Negar Asdaghi

Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal

Background and Purpose Anticoagulant-associated intracranial hemorrhage (aaICH) presents with larger hematoma volumes, higher risk of hematoma expansion, and worse outcome than spontaneous intracranial hemorrhage. Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of anticoagulation after aaICH. Given the lack of randomized controlled trial evidence of efficacy, and the potential for thrombotic complications, we aimed to determine outcomes in patients with aaICH treated with PCC. Methods We conducted a prospective multicenter registry of patients treated with PCC for aaICH in Canada. Patients were identified by local blood banks after the release of PCC. A chart review abstracted clinical, imaging, and laboratory data, including thrombotic events after therapy. Hematoma volumes were measured on brain CT scans and primary outcomes were modified Rankin Scale at discharge and in-hospital mortality. Results Between 2008 and 2010, 141 patients received PCC for aaICH (71 intraparenchymal hemorrhages). The median age was 78 years (interquartile range, 14), 59.6% were male, and median Glasgow Coma Scale was 14. Median international normalized ratio was 2.6 (interquartile range, 2.0) and median parenchymal hematoma volume was 15.8 mL (interquartile range, 31.8). Median post-PCC therapy international normalized ratio was 1.4: 79.5% of patients had international normalized ratio correction (<1.5) within 1 hour of PCC therapy. Patients with intraparenchymal hemorrhage had an in-hospital mortality rate of 42.3% with median modified Rankin Scale of 5. Significant hematoma expansion occurred in 45.5%. There were 3 confirmed thrombotic complications within 7 days of PCC therapy. Conclusions PCC therapy rapidly corrected international normalized ratio in the majority of patients, yet mortality and morbidity rates remained high. Rapid international normalized ratio correction alone may not be sufficient to alter prognosis after aaICH.

Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion

Background and Purpose— Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK–tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. Methods— TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK–tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ⩽5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0–1). Results— Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01–20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0–1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0–1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09–2.5; P=0.026). Conclusions— Administration of TNK–tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654445.

Acute Perfusion and Diffusion Abnormalities Predict Early New MRI Lesions 1 Week After Minor Stroke and Transient Ischemic Attack

Background and Purpose— Transient ischemic attack and minor stroke are associated with high ischemic recurrence in the first week. We prospectively studied the correlation between baseline diffusion/perfusion deficits and development of new ischemic lesions. Methods— Patients with transient ischemic attack and those with minor stroke (n=50) underwent MRI at admission. Acute perfusion-weighted imaging deficit (Tmax+2-second delay) and diffusion-weighted imaging (DWI) lesion volumes were measured planimetrically. Follow-up scans were examined for new DWI/fluid-attenuated inversion recovery lesions at Days 7 and 30. Results— Twenty-eight patients (56%) had acute DWI lesions. New DWI lesions developed in 9 of 50 patients (18%) at 1 week and 11 of 50 (cumulative 22%) at 4 weeks. Patients with new infarcts were more likely to have baseline DWI lesions (&khgr;2=8.264, P=0.003). Baseline DWI lesion volume was significantly larger in those who developed new lesions at Day 7 (median, 13.2 mL; interquartile range, 12 versus median 0.1 mL; interquartile range, 2 mL; P<0.001) and Day 30 (11.1 mL; interquartile range, 13 mL versus 0.1 mL; interquartile range, 13 mL; P<0.001). Thirty-eight patients had baseline perfusion-weighted imaging. Patients with recurrent lesions were more likely to have baseline perfusion deficits (&khgr;2=19.5, P<0.0001). All new lesions developed within the baseline hypoperfused regions. Baseline DWI lesion volume predicted new lesion development at day 7 (OR, 1.17 per mL; CI, 1.05 to 1.30; P=0.005) and Day 30 (OR, 1.39 per mL; CI, 1.03 to 1.26; P=0.009) by regression analysis. Conclusions— Early recurrence of stroke is much more likely in patients with larger baseline DWI and perfusion-weighted imaging lesions. MRI lesion “recurrence” appears to be related to completion of the natural history of the original cerebrovascular syndrome rather than de novo events in most patients.

Oxfordshire Community Stroke Project Classification Poorly Differentiates Small Cortical and Subcortical Infarcts

Background and Purpose— The Oxfordshire Community Stroke Project (OCSP) is a common clinical stroke classification tool. We evaluated the accuracy of OCSP classification with a prospective magnetic resonance imaging (MRI) study. Methods— Stroke/transient ischemic attack patients presenting within 48 hours of onset were included in the study (n=130). Following computed tomography scan, OCSP classification, total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), lacunar circulation infarcts (LACI), and posterior circulation infarcts (POCI) were performed by 3 independent examiners. All patients underwent diffusion-weighted MRI with planimetric volume measurement and classification into OCSP categories, organized by lesion location. Results— Patients were clinically classified as TACI (12 patients), PACI (62 patients), LACI (38 patients), and POCI (18 patients). In 101 patients with diffusion-weighted MRI lesions, correct classification rates were: TACI (83.3%), PACI (83%), LACI (39%), and POCI (86%). OCSP had the following sensitivity (SE), specificity (SP), and positive predictive value (PPV): TACI (SE, 100%; SP, 98%; PPV, 83%), PACI (SE, 73%; SP, 78%; PPV, 83%), LACI (SE, 47%; SP, 83%; PPV, 39%), and POCI (SE, 92%; SP, 98%; PPV, 86%). Sixty-one percent of patients in the LACI group had radiographic appearances consistent with PACI, and 15% of those classified as PACI had lacunar infarcts. No differences in stroke severity existed between patients classified correctly (median National Institutes of Health Stroke Scale [NIHSS]=4; interquartile range [IQR]=7) or incorrectly (median NIHSS=3; IQR=3). Patients classified correctly had larger infarct volume (median=6.75 mL; IQR=33.2) than did those who were incorrectly classified (1.86 mL; IQR=5; P=0.008). Conclusions— OCSP classification does not permit accurate discrimination between lacunar and small-volume cortical infarcts. Differential patterns of investigation for stroke etiology should not be based solely on clinical criteria.

Relationship between sodium intensity and perfusion deficits in acute ischemic stroke

To assess the relationship between sodium signal intensity changes and oligemia, measured with perfusion‐weighted imaging (PWI), in ischemic stroke patients.

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.

Perfusion MR Predicts Outcome in High-Risk Transient Ischemic Attack/Minor Stroke A Derivation–Validation Study

Background and Purpose— Transient or minor ischemic stroke is associated with an early risk of deterioration. Baseline perfusion–diffusion mismatch may predict clinical deterioration and infarct growth in this population. Methods— High-risk transient ischemic attack and minor stroke (National Institutes of Health Stroke Scale ⩽3) subjects were prospectively enrolled and imaged with MRI within 24 hours of symptom onset as part of sequential derivation and validation cohorts. Baseline diffusion-weighted imaging, perfusion-weighted imaging (Tmax≥4 s), mismatch (Tmax≥4 s-diffusion-weighted imaging), and follow-up fluid-attenuated inversion recovery infarct volumes were measured. Primary outcome was infarct growth on fluid-attenuated inversion recovery, and secondary outcome was symptom progression. Results— One hundred thirty-seven and 281 subjects were included in the derivation and validation cohorts, respectively. Infarct growth occurred in 18.5% of the derivation and 5.5% of the validation cohorts. Symptom progression occurred in 9.5% of the derivation and 4.5% of the validation cohorts. In the derivation cohort, subjects with baseline mismatch were significantly more likely to show infarct growth on fluid-attenuated inversion recovery (relative risk [RR], 13.5; 95% confidence interval [CI], 4.2–38.9) and symptom progression (RR, 7.0; 95% CI, 2.0–7.3). A baseline mismatch volume of 10 mL in the derivation cohort was the optimal threshold to predict infarct growth (area under the curve, 0.89; 95% CI, 0.80–0.98). This threshold was highly predictive of infarct growth in the validation cohort (P=0.001). Baseline mismatch was associated with clinical deterioration in the derivation (area under the curve, 0.81; 95% CI, 0.67–0.96) and validation cohorts (area under the curve, 0.66; 95% CI, 0.46–0.85). Conclusions— Among subjects with high-risk transient ischemic attack and minor stroke, diffusion-weighted imaging–perfusion-weighted imaging mismatch predicts infarct growth and clinical deterioration. These findings suggest that reperfusion strategies would be beneficial in this population.

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.

Magnetic Resonance Imaging versus Computed Tomography in Transient Ischemic Attack and Minor Stroke: The More Υou See the More You Know

Background: Magnetic resonance imaging (MRI) is proposed as the preferred imaging modality to investigate patients with transient ischemic attack (TIA). This is mainly based on a higher yield of small acute ischemic lesions; however, direct prospective comparisons are lacking. In this study, we aimed to directly compare the yield of acute ischemic lesions on MRI and computed tomography (CT) in the emergency diagnosis of suspected TIA or minor stroke. Methods: Consecutive patients aged 18 years or older presenting with minor stroke (NIHSS <4) or high-risk TIA and who were examined by a stroke neurologist within 24 h of symptom onset were prospectively enrolled in the CATCH study. Patients who had undergone both a baseline CT and an MRI within 24 h of symptom onset were included in this substudy. Baseline MRI and CT were interpreted independently to identify an acute ischemic lesion. The rates of acute ischemic lesions on CT and MRI were compared, and the volume of acute ischemic lesions was measured on MRI. In addition, the volume of acute ischemic lesions on MRI was compared between patients who had evidence of acute ischemia on CT and in those who did not. Results: A total of 347 patients were included, 168 with TIAs, 147 with minor strokes and 32 with a final diagnosis of a mimic. Acute ischemic lesions were detected in 39% of TIAs by using MRI versus 8% by using CT (p < 0.0001) and in 86% of minor strokes by using MRI versus 18% by using CT (p < 0.0001). Compared to MRI, CT had a sensitivity of 20% and a specificity of 98% in identifying an acute ischemic lesion. The infarct volume on diffusion-weighted MRI was larger in cases where the CT also showed an acute ischemic lesion (median 5.07 ml, IQR 10) as compared to lesions seen only on MRI (median 0.68 ml, IQR 1.31, p < 0.0001). Conclusion: MRI is superior to CT in detecting the small ischemic lesions occurring after TIA and minor stroke. Since these lesions are clinically relevant, MRI should be the preferred imaging modality in this setting.

Risks and benefits of thrombolysis in the elderly

Background and purpose Stroke incidence continues to rise exponentially with age even as temporal trends in some population risk factors increase and others decline. In general, older patients with stroke have worse outcomes compared to their younger counterparts. Stroke severity, concurrent medical problems, prestroke disability, and less-aggressive acute and chronic management are a few contributing factors to account for this poor prognosis. Acute thrombolysis therapy is the only proven treatment in acute ischemic stroke. However, elderly patients have mostly been excluded from acute revascularization studies, due predominantly to their overall poor prognosis and the fear of hemorrhagic complications from these treatments. Despite this, there is no evidence to suggest that the risk benefit ratio of thrombolysis treatment is substantially different in the elderly than in younger ischemic stroke patients. Summary of review In this review, we briefly examine the stroke risk factor profile and outcome in the elderly and review the current evidence regarding intravenous and intra-arterial revascularization treatments. Conclusion We feel that carefully selected patients who meet eligibility criteria for thrombolysis should not be denied this therapy on the basis of age alone.