Nandavar Shobha

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.

Risk Score for In-Hospital Ischemic Stroke Mortality Derived and Validated Within the Get With The Guidelines–Stroke Program

Background— There are few validated models for prediction of in-hospital mortality after ischemic stroke. We used Get With the Guidelines–Stroke Program data to derive and validate prediction models for a patients risk of in-hospital ischemic stroke mortality. Methods and Results— Between October 2001 and December 2007, there were 1036 hospitals that contributed 274 988 ischemic stroke patients to this study. The sample was randomly divided into a derivation (60%) and validation (40%) sample. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model. We also separately derived and validated a model in the 109 187 patients (39.7%) with a National Institutes of Health Stroke Scale (NIHSS) score recorded. Model discrimination was quantified by calculating the C statistic from the validation sample. In-hospital mortality was 5.5% overall and 5.2% in the subset in which NIHSS score was recorded. Characteristics associated with in-hospital mortality were age, arrival mode (eg, via ambulance versus other mode), history of atrial fibrillation, previous stroke, previous myocardial infarction, carotid stenosis, diabetes mellitus, peripheral vascular disease, hypertension, history of dyslipidemia, current smoking, and weekend or night admission. The C statistic was 0.72 in the overall validation sample and 0.85 in the model that included NIHSS score. A model with NIHSS score alone provided nearly as good discrimination (C statistic 0.83). Plots of observed versus predicted mortality showed excellent model calibration in the validation sample. Conclusions— The Get With the Guidelines–Stroke risk model provides clinicians with a well-validated, practical bedside tool for mortality risk stratification. The NIHSS score provides substantial incremental information on a patients short-term mortality risk and is the strongest predictor of mortality.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy

Objectives: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. Methods: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). Results: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = −0.66, p = 0.003) and more microbleeds (r = −0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). Conclusions: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Thrombolysis at 3-4.5 hours after acute ischemic stroke onset--evidence from the Canadian Alteplase for Stroke Effectiveness Study (CASES) registry.

Background: Extending the therapeutic window for thrombolysis is an important strategy in maximizing the proportion of patients treated. ECASS III examined a 3–4.5-hour window and showed a benefit to treated patients. We examined the experience in Canadian centres using intravenous tPA treatment in the 3–4.5-hour time window. Methods: The data were obtained from the CASES (Canadian Alteplase for Stroke Effectiveness Study) – a prospective, multicentric cohort study with patient enrollment from 60 centres across Canada over 2.5 years. The 90-day outcome, mortality and symptomatic intracranial hemorrhage of patients thrombolysed between 3 and 4.5 h and within 3 h of symptom onset were compared. A mRS 0–1 (no symptoms at all or no significant disability despite symptoms, able to carry out all usual duties and activities) at 90 days was defined as a favorable outcome. Results: A total of 1,112 patients with complete data were included. 129 (11.6%) patients received tPA between 3 and 4.5 h of symptom onset and 983 (88.4%) patients received tPA within 3 h. At 90 days, 39.4% of the patients in the 3–4.5-hour treatment group and 36.5% of patients in the under 3-hour treatment group attained a mRS ≤1. There were no differences between the two groups regarding their functional status at 3 months. There was a trend towards higher rate of sICH in the 3–4.5-hour group compared to the 0–3-hour group (7.8 vs. 3.8%, p = 0.06). Similarly there was a trend towards higher rate of deaths in the 3–4.5-hour group compared to the 0–3-hour group (28.4 vs. 21.4%, p = 0.09). A χ2 test for trend demonstrated a rising proportion of symptomatic ICH in later time windows (p = 0.013). A similar trend (non-significant) was observed for mortality. Conclusion: Our study suggests that patients with acute ischemic stroke may be successfully treated with intravenous tPA in the 3–4.5-hour treatment window, but cautions that later time window treatment may result in greater adverse events.

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.

A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.

Background We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods and Results Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines—Stroke database were used. In‐hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. Conclusions A single prediction score for all stroke types can be used to predict risk of in‐hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.

Effects of aging on the association between cerebrovascular responses to visual stimulation, hypercapnia and arterial stiffness

Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercapnia-evoked cerebral blood flow (CBF) responses. However, the interplay between arterial stiffness and reduced CBF responses is poorly understood. It was hypothesized that increased cerebral arterial stiffness is associated with reduced evoked responses to both, a flashing checkerboard visual stimulation (i.e., neurovascular coupling), and hypercapnia. To test this hypothesis, 20 older (64 ± 8 year; mean ± SD) and 10 young (30 ± 5 year) subjects underwent a visual stimulation (VS) and a hypercapnic test. Blood velocity through the posterior (PCA) and middle cerebral (MCA) arteries was measured concurrently using transcranial Doppler ultrasound (TCD). Cerebral and systemic vascular stiffness were calculated from the cerebral blood velocity and systemic blood pressure waveforms, respectively. Cerebrovascular (MCA: young = 76 ± 15%, older = 98 ± 19%, p = 0.004; PCA: young = 80 ± 16%, older = 106 ± 17%, p < 0.001) and systemic (young = 59 ± 9% and older = 80 ± 9%, p < 0.001) augmentation indices (AI) were higher in the older group. CBF responses to VS (PCA: p < 0.026) and hypercapnia (PCA: p = 0.018; MCA: p = 0.042) were lower in the older group. A curvilinear model fitted to cerebral AI and age showed AI increases until ~60 years of age, after which the increase levels off (PCA: R2 = 0.45, p < 0.001; MCA: R2 = 0.31, p < 0.001). Finally, MCA, but not PCA, hypercapnic reactivity was inversely related to cerebral AI (MCA: R2 = 0.28, p = 0.002; PCA: R2 = 0.10, p = 0.104). A similar inverse relationship was not observed with the PCA blood flow response to VS (R2 = 0.06, p = 0.174). In conclusion, older subjects had reduced neurovascular- and hypercapnia-mediated CBF responses. Furthermore, lower hypercapnia-mediated blood flow responses through the MCA were associated with increased vascular stiffness. These findings suggest the reduced hypercapnia-evoked CBF responses through the MCA, in older individuals may be secondary to vascular stiffening.

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.

Differences in stroke outcome based on sex

Objective: Stroke thrombolysis may have a differential effect by sex. We sought to examine the relationship between sex and outcome after thrombolysis. Methods: This is a retrospective cohort study of stroke patients from the Registry of Canadian Stroke Network phase 1 (June 2001-February 2002) and phase 2 (June 2002-December 2002). Variables including demographics, history, clinical data, process measures, and outcome were analyzed. The primary outcomes were the Stroke Impact Scale-16 score (SIS-16) and mortality at 6 months. We compared the outcomes of the thrombolyzed and nonthrombolyzed cohorts and examined the data for a tissue plasminogen activator (tPA)-by-sex interaction on the 2 primary outcomes. Results: The overall proportion of patients who achieved an excellent outcome (SIS-16 >75) was not different by gender. However, the proportion of patients achieving an excellent outcome in the non-tPA cohort was much greater in males, with an absolute risk difference of 11.8%. A multiplicative treatment by sex interaction was evident (p = 0.054). This interaction was not present for stroke case fatality. Conclusions: Women fared poorly compared to men in the placebo groups, but this negative prognostic sex effect was neutralized by thrombolysis.

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.