrhage pattern interpretation. Methods: From June 1994 to Oct., 2000, 83 patients admitted to our service with acute intracerebral hemorrhage (ICH) were investigated retrospectively; 41 patients with histologically proven diagnosis of cerebral amyloid angiography and 42 patients with clear history of hypertension were investigated. Results: Patients with a CAA-related ICH were significantly older than patients with a HTN-related ICH (74.0 years vs 66.5 years, P<0.05). There was a significantly higher number of hematomas≥30 ml in CAA (85.3%) when compared with HTN (59.5%). No basal ganglional hemorrhage was seen in CAA, but in 40.5% in HTN. In CAA-related ICH, subarachnoid hemorrhage (SAH) was seen in 26 patients (63.4%) compared to only 11 patients (26.2%) in HTN-related ICH. Intraventricular hemorrhage was seen in 24.4% in CAA, and in 26.2% in HTN. Typical features of CAA-related ICH included lobar distribution affecting mainly the lobar superficial areas, lobulated appearance, rupture into the subarachnoid space, and secondary IVH from the lobar hemorrhage. More specifically, multiplicity of hemorrhage, bilaterality, and repeated episodes also strongly suggest the diagnosis of CAA. Multiple hemorrhages, defined as 2 or more separate hematomas in multiple lobes, accounted for 17.1% in CAA-related ICH. Conclusion: There are certain features in CAA on CT and MRI and in clinical settings. To some extent, these features may contribute to distinguishing CAA from HTN related ICH.
Intracerebral hemorrhage; Cerebral amyloid angiopathy; Hypertension; Diagnosis; Computed tomography; Magnetic resonance imaging
Up to 40% of infants with persistent pulmonary hypertension (PPHN) remains refractory to conventional therapies, and extracorporeal membrane oxygenation (ECMO) is offered as an effective support for this group. However, ECMO is a highly invasive and risky procedure with devastating complications such as intracranial hemorrhage (ICH). In this study, we aimed to determine the risk factors for ICH in infants with PPHN.
A case-control study of patients admitted to the pediatric intensive care unit (PICU) with PPHN requiring ECMO support was conducted. The study was carried out at a 25-bed PICU in large urban tertiary care children’s hospital. A total number of 32 subjects were studied. Patients with and without ICH during ECMO were evaluated for activated clotting time (ACT), heparin dosing, platelet count, coagulation profile such as activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen level, vital signs including heart rate and mean arterial pressure (MAP), transfusion history, gestational age, and severity of pre-ECMO illness as possible risk factors.
Low fibrinogen level (115 ± 13 mg/dl) and low platelet counts (37.4 ± 18.3 Thousand/μl) were associated with higher incidence of ICH (p = 0.009 and p = 0.005, respectively). Elevated MAP (69 ± 4.34 mmHg) was also noticed in ICH patients (p = 0.006).
Results demonstrated that low fibrinogen level and low platelet count were associated with ICH in PPHN patients on ECMO. While on ECMO support, maintaining fibrinogen and platelet counts within normal ranges seems crucial to prevent ICH in PPHN patients. This is the first report identifying low fibrinogen level among the risk factors for ICH in infants with PPHN on ECMO support.
Intracranial hemorrhage; Neonates; ECMO; Pulmonary; Hypertension
Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between pre-existing antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether pre-existing antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders.
Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004, and 24 distinct hospitals from 2007 to 2010 as part of a cluster randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a pre-specified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to post-thrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques.
There were 830 patients included, with 47% having documented pre-existing antiplatelet treatment. The mean age was 69 years (SD ± 15 years), and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use, and 19.3% with antiplatelet use (absolute risk difference 4.2%, 95% CI = −1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference 3.1%, 95% CI = −1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio 1.1, 95% CI = 0.8 to 1.7), or sICH (odds ratio 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference 4%, 95% CI = 2.3% to 5.6%). The meta-analytic adjusted odds ratio of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4).
The authors did not find that pre-existing antiplatelet use was associated with post-thrombolysis ICH or sICH in this cohort of community treated patients. Pre-existing tobacco use, younger age, and lower severity were associated with lower odds of sICH. The meta-analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH, along with increased odds of sICH in patients with pre-existing antiplatelet use.
Intracranial haemorrhage (ICH) is one of the most serious side-effects of severe thrombocytopenia in haematology patients. ICH is rare, but can have devastating consequences (death or major morbidity). It is unknown why some patients with severe thrombocytopenia bleed and others do not.
Primary aim was to identify risk factors for ICH in patients with haematological malignancies. Secondary aims were to identify short-term outcomes for these patients at 30 days (major morbidity and mortality) and produce a more accurate estimate of ICH incidence in this population. This information is key to identifying means to improve treatment and quality of care.
This is a UK-wide case–control study of ICH nested within a 4-year prospective surveillance study set up specifically for the case–control study. Each case will be matched to one control. Cases will be adult haematology patients (≥16 years) who have had any type or severity of ICH who are receiving, about to receive or have just received myeloablative chemotherapy (defined as chemotherapy expected to cause a significant thrombocytopenia <50×109/L for >5 days) or a haemopoietic stem cell transplant. Only patients being treated with curative intent will be included. Controls will be patients who fulfil the same inclusion criteria as cases (apart from ICH) and were treated at the same hospital immediately before the index case. Cases and controls will be matched to type of treatment (myeloablative chemotherapy or haemopoietic stem cell transplant). Hospitals across the UK will participate in a monthly email reporting strategy (started June 2011), as to whether a case of ICH occurred during the preceding calendar month. Case and control forms will be sent to any hospital reporting an eligible case. Conditional logistic regression will be used to calculate ORs. Denominator data for incidence estimates will use national registry data.
ISRCTN05026912 (prospective registration). NIHR Portfolio (UKCRN ID 10712).
Reference: Dunning J, Batchelor J, Stratford-Smith P, et al. A meta-analysis of variables that predict significant intracranial injury in minor head trauma. Arch Dis Child. 2004;89:653–659.
Clinical Question: Which clinical signs or symptoms of minor head trauma are predictive of intracranial hemorrhage in children and adolescents?
Data Sources: Investigations were identified by MEDLINE and EMBASE searches from 1990 through 2002 by a search of the grey literature and by contacting experts for additional papers. The search terms were selected to find all studies reporting intracranial hemorrhage (ICH) or complications after head trauma.
Study Selection: A full systematic review was conducted, and all cohort or nested cohort studies that presented data on minor head injuries in children less than 18 years old, with or without ICH, were identified. Studies were then judged for inclusion based on the presentation of a series of at least 100 patients and a documented reliable standard for the detection of ICH for all patients in the study. The use of computed tomography (CT) and medical follow-up was considered an acceptable gold standard. Intracranial hemorrhage was defined as any abnormality detected on the CT scan due to the traumatic presence of extravascular blood. Minor head trauma was defined as patients presenting with a Glasgow Coma Scale (GCS) score of 13–15.
Data Extraction: Seven clinical correlates were used for data extraction, including skull fracture, headache, vomiting, focal neurology, seizure, loss of consciousness, and a GCS score of less than 15. Data were analyzed using a pooled estimate of the relative risk ratio with a random-effects model.
Main Results: The searches identified a total of 2134 studies for the initial review. After an abstract review by 2 independent examiners, 98 studies were identified for a full-paper review. Each study was graded on a 4-point scale according to the level of evidence provided, using scales consistent with the Oxford Centre for Evidence-Based Medicine and the National Institute for Clinical Excellence. Thirty-four of these articles were of adequate quality for inclusion; however, many did not include data that could be separated into a specific data set for children, had too small a sample size, or lacked enough data on individual correlates to head trauma. Nineteen studies provided data on children, but 3 of these were excluded due to poor quality or lack of a reported CT scan, leaving a total of 16 studies for the meta-analysis.
The analysis included a total of 22 420 patients ranging between 0 and 18 years of age. The meta-analysis showed a significant increased relative risk of ICH for patients sustaining loss of consciousness (2.23), GCS <15 (5.51), skull fracture (6.13), and focal neurology (9.43). No significant increases in risk for headache (1.02), vomiting (0.878), or seizure (2.82) were noted; however, heterogeneity was significant for this last correlate. The prevalence of ICH ranged from 1.3 to 36%, supporting the notion of a large amount of heterogeneity or variability in the inclusion criteria among the studies.
Conclusions: These findings demonstrate that loss of consciousness, decreased level of consciousness (GCS <15), skull fracture, and focal neurology are risk factors for ICH in the pediatric population. However, these findings are not definitive enough to establish pediatric head-injury guidelines regarding CT scanning or admission to hospital after minor head trauma.
To examine whether antiplatelet medication use at onset of intracerebral hemorrhage (ICH) is associated with hemorrhage growth and outcome after spontaneous ICH using a large, prospectively collected database from a recent clinical trial.
The Cerebral Hemorrhage and NXY-059 Treatment trial was a randomized, placebo-controlled trial of NXY-059 after spontaneous ICH. We analyzed patients in the placebo arm, and correlated antiplatelet medication use at the time of ICH with initial ICH volumes, ICH growth in the first 72 hours, and modified Rankin Score at 90 days. Patients on oral anticoagulation were excluded.
There were 282 patients included in this analysis, including 70 (24.8%) who were taking antiplatelet medications at ICH onset. Use of antiplatelet medications at ICH onset had no association with the volume of ICH at presentation, growth of ICH at 72 hours, initial edema volume, or edema growth. In multivariable analysis, there was no association of use of antiplatelet medications with any hemorrhage expansion (relative risk [RR] 0.85 [upper limit of confidence interval (UCI) 1.03], p = 0.16), hemorrhage expansion greater than 33% (RR 0.77 [UCI 1.18], p = 0.32), or clinical outcome at 90 days (odds ratio 0.67, 95% confidence interval 0.39–1.14, p = 0.14).
Use of antiplatelet medications at intracerebral hemorrhage (ICH) onset is not associated with increased hemorrhage volumes, hemorrhage expansion, or clinical outcome at 90 days. These findings suggest that attempts to reverse antiplatelet medications after ICH may not be warranted.
= Cerebral Hemorrhage and NXY-059 Treatment;
= confidence interval;
= intracerebral hemorrhage;
= interquartile range;
= modified Rankin Scale;
= relative risk;
= upper limit of confidence interval.
To compare surgical management and case-fatality rates of intracerebral hemorrhage (ICH) in 1988 and 2005.
We identified all adult residents (age ≥18) from the five-county Greater Cincinnati region hospitalized with ICH in 1988 and 2005. Demographics, severity of illness, ICH volume, ICH location, rates and timing of surgery, and 30-day case-fatality were compared between the 1988 and 2005 groups.
In 1988, 171 ICH patients met study criteria (67 lobar, 80 deep cerebral, 10 brainstem, 14 cerebellar), and in 2005, 259 ICH patients met criteria in (91 lobar, 123 deep cerebral, 19 brainstem, and 26 cerebellar). In 1988, 16% of the patients had surgical removal of their ICH versus 7% in 2005 (p=0.003). In both 1988 and 2005, patients treated with surgery were younger (p<0.001) and had a higher percentage of cerebellar hemorrhages than non-surgical patients. Timing of surgery was similar in 1988 and 2005. In 1988, 30-day case fatality was 32% in surgical patients versus 50% in non-surgical patients (p=0.06). In 2005, 30-day case-fatality was 16% (surgical) versus 45% (non-surgical) (p=0.02).
The frequency of surgery for ICH was lower in 2005 than in 1988, which may reflect recent clinical trial data showing no benefit for surgery over medical management. ICH case-fatality was essentially the same in 1988 and 2005. Innovative clinical trials to improve ICH outcomes are warranted.
Intracerebral hemorrhage; neurosurgery; surgery; outcome
Little is known about in-hospital care for hemorrhagic stroke. We examined quality of care in intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) admissions in the national Get With The Guidelines–Stroke (GWTG-Stroke) database, and compared them to ischemic stroke (IS) or TIA admissions.
Between April 1, 2003, and December 30, 2007, 905 hospitals contributed 479,284 consecutive stroke and TIA admissions. The proportions receiving each quality of care measure were calculated by dividing the total number of patients receiving the intervention by the total number of patients eligible for the intervention, excluding ineligible patients or those with contraindications to treatment. Logistic regression models were used to determine associations between measure compliance and stroke subtype, controlling for patient and hospital characteristics.
Stroke subtypes were 61.7% IS, 23.8% TIA, 11.1% ICH, and 3.5% SAH. Performance on care measures was generally lower in ICH and SAH compared to IS/TIA, including guideline-recommended measures for deep venous thrombosis (DVT) prevention (for ICH) and smoking cessation (for SAH) (multivariable-adjusted p < 0.001 for all comparisons). Exceptions were that ICH patients were more likely than IS/TIA to have door-to-CT times <25 minutes (multivariable-adjusted p < 0.001) and to undergo dysphagia screening (multivariable-adjusted p < 0.001). Time spent in the GWTG-Stroke program was associated with improvements in many measures of care for ICH and SAH patients, including DVT prevention and smoking cessation therapy (multivariable-adjusted p < 0.001).
Many hospital-based acute care and prevention measures are underutilized in intracerebral hemorrhage and subarachnoid hemorrhage compared to ischemic stroke /TIA. Duration of Get With The Guidelines–Stroke participation is associated with improving quality of care for hemorrhagic stroke.
= American Heart Association;
= deep venous thrombosis;
= generalized estimating equation;
= Get With The Guidelines–Stroke;
= intracerebral hemorrhage;
= ischemic stroke;
= Patient Management Tool;
= subarachnoid hemorrhage.
Background and Purpose:
Symptomatic intracranial hemorrhage (sICH) is the most serious adverse event in stroke patients who received i.v. rt-PA and is usually associated with poor outcomes. The SEDAN score is built up to predict sICH. We aim to externally validate the SEDAN score in Thai patients from single center in the real world practice.
Materials and Methods:
The SEDAN score of stroke patients treated with intravenous rt-PA at Thammasat University Hospital from January 2010 to June 2012 was calculated. Patients were divided into three groups including symptomatic intracranial hemorrhage (sICH), asymptomatic intracranial hemorrhage (AsICH) and no intracerebral hemorrhage (NoICH). The primary outcome of analyses was sICH. Each parameter of the SEDAN score and correlation between score and sICH were analyzed with univariate and multivariate model.
295 patients (18.6% of stroke admission) were treated with i.v. rt-PA. 13 patients (4.4%) had sICH and 31 patients (10.4%) had AsICH. Baseline blood sugar >12 mmol/l, early infarction, hyperdense cerebral artery, age >75 years-old and NIHSS ≥10(SEDAN) were associated with sICH by univariate analysis (P value = 0.018, <0.001, <0.001, 0.002 and 0.027 respectively). The rate of sICH occurrence was increased in accordance with the increasing of the SEDAN score. By multivariate analysis, odds ratio of baseline blood sugar >12 mmol/l, early infarction, hyperdense cerebral artery, age >75 years-old and NIHSS ≥10 were 1.248, 2.503, 1.107, 1.532 and 1.263 respectively.
The SEDAN score was practical to use and predictive in Thai population. Each parameter of the SEDAN score was an independent risk factor for sICH after treatment with i.v. rt-PA.
Acute ischemic stroke; intravenous recombinant tissue plasminogen activator; symptomatic intracranial hemorrhage; the SEDAN score
The use of antithrombotic therapy (anticoagulants and/or antiplatelets) in the setting of traumatic cervical arterial dissection (CAD) for the prevention of stroke remains controversial. This issue is further complicated by the frequent co-existence of intracranial hemorrhage (ICH) and other intracranial injuries, and also the wide variability in treatment due to a lack of evidence-based guidance. To address these controversies, a registry in a major Level I trauma center was created. The purpose of this investigation was to compare the safety of antithrombotic therapy in post-traumatic CAD. Analysis from the first year is presented.
All cervical dissections from the year 2005 were identified in patients at least 18 years of age by diagnosis code from radiology and trauma databases. Presence of arterial injury and grade, and other intracranial disease or injury such as stroke was diagnosed by a trauma radiologist and adjudicated by a neuroradiologist.
Fifty-five patients with cervical artery dissection were identified. Fourteen patients presented with a total of 20 acute, post-traumatic intracranial hemorrhages (ICH). Seven of the 14 patients with ICH were treated with antithrombotic therapy, and none extended their intracranial hemorrhages. Of the 41 patients without pre-existing ICH, 28 were treated with antithrombotic therapy and only one developed an interval hematoma. Among all 55 cases, two patients developed an acute ischemic stroke in the territory of the dissected artery after admission; both patients were in the untreated group.
In so far as antithrombotic therapy may offer benefit in preventing early ischemic stroke following cervical artery dissection, these data suggest withholding antiplatelet or other antithrombotics following trauma may not be warranted, even in the setting of intracranial hemorrhage. From a safety perspective, this registry-based case series indicates antithrombotic management of arterial injury did not contribute to development or progression of ICH, even in patients with pre-existing ICH. This data suggest that instituting early antithrombotic therapy presents a low risk of ICH or hemorrhage extension among traumatic cervical dissection patients.