Doojin Kim

Impact of collateral flow on tissue fate in acute ischaemic stroke

Background: Collaterals may sustain penumbra prior to recanalisation yet the influence of baseline collateral flow on infarct growth following endovascular therapy remains unknown. Methods: Consecutive patients underwent serial diffusion and perfusion MRI before and after endovascular therapy for acute cerebral ischaemia. We assessed the relationship between MRI diffusion and perfusion lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion lesion maps were generated and diffusion–perfusion mismatch regions were divided into Tmax ⩾4 s (severe delay) and Tmax ⩾2 but <4 s (mild delay). Results: Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20 (45.5%) and good in 17 (38.6%) patients. Although diffusion–perfusion mismatch volume was not different depending on the collateral grade, patients with good collaterals had larger areas of milder perfusion delay than those with poor collaterals (p = 0.005). Among 32 patients who underwent day 3–5 post-treatment MRIs, the degree of pretreatment collateral circulation (r = −0.476, p = 0.006) and volume of diffusion–perfusion mismatch (r = 0.371, p = 0.037) were correlated with infarct growth. Greatest infarct growth occurred in patients with both non-recanalisation and poor collaterals. Multiple regression analysis revealed that pretreatment collateral grade was independently associated with infarct growth. Conclusion: Our data suggest that angiographic collateral grade and penumbral volume interactively shape tissue fate in patients undergoing endovascular recanalisation therapy. These angiographic and MRI parameters provide complementary information about residual blood flow that may help guide treatment decision making in acute cerebral ischaemia.

Analysis of Thrombi Retrieved From Cerebral Arteries of Patients With Acute Ischemic Stroke

Background and Purpose— Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. Methods— This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. Results— The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. “Red” clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. Conclusions— Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.

CT and MRI Early Vessel Signs Reflect Clot Composition in Acute Stroke

Background and Purpose— The purpose of this study was to provide the first correlative study of the hyperdense middle cerebral artery sign (HMCAS) and gradient-echo MRI blooming artifact (BA) with pathology of retrieved thrombi in acute ischemic stroke. Methods— Noncontrast CT and gradient-echo MRI studies before mechanical thrombectomy in 50 consecutive cases of acute middle cerebral artery ischemic stroke were reviewed blinded to clinical and pathology data. Occlusions retrieved by thrombectomy underwent histopathologic analysis, including automated quantitative and qualitative rating of proportion composed of red blood cells (RBCs), white blood cells, and fibrin on microscopy of sectioned thrombi. Results— Among 50 patients, mean age was 66 years and 48% were female. Mean (SD) proportion was 61% (±21) fibrin, 34% (±21) RBCs, and 4% (±2) white blood cells. Of retrieved clots, 22 (44%) were fibrin-dominant, 13 (26%) RBC-dominant, and 15 (30%) mixed. HMCAS was identified in 10 of 20 middle cerebral artery stroke cases with CT with mean Hounsfield Unit density of 61 (±8 SD). BA occurred in 17 of 32 with gradient-echo MRI. HMCAS was more commonly seen with RBC-dominant and mixed than fibrin-dominant clots (100% versus 67% versus 20%, P=0.016). Mean percent RBC composition was higher in clots associated with HMCAS (47% versus 22%, P=0.016). BA was more common in RBC-dominant and mixed clots compared with fibrin-dominant clots (100% versus 63% versus 25%, P=0.002). Mean percent RBC was greater with BA (42% versus 23%, P=0.011). Conclusions— CT HMCAS and gradient-echo MRI BA reflect pathology of occlusive thrombus. RBC content determines appearance of HMCAS and BA, whereas absence of HMCAS or BA may indicate fibrin-predominant occlusive thrombi.

A Brief Prehospital Stroke Severity Scale Identifies Ischemic Stroke Patients Harboring Persisting Large Arterial Occlusions

Background and Purpose— The Los Angeles Motor Scale (LAMS) is a brief 3-item stroke severity assessment measure designed for prehospital and Emergency Department use. Methods— The LAMS and NIHSS were scored in under-12-hour acute anterior circulation ischemic stroke patients. Stroke severity ratings were correlated with cervicocerebral vascular occlusion on CTA, MRA, and catheter angiography. Receiver operating curves, c statistics, and likelihood ratios were used to evaluate the predictive value for vascular occlusion of stroke severity ratings. Results— Among 119 patients, mean age was 67 (±18), 45% were male. Time from onset to ED arrival was mean 190 minutes (range 10 to 660). Persisting large vessel occlusions (PLVOs) were present in 62% of patients. LAMS stroke severity scores were higher in patients harboring a vascular occlusion, median 5 (IQR 4 to 5) versus 2 (IQR 1 to 3). Similarly, NIHSS stroke severity scores were higher in PLVO patients, 19 (14 to 24) versus 5 (3 to 7). ROC curves demonstrated that the LAMS was highly effective in identifying patients with PLVOs, c statistic 0.854. At the optimal threshold of 4 or higher, LAMS scores showed sensitivity 0.81, specificity 0.89, and overall accuracy 0.85. LAMS performance was comparable to NIHSS performance (c statistic 0.933). The positive likelihood ratio associated with a LAMS score ≥4 was 7.36 and the negative likelihood ratio 0.21. Conclusions— Stroke severity assessed by the LAMS predicts presence of large artery anterior circulation occlusion with high sensitivity and specificity. The LAMS is a promising instrument for use by prehospital personnel to identify select stroke patients for direct transport to Comprehensive Stroke Centers capable of endovascular interventions.

Early Neutrophilia Is Associated With Volume of Ischemic Tissue in Acute Stroke

Background and Purpose— Few data exist on the relationship between differential subpopulations of peripheral leukocytes and early cerebral infarct size in ischemic stroke. Using diffusion-weighted MR imaging (DWI), we assessed the relationship of early total and differential peripheral leukocyte counts and volume of ischemic tissue in acute stroke. Methods— All included patents had laboratory investigations and neuroimaging collected within 24 hours of stroke onset. Total peripheral leukocyte counts and differential counts were analyzed individually and by quartiles. DWI lesions were outlined using a semiautomated threshold technique. The relationship between leukocyte quartiles and DWI infarct volumes was examined using multivariate quartile regression. Results— 173 patients met study inclusion criteria. Median age was 73 years. Total leukocyte counts and DWI volumes showed a strong correlation (Spearman rho=0.371, P<000.1). Median DWI volumes (mL) for successive neutrophil quartiles were: 1.3, 1.3, 3.2, and 20.4 (P for trend <0.001). Median DWI volumes (mL) for successive lymphocyte quartiles were: 3.2, 8.1, 1.3, and 1.5 (P=0.004). After multivariate analysis, larger DWI volume remained strongly associated with higher total leukocyte and neutrophil counts (both probability values <0.001), but not with lymphocyte count (P=0.4971). Compared with the lowest quartiles, DWI volumes were 8.7 mL and 12.9 mL larger in the highest quartiles of leukocyte and neutrophil counts, respectively. Conclusions— Higher peripheral leukocyte and neutrophil counts, but not lymphocyte counts, are associated with larger infarct volumes in acute ischemic stroke. Attenuating neutrophilic response early after ischemic stroke may be a viable therapeutic strategy and warrants further study.

Prediction of hemorrhagic transformation after recanalization therapy using T2*-permeability magnetic resonance imaging

Predicting hemorrhagic transformation (HT) is critical in the setting of recanalization therapy for acute stroke. Dedicated magnetic resonance imaging (MRI) sequences for detection of increased blood–brain barrier (BBB) permeability recently have been developed. We evaluated the ability of a novel MRI permeability technique to detect baseline derangements predictive of various forms of HT after recanalization therapy.

Premorbid antiplatelet use and ischemic stroke outcomes

Objective: To evaluate the independent effect of premorbid antiplatelet use on incident ischemic stroke severity and outcome at discharge. Methods: The authors studied consecutive patients presenting within 24 hours of ischemic stroke over a 1-year period. National Institutes of Health Stroke Scale (NIHSS) score at presentation was used as index of stroke severity and a modified Rankin scale of 0 to1 at discharge as index of good functional outcome. Patients were categorized according to their premorbid antiplatelet use as antiplatelet-inclusive (AI) and no antiplatelet (NA). Demographic data, risk factors, pertinent laboratory tests, other medications, and stroke mechanisms were controlled for across the two groups using multivariate logistic regression. Results: A total of 260 individuals met study criteria: 92 patients were on antiplatelet agents prior to admission, 168 were on no antiplatelets. Pretreatment with antiplatelet was associated with lower presenting median NIHSS (4.5 vs 7, p = 0.005). Antiplatelet use was associated with less severe stroke at presentation in those having no history of stroke or TIA (4.8 vs 8.0, p = 0.03) but not in those with a prior history of stroke or TIA (4.9 vs 4.9, p = 0.987). The likelihood of a good outcome was increased in those on antiplatelets after adjusting for other variables (OR 2.105, p = 0.0073). Conclusions: Prestroke use of antiplatelet may be associated with reduced severity of incident ischemic strokes in those with no prior history of stroke or TIA, and with an increased likelihood of a good discharge outcome regardless of prior cerebrovascular event history.

Leukoaraiosis Predicts Parenchymal Hematoma After Mechanical Thrombectomy in Acute Ischemic Stroke

Background and Purpose— The purpose of this study was to determine whether leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in patients with acute ischemic stroke treated by mechanical thrombectomy. Methods— We retrospectively analyzed patients with anterior circulation stroke treated with Merci devices and identified LA in the deep white matter (DWM) and periventricular white matter on the preintervention MR images. We dichotomized patients into those with moderate or severe LA in the DWM versus those without. Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the association of moderate or severe LA with hemorrhagic transformation and poor outcome. Results— Twenty-six of 105 patients had moderate or severe LA in the DWM. Patients with moderate or severe LA in the DWM were older, had more severe neurological deficits and worse outcome, had higher rates of hemorrhagic transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic infarct and subarachnoid hemorrhage when compared with those without. Patients with only periventricular LA did not have a higher rate of parenchymal hematoma. Moderate or severe LA in the DWM was an independent predictor of hemorrhagic transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005). Patients with parenchymal hematoma were less often independent (modified Rankin Scale ⩽2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50% versus 10.4%; P<0.001). Conclusions— Moderate or severe LA in the DWM increases the risk of parenchymal hematoma after Merci thrombectomy for patients with acute stroke. These findings require validation in a larger prospective study.

Predictors of Subarachnoid Hemorrhage in Acute Ischemic Stroke With Endovascular Therapy

Background and Purpose— Subarachnoid hemorrhage (SAH) is a potential hemorrhagic complication after endovascular intracranial recanalization. The purpose of this study was to describe the frequency and predictors of SAH in acute ischemic stroke patients treated endovascularly and its impact on clinical outcome. Methods— Acute ischemic stroke patients treated with primary mechanical thrombectomy, intra-arterial thrombolysis, or both were analyzed. Postprocedural computed tomography and magnetic resonance images were reviewed to identify the presence of SAH. We assessed any decline in the National Institutes of Health Stroke Scale score 3 hours after intervention and in the outcomes at discharge. Results— One hundred twenty-eight patients were treated by primary thrombectomy with MERCI Retriever devices, whereas 31 were treated by primary intra-arterial thrombolysis. Twenty patients experienced SAH, 8 with pure SAH and 12 with coexisting parenchymal hemorrhages. SAH was numerically more frequent with primary thrombectomy than in the intra-arterial thrombolysis groups (14.1% vs 6.5%, P=0.37). On multivariate analysis, independent predictors of SAH were hypertension (odds ratio=5.39, P=0.035), distal middle cerebral artery occlusion (odds ratio=3.53, P=0.027), use of rescue angioplasty after thrombectomy (odds ratio=12.49, P=0.004), and procedure-related vessel perforation (odds ratio=30.72, P<0.001). Patients with extensive SAH or coexisting parenchymal hematomas tended to have more neurologic deterioration at 3 hours (28.6% vs 0%, P=0.11), to be less independent at discharge (modified Rankin Scale ≤2; 0% vs 15.4%, P=0.5), and to experience higher mortality during hospitalization (42.9% vs 15.4%, P=0.29). Conclusions— Procedure-related vessel perforation, rescue angioplasty after thrombectomy with MERCI devices, distal middle cerebral artery occlusion, and hypertension were independent predictors of SAH after endovascular therapy for acute ischemic stroke. Only extensive SAH or SAH accompanied by severe parenchymal hematomas may worsen clinical outcome at discharge.

Indices of Kidney Dysfunction and Discharge Outcomes in Hospitalized Stroke Patients without Known Renal Disease

Background: The utility of clinical measurements of impairments in glomerular barrier or filtration rate among hospitalized stroke patients without known chronic kidney disease (CKD) has not been well studied. We determined whether various indices of CKD would predict discharge outcomes in persons hospitalized with a recent ischemic stroke. Methods: Presence of proteinuria and estimated low glomerular filtration rate (GFR) <60 ml/min per 1.73 m2 on admission were assessed in consecutive ischemic stroke and transient ischemic attack patients admitted to a university hospital over 18 months, who had no history of CKD. The primary discharge outcomes assessed (among stroke patients only) were death or disability (modified Rankin Scale score ≥2) and being discharged home directly from hospital. Independent effects of CKD indices on the outcomes were evaluated using multivariable regression modeling. Results: Of 251 patients with recent ischemic cerebrovascular events, 198 ischemic stroke patients (79%), met the study criteria. In crude analyses, persons with proteinuria or low GFR were significantly more likely to die in the hospital (p < 0.05). After adjusting for confounders, proteinuria was independently linked with lower odds of going home directly from the hospital (OR = 0.38, 95% CI = 0.16–0.92) and poorer discharge functional status (OR = 3.19, 95% CI = 1.37–7.46), but low GFR was not independently related to either of these outcomes. Conclusions: Among hospitalized ischemic stroke patients without known CKD, presence of proteinuria on admission is independently associated with poorer discharge functional activity and lower likelihood of being discharged home directly. Low GFR was not related to either outcome in these patients without known CKD.