American Heart Association

hemorrhage

Antiplatelet Therapy and Functional Outcomes After ICH

Lina Palaiodimou, MD

Murthy SB, Biffi A, Falcone GJ, Sansing LH, Torres Lopez V, Navi BB, et al. Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes. Stroke. 2019

Initiation of antithrombotic therapy (antiplatelet or anticoagulant) after intracerebral hemorrhage (ICH) has long been a matter of conflict among clinicians dealing with stroke patients. Given that the treatment of ICH in the acute phase is mostly supportive, one can understand the anxiety of the clinicians who want to prevent an ICH recurrence. However, according to American Heart Association/American Stroke Association (AHA/ASA) guidelines, the recommendation that “anticoagulation after nonlobar ICH and antiplatelet monotherapy after any ICH might be considered, particularly when there are strong indications for these agents” is not well established (Class IIb) and is based on evidence derived from nonrandomized studies (Level of Evidence B). That is why studies aiming to shed light on this matter are more than welcome from the scientific community of stroke.

The study by Murthy et al. is an attempt to enrich the scarce data regarding the impact of antiplatelet therapy (APT) initiation after ICH on functional outcomes. For that reason, the authors separately analyzed data from 3 large cohort studies [ICH study at Massachusetts General Hospital (MGH), Virtual International Stroke Trials Archive-ICH (VISTA-ICH), ICH database of Yale University School of Medicine], consisting of 1801 ICH patients in total. Inclusion criteria were: diagnosis of primary ICH in CT-scan, age >18 years, and complete follow up at 90 days. Exclusion criteria were: previous history of ICH, secondary cause of ICH, and prior use of anticoagulants.

Cerebral Amyloid Angiopathy and Disruption of the Blood-Brain Barrier

Kara Jo Swafford, MD

Freeze WM, Bacskai BJ, Frosch MP, Jacobs HIL, Backes WH, Greenberg SM, et al. Blood-Brain Barrier Leakage and Microvascular Lesions in Cerebral Amyloid Angiopathy. Stroke. 2019;50:328–335.

Cerebral amyloid angiopathy (CAA) is characterized by amyloid-b (Ab) deposition within walls of small to medium sized arteries, arterioles and capillaries in the cerebral cortex and leptomeninges. It is observed in approximately 33% of the general aged population and 90% of those with Alzheimer’s disease. CAA can lead to cerebral microbleeds (CMBs) and cerebral microinfarcts (CMIs), as well as cerebral atrophy, structural network disruption and cognitive decline. In the elderly, CAA is the most common cause of lobar intracerebral hemorrhage.

Freeze et al performed a postmortem study to investigate the role of blood-brain barrier (BBB) disruption in CAA-related brain injury, hypothesizing that BBB leakage is associated with CAA severity and is present predominantly in parietooccipital regions because of CAA’s predilection for affecting blood vessels in these regions. Eleven CAA confirmed cases were compared to 7 controls without neurological disease. BBB disruption was measured by plasma protein (fibrin, IgG) extravasation in the cortex. CAA severity was graded based on presence of Aβ. Microvascular lesions (CMBs, CMIs) were assessed using histopathology and MRI.

Large Analysis Confirms Poor Outcome of Intracerebral Hemorrhage in Patients on Treatment with Antiplatelets and Vitamin K Antagonists

Raffaele Ornello, MD

Sprügel MI, Kuramatsu JB, Gerner ST, Sembill JA, Beuscher VD, Hagen M, et al. Antiplatelet therapy in primary spontaneous and oral anticoagulation–associated intracerebral hemorrhage. Stroke. 2018

The exact effect of antiplatelet therapy (APT) on the characteristics and outcome of intracerebral hemorrhage (ICH) is interesting especially among patients treated with oral anticoagulation (OAC).

The present pooled analysis of two retrospective cohort studies and a prospective single-center study assessed the influence of APT on the characteristics and functional outcome of ICH in patients with primary spontaneous ICH, vitamin K antagonist (VKA)-associated ICH, and non-VKA-OAC (NOAC)-associated ICH. Compared with patients with VKA-associated ICH not under APT, those with VKA-associated ICH under APT had a lower proportion of 3-month favorable outcome, defined as modified Rankin Scale scores 0-3, higher 3-month mortality, and larger hematoma volume; on the other hand, APT did not influence the characteristics and outcome of ICH among patients with primary spontaneous or NOAC-associated ICH.

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.