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1.  Spontaneous intracerebral hemorrhage: Clinical and computed tomography findings in predicting in-hospital mortality in Central Africans 
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.
PMCID: PMC3409977  PMID: 22865958
Clinical and neuroimaging data; intracerebral hemorrhage; predictors of mortality; sub-Saharan Africa
2.  CT findings for intracerebral hemorrhage have little incremental impact on post-stroke mortality prediction model performance 
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.
PMCID: PMC3466471  PMID: 22814203
epidemiology; cerebral infarction; prediction of outcome; intracerebral hemorrhage
3.  Clinical features of recurrent stroke after intracerebral hemorrhage 
Neurology International  2012;4(2):e10.
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.
PMCID: PMC3490469  PMID: 23139848
stroke; brain infarction; intracerebral hemorrhage; stroke prevention.
4.  Immediate and Delayed Traumatic Intracranial Hemorrhage in Patients with Head Trauma and Pre-Injury Warfarin or Clopidogrel Use 
Annals of Emergency Medicine  2012;59(6):460-468.e7.
Study Objective
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.
PMCID: PMC3361700  PMID: 22626015
5.  Repeat Neuroimaging of Mild Traumatic Brain-injured Patients With Acute Traumatic Intracranial Hemorrhage: Clinical Outcomes and Radiographic Features 
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.
PMCID: PMC4283790  PMID: 25308130
6.  Efficacy and Safety of Panax notoginseng Saponin Therapy for Acute Intracerebral Hemorrhage, Meta-Analysis, and Mini Review of Potential Mechanisms of Action 
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.
PMCID: PMC4288044  PMID: 25620952
notoginsenosides; botanical medicine; nutraceuticals; TBI and stroke recovery; randomized controlled clinical trials; hemostasis; anti-coagulation; pharmacological mechanisms
7.  Effect of 20 mg/day Atorvastatin: Recurrent Stroke Survey in Chinese Ischemic Stroke Patients with Prior Intracranial Hemorrhage 
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.
PMCID: PMC3722464  PMID: 23894236
ischemic stroke; intracranial hemorrhage history; atorvastatin; stroke recurrence
8.  Location and Characteristics of Warfarin Associated Intracranial Hemorrhage 
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.
PMCID: PMC4205243  PMID: 25340019
Warfarin; Cerebral amyloid angiopathy; Intracerebral hemorrhage
9.  Ischemic stroke and intracranial hemorrhage in glioma patients on antiangiogenic therapy 
Journal of neuro-oncology  2011;105(2):281-289.
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.
PMCID: PMC3168718  PMID: 21603965
Glioma; Glioblastoma; Antiangiogenic agents; Bevacizumab; stroke; CNS hemorrhage
10.  Location characteristics of early perihaematomal oedema 
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.
PMCID: PMC2077688  PMID: 16484648
Intracerebral haemorrhage; perihaematomal oedema
11.  Arterial Stiffness in Patients with Deep and Lobar Intracerebral Hemorrhage 
Journal of Stroke  2014;16(3):184-188.
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.
PMCID: PMC4200589  PMID: 25328877
Hemorrhagic stroke; Intracerebral hemorrhage; Deep cerebral hemorrhage; Lobar cerebral hemorrhage; Arterial stiffness; Arterial hypertension
12.  Intracranial hemorrhage in full-term newborns: a hospital-based cohort study 
Neuroradiology  2010;52(6):567-576.
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.
PMCID: PMC2872016  PMID: 20393697
Intracranial hemorrhage; Intraparenchymal hemorrhage; Subdural hemorrhage; Full-term newborns
13.  Predictors of outcome in childhood intracerebral hemorrhage: a prospective consecutive cohort study 
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.
PMCID: PMC2821039  PMID: 20019325
intracerebral hemorrhage; outcome; childhood; vascular malformation
14.  Influence of stroke subtype on quality of care in the Get With The Guidelines–Stroke Program 
Neurology  2009;73(9):709-716.
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.
PMCID: PMC2734292  PMID: 19720978
15.  Surgical Management and Case-Fatality Rates of Intracerebral Hemorrhage in 1988 and 2005 
Neurosurgery  2008;63(6):1113-1118.
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.
PMCID: PMC2717618  PMID: 19057323
Intracerebral hemorrhage; neurosurgery; surgery; outcome
16.  Modified ASPECTS for DWI including deep white matter lesions predicts subsequent intracranial hemorrhage 
Journal of Neurology  2012;259(10):2045-2052.
We hypothesized that extensive early ischemic changes increase subsequent intracranial hemorrhage (ICH) in patients within 3 h of onset regardless of intravenous tPA (IV-tPA). We have established a modified scoring method, ASPECTS+W, including deep white matter lesions on DWI (DWI-W) in addition to the original ASPECTS regions. We aimed to elucidate whether CT-ASPECTS, DWI-ASPECTS, and ASPECTS+W could be useful tools in helping to predict subsequent ICH in acute ischemic stroke. One-hundred sixty-four consecutive patients with anterior circulation ischemic stroke were enrolled. All patients underwent both MRI and CT within 3 h of onset. ASPECTS+W was defined as an 11-point method combining the ten ASPECTS regions and DWI-W. The relationships of CT-ASPECTS, DWI-ASPECTS, and ASPECTS+W with ICH within the initial 36 h were assessed. Thirty-six patients (22%) were treated with IV-tPA. Follow-up CT was obtained in 159 patients, and 19 (12%) developed ICH. Patients with ICH had higher baseline NIHSS scores (median, 25 vs. 13, p = 0.010), a higher rate of IV-tPA (42 vs. 20%, p = 0.041), lower CT-ASPECTS (median, 7 vs. 10, p = 0.008), lower DWI-ASPECTS (6 vs. 9, p = 0.001), lower ASPECTS+W (6 vs. 9, p = 0.001), and higher DWI-W lesions (74 vs. 47%, p = 0.048) than those without ICH. ICA or M1 proximal occlusion was more frequently seen in patients with ICH (68 vs. 32%, p = 0.004) than in those without ICH. On multivariate regression analysis, lower ASPECTS+W (OR 0.75, 95% CI 0.58–0.96, p = 0.027) and administration of IV-tPA (OR 9.13, 95% CI 2.15–46.21, p = 0.004) independently predicted ICH development. In conclusion, ASPECTS+W is a useful tool for predicting ICH development independent of IV-tPA.
PMCID: PMC3464370  PMID: 22349869
Thrombolysis; Diffusion-weighted imaging; Tissue plasminogen activator; Alberta Stroke Programme Early CT Score; Intracranial hemorrhage; White matter
17.  Prognostic Value of ICH Score and ICH-GS Score in Chinese Intracerebral Hemorrhage Patients: Analysis From the China National Stroke Registry (CNSR) 
PLoS ONE  2013;8(10):e77421.
No strongevidenceofefficacycurrently exists for different intracerebral hemorrhage (ICH) scoring system in predicting the prognosis of ICH in the Chinese population. This study aimed to test the accuracyof the ICH score and the ICH grading scale (ICH-GS) score in predicting the favorable prognosis in a large cohort of ICH patients in China.
This study was a multicenter, prospective cohort study. Patients diagnosed with ICH between September 2007 and August 2008 from the nationwide China National Stroke Registry (CNSR) databasewere screened andenrolled in this study. Demographics of the patients, treatments, mortalityas well as the clinic and radiologic findings of ICH were collected.AnICH score and anICH-GS score were evaluated for all the patients atadmission. Follow-ups were conducted by phone at 3, 6 and 12 months after ICH onset. The modified Rankin scale (mRS) score was used to evaluate favorable functional outcome and was obtained at hospital dischargeand duringthe 3-, 6- and 12-month follow-up visits.
There were 410 (12.6%) in-hospitalmortalityout of a total of 3,255 ICH patients. Thevalues of the Area Under Curve (AUC)at discharge, 3-, 6- and 12-month follow-up for ICH score were 0.72, 0.76, 0.76 and 0.75, respectively; whilethe numbers for the ICH-GS score were 0.71, 0.77, 0.78 and 0.78, respectively. At 6-month and 12-month follow-up, the ICH-GS score presented a significant better value in predicting favorable prognosis than did the ICH score (P=0.0003 and <0.0001, respectively).
Both the ICH and ICH-GS scores were effective inaccurately predicting the favorable functional outcome of ICH in the Chinese population. For mid-term and long-term prediction, the ICH-GS score was superiorover the ICH score.
PMCID: PMC3797805  PMID: 24146993
18.  Predictors of the Intracerebral Hemorrhage Volume in Hypertensive Patients 
Hemorrhage volume is an important predictor of outcome in patients with intracerebral hemorrhage (ICH). It is not clear why in some patients ICH volume is larger than in others. Identification of modifiable factors responsible for large-volume hemorrhage in hypertensive patients may help to reduce ICH-related morbidity and mortality.
The objective of this study was to identify predictors of large-volume ICH in hypertensive patients.
At a tertiary care center in Karachi (Pakistan), 157 hypertensive patients with ICH were prospectively analyzed in 2008–2009, and hemorrhage volumes were determined using CT or MRI and various factors, including duration of hypertension, medical treatment, compliance, co-morbidity, and hematologic and coagulation profiles. Logistic regression analysis was used to identify predictors of high-volume hemorrhage. A volume >30 mm3 was defined as high-volume hemorrhage.
Of 157 patients with hypertensive ICH evaluated, 133 patients were included in the study, and 24 patients with brain stem, cerebellum and pure intraventricular hemorrhage were excluded. The mean age of the study patients was 55 years; 56 patients (70%) were male. High-volume hemorrhage (>30 mm3) was noted in 47 (35%) patients. Mortality was significantly increased in patients with high-volume ICH (32 vs. 6% in patients with low-volume ICH). In univariate analysis, factors significantly associated with large-volume ICH were male gender (p = 0.002), hypertension lasting >10 years (p = 0.03), warfarin treatment (p = 0.05), use of >1 anti-hypertensive agent (p = 0.001) and poor compliance with medication (p = 0.001). In multivariate analysis, use of >1 anti-hypertensive agent and poor compliance were also predictors of large-volume ICH.
High-volume hemorrhage was less common (28%) in our patients with hypertension and ICH. Use of >1 anti-hypertensive agent and poor compliance were predictors of large-volume ICH.
PMCID: PMC3343758  PMID: 22566977
Brain hemorrhage; Coagulation profile; Hemorrhage volume; Hypertension; Intracerebral hemorrhage; Warfarin
19.  Intraventricular hemorrhage 
Neurology  2008;70(11):848-852.
Spontaneous intracerebral hemorrhage (ICH) is frequently associated with intraventricular hemorrhage (IVH), which is an independent predictor of poor outcome. The purpose of this study was to examine the relationship between ICH volume and anatomic location to IVH, and to determine if ICH decompression into the ventricle is truly beneficial.
We retrospectively analyzed the CT scans and charts of all patients with ICH admitted to our stroke center over a 3-year period. Outcome data were collected using our prospective stroke registry.
We identified 406 patients with ICH. A total of 45% had IVH. Thalamic and caudate locations had the highest IVH frequency (69% and 100%). ICH volume and ICH location were predictors of IVH (p < 0.001). Within each location, decompression ranges (specific volume ranges where ventricular rupture tends to occur) were established. Patients with IVH were twice as likely to have a poor outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when compared to patients without IVH. Caudate location was associated with a good outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was not associated with better outcome, regardless of parenchymal volume reduction (p = 0.72).
Intraventricular hemorrhage (IVH) occurs in nearly half of patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH volume and location. IVH is likely to occur within the “decompression ranges” that take into account both ICH location and volume. Further, spontaneous ventricular decompression does not translate to better clinical outcome. This information may prove useful for future ICH trials, and to the clinician communicating with patients and families.
PMCID: PMC2745649  PMID: 18332342
20.  Intracerebral Hemorrhage Volume Predicts Poor Neurologic Outcome in Children 
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.
PMCID: PMC2830068  PMID: 19286576
child; intracerebral hemorrhage; stroke
21.  Study of clinical features of amyloid angiopathy hemorrhage and hypertensive intracerebral hemorrhage 
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.
PMCID: PMC1388732  PMID: 15362199
Intracerebral hemorrhage; Cerebral amyloid angiopathy; Hypertension; Diagnosis; Computed tomography; Magnetic resonance imaging
22.  Warfarin use leads to larger intracerebral hematomas 
Neurology  2008;71(14):1084-1089.
Among patients with intracerebral hemorrhage (ICH), warfarin use before onset leads to greater mortality. In a retrospective study, we sought to determine whether warfarin use is associated with larger initial hematoma volume, one determinant of mortality after ICH.
We identified all patients hospitalized with ICH in the Greater Cincinnati region from January through December 2005. ICH volumes were measured on the first available brain scan by using the abc/2 method. Univariable analyses and a multivariable generalized linear model were used to determine whether international normalized ratio (INR) influenced initial ICH volume after adjusting for other factors, including age, race, sex, antiplatelet use, hemorrhage location, and time from stroke onset to scan.
There were 258 patients with ICH, including 51 patients taking warfarin. In univariable comparison, when INR was stratified, there was a trend toward a difference in hematoma volume by INR category (INR <1.2, 13.4 mL; INR 1.2–2.0, 9.3 mL; INR 2.1–3.0, 14.0 mL; INR >3.0, 33.2 mL; p = 0.10). In the model, compared with patients with INR <1.2, there was no difference in hematoma size for patients with INR 1.2–2.0 (p = 0.25) or INR 2.1–3.0 (p = 0.36), but patients with INR >3.0 had greater hematoma volume (p = 0.02). Other predictors of larger hematoma size were ICH location (lobar compared with deep cerebral, p = 0.02) and shorter time from stroke onset to scan (p < 0.001).
Warfarin use was associated with larger initial intracerebral hemorrhage (ICH) volume, but this effect was only observed for INR values >3.0. Larger ICH volume among warfarin users likely accounts for part of the excess mortality in this group.
= anticoagulant-associated intracerebral hemorrhage;
= Genetic and Environmental Risk Factors for Hemorrhagic Stroke;
= hazard ratio;
= intracerebral hemorrhage;
= international normalized ratio;
= intraventricular hemorrhage.
PMCID: PMC2668872  PMID: 18824672
23.  High S100B levels in cerebrospinal fluid and peripheral blood of patients with acute basal ganglial hemorrhage are associated with poor outcome 
S100B is involved in brain injury. This study aimed to determine plasma and cerebral spinal fluid (CSF) levels of S100B in patients with spontaneous intracerebral hemorrhage (ICH), and to correlate S100B levels with Glasgow Coma Scale (GCS) scores, ICH volumes, presence of intraventricular hemorrhage (IVH), and survival rate, and to correlate CSF S100B levels with plasma S100B levels as well as CSF interleukin-1beta (IL-1β) levels.
Ten patients with suspicion of subarachnoid hemorrhage and 38 patients with spontaneous basal ganglia hemorrhage were included in the study. Their plasma and CSF samples were collected. The concentrations of IL-1β in CSF and S100B in plasma and CSF were analyzed by enzyme-linked immunosorbent assay.
Plasma or CSF S100B levels in the ICH group were significantly higher than those in the control group (178.7±74.2 versus 63.2±23.0 pg/ml; P<0.001 or 158.1±70.9 versus 1.8±0.7 ng/ml; P<0.001). S100B levels were highly associated with GCS scores, ICH volumes, presence of IVH, and survival rate (all P<0.05). CSF S100B levels were highly associated with plasma S100B levels as well as CSF IL-1β levels (both P<0.01) in patients with ICH. A receiver operating characteristic curve identified CSF and plasma S100B cutoff levels that predicted 1-week mortality of patients with a high sensitivity and specificity. The areas under curves (AUCs) of GCS scores and ICH volumes were larger than those of CSF and plasma S100B levels, but the differences were not statistically significant (P>0.05).
High levels of S100B are present in the cerebrospinal fluid and peripheral blood of patients with ICH and may contribute to the inflammatory processes of ICH. The levels of CSF and plasma S100B after spontaneous onset of ICH seem to correlate with clinical outcome in these patients. Increases in peripheral S100B properly reflect brain injury, and plasma S100B level may serve as a useful clinical marker for evaluating the prognosis of ICH.
PMCID: PMC4129764  PMID: 25214936
S100B; Interleukin-1 beta; Intracerebral hemorrhage; Intraventricular hemorrhage; Brain injury; Inflammation; Pathogenesis
24.  Intracranial haemorrhage in thrombocytopenic haematology patients—a nested case–control study: the InCiTe study protocol 
BMJ Open  2014;4(2):e004199.
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.
Study aims
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.
Study Registration
ISRCTN05026912 (prospective registration). NIHR Portfolio (UKCRN ID 10712).
PMCID: PMC3919001  PMID: 24508852
25.  Does Pre-existing Antiplatelet Treatment Influence Post-thrombolysis Intracranial Hemorrhage in Community-treated Ischemic Stroke Patients? An Observational Study 
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.
PMCID: PMC3576048  PMID: 23406073

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