Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Microbleeds and clinical outcome in acute mild stroke patients treated with antiplatelet therapy: ADS post-hoc analysis.

BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.

Cilostazol Addition to Aspirin could not Reduce the Neurological Deterioration in TOAST Subtypes: ADS Post-Hoc Analysis.

BACKGROUND: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. METHODS: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). RESULTS: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030). CONCLUSIONS: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

Risk factors, etiology, and outcome of ischemic stroke in young adults: A Japanese multicenter prospective study.

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

Cilostazol uncovers covert atrial fibrillation in non-cardioembolic stroke.

BACKGROUND: We hypothesized that administration of cilostazol may clarify the occult atrial fibrillation (AF) during hospitalization in mild stroke patients, who has no history of AF. METHODS: From our prospective non-cardioembolic stroke study, randomized to dual antiplatelet therapy using cilostazol and aspirin or aspirin alone trial (ADS), data on the presence or absence of AF were retrospectively analyzed. In the ADS, during hospitalization, as a routine examination, presence of AF was investigated using electrocardiogram (ECG), ECG monitoring and Holter ECG. Multivariate regression analysis was conducted to evaluate the independent parameters related to the AF. Clinical outcome at 3 months was evaluated using modified Rankin Scale (mRS) score. RESULTS: Data on 1194 patients (793 [66%] men; median age [interquartile range] of 69 [61-77] years, National Institutes of Health Stroke Scale score 2 [1-4], onset-to-admission 10.8 [4.7-20.5] hours) were retrospectively analyzed. AF was newly detected in 41 (3%) patients (3 by ECG, 21 by the ECG monitoring and 17 by the Holter ECG) during hospitalization. Patients treated with combined cilostazol and aspirin therapy frequently had the AF than those took aspirin alone (5% vs. 2%, p = .007). Multivariate regression analysis showed that cilostazol administration was one of the independent factors for new-AF (odds ratio 2.672, 95%CI: 1.205-5.927, p = .016). The frequency of mRS 0-1 was 68% in the new-AF group and 67% in the non-AF group (p = 1.000). CONCLUSION: Cilostazol therapy may increase the detectability of AF in acute non-cardioembolic stroke, though the new-AF was not related to clinical outcome at 3 months.

Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Acute Aspirin Plus Cilostazol Dual Therapy for Noncardioembolic Stroke Patients Within 48 Hours of Symptom Onset.

Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non-Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator-initiated, prospective, multicenter (34 hospitals in Japan), randomized, open-label, and aspirin-controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61-77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1-4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short-term neurological worsening. Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.

Impact of D-dimer levels for short-term or long-term outcomes in cryptogenic stroke patients.

BACKGROUND: D-dimer levels are used in several clinical settings, such as in predicting venous thrombosis, cardioembolic stroke and cancer status. In the present study, we investigated the associations between plasma D-dimer levels at admission, clinical characteristics and mortality at discharge in cryptogenic stroke patients. We also investigated whether D-dimer levels can predict long-term outcomes in those patients, including those with and without right-to-left shunt (RLS). METHODS: Acute cryptogenic stroke patients (n = 295, 72 ± 13 years old) were consecutively enrolled and retrospectively analyzed. We defined the cryptogenic stroke as an undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Plasma D-dimer levels at admission were evaluated. Assessments for RLS were performed using saline contrast-transcranial Doppler ultrasonography or contrast-transesophageal echography. Survivors (at discharge) underwent follow-up for up to 3 years after stroke onset. RESULTS: Of the total enrolled cohort, 17 patients died at discharge. D-dimer levels correlated with initial National Institutes of Health Stroke Scale (NIHSS) score (r = 0.391, P < 0.001) and were associated with mortality at discharge [odds ratio 1.04; 95% confidence interval (CI) 1.00-1.08, P = 0.049] after adjusting for age, sex and initial NIHSS score. Of the 278 survivors at discharge, 266 patients were evaluated to assess RLS during hospitalization, and 62 patients (23.3%) exhibited RLS. According to the median plasma D-dimer levels at admission (0.7 µg/ml), the patients were divided into a low D-dimer group (n = 136, < median) and a high D-dimer group (n = 130, ≥ median). Patients in the high D-dimer group were older, more frequently female, had a lower BMI, had a higher prevalence of cancer and had greater initial neurological severity compared to the patients in the low D-dimer group. During the follow-up period (median, 1093 days), 31 patients developed recurrent stroke and 33 patients died. High D-dimer levels at admission were independently associated with recurrent stroke and all-cause mortality [hazard ratio (HR) 3.76; 95% CI 1.21-14.1, P = 0.021) in patients with RLS, but not in those without RLS (HR 1.35; 95% CI 0.74-2.50, P = 0.335). CONCLUSIONS: Increased D-dimer levels at admission were associated with mortality at discharge in cryptogenic stroke patients. In addition, high D-dimer levels were also associated with long-term outcomes in cryptogenic stroke patients with RLS.

Thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis: a case report.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis has long been regarded as a benign asymptomatic clinical entity with an innocuous clinical course. Neurological complications are rare in diffuse idiopathic skeletal hyperostosis. However, if they do occur, the consequences are often significant enough to warrant major neurosurgical intervention. Neurological complications occur when the pathological process of ossification in diffuse idiopathic skeletal hyperostosis extends to other vertebral ligaments, causing ossification of the posterior longitudinal ligaments and/or ossification of the ligamentum flavum. Thoracic spondylolisthesis with spinal cord compression in diffuse idiopathic skeletal hyperostosis has not previously been reported in the literature. CASE PRESENTATION: A 78-year-old Japanese man presented with a 6-month history of gait disturbance. A magnetic resonance imaging scan of his cervical and thoracic spine revealed anterior spondylolisthesis and severe cord compression at T3 to T4 and T10 to T11, as well as high signal intensity in a T2-weighted image at T10/11. Computed tomography revealed diffuse idiopathic skeletal hyperostosis at T4 to T10. He underwent partial laminectomy of T10 and posterior fusion of T9 to T12. The postoperative magnetic resonance imaging revealed resolution of the spinal cord compression and an improvement in the high signal intensity on the T2-weighted image. CONCLUSIONS: We report the first case of thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis. Neurosurgical intervention resulted in a significant improvement of our patient's neurological symptoms.

YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

[Studies on cases of spontaneous regression of cancer in Japan in 2011, and of hepatic carcinoma, lung cancer and pulmonary metastases in the world between 2006 and 2011].

The PubMed and Ichushi databases were searched to identify cases of spontaneous regression of cancer that were featured in original papers and abstracts presented at conferences and these cases were examined. First,6 3 cases of spontaneous regression reported from Japan in 2011 were examined in detail. The most common types of cancer were lymphoma,hepatic carcinoma,and pulmonary cancer. The incidence of spontaneous regression was estimated at 1 per 12,000 patients with cancer and was calculated on the basis of the estimated number of patients who were newly diagnosed as having cancer during 1 year in Japan. Next, 83, 40,and 37 cases of spontaneous regression of hepatic carcinoma,pulmonary cancer,and lung metastases from primary malignant tumors,respectively,reported worldwide between 2006 and 2011, were analyzed. The cause of spontaneous regression in all 3 pathologies often involved an immunological mechanism. Other common factors that contributed to spontaneous regression were impaired tumor blood flow in patients with hepatic carcinoma,paraneoplastic syndrome in those with pulmonary cancer,and removal of the primary tumor in patients with lung metastasis.

[Cerebral amyloid angiopathy-related leukodystrophy: a case report].

An 86-year-old woman was admitted following generalized seizure. Postictally she showed disturbance of consciousness, right hemiparesis, and right spatial neglect. Brain fluid attenuated inversion recovery (FLAIR) imaging demonstrated mainly left-sided, but asymmetrical, subcortical white matter lesions. On the second day, level of consciousness improved, along with right hemiparesis and right spatial neglect. Electroencephalography displayed mainly α waves and sporadic θ waves without sharp waves. One week later, however, the patient again experienced somnolence and right hemiparesis. FLAIR revealed day-by-day enlargement of white matter lesions. The possibilities of hypoglycemia, hyperammonemia, hypothyroidism, Hashimoto encephalopathy, collagen disease, antineutrophil cytoplasmic antibody-related angiitis, and infection were excluded based on the results of blood biochemistry and cerebrospinal fluid. We initially suspected intravascular lymphoma, so random skin biopsy was performed, but the results were negative. We then suspected cerebral amyloid angiopathy because of the presence of dementia and multiple microbleeds on T(2)* weighted magnetic resonance imaging. Cerebral biopsy revealed amyloid deposition in cortical arterioles and CD3-positive T cells in the perivascular space. Cerebral amyloid angiopathy-related leukodystrophy was therefore diagnosed and immunosuppressive treatment was started. After 14 days of treatment, clinical symptoms and results of FLAIR imaging were significantly improved. When patients display asymmetrical subcortical white matter lesions with microbleeds on T(2)* weighted imaging, amyloid angiopathy-related inflammation should be considered.

Right-to-left-shunt detected by c-TCD using the orbital window in comparison with temporal bone windows.

PURPOSE: There have been some reports on right-to-left shunt as a cause of cryptogenic stroke. Although contrast transcranial Doppler (c-TCD) can detect RLS, an insufficient temporal window has occasionally restricted its applicability. Thus, we compared the rates of detecting RLS among temporal windows for the middle cerebral arteries (MCAs) and the orbital window for the internal carotid artery (ICA) on c-TCD. METHODS: We used c-TCD to detect RLS in patients with suspected ischemic stroke. We enrolled patients who had both sufficient bilateral temporal windows for MCAs and a right orbital window for ICA and performed c-TCD using all three windows simultaneously. RESULTS: We enrolled 106 consecutive patients and identified microembolic signals (MES) in 30 (28%) of them. Among these 30 patients, 15 had MES from all 3 windows. When these 30 patients were defined as being positive for RLS, the rates of detection were 67%, 73%, and 80% from the right temporal, left temporal, and right orbital windows, respectively (P= .795). CONCLUSION: The right orbital window as well as the temporal window for c-TCD could detect RLS. Insonation from the orbital window should be useful for patients who lack temporal windows.

Kurashiki Prehospital Stroke Subtyping Score (KP3S) as a means of distinguishing ischemic from hemorrhagic stroke in emergency medical services.

BACKGROUND AND PURPOSE: The aim of this study was to devise a new ischemic stroke (IS)/hemorrhagic stroke (HS) stroke score to distinguish IS from HS for emergency medical services (EMS). MATERIALS AND METHODS: We studied patients with IS and HS who were admitted within 6 h of onset and transferred by the EMS. We compared characteristics of IS and HS to devise a new IS/HS score. RESULTS: A total of 227 patients (median age, 71 years; 139 males; IS, 127 patients; HS, 100 patients) were included in the study. On multivariate analysis following univariate analysis, presence of atrial fibrillation, diastolic blood pressure <100 mm Hg and lack of disturbance of consciousness were independently associated with IS. The following score was devised to distinguish IS from HS in EMS: Kurashiki Prehospital Stroke Subtyping Score (KP3S) = (presence of atrial fibrillation) · 2 + (diastolic blood pressure <100 mm Hg) + (lack of disturbance of consciousness). When KP3S was greater than 1, sensitivity for IS was 64% and specificity 85%. The C statistic of KP3S was 0.805. CONCLUSION: KP3S is useful for distinguishing IS from HS and for the evaluation of stroke patients by EMS.

Intravenous thrombolysis based on diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch in acute stroke patients with unknown onset time.

BACKGROUND AND PURPOSE: Patients with unknown onset time would be able to receive intravenous thrombolysis when showing diffusion-weighted imaging (DWI)/fluid-attenuated inversion recovery (FLAIR) mismatch. METHODS: Consecutive acute stroke patients with unknown onset time were prospectively enrolled. We defined patients as having unknown onset time when the last known normal time (LNT) was not consistent with the first found abnormal time (FAT). Only patients with anterior-circulation stroke and presence of arterial lesion were enrolled. Intravenous thrombolysis was conducted within 3 h from FAT if the patient showed DWI/FLAIR mismatch. RESULTS: From June 2009 to May 2010, 10 patients [median age, 84 years (interquartile range, IQR, 64-90); National Institutes of Health Stroke Scale (NIHSS) score, 14 (IQR, 9-19)] were enrolled. Subjects included 4 patients who developed stroke during sleep, 5 with disturbance of consciousness, and 1 with aphasia. Median interval between LNT and thrombolysis was 5.6 h (IQR, 4.5-9.8) and median interval between FAT and thrombolysis was 2.5 h (IQR, 2.1-2.8). Three patients had internal carotid artery occlusion, 5 had M1 occlusion, and 2 had M2 occlusion. Early recanalization within 24 h was seen in 7 patients (complete recanalization, n = 4; partial recanalization, n = 3). No patients experienced symptomatic cerebral hemorrhage within 48 h. At day 7, 5 patients showed dramatic recovery (defined as ≥ 10-point reduction in total NIHSS score or score of 0 or 1). At 3 months, favorable outcome (modified Rankin scale score, 0-2) was seen in 4 patients. CONCLUSION: Acute stroke patients with DWI/FLAIR mismatch may be able to safely receive intravenous thrombolysis.

FLAIR can estimate the onset time in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: Although thrombolysis can be performed for acute ischemic stroke (AIS) within 6h of onset, patients with an unknown onset time cannot receive this treatment. The aim of the present study is to investigate a method for determining the onset time of stroke in AIS patients within 24 hours (h) of onset. METHODS: AIS patients with onset time clearly defined within 24h were enrolled. All patients were examined using diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR). We investigated the utility of FLAIR in estimating the onset time of stroke. RESULTS: We enrolled 333 consecutive patients (median age, 74 years [interquartile range, 63-81]; males, 207 [62%]). Fifty-three patients underwent multiple MRI examinations; thus, a total of 389 MRI studies were analyzed. When the MRI findings were DWI-positive and FLAIR-negative (DWI+/FLAIR-), the interval between onset and imaging time was estimated to be within 3h with sensitivity of 0.83, specificity of 0.71, positive predictive value (PPV) of 0.64, and negative predictive value (NPV) of 0.87; to be within 4.5h with sensitivity of 0.74, specificity of 0.85, PPV of 0.87, and NPV of 0.70; and to be within 6h with sensitivity of 0.69, specificity of 0.91, PPV of 0.94, and NPV of 0.59. When patients with infra-tentorial lesions, lacunar stroke on imaging, and mild neurological deficit were excluded, DWI+/FLAIR- estimated that the onset time was within 3h with sensitivity of 0.93 and PPV of 0.77; within 4.5h with sensitivity of 0.77 and PPV of 0.96; and within 6h with sensitivity of 0.74 and PPV of 1.00. CONCLUSION: FLAIR can estimate the onset time of stroke in AIS within 24h of onset.

Diameter of the basilar artery may be associated with neurological deterioration in acute pontine infarction.

PURPOSE: The present study investigated the factors related to neurological deterioration in pontine infarction. METHODS: Consecutive patients with acute pontine infarction without basilar artery (BA) occlusion were enrolled. Patients were classified into two groups (D, group with neurological deterioration; ND, group without neurological deterioration). After magnetic resonance angiography was performed to identify the diameters of internal carotid artery (ICA) and BA, the BA diameter/ICA diameter (BA/ICA) ratio was calculated. When the ischemic lesion on diffusion-weighted magnetic resonance imaging extended to the ventral basal pial surface, it was diagnosed as branch atheromatous disease (BAD). RESULTS: Neurological deterioration occurred in 16 (31%) of 51 patients. BAD was found in 13 (81%) of 16 patients of the D group and 14 (40%) of 35 in the ND group (p = 0.008). The BA/ICA ratio was 0.73 (0.59-0.84) in the D group and 0.64 (0.55-0.71) in the ND group (p = 0.049). Multivariate regression analysis demonstrated that BAD (OR 15.62, 95% CI 2.37-103.13, p = 0.004) and a BA/ICA ratio of >or=0.70 (OR 7.76, 95% CI 1.55-38.88, p = 0.013) were independent factors associated with neurological deterioration. CONCLUSION: The BA diameter may be associated with neurological deterioration in acute pontine infarction.

Recanalization of the MCA should play an important role in dramatic recovery after t-PA therapy in patients with ICA occlusion.

BACKGROUND AND PURPOSE: The intravenous t-PA thrombolysis is not thought to be effective in most patients with internal carotid artery (ICA) occlusion. However, we have sometimes observed dramatic recovery in patients with ICA occlusion after t-PA therapy. The aim of the present study was to investigate the mechanism of dramatic recovery in such patients. METHODS: Consecutive ICA occlusion patients treated with t-PA were prospectively studied. MRI, including MRA, was performed before and within 1 h and 24 h after t-PA thrombolysis. Patients were divided into 2 groups: dramatic recovery (D group) and non-dramatic recovery (ND group). RESULTS: The subjects consisted of 21 consecutive stroke patients (14 males; mean age, 76.5+/-8.4 years). Six (28.6%) patients (D group) had dramatic improvement and 15 (71.4%) patients (ND group) did not. The frequency of partial or complete recanalization within 1 h and 24 h after t-PA infusion was 14.3% and 50.0% for the ICA, 9.5% and 40.0% for the MCA, and 23.8% and 65.0% for the ICA or MCA, respectively. There was no difference in the frequency of ICA recanalization 24 h after t-PA infusion between the 2 groups (66.7% for D group vs. 42.9% for ND group, P=0.629); however, MCA recanalization was more frequent in the D group than in the ND group (100.0% vs. 14.3%, P=0.0004). CONCLUSION: Recanalization of the MCA, which provides collateral flow, appears to play an important role in dramatic recovery after t-PA therapy in patients with ICA occlusion.

M1 susceptibility vessel sign on T2* as a strong predictor for no early recanalization after IV-t-PA in acute ischemic stroke.

BACKGROUND AND PURPOSE: In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization of occluded arteries can improve the clinical outcome. The magnetic susceptibility effect of deoxygenated hemoglobin in red thrombi can present as hypointense signals on T2*-weighted gradient echo imaging. We investigated whether the gradient echo imaging M1 susceptibility vessel sign (M1 SVS) can predict no early recanalization after t-PA infusion. METHODS: Patients with internal carotid artery and M1 occlusion were prospectively studied. MRI studies, including DWI, T2*, and MRA, were performed before and within 30 minutes and 24 hours after t-PA infusion. The NIHSS score was obtained before and 7 days after t-PA administration. The relationship between the presence of the M1 SVS and no early recanalization and patient outcome was examined. RESULTS: A total of 48 patients (29 men; mean age, 74.6+/-11.2 years) were enrolled. M1 SVS was present in 13 (27.1%) patients and absent in 35 (72.9%) patients. There were no significant differences in clinical characteristics between the 2 groups. Follow-up MRA within 30 minutes after t-PA infusion revealed that 20 (57.1%) of the 35 patients without the M1 SVS had early recanalization, but that none of the 13 patients with the M1 SVS had early recanalization (P=0.0002). Seven days after t-PA infusion, dramatic improvement was more frequently observed in patients without the M1 SVS (51.4%) than in those with the M1 SVS (0%, P=0.0007). CONCLUSIONS: The M1 SVS on T2* appears to be a strong predictor for no early recanalization after t-PA therapy.