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hemorrhage

Combining CT Biomarkers for Prediction of Hematoma Expansion

Lina Palaiodimou, MD

Morotti A, Boulouis G, Charidimou A, Schwab K, Kourkoulis C, Anderson C, et al. Integration of Computed Tomographic Angiography Spot Sign and Noncontrast Computed Tomographic Hypodensities to Predict Hematoma Expansion. Stroke. 2018

Recently, there is increasing interest regarding available therapeutic options that can restrict hematoma expansion after spontaneous intracerebral hemorrhage (ICH) and may contribute to improved functional outcomes. Despite the initial enthusiasm in different therapeutic strategies (tranexamic acid, blood pressure lowering medication, etc.), the efficacy of such an approach has not been validated in the context of a randomized controlled clinical trial.

The question arises, whether these disappointing results would be different, if inclusion criteria were stricter (narrower time window) or based on patient selection using specific biomarkers. One proposed radiological biomarker is the presence of intrahematoma hypodensities (HD), which are defined as any hypodense region inside the hematoma, as seen in a non-contrast computed tomography (NCCT), having any morphology and size, disconnected from surrounding brain parenchyma. Another biomarker is the spot-sign (SS), which can be seen in a CT angiography (CTA) and is defined as presence of at least one focus of contrast, pooling within the hemorrhage and lack of connection with normal or abnormal vessels surrounding the hemorrhage. Both of these biomarkers have been shown to independently predict hematoma expansion in ICH and can be obtained by readily available imaging techniques.

Beware of Nonconvulsive Status Epileptics in Intracerebral Hemorrhage Patients

Mohammad Anadani, MD

Matsubara S, Sato S, Kodama T, Egawa S, Nakamoto H, Toyoda K, et al. Nonconvulsive Status Epilepticus in Acute Intracerebral Hemorrhage. Stroke. 2018

Nonconvulsive status epileptics (NCSE) is one of the known complications of intracerebral hemorrhage (ICH). However, the incidence and predictors of NCSE after ICH are not well reported.

In this article, the authors aimed to report the frequency and predictors of NCSE in the nontraumatic ICH and to investigate the effect of NCSE on the functional outcome.

This study was a retrospective, single-center study of patients with nontraumatic ICH who were admitted within three days of symptoms onset. NCSE was defined based on the modified Salzburg Consensus Criteria. Lobar hemorrhage was defined as ICH in the frontal, parietal, temporal, occipital or insular lobe.

Size of Ruptured Intracranial Aneurysm — Is Epidemiology Really Changing?

Tapan Mehta, MBBS, MPH

Korja M, Kivisaari R, Jahromi BR, Lehto H. Size of Ruptured Intracranial Aneurysms Is Decreasing: Twenty-Year Long Consecutive Series of Hospitalized Patients. Stroke. 2018

Since the 1980s, the epidemiology of cerebrovascular diseases has changed significantly. Primary, secondary and tertiary prevention interventions have advanced with technology, and they are sufficient enough to change the epidemiologic outlook of cerebrovascular diseases. In addition to the advances in medical and surgical interventions, awareness for controlling the vascular risk factors has also increased, including a significant decrease in prevalence of smoking. Understanding epidemiology of intracranial aneurysm has become even more important in today’s era given more and more treatment options are becoming available, which are effective and safe.

Korja et. al present an interesting and novel epidemiologic trend in Finnish population suggesting a decrease in size of ruptured intracranial aneurysms over the past two decades.

Association Between Prehospital Blood Pressure and Extent of Bleeding in Patients with Acute Intracerebral Hemorrhage

Andrea Morotti, MD

Rodriguez-Luna D, Rodriguez-Villatoro N, Juega JM, Boned S, Muchada M, Sanjuan E, et al. Prehospital Systolic Blood Pressure Is Related to Intracerebral Hemorrhage Volume on Admission. Stroke. 2018

Elevated blood pressure has been consistently associated with active bleeding and unfavorable prognosis in acute intracerebral hemorrhage (ICH). Dr. Rodriguez-Luna and colleagues investigated whether systolic blood pressure (SBP) in the prehospital phase correlates with admission SBP and extent of bleeding measured as baseline ICH volume. To explore this association, a prospectively collected cohort of ICH patients was retrospectively analyzed. A total of 219 patients qualified for the analysis (mean age 76, 54% males), with mean baseline ICH volume of 25 mL. Prehospital SBP was strongly correlated with admission SBP (r=0.552; P<0.001) and baseline ICH volume (ρ=0.189; P=0.006), as shown in the Figure.

Scatterplots showing the relationship between prehospital systolic blood pressure (SBP) and time from symptom onset (A), SBP on admission (B), and intracerebral hemorrhage (ICH) volume on admission (C).

Figure: Scatterplots showing the relationship between prehospital systolic blood pressure (SBP) and time from symptom onset (A), SBP on admission (B), and intracerebral hemorrhage (ICH) volume on admission (C).

When Should We Anticoagulate Atrial Fibrillation Patients After an Intracranial Hemorrhage?

Hatim Attar, MD

Pennlert J, Overholser R, Asplund K, Carlberg B, Rompaye BV, Wiklund PG, et al. Optimal Timing of Anticoagulant Treatment After Intracerebral Hemorrhage in Patients With Atrial Fibrillation. Stroke. 2017

To answer this question, Pennlert et al completed a large observational study in Swedish patients. The timing for anticoagulation (AC) after Intracerebral Hemorrhage (ICH) has been brought up several times, with a recent systemic review and meta-analysis published in Stroke by Murthy et al (Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis). Further, the specific time point at when it is considered safe to restart anticoagulation is in flux without any current international guideline. However, this paper by Pennlert et al provides clarity specifically targeting AC in A. fib patients who have had an ICH and at what time is it optimal to start anticoagulation.

The authors used the national Swedish Stroke Register, Riksstroke, which included first-time ICH with concurrent diagnosis of atrial fibrillation between July 1, 2005 and December 31, 2012 who survived their hospitalization. Patients with a first-time ICH with a concomitant diagnosis of AF were included. Two primary outcome events were defined; the first was overall ischemic stroke events and deaths related to any vascular thrombotic event. The second outcome was recurrent ICH, as well as death attributable to other hemorrhages. Follow-up was initiated only after day 28 of the first event. Patients on dual therapy antiplatelet and anticoagulant agents were excluded. Patients were then stratified into two groups, low risk and high risk, based on patient demographics and co-morbidities via the CHA2DS2-VASc scoring system.

Readmission after Subarachnoid Hemorrhage

Pouya Tahsili-Fahadan, MD

Dasenbrock HH, Angriman F, Smith TR, Gormley WB, Frerichs KU, Aziz-Sultan MA, et al. Readmission After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Readmission Database Analysis. Stroke. 2017

Readmission (within a pre-defined period of time from discharge) is frequently measured and reported as a quality measure for care provided by physicians and hospitals. However, it is debatable whether this measure is an appropriate quality metric for various indications and etiologies of the index hospitalization. Dasenbrock et al. investigated this question by analyzing the Nationwide Readmission Database (NRD) for readmission after aneurysmal subarachnoid hemorrhage (SAH).

Data from this longitudinal administrative database within 21 states were extracted for 3806 non-elective adult patients admitted for treatment of aneurysmal subarachnoid or intracerebral hemorrhage and discharged alive in 2013. Mortality during the index hospitalization and readmission were 11% and 1.7%, respectively, and about two thirds of survivors were discharged home. The median cost of the index and readmission hospitalizations were $266,304 and $45,091, respectively, and readmission was associated with increased total costs. Within the next 30 days from discharge, 10.2% of patients were readmitted with 34.4%, 65.6%, and 82.4% of readmissions within 1, 2, and 3 weeks from discharge, respectively. As expected, patients who were readmitted had higher SAH severity scale, higher incidence of cerebral edema, and complications during their index hospitalization, and were more likely to undergo tracheostomy or gastrostomy, and less likely to be discharged home. Treatment modality (clipping versus coiling) was not associated with increased rate of readmission. Independent predictors for readmission, however, were identified as comorbidity score equal or more than 3, higher SAH severity, and discharge destination other than home; the more predictors, the higher chance of readmission. Of note, high-volume institutions had lower risk of readmission and mortality. The most common reasons for readmission included hydrocephalus, other neurological complications, infections, and thromboembolic events. Neurosurgical procedures and surgeries were among the most common operations performed after readmission. Importantly, hydrocephalus during index hospitalization was associated with increased risk of readmission for hydrocephalus.

Author Interview: Søren Bache, MD

Søren Bache

Søren Bache

A conversation with Søren Bache, MD, from the Neurointensive Care Unit, Department of Neuroanaesthesiology and Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Denmark, about microRNA changes after subarachnoid hemorrhage.

Interviewed by José G. Merino, MD, Associate Professor of Neurology, University of Maryland School of Medicine.

They will be discussing the paper, “MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage,” published in the September 2017 issue of Stroke.

​Dr. Merino: Thank you for agreeing to the interview. First, I would like you to explain some things about delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) for our readers: How common is it? How soon after SAH does it develop? How does it affect outcome after SAH?

Dr. Bache: The reported prevalence of DCI after SAH varies, but newer randomized clinical trials have found a risk of 21–38% in patients who survive the initial bleeding and aneurism-securing surgery. The variation in calculated risk may be due to discrepancies both in case definition (i.e. the numerator) and in the definition of which patients are entered into the denominator. Today, most researchers base their case definition of DCI on the criteria suggested by Vergouwen et al. (Vergouwen MD, et al. Stroke. 2010). Before this consensus work, the definition varied even more, and many used their own criteria for DCI, delayed ischemic neurological deficits (DIND) or cerebral vasospasm. However, not all patients are conscious enough to be assessed clinically for a deterioration in consciousness, and such patients may be either included or excluded in the total number of patients; hence, the variation in the denominator. Based on Vergouwen’s criteria, in our center, we found a prevalence of 23% in 450 patients admitted from 2009–12 with SAH (unpublished data). These patients all receive prophylactic nimodipine, which lowers the risk of DCI; therefore, one should expect publications from the pre-nimodipine era to report a higher prevalence of DCI (Dorhout Mees SM, et al. Cochrane Database of Systematic Reviews. 2007).

Delayed cerebral ischemia occurs a median of 6–7 days after hemorrhage, but this varies, with a typical reported range from 3 to 14 days. DCI may be reversible, but in some cases it progresses to permanent brain injury, thereby affecting outcome.

The Complex Relationship Between Statins and Intracerebral Hemorrhage Outcomes

Mark R. Etherton, MD, PhD

Siddiqui FM, Langefeld CD, Moomaw CJ, Comeau MJ, Sekar P, Rosand J, et al. Use of Statins and Outcomes in Intracerebral Hemorrhage Patients. Stroke. 2017

In this entry, I discuss a recent publication by Fazeel Siddiqui and colleagues regarding the use of statins and outcomes after intracerebral hemorrhage (ICH).

The current evidence suggests a complex relationship between serum cholesterol levels, statin use, and outcomes after ICH. Low serum cholesterol levels have been associated with increased incidence of ICH, as well as hematoma expansion. However, a prior meta-analysis demonstrated antecedent statin use was associated with decreased risk of mortality and increased likelihood of a good outcome after ICH (Jung et al. Int J Stroke. 2015). The authors, therefore, set out to investigate the relationship of statin use with ICH outcomes by evaluating 3-month disability, mortality, and hematoma size/expansion.

Hematoma Shape, but not Density, is Predictive of Clinical Outcomes in ICH from the INTERACT2 Study

Peggy Nguyen, MD

Delcourt C, Zhang S, Arima H, Sato S, Al-Shahi Salman R, Wang X, et al. Significance of Hematoma Shape and Density in Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trial Study. Stroke. 2016

In patients with intracerebral hemorrhage (ICH), parameters such as hematoma volume has been shown to be predictive of hematoma growth and poor clinical outcomes; other characteristics, such as shape and density have been shown to be associated with growth, but evidence demonstrating its predictive value for clinical outcomes has been limited. Here, the authors used data from the INTERACT2 study and evaluated the association of hematoma shape (irregularity) and density (heterogeneity) on 90-day death or disability.

2066 subjects were included for analysis, with 946 subjects having irregular hematomas and 781 subjects having heterogenous hematomas. Of note, there were significant differences between patients with irregular versus regular hematomas, including older age, more severe neurological status, and lobar hemorrhages in the former group, among others. Similarly, patients with heterogenous hematomas, compared to those with homogenous hematomas, were more likely to have lobar hematomas and less likely to have intraventricular extension. Larger hematomas were more likely to be irregular and heterogenous, and this is likely reflected in the differences between each group and their comparators. In addition, the decision to withdraw treatment was more likely to be made among patients with irregular hematomas and among patients with heterogenous hematomas, when compared to their counterparts.


Nevertheless, when controlled for factors such as age, systolic blood pressure, NIHSS, prior use of antithrombotics, location and volume of baseline hematoma, IVH, and decision to withdraw active treatment, irregular hematomas were found to be independently associated with the primary outcome of risk of death or major disability at 90-days (OR 1.60) and major disability at 90 days (OR 1.60) although not with death alone. Heterogenous density did not predict the primary outcome, nor individually, the outcome of death nor disability.

This study is significant in providing some evidence for imaging markers which may be predictive of clinical outcomes in the emergent period, allowing clinicians to adjust decision making and provide better informed counseling to patients and their families.   


Administration of transdermal glycerol trinitrate does not affect functional outcomes in patients with ICH

Alexander E. Merkler, MD

Krishnan K, Scutt P, Woodhouse L, Adami A, Becker JL, Berge E, et al. Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis. Stroke. 2016

Outcomes in patients with intracerebral hemorrhage (ICH) are poor; more than two-thirds of survivors with ICH are left disabled at three months and less than half of patients with ICH are alive at 1 year. Ongoing research continues to address ways to improve outcomes – one such approach is acute blood pressure reduction. High blood pressure is common in acute ICH and is associated with worse outcomes, at least in part through hematoma expansion. Previous trials such as INTERACT have shown a trend towards improved functional outcomes using intensive BP lowering within the first 6 hours after ICH, but management of high BP in acute ICH remains uncertain.


The current subgroup analysis of the ENOS (Efficacy of Nitric Oxide in Stroke) trial evaluates the impact of transdermal glyceryl trinitrate (GTN) in patients with ICH. ENOS was a large multicenter trial that evaluated BP reduction in patients with both ischemic stroke and ICH using GTN. When GTN was given within 48 hours of stroke onset, BP was significantly reduced at day 1; however, functional outcome at 90 days was no different. When GTN was given within six hours of stroke though, functional outcomes were improved. In this current manuscript, the authors performed a pre-specified subgroup analysis, evaluating whether use of GTN in patients with ICH improved functional outcomes both overall, and within 6 hours of having an ICH.

629 patients with ICH presenting within 48 hours and initial SBP >140mmHg were included. Patients were randomized to receive GTN transdermally for one week versus no GTN. The mean time to randomization was 25 hours. 87% of hemorrhages were deep and 26% of patients had IVH. BP was significantly lower following the first dose of GTN versus no GTN (7.5/4.2 mmHg).

Overall, at 90 days, the median mRS was the same (3) in both the GTN and no GTN groups. In addition, there were no differences between secondary outcomes such as measures of disability, cognition, mood and quality of life. No differences in serious adverse events were seen.

Of the 61 (9.7%) patients randomized within 6 hours (and in whom the average time to treatment was 4.4 hours), patients randomized to GTN had an improved functional outcome as manifested by a positive shift on the mRS, improved mood and quality of life and reduced death.

GTN is a useful transdermal agent to acutely lower BP and does not seem to have serious adverse effects. The study adds further support that early BP lowering in patients with ICH may improve functional outcomes.

By |January 15th, 2016|hemorrhage|0 Comments