Simerpreet Bal

Low Rates of Acute Recanalization With Intravenous Recombinant Tissue Plasminogen Activator in Ischemic Stroke: Real-World Experience and a Call for Action

Background and Purpose— Acute rates of recanalization after intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in proximal vessel occlusion have been estimated sparingly, typically using transcranial Doppler (TCD). We aimed to study acute recanalization rates of IV rt-PA in CT angiogram-proven proximal (internal carotid artery [ICA], M1 middle cerebral artery [MCA], M2-MCA, and basilar artery) occlusions and their effects on outcome. Materials and Methods— The CT angiogram database of the Calgary stroke program was reviewed for the period 2002 to 2009. All patients with proximal vessel occlusions receiving IV rt-PA who were assessed for recanalization by TCD or angiogram (for acute endovascular treatment) were included for analysis. Rates of acute recanalization as observed on TCD/first run of angiogram and postendovascular therapy recanalization rates were noted. Modified Rankin Scale score ≤2 at 3 months was used as a good outcome. Results— Among 1341 patients in the CT angiogram database, 388 patients with proximal occlusion were identified. Of these, 216 patients had received IV rt-PA; 127 patients underwent further imaging to assess recanalization. Among the patients undergoing TCD (n=46) and cerebral angiogram (n=103), only 27 (21.25%) patients had acute recanalization. By occlusion subtype, the rates of recanalization were: distal ICA (with or without ICA neck occlusion or stenotic disease) 1 of 24 (4.4%); M1-MCA (with or without ICA neck occlusion or stenotic disease) 21 of 65 (32.3%); M2-MCA 4 of 13 (30.8%); and basilar artery 1 of 25 (4%). Onset to rt-PA time was comparable in patients with and without recanalization. Recanalization (P<0.0001; risk ratio, 2.7; 95% confidence interval, 1.5–4.6) was the strongest predictor of outcome (adjusted for age and National Institutes of Health Stroke Scale score). Conclusions— A low rate of acute recanalization was observed with IV rt-PA in proximal vessel occlusions identified by baseline CT angiogram. Recanalization was the strongest predictor of good outcome.

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P=0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

CT Angiographic Source Images Predict Outcome and Final Infarct Volume Better Than Noncontrast CT in Proximal Vascular Occlusions

Background and Purpose— Alberta Stroke Programme Early CT Score (ASPECTS) is widely used for assessment of early ischemic changes in acute stroke. We hypothesized that CT angiography source image (CTA-SI) ASPECTS correlates better with baseline National Institutes of Health Stroke Scale score, final ASPECTS and neurological outcomes when compared with noncontrast CT ASPECTS. Methods— We studied patients presenting with acute ischemic stroke and identified proximal arterial occlusions (internal carotid artery, middle cerebral artery M1, and proximal middle cerebral artery M2) from the Calgary CT Angiography database. CT scans were independently read by 3 observers for baseline noncontrast CT ASPECTS, CT angiography source image ASPECTS, and follow-up ASPECTS. Details of demographics and risk factors were noted. A modified Rankin Scale score ⩽2 at 3 months was considered a favorable outcome. Results— We identified 261 patients with proximal occlusions for analysis. We found a better correlation between CT angiography source image ASPECTS and follow-up ASPECTS (Spearman correlation coefficient r=0.65; 95% CI, 0.58 to 0.72; P<0.001) than between noncontrast CT ASPECTS and follow-up CT ASPECTS (r=0.46; 95% CI, 0.36 to 0.55; P<0.001). CT angiography source image ASPECTS correlated better with baseline National Institutes of Health Stroke Scale and 24-hour National Institutes of Health Stroke Scale when compared with noncontrast CT ASPECTS (P<0.001). In an adjusted model including both CT angiography source image ASPECTS and noncontrast CT ASPECTS, CT angiography source image ASPECTS was associated with good outcome (OR, 2.30; 95%, CI, 1.16 to 4.53), whereas noncontrast CT ASPECTS was not (OR, 1.54; 95% CI, 0.84 to 2.82). Among imaging parameters, CT angiography source image ASPECTS was the only independent predictor of good outcome (OR, 2.29; 95% CI, 1.16 to 4.53). Conclusions— CT angiography source image ASPECTS correlates better with baseline stroke severity, is a better predictor of final infarct extension, and independently predicts neurological outcome than noncontrast CT ASPECTS.

Time Dependence of Reliability of Noncontrast Computed Tomography in Comparison to Computed Tomography Angiography Source Image in Acute Ischemic Stroke

There is no consensus on how the reliability and predictive ability of noncontrast computed tomography (NCCT) and computed tomography angiography source image (CTASI) change over time from acute ischemic stroke onset. We hypothesized that the reliability for detecting early ischemic changes (EIC) would be lower in early time periods and that changes identified on CTASI would be more reliable across examiners than changes identified on NCCT. To address this, we compared the relationships between CTASI, NCCT, and final infarct in patients with initial computed tomography (CT) imaging at different time points after stroke onset. Patients with acute ischemic stroke with proximal anterior circulation occlusions (internal carotid artery, middle carotid artery M1, proximal M2) from Calgary CT Angiography (CTA) database were studied. The cohort was categorized in four groups based on time from stroke onset to baseline NCCT/CTA: 0–90 mins (n = 69), 91–180 mins (n = 88), 181–360 mins (n = 46), and >360 mins (n = 58). Median scores of NCCT-Alberta Stroke Program Early CT Score (ASPECTS), CTASI ASPECTS, and follow-up ASPECTS among different time categories were compared. To determine reliability, a subsample of NCCT brain and CTASI were interpreted at separate sessions weeks apart by two neuroradiologists and two stroke neurologists in random order. Median and mean ASPECTS ratings on NCCT and CTASI were higher than final ASPECTS in each time category (P < 0·001 for all comparisons). CTASI ASPECTS was lower than NCCT ASPECTS in each time category, and differences were significant at 0–90 mins and 91–180 mins (P < 0·001). The least agreement among readers was in detection of EIC on NCCT brain in the ultra-early phase (<90 mins) [intraclass correlation coefficient (ICC) = 0·48. By contrast, there was excellent agreement on EIC on CTASI regardless of time period (ICC = 0·87–0·96). Using ASPECTS methodology, CTASI is more reliable than NCCT at predicting final infarct extent particularly in the early time windows.

Measurement of length of hyperdense MCA sign in acute ischemic stroke predicts disappearance after IV tPA.

We sought to assess the hypothesis that length and volumes of middle cerebral artery (MCA) thrombus were associated with disappearance of the hyperdense middle cerebral artery sign (HMCAS) in acute ischemic stroke.

High Rate of Magnetic Resonance Imaging Stroke Recurrence in Cryptogenic Transient Ischemic Attack and Minor Stroke Patients

Background and Purpose— Cryptogenic stroke is common in patients with transient ischemic attack (TIA) and minor stroke. It is likely that the imaging recurrence risk is higher than the clinical recurrence rate. We sought to determine the rate of clinical and radiographic stroke recurrence in a population of cryptogenic TIA and minor stroke. Methods— Patients with TIA/minor stroke (National Institutes of Health Stroke Scale score ⩽3) were prospectively enrolled and imaged within 24 hours of symptom onset as part of 2 cohorts. Patients were assessed at 3 months to document any clinical recurrence and underwent repeat magnetic resonance imaging (MRI) at either 30 or 90 days. Stroke mechanism was categorized as cryptogenic after standard etiologic work-up was completed and was negative. Follow-up MRI was assessed for any new lesions in comparison with baseline imaging. Results— Three hundred thirty-three of 693 (48%) patients had cryptogenic stroke. Of these cryptogenic patients, 207 (62%) had follow-up imaging. At 30-day MRI follow-up, 6.6% (5/76) had new lesions (3 in a remote arterial territory). At 90-day MRI follow-up, 14.5% (19/131) had new lesions (9 in a remote arterial territory). Clinical recurrent stroke was seen in 1.2% (4/333) of patients within 90 days. Conclusions— Cryptogenic etiology is common in a TIA/minor stroke population. This population shows a high rate of silent radiographic recurrence, suggesting active disease. Use of MRI as a surrogate marker of disease activity is 1 potential way of assessing efficacy of new treatments in this population with reduced sample size.

Anterior Temporal Artery Sign in CT Angiography Predicts Reduced Fatal Brain Edema and Mortality in Acute M1 Middle Cerebral Artery Occlusions

Mortality in acute ischemic middle cerebral artery (MCA) stroke ranges from 5% to 45%. We identify a vascular imaging sign, presence of “prominent anterior temporal artery” on computed tomography (CT) angiography (CTA) and investigate whether it predicts mortality in acute M1‐MCA occlusions.

Routine CT Angiography in Acute Stroke Does Not Delay Thrombolytic Therapy

INTRODUCTION Lack of additional utility over non-contract computed tomography (NCCT) in decision making and delay in door to needle time are arguments used against routine computed tomographic angiography (CTA) use in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center. METHODS We reviewed 850 stroke thrombolysis patients in a university hospital in Canada from April 1996 to December 2009. Time to treatment was divided into the following interval times: onset-to-door, door-to-needle and onset-to-needle. Patients were categorized into: Group 1 (April 1996-Dec 2002) (Non-contrast CT Scan based thrombolysis) n=297, Group 2 (Jan 2004-Dec 2009) (CTA based thrombolysis) n=504. The period from Jan to Dec 2003 (n=49) was considered a washout period as we had started the CTA protocol that year. Interval times were compared between the two groups. RESULTS Interval times in Group 1 and Group 2 were: median onset-to-door times in Group 1 [55 minutes (IQR 48),] and Group 2 [61 minutes (IQR 57)] (p=0.019); median door-to-needle times in Group 1 [67 minutes(IQR 43)] and Group 2 [62.5 minutes (IQR 52)] (p=0.519); median onset-to-needle times in Group 1 (139 minute (IQR 73)] and Group 2 (141.5 min (IQR 109.5) (p=0.468). In multivariable linear regression analysis, age and onset-to-door time influenced the door-to-needle time. For every decade of age, door-to-needle times were 5.4 minutes faster. CONCLUSIONS CTA based thrombolytic approach for acute ischemic stroke does not significantly delay thrombolysis in routine clinical practice.

Malignant Emboli on Transcranial Doppler During Carotid Stenting Predict Postprocedure Diffusion-Weighted Imaging Lesions

Background and Purpose— Carotid angioplasty and stenting (CAS) has a higher incidence of periprocedural stroke compared with endarterectomy. Identifying CAS steps with the highest likelihood of embolization may have important implications. We evaluated CAS safety by correlating the findings of procedural transcranial Doppler with postprocedure diffusion-weighted imaging (DWI) lesions. Methods— In this prospective study, transcranial Doppler monitoring was performed during CAS procedures, which were divided into 11 steps. Embolic signals on transcranial Doppler were counted and classified based on the relative energy index of microembolic signals into microemboli ⩽1 or malignant macroemboli >1. Poststenting MRI was performed in all cases. A negative binomial regression model was used to evaluate the predictive value of transcranial Doppler emboli for new DWI lesions. Results— Thirty subjects were enrolled. Seven of 30 subjects (23.3%) were asymptomatic. The median embolic signal count was 212.5 (108 microemboli and 80 malignant macroemboli). Stent deployment phase showed the highest median embolic signals count at 58, followed by protection device deployment at 30 (P=0.0006). Twenty-four of 30 (80%) had new DWI lesions on post-CAS MRI. The median DWI count was 4 (interquartile range 7). Two of 30 (6.7%) had new or worsening clinical deficits post-CAS. For every malignant embolus, the expected count of DWI lesions increases by 1% ( 95% confidence interval, 0%–2%; P=0.032). Conclusions— We observed a high incidence of embolic signals during CAS procedure, especially, when devices were deployed. Most subjects developed new DWI lesions, but only 6.7% had deficits. Malignant macroemboli predicted new DWI lesions.

Association of metabolic syndrome with carotid atherosclerosis in the young North Indian population.

BACKGROUND Metabolic syndrome (MetS) and its components are associated with increased risk of stroke and cardiovascular disease. Relationship of MetS to carotid atherosclerosis has not been documented well in North Indian population. AIMS (1) To determine the incidence of metabolic syndrome in asymptomatic healthy young North Indian population; (2) to evaluate individuals with MetS patients for carotid atherosclerosis by carotid duplex ultrasound examination; (3) to determine the significance of each component of MetS in relation to carotid atherosclerosis in these patients. METHODS 440 individuals in the age group of 25-50 years, asymptomatic for cardiac or cerebrovascular disease were screened for metabolic syndrome. 162 patients from a hospital-based population fulfilled the criteria for MetS (as per NCEP ATP III criteria). Duplex ultrasound (DU) examination of extracranial carotid vessels was performed on all the subjects. 112 age- and sex-matched controls were screened, and they underwent DU examination for comparison. RESULTS Hypertriglyceridemia was the commonest component seen in 79.6% of the MetS subjects, followed by central obesity seen in 74.6% subjects. Carotid atherosclerotic disease was observed in 21.6% of patients with MetS. Mild atherosclerosis (intima media thickness (IMT) >0.09 cm) was observed in 82.8% and 17.3% had plaques with mild stenosis (<50%) in the extracranial carotid arteries. Among patients of MetS with carotid atherosclerotic disease 82.6% had hypertriglyceridemia and 71.5% had 4 or more components for MetS. Among controls, five subjects (4.46%) had evidence of mild carotid atherosclerosis (IMT >0.09 cm) on DU. MetS was significantly associated with carotid DU abnormalities (increased IMT >0.09 cm) compared to controls (Fischers exact test p<0.0001). Univariate analysis showed the relationship of hypertriglyceridemia to carotid atherosclerosis (p=0.03). On multivariate regression analysis none of the individual components of MetS contributed significantly to the presence of carotid atherosclerosis. CONCLUSIONS MetS is common in asymptomatic healthy North Indian population, with hypertriglyceridemia being the commonest component of MetS in this population, which may be predictive of carotid atherosclerotic disease. Serum triglyceride estimation can serve as a screen for asymptomatic healthy subjects to select the target population for cerebrovascular disease prevention.