Rebecca McCourt

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.

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.

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.

Acute Blood Pressure Reduction in Patients With Intracerebral Hemorrhage Does Not Result in Borderzone Region Hypoperfusion

Background and Purpose— The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) demonstrated blood pressure (BP) reduction does not affect mean perihematoma or hemispheric cerebral blood flow. Nonetheless, portions of the perihematoma and borderzones may reach ischemic thresholds after BP reduction. We tested the hypothesis that BP reduction after intracerebral hemorrhage results in increased critically hypoperfused tissue volumes. Methods— Patients with Intracerebral hemorrhage were randomized to a target systolic BP (SBP) of <150 or <180 mm Hg and imaged with computed tomographic perfusion 2 hours later. The volumes of tissue below cerebral blood flow thresholds for ischemia (<18 mL/100 g/min) and infarction (<12 mL/100 g/min) were calculated as a percentage of the total volume within the internal and external borderzones and the perihematoma region. Results— Seventy-five patients with intracerebral hemorrhage were randomized a median (interquartile range) of 7.8 (13.3) hours from onset. Acute hematoma volume was 17.8 (27.1) mL and mean SBP was 183±22 mm Hg. At the time of computed tomographic perfusion (2.3 [1.0] hours after randomization), SBP was lower in the <150 mm Hg (n=37; 140±18 mm Hg) than in the <180 mm Hg group (n=36; 162±12 mm Hg; P<0.001). BP treatment did not affect the percentage of total borderzone tissue with cerebral blood flow <18 (14.7±13.6 versus 15.6±13.7%; P=0.78) or <12 mL/100 g/min (5.1±5.1 versus 5.8±6.8%; P=0.62). Similar results were found in the perihematoma region. Low SBP load (fraction of time with SBP<150 mmHg) did not predict borderzone tissue volume with cerebral blood flow <18 mL/100 g/min (&bgr;=0.023 [−0.073, 0.119]). Conclusions— BP reduction does not increase the volume of critically hypoperfused borderzone or perihematoma tissue. These data support the safety of early BP reduction in intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.

Blood–Brain Barrier Compromise Does Not Predict Perihematoma Edema Growth in Intracerebral Hemorrhage

Background and Purpose— There are limited data on the extent of blood–brain barrier (BBB) compromise in acute intracerebral hemorrhage patients. We tested the hypotheses that BBB compromise measured with permeability-surface area product (PS) is increased in the perihematoma region and predicts perihematoma edema growth in acute intracerebral hemorrhage patients. Methods— Patients were randomized within 24 hours of symptom onset to a systolic blood pressure (SBP) treatment of <150 (n=26) or <180 mm Hg (n=27). Permeability maps were generated using computed tomographic perfusion source data acquired 2 hours after randomization, and mean PS was measured in the hematoma, perihematoma, and hemispheric regions. Hematoma and edema volumes were measured on noncontrast computed tomographic scans obtained at baseline, 2 hours and 24 hours after randomization. Results— Patients were randomized at a median (interquartile range) time of 9.3 hours (14.1) from symptom onset. Treatment groups were balanced with respect to baseline SBP and hematoma volume. Perihematoma PS (5.1±2.4 mL/100 mL per minute) was higher than PS in contralateral regions (3.6±1.7 mL/100 mL per minute; P<0.001). Relative edema growth (0–24 hours) was not predicted by perihematoma PS (&bgr;=−0.192 [−0.06 to 0.01]) or SBP change (&bgr;=−0.092 [−0.002 to 0.001]). SBP was lower in the <150 target group (139.2±22.1 mm Hg) than in the <180 group (159.7±12.3 mm Hg; P<0.0001). Perihematoma PS was not different between groups (4.9±2.4 mL/100 mL per minute for the <150 group, 5.3±2.4 mL/100 mL per minute for the <180 group; P=0.51). Conclusions— BBB permeability is focally increased in the hematoma and perihematoma regions of acute intracerebral hemorrhage patients. BBB compromise does not predict acute perihematoma edema volume or edema growth. SBP reduction does not affect BBB permeability. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.

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.

Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: A CT Perfusion Study

BACKGROUND AND PURPOSE: Although blood pressure reduction has been postulated to result in a fall in cerebral perfusion pressure in patients with intracerebral hemorrhage, the latter is rarely measured. We assessed regional cerebral perfusion pressure in patients with intracerebral hemorrhage by using CT perfusion source data. MATERIALS AND METHODS: Patients with acute primary intracerebral hemorrhage were randomized to target systolic blood pressures of <150 mm Hg (n = 37) or <180 mm Hg (n = 36). Regional maps of cerebral blood flow, cerebral perfusion pressure, and cerebrovascular resistance were generated by using CT perfusion source data, obtained 2 hours after randomization. RESULTS: Perihematoma cerebral blood flow (38.7 ± 11.9 mL/100 g/min) was reduced relative to contralateral regions (44.1 ± 11.1 mL/100 g/min, P = .001), but cerebral perfusion pressure was not (14.4 ± 4.6 minutes−1 versus 14.3 ± 4.8 minutes−1, P = .93). Perihematoma cerebrovascular resistance (0.34 ± 0.11 g/mL) was higher than that in the contralateral region (0.30 ± 0.10 g/mL, P < .001). Ipsilateral and contralateral cerebral perfusion pressure in the external (15.0 ± 4.6 versus 15.6 ± 5.3 minutes−1, P = .15) and internal (15.0 ± 4.8 versus 15.0 ± 4.8 minutes−1, P = .90) borderzone regions were all similar. Borderzone cerebral perfusion pressure was similar to mean global cerebral perfusion pressure (14.7 ± 4.7 minutes−1, P ≥ .29). Perihematoma cerebral perfusion pressure did not differ between blood pressure treatment groups (13.9 ± 5.5 minutes−1 versus 14.8 ± 3.4 minutes−1, P = .38) or vary with mean arterial pressure (r = −0.08, [−0.10, 0.05]). CONCLUSIONS: Perihematoma cerebral perfusion pressure is maintained despite increased cerebrovascular resistance and reduced cerebral blood flow. Aggressive antihypertensive therapy does not affect perihematoma or borderzone cerebral perfusion pressure. Maintenance of cerebral perfusion pressure provides physiologic support for the safety of blood pressure reduction in intracerebral hemorrhage.

National Institutes of Health Stroke Scale score is an unreliable predictor of perfusion deficits in acute stroke.

Background Perfusion-weighted magnetic resonance imaging is not routinely used to investigate stroke/transient ischemic attack. Many clinicians use perfusion-weighted magnetic resonance imaging selectively in patients with more severe neurological deficits, but optimal selection criteria have never been identified. Aims and/or Hypothesis We tested the hypothesis that a National Institutes of Health Stroke Scale score threshold can be used to predict the presence of perfusion-weighted magnetic resonance imaging deficits in patients with acute ischemic stroke/transient ischemic attack. Methods National Institutes of Health Stroke Scale scores were prospectively assessed in 131 acute stroke/transient ischemic attack patients followed by magnetic resonance imaging, including perfusion-weighted magnetic resonance imaging within 72 h of symptom onset. Patients were dichotomized based on the presence or absence of perfusion deficits using a threshold of Tmax (time to peak maps after the impulse response) delay ≥four-seconds and a hypoperfused tissue volume of ≥1 ml. Results Patients with perfusion deficits (77/131, 59%) had higher median (interquartile range) National Institutes of Health Stroke Scale scores (8 [12]) than those without perfusion deficits (3 [4], P < 0·001). A receiver operator characteristic analysis indicated poor to moderate sensitivity of National Institutes of Health Stroke Scale scores for predicting perfusion deficits (area under the curve = 0·787). A National Institutes of Health Stroke Scale score of ≥6 was associated with specificity of 85%, but sensitivity of only 69%. No National Institutes of Health Stroke Scale score threshold identified all cases of perfusion-weighted magnetic resonance imaging deficits with sensitivity >94%. Conclusions Although higher National Institutes of Health Stroke Scale scores are predictive of perfusion deficits, many patients with no clinically detectable signs have persisting cerebral blood flow changes. A National Institutes of Health Stroke Scale score threshold should therefore not be used to select patients for perfusion-weighted magnetic resonance imaging. Perfusion-weighted magnetic resonance imaging should be considered in all patients presenting with acute focal neurological deficits, even if these deficits are transient.