Association of CYP2C19 Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke.

BACKGROUND: CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups. CONCLUSIONS: Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.

A Case of Intrathoracic Carotid Bifurcation Without Klippel-Feil Syndrome.

BACKGROUND: Intrathoracic carotid bifurcation is a rare vascular anomaly, with only 8 cases reported. This vascular anomaly was recently correlated with Klippel-Feil syndrome, a rare congenital disorder involving fusion of the cervical vertebrae. METHODS: A 70-year-old deaf mute man was admitted to our department because of right hemiparesis and right sensory disturbance. He displayed no abnormalities associated with Klippel-Feil syndrome. Diffusion-weighted imaging revealed acute multiple infarcts in bilateral hemispheres. Computed tomography angiography showed that the left common carotid artery bifurcated at the T2 vertebral level. No significant stenosis was seen in the carotid arteries. Transesophageal echocardiography confirmed a complicated atheromatous lesion at the aortic arch. RESULTS: This case was diagnosed with aortogenic brain embolism, incidentally accompanied by left intrathoracic carotid bifurcation without Klippel-Feil syndrome. CONCLUSIONS: Intrathoracic carotid bifurcation can occur in cases without Klippel-Feil syndrome. The knowledge of this anatomic variation is important in evaluating vascular lesions of the carotid arteries in patients with stroke.

[Characteristics of Headache and Neck Pain in Spontaneous Vertebral Artery Dissections].

PURPOSE: Sudden onset severe occipital/nuchal pain is believed to be a typical symptom of vertebral artery dissection(VAD). However, recent developments in diagnostic imaging have suggested that VAD is not always associated with such pain. This study aimed to analyze the clinical features of initial symptoms in patients with VAD. METHODS: In total, this study included 29 consecutive patients who were referred to our hospital because of only headache and/or nuchal pain due to VAD between 2011 and 2016. In this study, their clinical features were precisely assessed, including the pain location, onset pattern, duration, intensity, disease period, diagnosis modality, and prognosis. Both MRI and MRA were performed for all subjects. Cerebral angiography and thin-slice T1-weighted MRI were additionally performed in selected cases. RESULTS: Of the 29 patients, 23 presented with occipital headache and/or nuchal pain. The pain was persistent in 26/29 and ipsilateral in 29/29. However, only 16/29 reported a typical sudden onset. Only 12/29 complained of severe pain, while the other 17/29 presented with dull pain. The mean interval between onset and hospitalization was 7.4 days(0 to 30 days)and the mean interval between hospitalization and diagnosis was 3.9 days(0 to 21 days). Intramural hematoma was identified in 21/29 patients using thin-slice T1-weighted MRI. CONCLUSION: Only 55% of patients with VAD demonstrate typical occipital/nuchal pain with sudden onset. Both MRI and MRA should be indicated for patients who complain of persistent, unilateral pain in the occipital/nuchal regions to prevent VAD being missed during diagnosis.

Damage to the Left Precentral Gyrus Is Associated With Apraxia of Speech in Acute Stroke.

BACKGROUND AND PURPOSE: Apraxia of speech (AOS) is a motor speech disorder, which is clinically characterized by the combination of phonemic segmental changes and articulatory distortions. AOS has been believed to arise from impairment in motor speech planning/programming and differentiated from both aphasia and dysarthria. The brain regions associated with AOS are still a matter of debate. The aim of this study was to address this issue in a large number of consecutive acute ischemic stroke patients. METHODS: We retrospectively studied 136 patients with isolated nonlacunar infarcts in the left middle cerebral artery territory (70.5±12.9 years old, 79 males). In accordance with speech and language assessments, the patients were classified into the following groups: pure form of AOS (pure AOS), AOS with aphasia (AOS-aphasia), and without AOS (non-AOS). Voxel-based lesion-symptom mapping analysis was performed on T2-weighted images or fluid-attenuated inversion recovery images. Using the Liebermeister method, group-wise comparisons were made between the all AOS (pure AOS plus AOS-aphasia) and non-AOS, pure AOS and non-AOS, AOS-aphasia and non-AOS, and pure AOS and AOS-aphasia groups. RESULTS: Of the 136 patients, 22 patients were diagnosed with AOS (7 patients with pure AOS and 15 patients with AOS-aphasia). The voxel-based lesion-symptom mapping analysis demonstrated that the brain regions associated with AOS were centered on the left precentral gyrus. CONCLUSIONS: Damage to the left precentral gyrus is associated with AOS in acute to subacute stroke patients, suggesting a role of this brain region in motor speech production.

Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Than Those With Paroxysmal Atrial Fibrillation.

BACKGROUND AND PURPOSE: The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. METHODS: Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. RESULTS: The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08). CONCLUSIONS: Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502.

Paradoxical Brain Emboli Related to Heparin-Induced Thrombocytopenia after Catheter Ablation.

BACKGROUND: Thromboembolism associated with catheter ablation of atrial fibrillation has been considered to be derived from catheters, ablation sites, or a left atrial appendage. Paradoxical brain embolism due to iatrogenic shunt after catheter ablation has yet to be described. METHODS: We described a patient with atrial fibrillation who developed acute ischemic stroke while coughing 36 hours after successful catheter ablation. He had venous thrombosis due to heparin-induced thrombocytopenia and a right-to-left shunt, likely due to a trans-septal puncture during catheter ablation. RESULTS: The final diagnosis was paradoxical brain embolism associated with heparin-induced thrombocytopenia. CONCLUSIONS: In addition to anticoagulation, we should pay attention to deep venous thrombosis including preventive intermittent compression for high-risk patients to reduce the risk of stroke after catheter ablation.

Reduced estimated glomerular filtration rate affects outcomes 3 months after intracerebral hemorrhage: the stroke acute management with urgent risk-factor assessment and improvement-intracerebral hemorrhage study.

BACKGROUND: The effect of renal dysfunction on intracerebral hemorrhage (ICH) remains unclear. We investigated associations of renal dysfunction assessed by estimated glomerular filtration rate (eGFR) with clinical courses and outcomes in ICH patients. METHODS: From a prospective, multicenter, observational study, 203 patients who had supratentorial ICH within 3 hours of onset were included. Patients were classified into 3 groups based on eGFR: Group 1 (eGFR < 60 mL/minute/m(2)), Group 2 (60-89), and Group 3 (≥ 90). Outcomes included neurologic deterioration within 72 hours, hematoma expansion (> 33% in volume) at 24 hours, and favorable (modified Rankin Scale [mRS] ≤ 2) or unfavorable (mRS ≥ 5) outcome at 3 months. RESULTS: Thirty-seven patients (16 women, 74.6 ± 13.2 years) were assigned to Group 1, 99 (34 women, 65.2 ± 11.4 years) to Group 2, and 67 (30 women, 61.3 ± 9.4 years) to Group 3. Significant differences were found in age (P < .001) and initial systolic blood pressure among the groups (208.4 ± 18.0, 201.9 ± 15.1, and 198.1 ± 14.2 mm Hg for Group 1, 2, and 3, respectively; P = .006). Similar rates of neurologic deterioration (14%, 6%, and 6%) and hematoma expansion (16%, 14%, and 18%) were observed among the groups. However, in Group 1, favorable outcome was less frequent (17%, 48%, and 42%; P = .002) and unfavorable outcome was more frequent (24%, 7%, and 6%; P = .013) than in the other groups. After adjustment for confounders, eGFR < 60 mL/minute/m(2) was independently associated with both favorable outcome (odds ratio [OR], .21; 95% CI, .07-.54) and unfavorable outcome (OR, 5.64; 95% CI, 1.80-18.58). CONCLUSIONS: Renal dysfunction (eGFR < 60 mL/minute/m(2)) was associated with poor clinical outcome after ICH.

Continuous antihypertensive therapy throughout the initial 24 hours of intracerebral hemorrhage: the stroke acute management with urgent risk-factor assessment and improvement-intracerebral hemorrhage study.

BACKGROUND AND PURPOSE: A short duration (<24 hours) of antihypertensive therapy (AHT) after acute intracerebral hemorrhage (ICH) may be sufficient because active bleeding generally ceases within several hours. We aimed to determine the association between sequential systolic blood pressure (SBP) levels during AHT and outcomes in ICH patients. METHODS: In 211 hyperacute ICH patients who underwent AHT based on predefined protocol, the mean of hourly SBP (mSBP) measurements was calculated over 1 to 8 hours (first mSBP), 9 to 16 hours (second mSBP), and 17 to 24 hours (third mSBP) after the initiation of AHT. Outcomes included neurological deterioration (72-hour Glasgow Coma Scale decrease ≥2 or National Instititutes of Health Stroke Scale increase ≥4), hematoma expansion (>33%), and unfavorable outcome (3-month modified Rankin Scale score 4-6). RESULTS: The median first, second, and third mSBPs were 132, 131, and 137 mm Hg, respectively. A higher first mSBP (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.34-4.69 per 10 mm Hg) or second mSBP (OR, 2.08; 95% CI, 1.20-3.80) was independently associated with neurological deterioration, and a higher second mSBP (OR, 1.40; 95% CI, 1.02-2.00) or third mSBP (OR, 1.45; 95% CI, 1.05-2.05) was associated with unfavorable outcome. None of the mSBPs was associated with hematoma expansion. CONCLUSIONS: The continuation of AHT throughout the initial 24 hours after ICH may improve outcomes.

Blood pressure variability on antihypertensive therapy in acute intracerebral hemorrhage: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-intracerebral hemorrhage study.

BACKGROUND AND PURPOSE: The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort. METHODS: Patients with hyperacute (<3 hours from onset) intracerebral hemorrhage with initial systolic BP (SBP) >180 mm Hg were registered in a prospective, multicenter, observational study. All patients received antihypertensive therapy based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine. BPs were measured hourly during the initial 24 hours. BP variability was determined as SD and successive variation. The associations between BP variability and hematoma expansion (>33%), neurological deterioration within 72 hours, and unfavorable outcome (modified Rankin Scale, 4-6) at 3 months were assessed. RESULTS: Of the 205 patients, 33 (16%) showed hematoma expansion, 14 (7%) showed neurological deterioration, and 81 (39%) had unfavorable outcomes. The SD and successive variation of SBP were 13.8 (interquartile range, 11.5-16.8) and 14.9 (11.7-17.7) mm Hg, respectively, and those of diastolic BP were 9.4 (7.5-11.2) and 13.1 (11.2-15.9) mm Hg, respectively. On multivariate regression analyses, neurological deterioration was associated with the SD of SBP (odds ratio, 2.75; 95% confidence interval, 1.45-6.12 per quartile) and the successive variation of SBP (2.37; 1.32-4.83), and unfavorable outcome was associated with successive variation of SBP (1.42; 1.04-1.97). Hematoma expansion was not associated with any BP variability. CONCLUSIONS: SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes. Stability of antihypertensive therapy may improve clinical outcomes.

Incidence of cardioembolic stroke including paradoxical brain embolism in patients with acute ischemic stroke before and after the Great East Japan Earthquake.

BACKGROUND: The incidence of heart disease or deep vein thrombosis (DVT) reportedly increased after the Great East Japan Earthquake. We hypothesized that the incidence of cardioembolic stroke (CES) including paradoxical brain embolism (PBE) among patients with acute stroke would increase after the earthquake due to cessation of antithrombotic therapy or the increase in heart disease and DVT associated with the evacuation. The aim of this study is to evaluate the changes in the prevalence of DVT and the incidence of CES including PBE in acute ischemic stroke before and after the earthquake. METHODS: We retrospectively studied 1,044 consecutive ischemic stroke patients (73.1 ± 12.5 years old, male 61.5%) who were admitted to a comprehensive stroke center (from January 2010 through March 2012) located in the earthquake disaster area within 7 days after stroke onset. The prevalence of DVT and the incidence of CES including PBE were compared before and after the earthquake of 11 March 2011. RESULTS: The median of the initial National Institutes of Health Stroke Scale (NIHSS) scores was 4 (interquartile range: 1-8). Two hundred and eighty-two patients (27.0% of those surveyed) were diagnosed with CES. After adjustment for sex, age, NIHSS score, and patient's residential address, the proportion of CES patients was significantly increased after the earthquake (odds ratio, OR 1.61, 95% confidence interval, 95% CI: 1.20-2.17). Eighty-nine patients (8.5% of those surveyed) had DVT. Compared with 2010 findings, the prevalence of DVT was significantly increased in the fourth quarter of 2011 and the first quarter of 2012 (OR 1.85, 95% CI: 1.05-3.24). Nineteen (1.8% of those surveyed) were diagnosed with PBE. The proportion of PBE patients was also significantly increased in the second half of 2011 (OR 3.69, 95% CI: 1.28-12.1). CONCLUSIONS: The incidence of CES was significantly increased after the earthquake, compared with the period before the earthquake. We encountered more PBE in the period from 3 to 9 months after the earthquake and found more DVT in the acute ischemic stroke patients in the period from 6 through 12 months after the earthquake. In these types of disasters, we have to ensure the distribution of drugs, including antithrombotics, and support the prevention of DVT in the refugees.

A dilated surface appearance on basiparallel anatomic scanning-magnetic resonance imaging is a useful tool for the diagnosis of spontaneous vertebral artery dissection in lateral medullary infarction.

Spontaneous dissection of the vertebral artery (VA) is a major vascular lesion causing lateral medullary infarction (LMI). A dilated surface appearance of the VA is a feature of VA dissection and can be observed on basiparallel anatomic scanning (BPAS)-magnetic resonance imaging (MRI). The aim of this study was to validate BPAS-MRI in the diagnosis of VA dissection in patients with LMI. The subjects of the present study were 41 consecutive patients with LMI within 7 days of onset. The diagnosis of VA dissection was made with the clinical criteria-based diagnosis. Percent (%) dilatation of the VA on BPAS-MRI was calculated by comparing the maximum surface diameter of the intracranial VA to the diameter of the distal normal surface of the VA. Fourteen patients (34%) were diagnosed with VA dissection. The optimal cutoff % dilatation of the VA for dissection was more than 169%. The sensitivity and specificity of % dilatation of VA more than 169% and aneurysmal dilatation, stenosis, or occlusion on magnetic resonance angiography (MRA) for VA dissection were 92.9% and 81.5%, respectively. BPAS-MRI combined with time-of-flight-MRA is a useful tool for the diagnosis of VA dissection in patients with acute LMI.

Intravenous nicardipine dosing for blood pressure lowering in acute intracerebral hemorrhage: the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-Intracerebral Hemorrhage study.

BACKGROUND: Intravenous nicardipine is commonly used to reduce elevated blood pressure in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dosing and the association of dose with clinical outcomes in hyperacute ICH. METHODS: Hyperacute (<3 hours from onset) ICH patients with initial systolic blood pressure (SBP) greater than 180 mm Hg were included. All patients initially received 5 mg/hour of intravenous nicardipine. The dose was adjusted to maintain SBP between 120 and 160 mm Hg. Associations of maximum hourly and total doses with early neurologic deterioration (END), hematoma expansion (>33%), and modified Rankin Scale score 4-6 at 3 months were assessed. RESULTS: Two hundred six patients (81 women, 65.8 ± 11.8 years) were studied. Initial SBP was 201.9 ± 15.9 mm Hg. Maximum and total nicardipine doses were 9.1 ± 4.2 mg/hour and 123.7 ± 100.2 mg/day, respectively. Multivariate analyses revealed that men (standardized regression coefficient [ß] = .20, P = .0030 for maximum dose; ß = .25, P = .0002 for total dose), age (ß = -.28, P = .0002; ß = -.25, P = .0005), and initial SBP (ß = .19, P = .0018; ß = .18, P = .0021) were independently associated with both maximum and total doses. Body weight (ß = .20, P = .0084) was independently associated with total dose. After multivariate adjustment, maximum dose (per 1 mg/hour; odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.45) was independently, and total dose (per 10 mg/day; OR, 1.06; 95% CI, .998-1.132) tended to be independently, associated with END. Nicardipine dose was not associated with hematoma expansion or 3-month outcome. CONCLUSIONS: Nicardipine dose is roughly predictable with sex, age, body weight, and initial SBP in acute ICH. The maximum dose was associated with neurologic deterioration.

Progressive Supranuclear Palsy Diagnosed After a Severe Fall Trauma in a Patient Who Experienced Episodes of Easy Falling.

Progressive supranuclear palsy (PSP) is characterized by parkinsonism, downward gaze disorder, and a tendency to fall due to degeneration of the basal ganglia, the brain stem, and the cerebellum. We report a case of PSP that was diagnosed following a traumatic hemopneumothorax caused by a fall while descending stairs. A 79-year-old man experienced lightheadedness and frequent falls for two years. He fell on stairs at home and was transferred to our hospital due to mobility issues. He was hospitalized and treated for traumatic hemopneumothorax. Neurological examination revealed vertical ocular motility disorder, positive Myerson's sign, increased muscle stiffness, and increased limb tendon reflexes. Brain MRI showed a hummingbird sign. In this case, a midbrain area of 58.1 mm2 was consistent with PSP. He had no medication history that could have caused falls. He was diagnosed with PSP based on clinical and imaging findings, and treatment with levodopa was initiated. Two months later, walking showed limited improvement, and living at home became difficult. He was discharged to a care facility. PSP is a risk factor for frequent falls in the elderly. PSP usually requires three to four years for diagnosis, although falls appear earlier than in other forms of degenerative parkinsonism. Additionally, PSP often results in repeated dynamic falls due to a decreased perception of danger associated with reduced frontal lobe function. As a result, the severity of trauma from falls in PSP tends to be higher than in other neurodegenerative diseases. Therefore, early diagnosis of PSP may help improve patients' quality of life and prevent trauma. Despite frequent falls over two years, the cause was not thoroughly investigated until the patient experienced severe trauma. The lesson from this case is the importance of a thorough neurological examination and sagittal MRI for elderly patients experiencing repeated falls, to consider the possibility of PSP. Furthermore, quantitative evaluation of MRI enhances the diagnostic accuracy of PSP.

Impact of early blood pressure variability on stroke outcomes after thrombolysis: the SAMURAI rt-PA Registry.

BACKGROUND AND PURPOSE: The present study determines associations between early blood pressure (BP) variability and stroke outcomes after intravenous thrombolysis. METHODS: In 527 stroke patients receiving intravenous alteplase (0.6 mg/kg), BP was measured 8 times within the first 25 hours. BP variability was determined as ΔBP (maximum-minimum), standard deviation (SD), coefficient of variation, and successive variation. RESULTS: The systolic BP course was lower among patients with modified Rankin Scale (mRS) 0 to 1 than those without (P<0.001). Most of systolic BP variability profiles were significantly associated with outcomes. Adjusted odds ratios (95% confidence interval) per 10 mm Hg (or 10% for coefficient of variation) on symptomatic intracerebral hemorrhage were as follows: ΔBP, 1.33 (1.08-1.66); SD, 2.52 (1.26-5.12); coefficient of variation, 3.15 (1.12-8.84); and successive variation, 1.82 (1.04-3.10). The respective values were 0.88 (0.77-0.99), 0.73 (0.48-1.09), 0.77 (0.43-1.34), and 0.76 (0.56-1.03) for 3-month mRS 0 to 1; and 1.40 (1.14-1.75), 2.85 (1.47-5.65), 4.67 (1.78-12.6), and 1.99 (1.20-3.25) for death. Initial BP values before thrombolysis were not associated with any outcomes. CONCLUSIONS: Early systolic BP variability was positively associated with symptomatic intracerebral hemorrhage and death after intravenous thrombolysis.

Systolic blood pressure after intravenous antihypertensive treatment and clinical outcomes in hyperacute intracerebral hemorrhage: the stroke acute management with urgent risk-factor assessment and improvement-intracerebral hemorrhage study.

BACKGROUND AND PURPOSE: Blood pressure (BP) lowering is often conducted as part of general acute management in patients with acute intracerebral hemorrhage. However, the relationship between BP after antihypertensive therapy and clinical outcomes is not fully known. METHODS: Hyperacute (<3 hours from onset) intracerebral hemorrhage patients with initial systolic BP (SBP) >180 mm Hg were included. All patients received intravenous antihypertensive treatment, based on predefined protocol to lower and maintain SBP between 120 and 160 mm Hg. BPs were measured every 15 minutes during the initial 2 hours and every 60 minutes in the next 22 hours (a total of 30 measurements). The mean achieved SBP was defined as the mean of 30 SBPs, and associations between the mean achieved SBP and neurological deterioration (≥2 points' decrease in Glasgow Coma Score or ≥4 points' increase in National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin Scale score 4-6 at 3 months) were assessed with multivariate logistic regression analyses. RESULTS: Of the 211 patients (81 women, median age 65 [interquartile range, 58-74] years, and median initial National Institutes of Health Stroke Scale score 13 [8-17]) enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, mean achieved SBP was independently associated with neurological deterioration (odds ratio, 4.45; 95% confidence interval, 2.03-9.74 per 10 mm Hg increment), hematoma expansion (1.86; 1.09-3.16), and unfavorable outcome (2.03; 1.24-3.33) after adjusting for known predictive factors. CONCLUSIONS: High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes.

Effect of cilostazol in the treatment of acute ischemic stroke in the lenticulostriate artery territory.

BACKGROUND: Cilostazol, an inhibitor of phosphodiesterase 3, has various pleiotropic effects besides its antiplatelet activity. This study examined the efficacy of cilostazol for the treatment of acute perforating artery infarction. METHODS: In this prospective, randomized, open-label, blinded-end point trial, 100 patients with cerebral infarction in the territory of the lenticulostriate arteries were enrolled within 48 h of onset. Patients were randomly treated with both cilostazol and ozagrel for 14 days (n = 50, cilostazol group) or ozagrel alone for 14 days (n = 50, control group). The primary end point was the proportion of favorable outcomes 30 days after randomization as defined by a modified Rankin Scale (mRS) score of 0-2. Secondary end points included the incidence of neurological deterioration (an increase of ≥ 2 on the National Institutes of Health Stroke Scale within 7 days). RESULTS: Favorable outcomes (mRS scores 0-2) were similar in both groups (81.3 and 82.0% in the cilostazol and control groups, respectively). The incidence of neurological deterioration was lower in the cilostazol group than the control group (12.5 and 16.0%, respectively) with a 21.9% relative risk reduction, although the difference was not statistically significant. CONCLUSIONS: Cilostazol did not prevent the neurological deterioration of perforating artery infarction.

Stroke outcomes of Japanese patients with major cerebral artery occlusion in the post-alteplase, pre-MERCI era.

This study examined outcomes of patients with acute ischemic stroke (AIS) with major cerebral artery occlusion after the approval of intravenous recombinant tissue-type plasminogen activator (IV rt-PA) but before approval of the MERCI retriever. We retrospectively enrolled 1170 consecutive patients with AIS and major cerebral artery occlusion (496 women; mean age, 73.9 ± 12.3 years) who were admitted within 24 hours after the onset of symptoms to 12 Japanese stroke centers between October 2005 and June 2009. Cardioembolism was a leading cause of AIS in this group (68.2%). The occlusion sites of the major cerebral arteries included the common carotid artery and internal carotid artery (ICA; 29.6%), middle cerebral artery (52.2%), and basilar artery (7.6%). Recanalization therapy (RT) was performed in 32.0% of patients (IV rt-PA, 20.0%; neuroendovascular therapy, 9.4%; combined, 2.5%). Symptomatic intracerebral hemorrhage within 36 hours with a ≥ 1-point increase in the National Institutes of Health Stroke Scale score occurred in 5.3% of the patients. At 3 months (or at hospital discharge), 29.3% of the patients had a favorable outcome (based on a modified Rankin scale score of 0-2), 23.8% were bedridden, and 15.6% died. After multivariate adjustment, RT was positively associated with a favorable outcome and negatively associated with death, whereas age, baseline National Institutes of Health Stroke Scale score, and ICA occlusion were negatively associated with a favorable outcome and positively associated with death. One-third of the patients with AIS and major cerebral artery occlusion were treated with RT, which was independently associated with favorable outcomes and death. However, 40% of the patients became bedridden or died during the post-alteplase, pre-MERCI era in Japan.

Intravenous alteplase at 0.6 mg/kg for acute stroke patients with basilar artery occlusion: the stroke acute management with urgent risk factor assessment and improvement (SAMURAI) Recombinant tissue plasminogen activator registry.

BACKGROUND: The therapeutic efficacy of low-dose intravenous alteplase (0.6 mg/kg) for basilar artery occlusion (BAO) remains unknown. METHODS: BAO patients enrolled from the Japanese multicenter registry involving 600 stroke patients treated with the low-dose intravenous alteplase were studied. RESULTS: Twenty-five patients had BAO (8 women ranging from 32-92 years of age; mean baseline National Institutes of Health Stroke Scale [NIHSS] score 16). The stroke subtype was cardioembolic in 15 patients and atherothrombotic in 4 patients. BAO was recanalized during hospitalization in 18 (78%) of 23 patients undergoing follow-up angiography. Within the initial 24 hours, 14 patients (56%) had a ≥ 8-point decrease in the NIHSS score, being more common than 267 patients with middle cerebral artery occlusion (MCO) from the same registry (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.06-5.97) after adjustment by sex, age, and baseline NIHSS score. In addition, 4 patients (16%) had a ≥ 4-point increase in the score, being marginally more common than MCO patients (OR 3.13; 95% CI 0.81-10.25). Symptomatic intracranial hemorrhage within the initial 36 hours (8% v 5%), independence at 3 months (modified Rankin Scale score ≤ 2, 48% v 52%), and mortality at 3 months (4% v 6%) were similar when comparing BAO and MCO patients. When compared with previous studies of BAO, vital and functional outcomes at 3 months were relatively better in our study. CONCLUSIONS: The use of low-dose alteplase resulted in similar outcomes when comparing acute BAO and MCO patients.

P2Y12 Reaction Units and Clinical Outcomes in Acute Large Artery Atherosclerotic Stroke: A Multicenter Prospective Study.

AIMS: We aimed to determine the association between acute platelet reactivity and clinical outcome in acute ischemic stroke (AIS) or transient ischemic attack (TIA) with large-artery atherosclerosis (LAA). METHODS: In this prospective, 16-multicenter study, we enrolled AIS/TIA patients with LAA receiving clopidogrel. We assessed the association of P2Y12 reaction units (PRU) 24 hours after initiation of antiplatelets with the CYP2C19 genotype and recurrent ischemic stroke within 90 days, and the difference between acute (≤ 7 days) and subacute (8-90 days) phases. RESULTS: Among the 230 AIS/TIA patients enrolled, 225 with complete outcome data and 194 with genetic results were analyzed. A higher PRU was significantly associated with recurrent ischemic stroke within 90 days (frequency, 16%), and within 7 days (10%). Twenty-nine patients (15%) belonged to a CYP2C19 poor metabolizer group (CYP2C19＊2/＊2, ＊2/＊3, or ＊3/＊3). Multivariable receiver-operating characteristic analysis showed a greater area-under-the-curve (AUC) in predicting recurrence within 7 days, compared to 8-90 days (AUC, 0.79 versus 0.64; p=0.07), with a cut-off PRU of 254. Multivariable analysis showed high PRU (≥ 254), which had a comparable predictive performance for recurrent ischemic stroke within 7 days (odds ratio, 6.82; 95% CI, 2.23-20.9; p＜0.001) to the CYP2C19 poor metabolizer genotype. The net reclassification improvement, calculated by adding high PRU (≥ 254) to a model including the CYP2C19 poor metabolizer genotype in the prediction of recurrence within 7 days, was 0.83 (p＜0.001). CONCLUSIONS: Acute PRU evaluation possesses predictive value for recurrent ischemic stroke, especially within 7 days in AIS/TIA with LAA.

Low-dose intravenous recombinant tissue-type plasminogen activator therapy for patients with stroke outside European indications: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA Registry.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license. METHODS: Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group). RESULTS: The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29-0.84), positively associated with an unfavorable outcome (2.48; 1.55-3.94) and mortality (2.04; 1.02-4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11-1.79) or complete independency (0.65; 0.40-1.03) after multivariate adjustment. CONCLUSIONS: Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.