Untreated hypertension and prognosis paradox in acute ischemic stroke.

INTRODUCTION: This study is to explore the long-term functional outcome of antihypertensive medication-naïve, untreated hypertension (HTN) patients with acute ischemic stroke compared to those with no prior HTN and those with treated HTN. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of all patients with acute ischemic stroke consecutively admitted to Incheon St. Mary's Hospital. Patients who received reperfusion therapy were excluded. Long-term functional outcomes were assessed at a 3-month follow-up visit using the modified Rankin Scale. RESULTS: A total of 1044 patients was enrolled. Compared to patients with no or treated HTN, those with untreated HTN had higher odds for more favorable outcomes (adjusted odds ratio (OR): 1.7 [95% CI: 1.0-2.7, p = 0.050*] and 1.7 [95% CI: 1.0-2.8, p = 0.047*], respectively) when the stroke was large vessel atherosclerosis (LAA)/cardioembolic (CE) with large vessel occlusion/stenosis. However, no such association was observed when there was no large vessel occlusion or stenosis, in total patients, or if the index stroke was related to SVO. In untreated HTN patients with LAA/CE and large vessel occlusion/stenosis compared to patients in the lowest mean arterial pressure quartile (< 96.7 mmHg), patients in the second and third highest quartiles had higher odds of favorable outcomes. CONCLUSIONS: Patients with untreated HTN had significantly more favorable outcomes at 3 months after ischemic stroke compared to those with no or treated HTN when the stroke was LAA/CE with large vessel occlusion/stenosis. Untreated HTN patients also showed an association between higher MAP and favorable outcomes.

Multiple chronic lacunes predicting early neurological deterioration and long-term functional outcomes according to TOAST classification in acute ischemic stroke.

INTRODUCTION: Studies regarding multiple chronic lacunes (MCLs) and clinical outcome according to stroke etiology are scarce. We sought to evaluate the association between MCL and short-term/long-term clinical outcomes according to stroke etiology. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of acute ischemic stroke patients over 4 years. The enrolled patients were classified as having large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic (CE) stroke, and other etiology. The early neurological deterioration (END) and favorable outcome at 3 months were assessed. RESULTS: A total of 1070 patients were enrolled. Patients with MCL had significantly more END compared to those without MCL both in total population (adjusted odds ratio (OR), 1.7; 95% confidence interval [CI], 1.1-2.5; p = 0.013*) and in the LAA group (adjusted OR, 2.3; 95% CI, 1.3-4.2, p < 0.006). Patients with MCL had a significantly lower OR for favorable outcome at 3 months compared to those without MCL both in total population (adjusted OR, 0.7; 95% CI, 0.5-1.0, p = 0.035) and in the LAA group (adjusted OR, 0.6; 95% CI, 0.3-1.0, p = 0.043). However, MCL was not associated with END or long-term functional outcome in patients with SVO, CE, or other etiology. CONCLUSIONS: The presence of MCL was an independent predictive factor for END as well as long-term poor functional outcome in acute ischemic stroke patients. These associations were only observed in patients with LAA, not in those with SVO, CE, or other etiology.

Simultaneously Occurring Ischemic Stroke, Leg Artery Occlusion, and Pulmonary Embolism Induced by a Uterine Myoma.

OBJECTIVES: Paradoxical embolism from venous thrombosis through the patent foramen ovale is a rare but well-known cause of stroke in young adults. Here, we report a case of simultaneous middle cerebral artery infarction, multiple occlusions of the leg arteries, and pulmonary thromboembolism from the venous thrombus, all due to compression of the external iliac vein by a uterine leiomyoma. MATERIALS AND METHODS (CASE PRESENTATION): A 44-year-old woman presented with left hemiparesis and central-type left facial palsy. She denied a history of hypertension, diabetes mellitus, previous cerebral infarction, myocardial infarction, smoking, or oral contraceptive use. The patient recovered completely after injection of tissue plasminogen activator. Brain diffusion-weighted imaging showed an acute right middle cerebral artery infarction. Transcranial Doppler with saline agitation test revealed a right-to-left shunt, suggesting a patent foramen ovale. Chest computed tomography revealed multiple pulmonary thromboembolisms. Lower extremity sonography and lower extremity computed tomography revealed a multifocal thrombus in the major veins and arteries of the left leg. Moreover, a large uterine myoma compressing the left external iliac vein was noted on lower extremity computed tomography. RESULTS: After the treatment of pulmonary thromboembolism and venous thrombosis with rivaroxaban, surgical thrombectomy of the left popliteal artery, patent foramen ovale closure, and total hysterectomy were performed. Subsequently, she had no recurrent paradoxical embolism or pulmonary thromboembolism. CONCLUSION: Structural abnormalities in the pelvic cavity are not commonly suspected as stroke etiology. However, examination of the pelvic cavity is advisable in young female stroke patients with pulmonary thromboembolism or other paradoxical embolisms.

Multiphasic Computed Tomography Angiography Findings for Identifying Pseudo-Occlusion of the Internal Carotid Artery.

BACKGROUND AND PURPOSE: Differentiation between pseudo-occlusion and true occlusion of internal carotid artery (ICA) is important in treatment planning for acute ischemic stroke patients. We compared the findings of multiphasic computed tomography angiography between cervical ICA pseudo-occlusion and true occlusion at the cervical ICA in patients with anterior circulation acute ischemic stroke to determine their diagnostic value. METHODS: Thirty patients with nonvisualization of the proximal ICA were included. Diagnosis of pseudo- or true occlusion of the ICA was made based on digital subtraction angiography. Diagnostic performances of multiphasic computed tomography angiography findings-(1) a flame-shaped stump and (2) delayed contrast filling at the cervical ICA- were evaluated and compared. The Fisher exact test, χ2 test, or Wilcoxon rank-sum test and McNemar test were used in the data analysis. RESULTS: Twelve patients had true proximal ICA occlusion and 18 had pseudo-occlusion. Delayed contrast filling at the cervical ICA on multiphasic computed tomography angiography was found in all patients with pseudo-occlusion of the ICA, while 1 case of true occlusion showed delayed contrast filling (P<0.001). The presence of a flame-shaped stump was not significantly different between the pseudo- and true occlusion groups. The sensitivity of delayed contrast filling (0.94 [95% CI, 0.73-1]) was significantly higher than that of flame-shaped stump (0.75 [95% CI, 0.36-0.83]). CONCLUSIONS: We demonstrated that the delayed filling sign on multiphasic computed tomography angiography could be a useful and readily available finding for differentiating proximal ICA pseudo-occlusion from true occlusion.

Delayed Intravenous Thrombolysis in Patients with Minor Stroke.

BACKGROUND: The actions and responses of the hospital personnel during acute stroke care in the emergency department (ED) may differ according to the severity of a patient's stroke symptoms. We investigated whether the time from arrival at ED to various care steps differed between patients with minor and non-minor stroke who were treated with intravenous tissue plasminogen activator (IV tPA). METHODS: We included consecutive patients who received IV tPA during a 1.5 year-period in 5 hospitals. Minor stroke was defined as a National Institutes of Health Stroke Scale (NIHSS) score < 5. We compared various intervals from arrival at the ED to treatment between patients with minor stroke and those with non-minor stroke (NIHSS score ≥5). Delayed treatment was defined as a door-to-needle time > 40 min. RESULTS: During the study period, 356 patients received IV tPA treatment. The median door-to-needle time was significantly longer in the minor stroke group than it was in the non-minor stroke group (43 min [interquartile range [IQR] 35.5-55.5] vs. 37 min [IQR 30-46], p < 0.001). The minor stroke group had a significantly longer door-to-notification time (7 min [IQR 4.5-12] vs. 5 min [IQR 3-8], p < 0.001) and door-to-imaging time (20 min [IQR 15-26.5] vs. 16 min [IQR 11-21], p < 0.001) than did the non-minor stroke group. However, the imaging-to-needle time was not different between the groups. Multivariable analyses revealed that minor stroke was associated with delayed treatment (OR 2.54 [95% CI 1.52-4.30], p = 0.001). CONCLUSIONS: Our findings show that the door-to-needle time was longer in patients with minor stroke than it was in those with non-minor stroke, mainly owing to delayed action in the initial steps of neurology notification and imaging. Our findings suggest that some quality improvement initiatives are necessary for patients with suspected stroke with minor symptoms.

Blood-brain barrier permeability assessed by perfusion computed tomography predicts hemorrhagic transformation in acute reperfusion therapy.

Hemorrhagic transformation (HT) is one of the most feared complications of acute recanalization therapies. The aim of this study was to evaluate whether blood-brain barrier permeability (BBBP) imaging can predict HT in the setting of acute recanalization therapy and to determine the sensitivity and specificity of BBBP for the prediction of HT according to the type of reperfusion therapy. We assessed a total of 46 patients who received recanalization therapy (intravenous (IV) recombinant tissue plasminogen activator (tPA), mechanical thrombectomy with a stent retriever or both) for acute ischemic stroke within the internal carotid artery or middle cerebral artery. BBBP above the threshold was significantly associated with HT after adjustment for confounding factors in all patients (OR 45.4, 95% CI 2.9~711.2, p = 0.007), patients who received IV tPA (OR 20.1, 95% CI 1.2-336.7, p = 0.037), and patients who received endovascular therapy (OR 47.2, 95% CI 1.9-1252.5, p = 0.022). The sensitivity and specificity of the initial BBBP measurement as a predictor of HT in the overall 46 patients were 80 and 71%, respectively. These values were 75 and 64% in only IV tPA group, 100 and 80% in only endovascular group, 77 and 67% in IV tPA with or without endovascular therapy group, and 86 and 76% in endovascular therapy with or without bridging IV tPA therapy group. Increased pretreatment BBBP values were significantly associated with HT after acute recanalization therapy. This correlation with HT was stronger in patients receiving endovascular mechanical thrombectomy than in patients receiving IV rtPA.

Non-stenotic intracranial arteries have atherosclerotic changes in acute ischemic stroke patients: a 3T MRI study.

INTRODUCTION: The aim of this study is to evaluate the degree of atherosclerotic changes in intracranial arteries by assessing arterial wall thickness using T1-weighted 3D-turbo spin echo (3D-TSE) and time-of-flight MR angiography (TOF-MRA) in patients with acute ischemic stroke as compared with unaffected controls. METHODS: Thirty-three patients with acute ischemic stroke and 36 control patients were analyzed. Acute ischemic stroke patients were divided according to TOAST classification. At both distal internal carotid arteries and basilar artery without stenosis, TOF-MRA was used to select non-stenotic portion of assessed arteries. 3D-TSE was used to measure the area including the lumen and wall (AreaOuter) and luminal area (AreaInner). The area of the vessel wall (AreaVW) of assessed intracranial arteries and the ratio index (RI) of each patient were determined. RESULTS: AreaInner, AreaOuter, AreaVW, and RI showed good inter-observer reliability and excellent intra-observer reliability. AreaInner did not significantly differ between stroke patients and controls (P = 0.619). However, AreaOuter, AreaVW, and RI were significantly larger in stroke patients (P < 0.001). The correlation coefficient between AreaInner and AreaOuter was higher in the controls (r = 0.918) than in large vessel disease patients (r = 0.778). RI of large vessel disease patients was significantly higher than that of normal control, small vessel disease, and cardioembolic groups. CONCLUSION: In patients with acute ischemic stroke, wall thickening and positive remodeling are evident in non-stenotic intracranial arteries. This change is more definite in stroke subtype that is related to atherosclerosis than that in other subtypes which are not.

Carotid artery thickening and neurocirculatory abnormalities in de novo Parkinson disease.

Cognitive dysfunction constitutes a major non-motor manifestation of Parkinson disease (PD), but the mechanisms remain incompletely understood. Neurocirculatory abnormalities such as supine hypertension (SH) and orthostatic hypotension (OH), white matter hyperintensities upon magnetic resonance imaging, and dementia are inter-related in PD, even in patients with early, levodopa-untreated disease. These abnormalities might in turn be associated with carotid atherosclerosis which, by a variety of interacting means could contribute to repeated episodes of cerebral hypo- and hyper-perfusion. We investigated inter-correlations among neurocirculatory and carotid sonographic measurements [intimal-medial thickness (IMT) and wall:lumen ratios (WLR)] in 65 patients with levodopa-untreated, de novo PD who underwent tilt table testing and 24-h ambulatory blood pressure monitoring. Increased mean IMT and WLR were associated with OH and supine and overnight blood pressures. Across individuals the orthostatic fall in systolic pressure was correlated with both IMT and WLR. Since arteriosclerosis would be expected to splint carotid sinus baroreceptors, complex positive interactions among carotid wall thickening, SH, and OH may result in myriad episodes of cerebral hypo- and hyper-perfusion, contributing to microvascular injury and consequently to the cognitive dysfunction attending PD.

Cerebral microbleeds and functional outcomes after ischemic stroke.

BACKGROUND: Whether an association exists between cerebral microbleeds (CMBs) and functional recovery after ischemic stroke is unclear. We aimed to evaluate the association between CMBs and functional outcome after acute ischemic stroke. METHODS: Consecutive patients with acute stroke were enrolled, and all patients were stratified into good and poor functional outcome groups at discharge and 6 months after ischemic stroke by using a modified Rankin Scale score. Cardiovascular risk factors, CMBs, and white matter hyperintensities were compared between these two outcome groups. Logistic regression analysis was used to estimate the risk of poor functional outcomes. RESULTS: A total of 225 patients were enrolled, 121 of whom were classified as having a good functional outcome at discharge and 142 as having a good 6-month functional outcome. The presence of CMBs was associated with a poor functional outcome at discharge [CMBs (+) patients in poor vs. good functional group; 48.1% vs. 30.6%; p=0.007] and 6 months [53.0% vs. 30.3%; p=0.001]. After adjustment for confounding factors, only the presence of infratentorial CMBs was associated with a poor functional outcome at discharge and 6 months. The poor functional outcome group had more CMBs than the good outcome group at 6 months. CONCLUSIONS: Infratentorial cerebral microbleeds were significantly associated with worse functional outcomes not only in the early phase of ischemic stroke but also in the chronic phase. These findings suggest that the presence of infratentorial CMBs can predict poor functional outcome after acute ischemic stroke.

Early apixaban administration considering the size of infarction and functional outcome in acute ischemic stroke.

Background and purpose: Atrial fibrillation-related stroke (AF-stroke) is associated with an adverse prognosis, characterized by a high incidence of progression, recurrence, and hemorrhagic transformation. Our study aims to investigate the potential benefits of stratified early administration of apixaban, taking into account infarct size during the acute phase, in order to enhance functional outcomes. Methods: We conducted this study at a tertiary referral stroke center, enrolling acute AF-stroke patients who received apixaban during the acute phase. Infarct size was categorized as small, medium, or large based on diffusion-weighted imaging. Patients were divided into two groups: standard initiation (apixaban initiation based on guidelines, i.e., small: 4 days, medium: 7 days, large: 14 days after stroke) and early initiation (initiation before guideline recommendations) groups. We compared favorable outcomes (modified Rankin scale score ≤ 2) at 3 months post-stroke, stroke progression, early recurrence, and symptomatic hemorrhagic transformation (sHT) between the groups. Results: Out of 299 AF-stroke patients, 170 (56.9%) were in the early initiation group. A favorable outcome was observed in 105 (61.8%) patients in the early initiation group and 62 (48.1%) patients in the standard initiation group (p = 0.019). Stroke progression or early recurrence occurred less frequently in the early initiation group (4.7% versus 13.2%, p = 0.007). Nevertheless, no difference in sHT was noted between the groups. Early initiation of apixaban was independently associated with favorable outcomes (odds ratio: 2.75, 95% confidence interval: 1.44-5.28, p = 0.002). Conclusion: Our findings suggest that early initiation of apixaban, tailored to infarct size, could serve as a viable strategy to enhance functional outcomes. This approach may potentially decrease stroke progression and early recurrence without elevating the risk of sHT.

Intramural hematoma detection by susceptibility-weighted imaging in intracranial vertebral artery dissection.

BACKGROUND: The radiologic diagnosis of vertebral artery dissection (VAD) depends on characteristic intraluminal findings on angiography and intramural hematoma or a double-lumen sign on high-resolution vessel wall imaging. We aimed to evaluate the accuracy of intramural hematoma sign on susceptibility-weighted imaging (SWI) in VAD. METHODS: We retrospectively analyzed SWI, phase map images and brain computed tomography (CT) of the consecutive patients who suffered an ischemic stroke in the vertebral artery territory from August 2010 to July 2012. We divided the patients into 2 groups: the VAD group and the nondissection group. VAD was diagnosed by conventional catheter angiographic findings (aneurysmal dilatation, pearl-and-string or tapered steno-occlusion) and pathognomonic findings such as intramural hematoma or a double-lumen sign on the source images of TOF-MRA, high-resolution T1-weighted MRI or high-resolution T2-weighted MRI. Intramural hematoma sign was considered positive if the patient had an eccentric or concentric hypointense signal lesion in the vertebral artery on SWI, a corresponding hyperintense signal on phase map and no evidence of calcification on the brain CT, suggesting blood products other than calcification. Two experienced neuroradiologists blinded to clinical information and angiographic findings were asked to judge for the presence of intramural hematoma sign on SWI. The accuracy of intramural hematoma sign on SWI was evaluated. Phase value, demographic and clinical data were compared between the VAD and the nondissection groups. RESULTS: Thirty-nine patients were included: 10 in the VAD group and 29 in the non-dissection group. Among the VAD group cases, intramural hematoma sign on SWI was positive in 9 of the 10 VAD cases and in 1 out of the 29 cases in the nondissection group. The intramural hematoma sign on SWI was significantly associated with VAD (p < 0.001), and showed sensitivity of 90% and specificity of 96.6%. Mean phase values of intramural hematomas (n = 9) were all positive and those of calcified lesions (n = 13) were all negative (0.45 radian vs. -0.42 radian, p < 0.001). CONCLUSIONS: The intramural hematoma sign on SWI was significantly associated with VAD and the phase map values were higher in intramural hematomas when compared with atherosclerotic calcifications.

Greater stroke severity predominates over all other factors for the worse outcome of cardioembolic stroke.

BACKGROUND: Cardioembolic (CE) strokes are more disabling and more fatal than non-CE strokes. Multiple prognostic factors have been recognized, but the magnitude of their relative contributions has not been well explored. METHODS: Using a prospective stroke outcome database, we compared the 3-month outcomes of CE and non-CE strokes. We assessed the relative contribution of each prognostic factor of initial stroke severity, poststroke complications, and baseline characteristics with multivariable analyses and model fitness improvement using -2 log-likelihood and Nagelkerke R2. RESULTS: This study included 1233 patients with acute ischemic stroke: 193 CE strokes and 1040 non-CE strokes. Compared with the non-CE group, CE group had less modified Rankin Scale (mRS) 0-2 outcomes (47.2% versus 68.5%; odds ratio [95% confidence interval], .41 [.30-.56]), less mRS 0-1 outcomes (33.7% versus 53.5%; .44 [.32-.61]), more mRS 5-6 outcomes (32.1% versus 10.9%; 3.88 [2.71-5.56]), and higher mortality (19.2% versus 5.2%; 4.33 [2.76-6.80]) at 3 months. When adjusting either baseline characteristics or poststroke complications, the outcome differences between the 2 groups remained significant. However, adjusting initial National Institute of Health Stroke Scale (NIHSS) score alone abolished all outcome differences except for mortality. For mRS 0-2 outcomes, the decrement of -2 log-likelihood and the Nagelkerke R2 of the model adjusting initial NIHSS score alone approached 70.2% and 76.7% of the fully adjusting model. CONCLUSION: Greater stroke severity predominates over all other factors for the worse outcome of CE stroke. Primary prevention and more efficient acute therapy for stroke victims should be given top priorities to reduce the burden of CE strokes.

Effects of the home-based exercise program with an augmented reality system on balance in patients with stroke: a randomized controlled trial.

PURPOSE: To investigate the therapeutic potentials of the home-based exercise program (HEP) with an augmented reality (AR) system to improve balance in patients with stroke. METHODS: Sixty-eight patients with stroke were recruited in this randomized controlled study with blind observer. Patients in the smart-rehab group underwent HEP with an AR system for four weeks, whereas patients in the control group underwent the written and pictorial HEP. Assessments of balance and fear of falling were performed three times: at baseline (T0), immediately (T1), and four weeks (T2) after cessation of HEP. RESULTS: The change in balance from T0 to T1 was significantly higher in the smart-rehab group than in the control group (p < 0.017). The change in fear of falling from T0 to T1 and T2 was significantly higher in the smart-rehab group than in the control group, respectively (p < 0.017). One participant with vertebral artery dissection in the smart-rehab group discontinued participation due to a transient ischemic attack which resolved during the study period. CONCLUSIONS: The results of this study suggest that the HEP with the AR system might be effective to improve balance in patients with stroke. However, more careful precautions for the HEP using the AR system are also required. Implications for rehabilitationBalance was modestly improved in both home-based exercise programs, slightly more in AR home exercise group.AR home-based program was significantly better in reducing fear of falling compared to the control group.No falls were recorded, however, safety for patients with arterial dissection needs to be carefully considered due to the possibility of adverse effects.

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. METHODS: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. RESULTS: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. CONCLUSION: Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

Predictors of recurrent stroke in patients with symptomatic intracranial arterial stenosis.

BACKGROUND AND PURPOSE: Our goal was to investigate whether initial ischemic lesion pattern can predict stroke recurrence in patients with symptomatic intracranial arterial stenosis. METHODS: Of the Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis (TOSS)-2 trial participants, we included patients who underwent diffusion-weighted imaging and fluid attenuation inversion recovery imaging at baseline with a follow-up fluid attenuation inversion recovery imaging at 7 months. Based on the diffusion-weighted imaging findings, we classified the initial ischemic lesion patterns according to location (subcortical versus cortical versus subcorticocortical) and multiplicity (single versus multiple). We also evaluated the occurrence of new ischemic lesions on follow-up fluid attenuation inversion recovery as well as clinical stroke in the symptomatic intracranial arterial stenosis territory. RESULTS: Of 353 patients included in this study, 44 (12.5%) and 13 (3.7%) patients had new ischemic lesions and clinical recurrent stroke in the initial symptomatic intracranial arterial stenosis territory, respectively. On multivariable analysis, the initial lesion patterns of subcorticocortical and multiple lesions were independent predictors of new ischemic lesions in the symptomatic intracranial arterial stenosis territory (OR, 3.01; 95% CI, 1.33-7.01; P=0.03; OR, 2.81; 95% CI, 1.34-5.9; P=0.006). These patterns also predicted clinical recurrent stroke. CONCLUSIONS: Subcorticocortical lesions and multiple lesions are radiological predictors of recurrent ischemic stroke in symptomatic patients with intracranial arterial stenosis. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT00130039.

Reperfusion therapy in unclear-onset stroke based on MRI evaluation (RESTORE): a prospective multicenter study.

BACKGROUND AND PURPOSE: Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke. METHODS: This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch>20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries. RESULTS: Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5±10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14-4.49). CONCLUSIONS: In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.

Association between changes in lipid profiles and progression of symptomatic intracranial atherosclerotic stenosis: a prospective multicenter study.

BACKGROUND AND PURPOSE: Predictors of progression of intracranial atherosclerotic stenosis have not been clearly identified. We investigated whether poststroke changes in lipid profiles would affect the prognosis of symptomatic intracranial atherosclerotic stenosis. METHODS: This is a substudy of Trial of cilOstazol in Symptomatic intracranial Stenosis 2 (TOSS-2). From 10 centers we enrolled 230 subjects with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or basilar artery. At baseline and 7 months after stroke, subjects underwent MR angiogram and assessment of cardiovascular risk factors including lipoprotein levels. Progression of intracranial atherosclerotic stenosis was determined by comparing stenosis on the baseline and follow-up MR angiograms. RESULTS: Cilostazol treatment was more frequently seen in the nonprogression group (109 of 198 [55.1%]) than in the progression group (11 of 32 [34.4%]). At 7 months after stroke when compared with baseline, low-density lipoprotein cholesterol and total cholesterol levels decreased in both groups. However, only nonprogressors showed increase in high-density lipoprotein cholesterol levels between baseline and follow-up. Changes in apolipoprotein B/apolipoprotein A-I levels were not different between the groups, although apolipoprotein B/A-I at 7 months was higher in progressors than in nonprogressors. Remnant lipoprotein cholesterol levels decreased in nonprogressors, whereas they did not change in progressors. In multivariable analyses, after adjusting for cilostazol treatment and remnant lipoprotein cholesterol reduction or apolipoprotein B/A-I at 7 months, high-density lipoprotein cholesterol elevation remained as a significant predictor for the nonprogression. CONCLUSIONS: This is the first prospective multicenter study to demonstrate that high-density lipoprotein cholesterol elevation, along with remnant lipoprotein cholesterol reduction and low apolipoprotein B/A-I, is associated with prevention of angiographic progression of symptomatic intracranial atherosclerotic stenosis. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00130039.

Acute Ischemic Stroke Caused by Internal Carotid Artery Occlusion: Impact of Occlusion Type on the Prognosis.

BACKGROUND: We aimed to compare clinical outcomes of acute ischemic stroke (AIS) due to internal carotid artery (ICA) occlusion following mechanical thrombectomy (MT), focusing on occlusion types. METHODS: We retrospectively reviewed 67 AIS patients who had an ICA occlusion on computed tomography angiography and underwent MT in a single tertiary center. ICA occlusion types were categorized as (1) true cervical ICA (cICA) occlusion (true occlusion), (2) pseudo-occlusion of the cICA (pseudo-occlusion), and (3) distal ICA (dICA) occlusion. We compared the clinical characteristics and their outcomes according to the ICA occlusion type. RESULTS: Fourteen patients were diagnosed with true occlusion, 32 with pseudo-occlusion, and 21 with dICA occlusion. The main etiologies were atherothrombotic in true occlusion (64.3%) and cardioembolic in pseudo-occlusion (81.3%) and dICA occlusion (71.4%) (P < 0.001). Pseudo-occlusion showed lower rates of successful reperfusion (37.5%, P = 0.009, 78.6% in true occlusion and 71.4% in dICA occlusion) and poor functional outcome at 3 months (18.8%, P = 0.037, 50% in true occlusion and 47.6% in dICA occlusion) with statistical significance. The infarction volume (169.4 ± 154.4 mL, P = 0.004, 29.2 ± 52.7 mL in true occlusion and 105.8 ± 13.4 mL in dICA occlusion) was significantly higher in pseudo-occlusion. On multivariate logistic analysis, pseudo-occlusion (odds ratio [OR]: 4.84, 95% confidence interval [CI] 1.02-22.87, P = 0.023) was an independent risk factor for poor reperfusion, which was significantly associated with a poor functional prognosis (OR: 22.04, 95% CI 1.99-243.83, P = 0.012). CONCLUSIONS: Patients with pseudo-occlusion showed poorer clinical outcomes compared with other ICA occlusion types, possibly due to a poor reperfusion rate after MT.

Apixaban for Secondary Stroke Prevention: Coexistant Cerebral Atherosclerosis May Increase Recurrent Strokes.

BACKGROUND AND PURPOSE: Oral anticoagulants are needed in stroke patients with atrial fibrillation (AF) for the prevention of recurrent stroke. However, the risk of major events or bleeding may be greater in stroke patients than in those without, because the presence of cerebral atherosclerosis or small vessel disease may increase these risks. This study aimed to investigate the outcomes of apixaban-treated stroke patients with AF and assess whether these factors are associated with the outcome. METHODS: This was a sub-analysis of stroke patients with AF enrolled in a prospective, open-label, multicenter, post-marketing surveillance study in South Korea, who were treated with apixaban and underwent magnetic resonance imaging (MRI) (Clinical trial registration: NCT01885598). RESULTS: A total of 651 patients (mean age, 72.5±8.7 years) received apixaban for a mean duration of 82.7±37.4 weeks. Fifty-three bleeding events occurred in 39 patients (6.0%), and 10 (1.5%) experienced major bleeding. Seventeen patients (2.6%) had major events (stroke, n=15, 2.3%; all ischemic), systemic embolism (n=1, 0.2%), and death (n=3, 0.5%). MRI data showed no significant association between white matter ischemic changes and microbleeds, and major events or bleeding. Patients with cerebral atherosclerotic lesions had a higher rate of major events than those without (4.6% [n=10/219] vs. 1.7% [n=7/409], P=0.0357), which partly explains the increased prevalence of major outcomes in this group versus patients without stroke (0.7%, P=0.0002). CONCLUSIONS: Apixaban is generally safe for patients with ischemic stroke. Increased primary outcomes in stroke patients may in part be attributed to the presence of cerebral atherosclerotic lesions, suggesting that further studies are needed to establish therapeutic strategies in this population.