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.
As clopidogrel is being increasingly used, intracerebral hemorrhage (ICH) associated with clopidogrel are expected to increase. We assessed the prevalence and clinical characteristics of of ICH with clopidogrel in a consecutive series of patients in two hospitals.
We retrospectively reviewed the medication history of 204 patients (112 in one hospital and 92 in another – both individually consecutive) admitted with ICH. We identified the patients who were using clopidogrel prior to ICH occurrence. The etiology of the ICH was categorized on the basis of clinical history and diagnostic imaging, and outcome was subsequently evaluated.
A total of 8 (4%) of the 204 patients were using clopidogrel prior to onset of ICH. Clopidogrel was the only medication in 3 patients and was used with aspirin or warfarin in 3 and 2 patients, respectively. Aspirin or warfarin was the only medication in 23 (%) and 14 (%) patients associated with ICH, respectively. The hematoma was located in the basal ganglia (n=2), lobes (n=2), thalamus (n=1), intraventricular (n=2), and cerebellar (n=2). One patient had secondary intraventricular extension. All patients using a combination of clopidogrel and warfarin prior to ICH died.
The prevalence of ICH associated with clopidogrel is approximating the prevalence of aspirin- or warfarin-associated ICH. The mortality with clopidogrel related ICH appears to be high particularly when in combination with another antithrombotic agent.
Clopidogrel; warfarin; aspirin; hypertension; intracerebral hemorrhage; intraventricular hemorrhage; mortality; neurological outcome
To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset.
Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010.
13 tertiary referral centres from nine countries across the world.
37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed.
Primary and secondary outcome measures
Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures.
From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH.
ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.
The ICH Score is a commonly used clinical grading scale for outcome after acute intracerebral hemorrhage (ICH) and has been validated for 30-day mortality, but not long-term functional outcome. The goals of this study were to assess whether the ICH Score accurately stratifies patients with regard to 12-month functional outcome and to further delineate the pace of recovery of patients during the first year post-ICH.
We performed a prospective observational cohort study of all patients with acute ICH admitted to the emergency departments of San Francisco General Hospital and UCSF Medical Center from June 1, 2001, through May 31, 2004. Components of the ICH Score (admission Glasgow Coma Scale score, initial hematoma volume, presence of intraventricular hemorrhage, infratentorial ICH origin, and age) were recorded along with other clinical characteristics. Patients were then assessed with the modified Rankin Scale (mRS) at hospital discharge, 30 days, and 3, 6, and 12 months post-ICH.
Of 243 patients, 95 (39%) died during initial acute hospitalization. The ICH Score accurately stratified patients with regard to 12-month functional outcome for various dichotomous cutpoints along the mRS (p < 0.05). Many patients continued to improve across the first year, with a small number of patients becoming disabled or dying due to late events unrelated to the initial ICH.
The ICH Score is a valid clinical grading scale for long-term functional outcome after acute intracerebral hemorrhage (ICH). Many ICH patients improve after hospital discharge and this improvement may continue even after 6 months post-ICH.
= Committee on Human Research;
= emergency department;
= Glasgow Coma Scale;
= intracerebral hemorrhage;
= intraventricular hemorrhage;
= modified Rankin Scale;
= San Francisco General Hospital.
To evaluate the incidence, characteristics, and clinical consequences of delayed intraventricular hemorrhage (dIVH).
Patients with primary intracerebral hemorrhage (ICH) were enrolled into a prospective registry between December 2006 and February 2012. Patients were managed, and serial neuroimaging obtained, per a structured protocol. Initial and delayed IVH were identified on imaging, along with ICH volumes, with outcomes blinded. Multivariate models were developed to test whether the occurrence of dIVH was a predictor of functional outcomes independent of known predictors, including the ICH score elements and ICH growth.
A total of 216 patients were studied, and 104 (48%) had IVH on initial imaging. Of the 112 with no IVH, 23 (21%) subsequently developed IVH. Emergent surgical intervention, mostly ventriculostomy placement, was required after discovery of dIVH in 10 (43%) of these 23. In multivariate models adjusting for all elements of the ICH score and hematoma growth, dIVH was an independent predictor of death at 14 days (p = 0.015) and higher modified Rankin Scale scores at 3 months (all p = 0.037). The effect of dIVH remained significant in a secondary analysis that adjusted for all other variables significant in the univariate analysis.
Similar to hematoma expansion dIVH is independently associated with death and poor outcomes. Because IVH is easily detected by serial neuroimaging and often requires emergent surgical intervention, monitoring for dIVH is recommended.
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.
To evaluate disparities in stroke risk factors and outcome among the Native Hawaiians and other Pacific Islanders (NHPI) in Hawaii who are hospitalized with intracerebral hemorrhage (ICH).
We performed a retrospective study on consecutive patients hospitalized for acute ICH at a single tertiary center on Oahu between 2004 and 2010. Clinical data were obtained from the Get With the Guidelines–Stroke database. Multivariable logistic regression was used to assess the predictors for young ICH (age <45).
A total of 562 patients hospitalized for acute ICH (Asian 63%, NHPI 18%, white 16%, other 3%) were studied. The NHPI were younger (mean ages, NHPI 55 ± 16 vs white 66 ± 16 years, p < 0.0001), and had higher prevalence of diabetes (NHPI 35% vs white 20%, p = 0.01) and history of hypertension (NHPI 77% vs white 64%, p = 0.04) compared to white patients. Independent predictors for young ICH were NHPI race (odds ratio [OR] 3.55; 95% confidence interval [CI] 1.33–9.45), being transferred from another hospital (OR 2.03; 95% CI 1.05–3.93), hypertension (OR 0.49; 95% CI 0.27–0.91), previous stroke or TIA (OR 0.21; 95% CI 0.05–0.91), and dyslipidemia (OR 0.15; 95% CI 0.05–0.50).
NHPI with ICH are younger and have higher burden of risk factors compared to white patients. Further studies controlling for socioeconomic modifiers are needed to determine factors contributing to the younger age at presentation in this racial group.
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
Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated.
Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes.
Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs.
TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity.
Mycobacterium tuberculosis (TB); Hematological malignancy; Febrile neutropenia
To date there is only one single-center study that has exclusively reported characteristics, location, and outcomes of spontaneous intracerebral hemorrhages (ICH) among cocaine users. We aimed to describe the radiological location and characteristics along with clinical outcomes of spontaneous ICH in a similar population. We conducted a retrospective chart review of consecutive patients admitted to a tertiary care hospital, with a spontaneous ICH, who had a urine drug screen performed within 48 hours of admission. Exposure to cocaine was defined by a positive urine drug screen within 48 hours of hospital admission. Demographics, radiographic features of ICH, and short-term clinical outcomes of patients with a positive urine drug screen were analyzed and compared with the cocaine negative group. Among the 102 patients analyzed, 20 (19.6%) had documented exposure to cocaine. There was a predominance of males in both groups with significantly more Blacks in the cocaine positive group (P = 0.0246). A statistically significant number of patients with cocaine use had ICH in a subcortical location (P = 0.0224) when compared to cocaine negative patients. There was no difference in GCS, ICH volume, intraventricular extension, ICU days, hospital days, hospital cost, mortality, and ICH score. ICH in cocaine use is more frequently seen in the subcortical location.
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
Intracerebral hemorrhage (ICH) is a devastating disease that carries a 30 day mortality of approximately 45%. Only 20% of survivors return to independent function at 6 months. The role of inflammation in the pathophysiology of ICH is increasingly recognized. Several clinical studies have demonstrated an association between inflammatory markers and outcomes after ICH; however the relationship between serum biomarkers and functional outcomes amongst survivors has not been previously evaluated. Activation of the inflammatory response as measured by change in peripheral leukocyte count was examined and assessment of mortality and functional outcomes after ICH was determined.
Patients with spontaneous ICH admitted to a tertiary care center between January 2005 and April 2010 were included. The change in leukocyte count was measured as the difference between the maximum leukocyte count in the first 72 hours and the leukocyte count on admission. Mortality was the primary outcome. Secondary outcomes were mortality at 1 year, discharge disposition and the modified Barthel index (MBI) at 3 months compared to pre-admission MBI. 423 cases were included. The in-hospital mortality was 30.4%. The change in leukocyte count predicted worse discharge disposition (OR = 1.258, p = 0.009). The change in leukocyte count was also significantly correlated with a decline in the MBI at 3 months. These relationships remained even after removal of all patients with evidence of infection.
Greater changes in leukocyte count over the first 72 hours after admission predicted both worse short term and long term functional outcomes after ICH.
Intracerebral Hemorrhage; Outcomes; Inflammation; Leukocyte Count
Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH.
We performed a retrospective analysis of all patients admitted to our stroke service from 2004 to 2007 who had non-traumatic ICH and urine drug screens positive for cocaine and compared them with similar patients who had a negative drug screen for cocaine.
We identified 45 patients with cocaine-associated ICH and 105 patients with cocaine-negative ICH. There were no significant differences in age or gender but there was a significantly higher incidence of African-American patients in the cocaine positive group. Cocaine-associated ICH patients had higher admission blood pressures, significantly more subcortical hemorrhages, and higher rates of intraventricular hemorrhage (IVH) compared to patients with cocaine-negative ICH. Cocaine-positive patients had worse functional outcome, defined as an mRS>3 at the time of discharge (OR 4.90, 95% CI 2.19–10.97), and were less likely to be discharged home or to inpatient rehab. Patients with cocaine-associated ICH were nearly 3 times more likely to die during their acute hospitalization when compared to cocaine-negative patients.
Recent cocaine ingestion is associated with hemorrhages that occur more frequently in subcortical locations, have a higher risk of IVH, and carry a poor prognosis compared to patients with cocaine-negative, spontaneous ICH.
Intracerebral hemorrhage; cocaine; outcome
Intracerebral hemorrhage (ICH) is a highly lethal disease of the elderly. Use of statins is increasingly widespread among the elderly, and therefore common in patients who develop ICH. Accumulating data suggests that statins have neuroprotective effects, but their association with ICH outcome has been inconsistent. We therefore performed a meta-analysis of all available evidence, including unpublished data from our own institution, to determine whether statin exposure is protective for patients who develop ICH.
In our prospectively ascertained cohort, we compared 90-day functional outcome in 238 pre-ICH statin cases and 461 statin-free ICH cases. We then meta-analyzed results from our cohort along with previously published studies using a random effects model, for a total of 698 ICH statin cases and 1,823 non–statin-exposed subjects.
Data from our center demonstrated an association between statin use before ICH and increased probability of favorable outcome (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.37–3.17) and reduced mortality (OR = 0.47, 95% CI 0.32–0.70) at 90 days. No compound-specific statin effect was identified. Meta-analysis of all published evidence confirmed the effect of statin use on good outcome (OR = 1.91, 95% CI 1.38–2.65) and mortality (OR = 0.55, 95% CI 0.42–0.72) after ICH.
Antecedent use of statins prior to ICH is associated with favorable outcome and reduced mortality after ICH. This phenomenon appears to be a class effect of statins. Further studies are required to clarify the biological mechanisms underlying these observations.
Primary intracerebral hemorrhage is two to three times more common in many racial populations, including black patients. Previous studies have shown that microbleeds, identified on gradient echo MRI (GRE), are present in 50–80% of patients with primary ICH. The objective of this study was to compare, by race, the rates, risk factors, and topography of microbleeds in patients hospitalized for primary ICH.
Patients diagnosed with primary ICH at two metropolitan stroke centers were included. Clinical and neuroimaging data were recorded for each patient. Analyses were performed to compare baseline characteristics as well as imaging findings by race.
A total of 87 patients met inclusion criteria (42 black subjects, 45 white subjects). The black cohort was younger (p < 0.001), and had a greater rate of hypertension (p = 0.001), but not other vascular risk factors. Microbleeds were more prevalent in the black population, with 74% of blacks having one or more microbleeds compared to 42% of whites (p = 0.005). The black population also tended to have a greater frequency of microbleeds in multiple territories than the white population (38% vs 22%, p = 0.106). When adjusting for age, hypertension, and alcohol use, race was an independent predictor of microbleeds (OR 3.308, 95% CI 1.144–9.571, p = 0.027).
These pilot data suggest that significant racial differences exist in the frequency and topography of microbleeds in patients with primary ICH. Microbleeds may be an important emerging imaging biomarker with the potential to provide insights into ICH pathophysiology, prognosis, and disease progression, as well as possible therapeutic strategies, particularly in medically underserved populations.
= cerebral amyloid angiopathy;
= fluid-attenuated inversion recovery;
= field of view;
= gradient echo imaging;
= socioeconomic status;
= echo time;
= repetition time.
To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary non-traumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH.
Retrospective analysis of data collected in a prospective cohort study.
Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH.
Main Outcome Measures
Presence of SDH and mortality.
Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH (P<.001 for comparison with lobar ICH). Intracerebral hemorrhage volume higher than 60 cm3 was the only independent predictor of SDH (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.14–6.34; P=.02). Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality (OR, 7.60; 95% CI, 1.86–30.99; P=.005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume (OR, 12.85; 95% CI, 2.42–68.23; P=.003 for those with ICH volume <30 cm3). Cerebral amyloid angiopathy was present in 8 of 9 patients with pathological specimens.
Nontraumatic SDH frequently accompanies primary lobar ICH and is associated with higher 30-day mortality, particularly when the ICH volume is relatively low. Rupture of an amyloid-laden leptomeningeal vessel, with extravasation into the brain parenchyma and subdural space, may be the pathogenic mechanism.
Intracranial hemorrhage (ICH) in full-term neonates with hemophilia is uncommon. Retrospective studies estimate the incidence to be 3.4%-4.0%. However, ICH is the second most common initial hemorrhage for all infants with congenital hemophilia. Nearly half (41%) of the hemorrhages occur within the first week of life, and most hemorrhages are related to traumatic deliveries. But clinical signs of ICH in neonates are difficult to assess and often result in a delay in the diagnosis. The timely diagnosis of ICH is critical; however, the early and intensive factor replacement therapy that the patient needs is associated with the risk of inhibitor formation. We report a case of ICH in a neonate with severe hemophilia A, no family history, and inhibitor development after intensive therapy.
Hemophilia; intracranial hemorrhage; neonatology
Super-infection in adult bacterial meningitis (ABM) is a condition wherein the cerebrospinal fluid (CSF) grows new pathogen(s) during the therapeutic course of meningitis. It is an uncommon but clinically important condition rarely examined in literature.
Twenty-seven episodes of super-infection states in 21 ABM patients collected in a 9.5-year study period (January 2001 to June 2010) were evaluated. The clinical characteristics, implicated pathogens, results of antimicrobial susceptibility tests, and therapeutic outcomes were analyzed.
Twenty-one patients (13 men, 8 women) aged 25-73 years (median, 45 years) had post-neurosurgical state as the preceding event and nosocomial infection. The post-neurosurgical states included spontaneous intracranial hemorrhage (ICH) with craniectomy or craniotomy with extra-ventricular drainage (EVD) or ventriculo-peritoneal shunt (VPS) in 10 patients, traumatic ICH with craniectomy or craniotomy with EVD or VPS in 6 patients, hydrocephalus s/p VPS in 2 patients, and one patient each with cerebral infarct s/p craniectomy with EVD, meningeal metastasis s/p Omaya implant, and head injury. All 21 patients had EVD and/or VP shunt and/or Omaya implant during the whole course of ABM. Recurrent fever was the most common presentation and the implicated bacterial pathogens were protean, many of which were antibiotic resistant. Most patients required adjustment of antibiotics after the pathogens were identified but even with antimicrobial therapy, 33.3% (7/21) died. Morbidity was also high among survivors.
Super-infection in ABM is usually seen in patients with preceding neurosurgical event, especially insertion of an external drainage device. Repeat CSF culture is mandatory for diagnostic confirmation because most of the implicated bacterial strains are non-susceptible to common antibiotics used. Unusual pathogens like anaerobic bacteria and fungi may also appear. Despite antimicrobial therapy, prognosis remains poor.
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.
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
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.
Brain hemorrhage; Coagulation profile; Hemorrhage volume; Hypertension; Intracerebral hemorrhage; Warfarin
Brain arteriovenous malformations (BAVM) are a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation and an important cause of intracranial hemorrhage (ICH). EphB4 is involved in arterial-venous determination during embryogenesis; altered signaling could lead to vascular instability resulting in ICH. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes in EPHB4 with risk of ICH at clinical presentation in BAVM patients.
Methods and Results
Eight haplotype-tagging SNPs spanning ∼29 kb were tested for association with ICH presentation in 146 Caucasian BAVM patients (phase I: 56 ICH, 90 non-ICH) using allelic, haplotypic, and principal components analysis. Associated SNPs were then genotyped in 102 additional cases (phase II: 37 ICH, 65 non-ICH) and data combined for multivariable logistic regression. Minor alleles of 2 SNPs were associated with reduced risk of ICH presentation (rs314313 C, P=0.005; rs314308 T, P=0.0004). Overall, haplotypes were also significantly associated with ICH presentation (χ2=17.24, 6 df, P=0.008); 2 haplotypes containing the rs314308 T allele (GCCTGGGT, P=0.003; GTCTGGGC, P=0.036) were associated with reduced risk. In principal components analysis, 2 components explained 91% of the variance, and complemented haplotype results by implicating 4 SNPs at the 5′ end, including rs314308 and rs314313. These 2 SNPs were replicated in the phase II cohort, and combined data resulted in greater significance (rs314313, P=0.0007; rs314308, P=0.00008). SNP association with ICH presentation persisted after adjusting for age, sex, BAVM size, and deep venous drainage.
EPHB4 polymorphisms are associated with risk of ICH presentation in BAVM patients, warranting further study.
cerebrovascular disorders; genetics; hemorrhage; receptors; risk factors
Little is known about the incidence and risk of seizures after stroke in young adults. Especially in the young seizures might dramatically influence prognosis and quality of life. We therefore investigated the long-term incidence and risk of post-stroke epilepsy in young adults with a transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH).
Methods and Findings
We performed a prospective cohort study among 697 consecutive patients with a first-ever TIA, IS or ICH, aged 18–50 years, admitted to our hospital between 1-1-1980 till 1-11-2010. The occurrence of epilepsy was assessed by standardized questionnaires and verified by a neurologist. Cumulative risks were estimated with Kaplan-Meier analysis. Cox proportional hazard models were used to calculate relative risks. After mean follow-up of 9.1 years (SD 8.2), 79 (11.3%) patients developed post-stroke epilepsy and 39 patients (5.6%) developed epilepsy with recurrent seizures. Patients with an initial late seizure more often developed recurrent seizures than patients with an initial early seizure. Cumulative risk of epilepsy was 31%, 16% and 5% for patients with an ICH, IS and TIA respectively (Logrank test ICH and IS versus TIA p<0.001). Cumulative risk of epilepsy with recurrent seizures was 23%, 8% and 4% respectively (Logrank ICH versus IS p = 0.05, ICH versus TIA p<0.001, IS versus TIA p = 0.01). In addition a high NIHSS was a significant predictor of both epilepsy and epilepsy with recurrent seizures (HR 1.07, 95% CI 1.03–1.11 and 1.08, 95% CI 1.02–1.14).
Post-stroke epilepsy is much more common than previously thought. Especially patients with an ICH and a high NIHSS are at high risk. This calls upon the question whether a subgroup could be identified which benefits from the use of prophylactic antiepileptic medication. Future studies should be executed to investigate risk factors and the effect of post-stroke epilepsy on quality of life.
Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke vs. ICH in a large community-based cohort of patients with atrial fibrillation.
We followed 13,559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio (INR) at presentation with 30-day mortality was modeled using multivariable logistic regression, adjusting for clinical factors.
We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted odds ratio and 95% confidence interval [OR] = 0.64 [0.45, 0.91]), but a higher mortality from ICH (OR = 1.62 [0.88, 2.98]). Therapeutic INRs (2-3) were associated with an especially low ischemic stroke mortality (OR = 0.38 [0.20, 0.70]) while INRs > 3 increased the odds of dying of ICH by 2.66 fold (95% confidence interval: 1.21, 5.86).
Warfarin reduces 30-day mortality from ischemic stroke, but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.
Acute stroke; Intracranial hemorrhage; Anticoagulants; Warfarin; Atrial fibrillation
Hematoma volume is a major determinant of outcome in patients with intracerebral hemorrhage (ICH). Accurate volume measurements are critical for predicting outcome and are thought to be more difficult in patients with oral anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular shape. We examined hematoma shape and methods of volume assessment in patients with OAT-ICH.
We performed a case–control analysis of a prospectively identified cohort of consecutive patients with ICH. We retrospectively reviewed 50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH controls. Two independent readers analyzed CT scans for hematoma shape and volume using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical variables including warfarin status. Gold-standard ICH volumes were determined using validated computer-assisted planimetry.
Within this cohort, median INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly different between non-OAT-ICH and OAT-ICH (35 ± 38 cc vs. 53 ± 56 cc, P = 0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated median volume by 9 (3–28) cc, while the ABC/2 calculation did so by 4 (0.8–12) cc.
Hematoma shape was not statistically significantly different in patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH.
Cerebral hemorrhage; Tomography; X-ray computed; Warfarin