Seet, Raymond C.S.

Background and Objective Hyperdense middle cerebral artery (HDMCA) sign is an early sign seen on CT head after acute ischemic stroke indicating acute arterial thrombosis. We aimed to measure HDMCA sign objectively. Methods We conducted a retrospective analysis of prospectively collected data from 151 cases of acute ischemic stroke eligible for IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. Admission CT Head was studied to identify HDMCA sign. All patients had either 24 hour CT head or MRI head to confirm the stroke in the same vessel territory. MCA was measured in Hounsfield units and was compared to the contralateral MCA. Receiver Operating Characteristic (ROC) curve analysis was performed to calculate sensitivity and specificity. Results Mean admission NIHSS score was 11±7. HDMCA sign was seen in 93 (62%) patients. ROC curve analysis for ipsilateral MCA Hounsfield units had an area under the curve 0.88 (p<0.001, CI 0.83-0.94) which showed 50 HU or more had 48% sensitivity and 98% specificity. Ratio of ipsilateral to contralateral MCA HU had an area under the curve 0.94 (p<0.001, CI 0.90-0.98) which showed ratio of 1.23 had 67% sensitivity and 98% specificity. A combination of either ipsilateral HU more than equal to 50 or a ratio of ipsilateral to contralateral MCA HU more than equal to 1.23 had 77% sensitivity, 95% specificity, 96% positive predictive value and 72% negative predictive value. Conclusion A combination of ipsilateral HU more than equal to 50 or a ratio of ipsilateral to contralateral MCA HU more than equal to 1.23 can objectively identify HDMCA sign with good sensitivity and high specificity.

Background and Objective Hyperdense MCA (HDMCA) sign is an early sign seen on CT head after acute ischemic stroke indicating acute arterial thrombosis. It has been reported as a predictor of stroke morbidity and mortality. The relationship of size of hyperdense middle cerebral artery (MCA) sign with stroke volume and functional outcome has not been sufficiently studied. Methods We did a retrospective analysis of prospectively collected data from 206 cases of acute ischemic stroke eligible for IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. Admission CT Head was studied to identify HDMCA sign which was further subcategorized according to size. CT head at 24 hours after intravenous tissue plasminogen activator was used to calculate Alberta Stroke Program Early CT Score (ASPECTS) to measure ischemic damage area. Functional outcome was assessed using the modified Rankin score at 3 months and dichotomized into less than equal to 2 (good outcome) and more than 2 (bad outcome). Univariate analysis including t-test, Chi-square, and Fisher Exact test was used when appropriate. Results Mean admission NIHSS score was 11±7. HDMCA sign was seen in 99 (48%) patients: 100% MCA occlusion (7) 76-100% M1 (17), 50-75% M1 (17), less than 50% M1 (6), MCA dot sign (23), sylvian dot sign (21) and sylvian MCA sign, defined as any sylvian MCA occlusion bigger than a dot (8). Univariate analysis showed statistically significant associations between our HDMCA classification and ASPECTS at 24 hours (p<0.001) and modified Rankin score at 3 months (p<0.001). Smaller infarctions (ASPECTS >8) were observed more often with lower MCA clot burden; MCA dot (48%), less than 50% MCA (80%), sylvian dot (57%) and sylvian MCA (38%), 50-75% M1 (6%), 75-100% M1 (0%) and 100% MCA (0%). Good outcome (mRS≤2 at 3 months) was seen more often with lower MCA clot burden; MCA dot (52%), less than 50% MCA (67%), sylvian dot (67%) and sylvian MCA (63%). Conversely, larger HDMCA size was associated with poor outcome (mRS>2); 50-75% M1 (100%), 75-100% (88%) and 100% MCA (100%). Conclusion The size of the HDMCA sign size is an important predictor of ischemic stroke mortality and morbidity. HDMCA should be measured upon admission as it may help refine prognostication and identify patients who could benefit from endovascular rescue therapy after intravenous thrombolysis.

Background: Whether a significant proportion of cryptogenic stroke (CS) is caused by under-detected paroxysmal atrial fibrillation (PAF) is not known. Prolonged ambulatory cardiac monitoring may detect episodes of PAF in patients with stroke of unknown cause (cryptogenic stroke, CS). However, it is unclear whether PAF is more common in patients wtih CS compared with patients with stroke of known cause (SKC). We performed a case control study to compare the rates of detection of PAF in CS vs SKC using prolonged ambulatory cardiac rhythm monitoring. Methods and Results: We prospectively enrolled 132 patients within 3 months of a stroke (66 with CS and 66 with SKC) to undergo 3-week ambulatory cardiac rhythm monitoring using the CardioNet MCOT system. Stroke group was assigned by consensus between two vascular neurologists upon enrollment based on the Causative Classification of Stroke system. Primary endpoint was detection of PAF of any duration independently confirmed by two cardiologists blinded to the stroke group. The groups were well balanced except that patients with CS tended to be older and to have less hypertension and diabetes. Four patients (2 in each group) were excluded because of insufficient stroke evaluation or early discontinuation of monitoring. Episodes of PAF were detected in 16/64 (25%) patients with CS and 9/64 (14%) patients with SKC (p=0.12). Only 5 patients had episodes of PAF lasting > 30 seconds (3 with CS and 2 with SKC). Six of the 9 patients from the SKC group with PAF had small subcortical infarctions; the other 3 had cortical strokes ascribed to artery-to-artery embolism (2 with complex aortic plaques, 1 with severe vertebrobasilar stenosis). In patients under age 65, episodes of PAF were more common in the CS group (22% vs 3; p=0.07) while in patients age 65 or older the rates of detection were very similar (29% in CS vs 28% in SKC; p=0.9). Conclusions: Very short episodes of PAF are relatively common in patients with CS and with SKC, and their pathogenic significance is unclear. However, considering only patients under 65, a greater proportion of cryptogenic stroke patients had PAF, suggesting it might be pathogenic.

Background We sought to determine the occurrence of major bleeding events in a population-based cohort of stroke patients with atrial fibrillation in a population-based cohort who were risk-stratified at baseline, one and five years, following initiation of warfarin treatment. Methods The resources of the Rochester Epidemiology Project Medical Linkage System were used to identify acute ischemic stroke patients with atrial fibrillation undergoing warfarin treatment for secondary stroke prevention from 1980 to 1995. These patients were risk-stratified according to the HAS-BLED and HEMORRHAGES scores prior to warfarin initiation following stroke onset; these scores were reassessed one and five years later. Major bleeding was considered in patients with fatal or clinically overt bleeding associated with either transfusion of >2 units of blood or >2 g/dl decrease in hemoglobin. Results One hundred patients (mean age, 79.3 years; 68% women) were studied. Median duration of warfarin treatment was 2.4 years (interquartile range, 0.4-6.6) and duration from stroke onset to death was 3.7 years (1.1-8.8). Major bleeding events occurred in 41 patients at a median duration of 19 months (5-58) following warfarin initiation. Sixteen events occurred within a year of treatment, 25 events from years 1-5, and 14 events in patients treated for >5 years. Patients with baseline HAS-BLED scores ≥2 had higher life-time risks of major bleeding events compared with those ≤1 (95% vs 5%, p=0.002), while those with HEMORRHAGES score ≥2 had higher life-time risks of major bleeding events compared with those ≤1 (90% vs 10%, p=0.030). Periodic reassessments of these risks were associated with a higher detection of major bleeding events. Patients with an increase in the HAS-BLED scores had a higher subsequent risk of major bleeding events compared with those with no change (year one, 64% vs 34%, p=0.043; year five, 75% vs 29%, p=0.018). Similarly, patients with an increase in the HEMORRHAGES scores had a higher risks of major bleeding events compared to those with no change (year one, 57% vs 33%, p=0.063; year five, 71% vs 10%, p<0.001). Conclusions Periodic assessments of bleeding risks using prognostic scales are associated with a higher detection of major bleeding events. These scales should be periodically reassessed in the years following warfarin initiation to determine if the benefit of ongoing use outweighs the bleeding risk.

Background: Symptomatic intracranial hemorrhage (SICH) is the most feared complication of intravenous recombinant tissue plasminogen activator (rtPA). Differences exist in the criteria used to define neurologic decline, cerebral hemorrhage and interval between rtPA treatment and onset of cerebral hemorrhage. Methods: We performed a systematic review to investigate SICH rates following rtPA treatment and assess their consistency with respect to mortality rates reported in the literature. Studies were identified from the PubMed and EMBASE databases from January 1994 to June 2011 by cross-referencing the following MeSH terms: “thrombolysis”, “recombinant tissue plasminogen activator”, “rtPA”, “TPA”, “Alteplase”, “thrombolytics”, “cerebral ischemia” and “stroke”. We restricted our selection to stroke registries and larger cohort studies that comprised consecutively recruited stroke patients with an operational cutoff of >200 subjects. Studies that (1) involve endovascular-treated patients, (2) applied pre-selection criteria (e.g. the presence of demonstrable arterial occlusion and pretreatment MRI), and (3) did not report both SICH and mortality rates, were excluded. We calculated the age, baseline NIHSS scores, time from stroke onset to rtPA treatment, SICH and mortality rates using published data from these studies. Results: The initial search identified 3538 studies which were reduced to 211 potentially eligible studies that were relevant to our investigation. After application of exclusion criteria, 7 clinical trials, 7 stroke registries and 10 cohort studies (4 multi-center and 6 single-center) were included in this analysis. The mean (SD) age of these patients is 68.8 years (2.9), of whom 56.3% (4.5%) were men. These patients presented with mean baseline NIHSS 12.5 (1.4) and received intravenous rtPA 175 (62) minutes from stroke onset. The mean SICH and mortality rates were 5.6% (2.3%) and 14.7% (4.8%) respectively. Higher SICH rates were reported in randomized controlled trials (mean, 7.45%) compared with those in stroke registries (mean, 3.50%). Studies that defined SICH as parenchymal hemorrhage with neurologic decline NIHSS≥4 occurring within 36 hours of rtPA treatment have a higher consistency between SICH and mortality rates (correlation coefficient, 0.631). Conclusion: We highlight several inconsistencies in the criteria used to define the neurologic decline, neuroimaging classification and interval between rtPA treatment and cerebral hemorrhage. These discrepancies may, in part, explain the rather striking disparities between SICH and mortality rates reported in randomized controlled trials, stroke registries and cohort studies.

Background and Objective The Alberta Stroke Program Early CT Score (ASPECTS) is a validated grading system to assess ischemic changes on CT in acute ischemic stroke. Magnetic resonance imaging with diffusion weighted imaging (DWI) sequence is commonly used to identify the final ischemic changes. We examined the difference between the relationship of NIHSS at admission and ASPECT score calculated using CT scan versus MRI DWI sequence. Methods We conducted a retrospective analysis of prospectively collected data from 99 cases of acute ischemic stroke treated with IV rt-PA by time criteria, admitted to Mayo Clinic from March, 2002 through June, 2011. CT head at 24 hours and MRI DWI sequence were used to assign ASPECT score. We dichotomized ASPECTS (categorized as 0 to 7 versus 8 to 10) and favorable patient outcome at 3 month (modified Rankin score less than equal to 2 and more than 2). Univariate analysis including t-test, Chi-square, and Fisher Exact test was used when appropriate. Results Mean age was 70±14 years. Mean admission NIHSS score was 8±4. DWI ASPECTS (p<0.001) and CT ASPECTS (p=0.127) were inversely associated with admission NIHSS. Higher (8-10) CT ASPECTS (p=0.001) or DWI ASPECTS (p=0.002) were associated with good outcome (mRS ≤2) at 3 months. Sensitivity, specificity, positive predictive value and negative predictive value for good outcome identified by CT ASPECTS versus DWI ASPECTS were 81% vs 52%, 54% vs 54%, 83% vs 59% and 50% vs 47% respectively. Conclusion CT and MRI DWI are comparably useful to calculate the ASPECTS for estimation of functional outcome, but CT scan at 24 hours may be more sensitive for the prediction of good recovery.

Background: The influence of high body mass index (BMI) in acute stroke patients treated with intravenous thrombolysis has not been extensively studied. Previous studies have observed an “obesity paradox” among stroke patients, where better outcomes were observed among overweight and obese patients. The purpose of this study is to determine the influence of obesity and risk components of metabolic syndrome to stroke recovery in patients undergoing intravenous recombinant tissue plasminogen activator (rtPA) treatment. Methods: Patients with acute ischemic stroke who received intravenous rtPA within three-hour from symptom onset at St. Marys Hospital, Mayo Clinic, Rochester, between April 2006 and January 2011, were included in this study. Information on vascular risk factors, stroke severity, and baseline hemodynamic and laboratory indices, were collected. Study outcomes, consisting symptomatic intracerebral hemorrhage (sICH) and poor functional recovery (modified Rankin scale >2), were compared between obese (body mass index, BMI >30 kg/m 2 ), overweight (BMI 25-30 kg/m 2 ) and normal weight (BMI <25 kg/m 2 ) patients. The association between BMI, risk components of the metabolic syndrome and dose of rtPA per kg body weight to stroke outcomes were assessed in a multivariable model. Results: A total of 158 patients (mean age, 75 years; baseline NIHSS, 11), frequency-matched by age and baseline stroke severity, were included in this study. No differences in the frequency of SICH and poor functional recovery were observed among obese, overweight and normal weight patients, before and after adjusting for their baseline characteristics. A linear trend towards worse stroke recovery was observed in patients with a greater number of metabolic risk components (p-trend=0.043). By contrast, there were no significant associations between the number of risk components of metabolic syndrome with respect to sICH. Using stepwise regression analyses, age, baseline stroke severity and the number of risk components of the metabolic syndrome accounted for 52% variation in functional recovery following rtPA treatment. Conclusions: Acute stroke outcomes do not differ between obese and overweight patients. The presence of metabolic risk factors contributes significantly to functional outcomes following rtPA treatment. These results suggest that decreasing the prevalence of metabolic syndrome in the community could reduce the societal burden of stroke-related disability.

Background and Purpose— There is uncertainty whether warfarin-treated patients (despite international normalized ratio <1.7) have increased risks of symptomatic intracerebral hemorrhage after intravenous thrombolysis. Methods— Vascular risk factors, stroke subtype, and outcome measures were compared between warfarin- and nonwarfarin-treated patients undergoing acute thrombolysis within 3 hours of symptom onset. Results— From 212 patients (mean age, 74±14 years; 50% men) studied, 14 (6.5%) had prior warfarin use. After adjusting for age, baseline National Institutes of Health Stroke Scale, and stroke subtype, warfarin-treated patients had significantly increased risks of developing symptomatic intracerebral hemorrhage (adjusted OR, 14.7; 95% CI, 1.3 to 54.3). A trend for poorer stroke recovery and increased mortality was observed in warfarin-treated patients on univariate, but not on multivariable, analyses. Conclusions— Warfarin-treated patients with stroke have increased risks of symptomatic intracerebral hemorrhage after thrombolytic treatment. These data raise safety concerns of thrombolytic treatment in warfarin-treated patients with subtherapeutic international normalized ratio.