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Stereotactic Radiosurgery Performance in Brain AVMs: Risk Factors for Hemorrhage

Elena Zapata-Arriaza, MD
@ElenaZaps

Ding D, Chen C-J, Starke RM, Kano H, Lee JYK, Mathieu D, et al. Risk of Brain Arteriovenous Malformation Hemorrhage Before and After Stereotactic Radiosurgery: A Multicenter Study. Stroke. 2019;50:1384–1391.

Stereotactic radiosurgery (SRS) has emerged as an alternative to neurosurgery or endovascular treatment for selected brain arteriovenous malformations (bAVM) management. Localization, size or perioperative risk are some of the selection criteria for SRS employment. Hemorrhagic risk of bAVM after SRS is based on single center studies. This study aims to obtain scientific evidence about bAVM hemorrhage rates before and after SRS and identify predictors of pre-post SRS AVM hemorrhage.

Patients with AVM treated with SRS in a single session from 1987 to 2014 were collected for the International Radiosurgery Research Foundation, formed by 8 institutions. For each AVM, Spetzler-Martin(SM) grade, virginia Radiosurgery AVM scale and modified radiosurgery-based AVM score were collected. In terms of SRS variables, margin dose, maximum dose and number of isocenters were analyzed. Radiological follow-up (with magnetic resonance image with/without contrast and computed tomography as alternative) was performed every 6 months for the first 2 years after SRS, and yearly thereafter. If the patient developed new or symptoms worsening, additional neuroimagen was performed.

Article Commentary: “Decreases in Blood Pressure During Thrombectomy Are Associated With Larger Infarct Volumes and Worse Functional Outcomes”

Matthew Maximillian Padrick, MD

Petersen NH, Ortega-Gutierrez S, Wang A, Lopez GV, Strander S, Kodali S, et al. Decreases in Blood Pressure During Thrombectomy Are Associated With Larger Infarct Volumes and Worse Functional Outcome. Stroke. 2019;50:1797–1804.

This study recapitulates what should be a well-known phenomenon in the vascular neurology community: Decreases in blood pressure (BP) in patients undergoing endovascular thrombectomy (EVT) tend to result in poorer outcomes compared to outcomes of patients with sustained, stable blood pressure throughout diagnosis and EVT.

In this retrospective, observational study, the authors identified consecutive acute ischemic stroke patients with large vessel occlusion undergoing EVT at Yale-New Haven Hospital and University of Iowas and Clinics between 2014 and 2018. BP data was collected on admission and throughout EVT via anesthesia records. Decreases in BP were calculated between admission mean arterial pressure (MAP) and the single lowest MAP before recanalization during EVT. Sustained relative hypotension was measured as the area between baseline admission MAP and continuous measurements of intraprocedural MAP from procedure start to vessel recanalization. Primary imaging outcome was infarct volume assessed via admission computed tomography and at 24 hours post EVT via magnetic resonance imaging. Primary functional outcome was assessed via patient’s modified Rankin scale (mRS) at discharge and at 90 days post discharge.

Article Commentary: “Sex Differences in Management and Outcomes of Acute Ischemic Stroke With Large Vessel Occlusion”

Anusha Boyanpally, MD

Uchida K, Yoshimura S, Sakai N, Yamagami H, Morimoto T. Sex Differences in Management and Outcomes of Acute Ischemic Stroke With Large Vessel Occlusion. Stroke. 2019;50:1915–1918.

Although the incidence of acute ischemic strokes with large vessel occlusion (LVO) are identified more in males, sex disparities in clinical outcomes with endovascular therapy (EVT) were inconclusive. These authors have investigated sex disparities in patients with acute ischemic stroke with LVO treated with EVT in a prospective, multicenter RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism)-Japan Registry 2 patient database.

A total of 2420 patients with acute ischemic stroke with LVO were enrolled in this study. The primary outcome was good outcome, defined as a modified Rankin Scale score of 0 to 2 at 90 days after onset. Secondary outcomes were mortality within 90 days, any or symptomatic intracranial hemorrhage within 72 hours after onset, and recurrence of stroke or transient ischemic attack within 90 days. Among 2399 patients, 1087 patients were female and 1312 were male; in those, 521 (47.9%) of females and 757 (57.7%) of males received EVT, respectively.

Low Molecular Weight Heparin + tPA: Safe or Not Safe?

Elizabeth M. Aradine, DO

Cooray C, Mazya M, Mikulik R, Jurak L, Brozman M, Ringleb P, et al. Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset. Stroke. 2019;50:1149-1155.

In 2018, the American Heart Association updated its stroke guidelines and allowed patients on prophylactic low molecular weight heparin (LMWH) to be considered for thrombolytic therapy. This has led to an increased number of patients receiving thrombolysis; however, less is known about the safety of doing so. Prior observational studies demonstrated increased risk of symptomatic hemorrhage and death with administration of thrombolytic therapy and concomitant use of LMWH; however, this was in studies with a limited sample size. The article, “Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset,” published in Stroke sought to elucidate the safety of thrombolysis in a large sample size.

In this observational study, 109,291 patients with acute ischemic stroke not on anticoagulation or heparin were treated with intravenous thrombolysis. 1,411 (1.3%) were on prophylactic LMWH at stroke onset. The primary outcome of symptomatic intracranial hemorrhage (ICH) using the SICH SITS-MOST definition did not show a difference in rates of hemorrhage between the prophylactic LMWH and non LMWH groups. Using the SICH-NINDS definition, there was an increased rate of hemorrhage in the prophylactic LMWH group. However, after baseline variables were matched, the rates of hemorrhage were similar. Three-month mortality was higher in the prophylactic LMWH group both before and after matching of baseline variables. Seven-day mortality and three-month functional disability using the modified Rankin Scale score were higher in the LMWH group. When variables were matched, mortality and disability were equal in both groups.

The Relationship Between Intracerebral Hemorrhage Location and Outcome

Stephanie M. Lyden, MD

Eslami V, Tahsili-Fahadan P, Rivera-Lara L, Gandhi D, Ali H, Parry-Jones A, et al. Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage. Stroke. 2019;50:1688–1695.

The authors of this study investigated the prognostic significance of small spontaneous intracerebral hemorrhage (ICH) (<30 mL) with associated obstructive intraventricular hemorrhage (IVH), which has not been done before. They performed a prospective observational cohort study using subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. The CLEAR III trial assessed the use of intraventricular alteplase vs saline in patients with non-traumatic, obstructive IVH. It found that there was no difference in good functional outcome between the two interventions, but that patients who received the alteplase had a lower risk of death and was not associated with increased adverse events.

These investigators analyzed computed tomography (CT) scans from 467/500 CLEAR III subjects and measured the specific anatomic locations affected by the intracerebral hemorrhage using lesion topography with a structured atlas based approach. They assessed stroke outcomes by looking at mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models.

Article Commentary: “Five-Year Risk of Major Ischemic and Hemorrhagic Events After Intracerebral Hemorrhage”

Adeola Olowu, MD

Casolla B, Moulin S, Kyheng M, Hénon H, Labreuche J, Leys D, et al. Five-Year Risk of Major Ischemic and Hemorrhagic Events After Intracerebral Hemorrhage. Stroke. 2019;50:1100–1107.

Spontaneous intracerebral hemorrhage (sICH) management involves stabilization, management, and secondary prevention. When treating sICH patients, it’s intuitive to create a medical plan to prevent recurrent ICH. However, what if ischemic vascular processes need to be considered as a complication in this population?

The authors of “Five-Year Risk of Major Ischemic and Hemorrhagic Events After Intracerebral Hemorrhage” conducted a prospective observational study of patients from the Prognosis of Intracerebral Hemorrhage (PITCH) trial from November 3, 2004 to March 29, 2009. A total of 310 sICH survivors (defined as being alive at 30 days) were observed with a 6-month follow up and an annual follow-up for 6 years. 55% were men, the median age was 70 years old, ICH was divided into deep and lobar with 195 and 115 patients, respectively. During this time, the study found a 20% incidence of major vascular events 5 years after ICH. Both major ischemic and hemorrhagic events incidences increased from 1 year to 5 years. Major ischemic events described as ischemic stroke, coronary events, acute limb ischemia, severe peripheral artery disease, and severe internal carotid stenosis occurred at 5.9% at 1 year to 15.2% at 5 years. Major hemorrhagic events were intracerebral hemorrhage and major systemic bleeding which occurred at 4.9% at 1 year and increased to 6.2% at 5 years. Rate of ischemic events was 6x higher than hemorrhagic events in the deep sICH population. The supplemental data was significant for demonstrating small vessel disease as the highest proportion of ischemic stroke etiology for patients with deep sICH during follow up, deep sICH patients were at high risk for having coronary events and severe peripheral artery disease, while patients with lobar sICH developed ischemic stroke, ICH, and major systemic bleeding using the Bleeding Academic Research Consortium (BARC) classifications.

Article Commentary: “Sleep and Stroke”

Rachel Forman, MD

Khot SP, Morgenstern LB. Sleep and Stroke. Stroke. 2019;50:1612–1617.

The importance of sleep is becoming increasingly evident as it pertains to stroke. The article “Sleep and Stroke” in the June issue of Stroke by Drs. Khot and Morgenstern highlights the importance of post-stroke sleep disturbance and sleep disordered breathing as a vascular risk factor.

Over 50% of stroke patients experience sleep disorders; however, as little as 6% undergo any formal sleep testing (with only 3% in the 3-month post-stroke period).  This is likely because of the lack of provider awareness. This article reviews types of sleep-disordered breathing (SDB): central sleep apnea (CSA) and obstructive sleep apnea (OSA). Central apneas are typically seen in heart failure and opioid use and occur in stroke patients due to distinct brainstem lesions, although this is rare. More commonly, patients have OSA, and this appears to be more significant in post-stroke patients. 

When a patient undergoes a sleep study, they are given an apnea-hypopnea index (AHI), which is the number of respiratory events per hour of sleep. Based on the number, they are classified as having mild (5-14 per hour), moderate (15-29 per hour), or severe (>30 per hour) obstructive sleep apnea. In a meta-analysis of SDB after stroke or TIA, 72% of patients had an AHI of at least 5. The reason for such high rates is not entirely clear, but it is thought to be related to positional sleep apnea, stroke-related upper airway tone changes, and untreated OSA preceding the stroke. 

Article Commentary: “Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow”

Yan Hou, MD, PhD

Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, et al.. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow. A Randomized, Sham-Controlled Trial. Stroke. 2019;50:00-00.

Preclinical studies have demonstrated that sphenopalatine ganglion (SPG) stimulation is a potent method to enhance collateral flow and reduce infarct size in stroke animal models. The ImpACT-24A Investigators performed a sham-controlled, randomized trial to test the efficacy and safety of SPG stimulation as a potential therapy for patients with acute anterior circulation ischemic stroke who are not eligible for reperfusion therapy.

A total of 253 patients with acute anterior circulation ischemic stroke with moderate deficit (median NIHSS of 11) within 24 hours of onset not treated with tPA or thrombectomy either received SPG (n=153) or sham (n=100) stimulation. The primary efficacy outcome is mRS improvement beyond expectation at 90 days, which was defined as an mRS score one or more points better than expected based on a prognostic model. Although SPG stimulation only showed a 9.7% higher rates of mRS improvement beyond expectations in the intention to treat population (SPG vs. sham: 49.7% vs. 40%, odd ratio 1.48, p=0.13); there was a 23% higher rate of mRS improvement beyond expectations in the subgroup of patients with confirmed cortical involvement (SPG vs. sham: 50% vs. 27%, odd ratio 2.7, p=0.03). The different beneficial effects of SPG stimulation between patients with cortical infarcts and deep subcortical infarcts was considered due to more robust collateral arterial networks in superficial leptomeningeal arteries supplying the cortical layers. SPG stimulation was not associated with any increase in serious adverse events, symptomatic intracranial hemorrhage, or mortality. Only two serious adverse events were considered possibly related to the implantation (one epistaxis and one torn extraction).

Thrombectomy for Intracranial Atherosclerosis-Related Large Vessel Occlusions

Robert W. Regenhardt, MD, PhD
@rwregen

Tsang ACO, Orru E, Klostranec JM, Yang IH, Lau KK, Lau KK, et al. Thrombectomy outcomes of intracranial atherosclerosis-related occlusions: A systematic review and meta-analysis. Stroke. 2019; 50:1460–1466.

In the new era of endovascular thrombectomy (EVT) for large vessel occlusions (LVOs) up to 24 hours from symptom onset, focus has shifted to broadening patient selection and improving EVT technique. This manuscript sought to understand the unique features of EVT for a particular LVO etiology, intracranial atherosclerosis (ICAS). ICAS is less common than cardioembolism or carotid atheroembolism, making up about 6-8% of LVOs in Western populations and up to 25% in Asia. Owing in part to their decreased prevalence, ICAS-related LVOs are only recently being described as posing unique challenges to treatment. EVT may be less efficacious for these LVOs, and rescue treatments may be necessary given high re-occlusion rates.

White Matter Hyperintensity and Brain Atrophy — A New Imaging Measure of Cognitive Impairment

Kristina Shkirkova, BSc

Wyss A, Dawson J, Arba F, Wardlaw JM, Dickie DA, on behalf of the VISTA-Prevention Collaborators. “Combining Neurovascular and Neurodegenerative Magnetic Resonance Imaging Measures in Stroke.” Stroke. 2019; 50:1136-1139.

To characterize age and stroke-related tissue damage, the total small vessel disease score and the brain health index have recently been developed for clinical use. The total small vessel disease score combines presence of lacunes, microbleeds, and moderate to severe white matter hyperintensities (WMH) by visual scoring based on clinical imaging. The brain health index uses automatic processing of MRI scans to quantify visible injury from small vessel disease and brain atrophy. However, the total small vessel disease score is prone to granularity and measurement limitations, whereas the brain health index requires high-resolution T1, T2, T2 gradient echo, and fluid attenuated inversion recovery scans, which are not often available in routine clinical imaging.

The study by Wyss et al. argues that individual markers of cerebral small vessel disease and brain atrophy have limited potential to explain high proportion of variance in neurovascular and neurodegenerative disease. The authors propose to combine markers of white matter hyperintensity and cerebral atrophy, represented by cerebrospinal fluid (CSF) volume, into a single measure capable of more accurate predictions of cognitive impairment.