Dariush Dowlatshahi

Pre admission antithrombotics are associated with improved outcomes following ischaemic stroke: a cohort from the Registry of the Canadian Stroke Network.

Background Several studies have attempted to identify predictors of outcome following ischaemic stroke. Reduced stroke severity has been reported with pre admission ASA use, and improved outcomes have been reported with pre admission statin treatment. The interaction between pre treatment medications and clinical response to tPA is less clear. The objective of our study was to assess clinical outcomes in patients with acute ischaemic stroke with respect to pre treatment medications. Methods The Registry of the Canadian Stroke Network collected pre morbid and prospective outcome data on 5568 patients with ischaemic stroke. We applied multivariate analyses to correlate pre admission medications with stroke severity on presentation, in-hospital mortality, and modified Rankin at discharge. Analyses were adjusted for age, gender, medical history, tPA administration, blood pressure, and glucose on presentation. Results Pre admission treatment with ASA and clopidogrel was associated with less severe stroke upon presentation. A similar trend was seen with dipyridamole and ticlopidine, but did not reach statistical significance. Pre treatment with ASA and warfarin was associated with improved Rankin scores at discharge. There was no interaction between tPA treatment and pre admission antiplatelets with respect to in-hospital mortality or disability at discharge, although tPA treatment was independently associated with improved Rankin at discharge. Pre treatment antiplatelet use did not result in increased intracerebral haemorrhage following tPA administration. Conclusions Patients with acute ischaemic stroke taking antithrombotic medications at hospital admission have improved functional outcomes. No interaction is noted between use of these medications and outcome following thrombolysis. This large prospective cohort study is consistent with previous published reports, and supports the notion that pre admission antithrombotics may mitigate brain injury during acute stroke.

Cerebral Perfusion and Blood Pressure Do Not Affect Perihematoma Edema Growth in Acute Intracerebral Hemorrhage

Background and Purpose— The pathogenesis of perihematoma edema in intracerebral hemorrhage (ICH) is unknown but has been hypothesized to be ischemic. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), perihematoma cerebral blood flow (CBF) was reduced but was unaffected by blood pressure (BP) reduction. Using ICH ADAPT data, we tested the hypotheses that edema growth is associated with reduced CBF and lower systolic BP. Methods— Noncontrast computed tomographic scans in patients with ICH were obtained at baseline, 2 hours, and 24 hours after randomization to target systolic BPs of <150 or <180 mm Hg. Computed tomography perfusion imaging was performed at 2 hours, and mean relative CBF was calculated in visibly edematous perihematoma tissue. Edema volumes were measured using a Hounsfield unit threshold of 5 to 23 at each time-point. Results— Patients were randomized at a median (interquartile range) of 7.4 (12.8) hours after onset. Treatment groups (n=34, <150 and n=33, <180 target) were balanced with respect to baseline systolic BP and acute ICH volume. Relative edema growth at 24 hours in the <150 group (0.11±0.19) was similar to that in the <180 group (0.09±0.16 mL; P=0.727). Absolute CBF was lower in the edematous region (35.67±13.1 mL/100 g per minute) when compared with that in the contralateral tissue (43.7±11.7 mL/100 g per minute; P<0.0001). Linear regression indicated that neither systolic BP change (&bgr;=–0.022; 95% confidence interval, –0.002 to 0.001) nor perihematoma relative CBF (&bgr;=–0.144; 95% confidence interval, –0.647 to 0.167) predicted edema growth. Conclusions— Lower perihematoma CBF and BP treatment do not exacerbate edema growth. These data do not support a cytotoxic edema pathogenesis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.

The Spot Sign Is More Common in the Absence of Multiple Prior Microbleeds

Background and Purpose— Mural thickening and permeability changes in patients with amyloid angiopathy (CAA) and chronic hypertension are implicated in the pathophysiology of multiple, chronic subclinical microbleeds. The Spot sign, contrast extravasation on CT angiography, predicts hematoma expansion and is presumed to represent acute vessel damage. We hypothesize that the Spot sign is more common in patients without multiple prior chronic microbleeds. Methods— A retrospective study was conducted of 59 patients presenting within 6 hours of primary intracranial hemorrhage onset undergoing CT angiography and MRI. CT angiography spot sign presence was documented blinded to MRI. Hematoma expansion was defined as >6 mL or 30% enlargement. The Boston criteria were applied to microbleed interpretation dichotomizing subjects into probable and negative CAA. Basal ganglia, thalamic, and brain stem microbleed location were interpreted as chronic hypertensive pattern. Univariate logistic regression and ordinal logistic regression analysis identified significant predictive factors between spot-positive and -negative patients or microbleed pattern. Results— The incidence of spot positivity was 42%, 22%, and 0% for CAA-negative, chronic hypertensive, and CAA-positive patients, respectively (P=0.01). CAA-negative patients had higher baseline National Institutes of Health Stroke Scale (P=0.039), larger follow-up hematoma volume (P=0.02), and poorer Rankin score (P=0.049) than chronic hypertensive or CAA-positive patients. After age adjustment, spot-positive (P=0.023), age-related white matter change (P=0.041), number of microbleeds (P<0.0001), and modified Rankin score (P=0.027) remained significantly different between groups. Conclusion— Boston criteria-defined CAA-negative status demonstrates the highest risk of spot positivity compared with patients with probable CAA and chronic hypertension.

Autoregulation of Cerebral Blood Flow Is Preserved in Primary Intracerebral Hemorrhage

Background and Purpose— Treatment of acute hypertension after intracerebral hemorrhage (ICH) is controversial. In the context of disrupted cerebral autoregulation, blood pressure (BP) reduction may cause decreased cerebral blood flow (CBF). We used serial computed tomography perfusion to test the hypothesis that CBF remains stable after BP reduction. Methods— Patients recruited within 72 hours of ICH were imaged with computed tomography perfusion before and after BP treatment. Change in perihematoma relative (r) CBF after BP treatment was the primary end point. Results— Twenty patients were imaged with computed tomography perfusion at a median (interquartile range) time from onset of 20.2 (25.7) hours and reimaged 2.1 (0.5) hours later, after BP reduction. Mean systolic BP in treated patients (n=16; 4 untreated as BP<target at baseline) decreased significantly between the first (168±21 mm Hg) and second (141±19 mm Hg; P<0.0001) computed tomography perfusion scans. The primary end point of rCBF was not affected by BP reduction (pretreatment=0.89±0.11; post-treatment=0.87±0.11 mL/100 g per minute; P=0.37). Linear regression showed no relationship between changes in systolic BP and perihematoma rCBF (&bgr;=0.001 [−0.002 to 0.003]; P=0.63). Conclusions— CBF remained stable after acute BP reduction, suggesting some preservation of cerebral autoregulation.

Minimally Invasive Subcortical Parafascicular Transsulcal Access for Clot Evacuation (Mi SPACE) for Intracerebral Hemorrhage

Background. Spontaneous intracerebral hemorrhage (ICH) is common and causes significant mortality and morbidity. To date, optimal medical and surgical intervention remains uncertain. A lack of definitive benefit for operative management may be attributable to adverse surgical effect, collateral tissue injury. This is particularly relevant for ICH in dominant, eloquent cortex. Minimally invasive surgery (MIS) offers the potential advantage of reduced collateral damage. MIS utilizing a parafascicular approach has demonstrated such benefit for intracranial tumor resection. Methods. We present a case of dominant hemisphere spontaneous ICH evacuated via the minimally invasive subcortical parafascicular transsulcal access clot evacuation (Mi SPACE) model. We use this report to introduce Mi SPACE and to examine the application of this novel MIS paradigm. Case Presentation. The featured patient presented with a left temporal ICH and severe global aphasia. The hematoma was evacuated via the Mi SPACE approach. Postoperative reassessments showed significant improvement. At two months, bedside language testing was normal. MRI tractography confirmed limited collateral injury. Conclusions. This case illustrates successful application of the Mi SPACE model to ICH in dominant, eloquent cortex and subcortical regions. MRI tractography illustrates collateral tissue preservation. Safety and feasibility studies are required to further assess this promising new therapeutic paradigm.

Blood pressure reduction does not reduce perihematoma oxygenation: a CT perfusion study

Blood pressure (BP) reduction after intracerebral hemorrhage (ICH) is controversial, because of concerns that this may cause critical reductions in perihematoma perfusion and thereby precipitate tissue damage. We tested the hypothesis that BP reduction reduces perihematoma tissue oxygenation. Acute ICH patients were randomized to a systolic BP target of <150 or <180 mm Hg. Patients underwent CT perfusion (CTP) imaging 2 hours after randomization. Maps of cerebral blood flow (CBF), maximum oxygen extraction fraction (OEFmax), and the resulting maximum cerebral metabolic rate of oxygen (CMRO2max) permitted by local hemodynamics, were calculated from raw CTP data. Sixty-five patients (median (interquartile range) age 70 (20)) were imaged at a median (interquartile range) time from onset to CTP of 9.8 (13.6) hours. Mean OEFmax was elevated in the perihematoma region (0.44±0.12) relative to contralateral tissue (0.36±0.11; P<0.001). Perihematoma CMRO2max (3.40±1.67 mL/100 g per minute) was slightly lower relative to contralateral tissue (3.63±1.66 mL/100 g per minute; P=0.025). Despite a significant difference in systolic BP between the aggressive (140.5±18.7 mm Hg) and conservative (163.0±10.6 mm Hg; P<0.001) treatment groups, perihematoma CBF was unaffected (37.2±11.9 versus 35.8±9.6 mL/100 g per minute; P=0.307). Similarly, aggressive BP treatment did not affect perihematoma OEFmax (0.43±0.12 versus 0.45±0.11; P=0.232) or CMRO2max (3.16±1.66 versus 3.68±1.85 mL/100 g per minute; P=0.857). Blood pressure reduction does not affect perihematoma oxygen delivery. These data support the safety of early aggressive BP treatment in ICH.

Dynamic 'Spot Sign' Resolution following INR Correction in a Patient with Warfarin-Associated Intracerebral Hemorrhage

Hematoma expansion in intracerebral hemorrhage is associated with poor clinical outcome. The ‘spot sign’ is a radiological marker that is associated with hematoma expansion, and thought to represent active extravasation of contrast. This case demonstrates the use of dynamic CT angiography in identifying the time-dependent appearance of a spot sign in a patient with warfarin-associated intracerebral hemorrhage. Repeat imaging is also presented which verified cessation of the spot sign after INR correction.

Perihematoma cerebral blood flow is unaffected by statin use in acute intracerebral hemorrhage patients

Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting < 24 hours from ICH onset were randomized to a systolic blood pressure target < 150 or < 180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P = 0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P = 0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume.

Canadian stroke best practice consensus statement: Secondary stroke prevention during pregnancy:

The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy, is the first of a two-part series devoted to stroke in pregnancy. This document focuses on unique aspects of secondary stroke prevention in a woman with a prior history of stroke or transient ischemic attack who is, or is planning to become, pregnant. Although stroke is relatively rare in this cohort, several aspects of pregnancy can increase stroke risk during or immediately after pregnancy. The rationale for the development of this consensus statement is based on the premise that stroke in this group requires a specifically-tailored management approach. No other broad-based, stroke-specific guidelines or consensus statements exist currently. Underpinning the development of this document was the concept that maternal health is vital for fetal wellbeing; therefore, management decisions should be based on the confluence of two clinical considerations: (a) decisions that would be made if the patient was not pregnant and (b) decisions that would be made if the patient had not had a stroke. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include general management considerations for secondary stroke prevention, the use of antithrombotics, blood pressure management, lipid management, diabetes care, and management for specific ischemic stroke etiologies in pregnancy. The focus is on maternal and fetal health while minimizing risks of a recurrent stroke, through counseling, monitoring, and the safety of select pharmacotherapy. These statements are appropriate for health care professionals across all disciplines.

Canadian Stroke Best Practice Recommendations: Telestroke Best Practice Guidelines Update 2017:

Every year, approximately 62,000 people with stroke and transient ischemic attack are treated in Canadian hospitals. The 2016 update of the Canadian Stroke Best Practice Recommendations Telestroke guideline is a comprehensive summary of current evidence-based and consensus-based recommendations appropriate for use by all healthcare providers and system planners who organize and provide care to patients following stroke across a broad range of settings. These recommendations focus on the use of telemedicine technologies to rapidly identify and treat appropriate patients with acute thrombolytic therapies in hospitals without stroke specialized expertise; select patients who require to immediate transfer to stroke centers for Endovascular Therapy; and for the patients who remain in community hospitals to facilitate their care on a stroke unit and provide remote access to stroke prevention and rehabilitation services. While these latter areas of Telestroke application are newer, they are rapidly developing, with new opportunities that are yet unrealized. Virtual rehabilitation therapies offer patients the opportunity to participate in rehabilitation therapies, supervised by physical and occupational therapists. While not without its limitations (e.g., access to telecommunications in remote areas, fragmentation of care), the evidence-to-date sets the foundation for improving access to care and management for patients during both the acute phase and now through post stroke recovery.