Cancer-Associated Hypercoagulation Increases the Risk of Early Recurrent Stroke in Patients with Active Cancer.

BACKGROUND: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. METHODS: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. RESULTS: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher -D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42-30.7, p = 0.015). CONCLUSIONS: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk.

High Morning and Bedtime Home Blood Pressures Strongly Predict for Post-Stroke Cognitive Impairment.

BACKGROUND: Hypertension may be the most modifiable risk factor for post-stroke cognitive impairment (PSCI). We investigated how home blood pressure (HBP) can predict PSCI as well as stroke recurrence. METHODS: We studied 249 consecutive patients with noncardioembolic minor ischemic stroke including single lacunar infarct (sLI), multiple lacunae (mLI), and atherothrombotic infarction, which were tracked at our outpatient clinic. HBP was measured in the early morning (m-HBP) and just before going to bed (b-HBP). HBP categories based on systolic blood pressure were created as follows: HB1, both m-HBP and b-HBP less than 135 (mmHg); HB2, m-HBP less than or equal to135 and b-HBP less than 135; HB3, m-HBP less than 135 and b-HBP less than or equal to 135; HB4, both m-HBP and b-HBP less than or equal to 135. After 4.1 years of tracking, the patients were divided into 4 groups: Group 1, good outcome (n = 188); Group 2, the development of silent infarcts (n = 16); Group 3, the development of PSCI (n = 33); and Group 4, stroke recurrence (n = 15). RESULTS: HB2 and HB4 (versus HB1) (hazard ratio [HR]: 6.5, P = .0068 and HR: 9.5, P = .0008, respectively) and mLI (versus sLI) (HR: 4.0, P = .021) were independently associated with Group 2. HB3 and HB4 (HR: 4.2, P = .037; HR: 5.4, P < .0001) and mLI (HR: 6.4, P < .0001) were significantly associated with Group 3. HB4 (HR: 8.1, P = .0002) and mLI (HR: 10.2, P = .0003) were significantly associated with Group 4. Clinic blood pressure (BP) was not significantly associated with any adverse groups. CONCLUSIONS: High HBP and mLI were strongly associated with PSCI as well as stroke recurrence. BP should be monitored based on HBP, especially bedtime HBP, for the prevention of PSCI.

Stroke education using an animated cartoon and a manga for junior high school students.

BACKGROUND: We investigated whether junior high school students could be educated regarding stroke with an animated cartoon and a Manga that we produced for the purpose of dissemination of this knowledge. METHODS: We produced a 10-minute animated cartoon and a Manga that provided information regarding stroke risk factors, stroke signs and symptoms, and awareness to immediately contact emergent medical service (EMS) on identification of stroke signs and symptoms. From December 2011 to March 2012, 493 students in 15 classes of the first grade (age 12-13 years) of 3 junior high schools were enrolled in the study. Each subject watched the animated cartoon and read the Manga; this was referred to as "training." Lessons about stroke were not given. Questionnaires on stroke knowledge were evaluated at baseline, immediately after the training, and 3 months after the training. RESULTS: The proportion of correct answers given immediately after the training was higher for all questions, except those related to arrhythmia, compared with baseline. Percentage of correct answers given at 3 months was higher than that at baseline in questions related to facial palsy (75% versus 33%), speech disturbance (91% versus 60%), hemiplegia (79% versus 52%), numbness of 1 side (58% versus 51%), calling for EMS (90% versus 85%), alcohol intake (96% versus 72%), and smoking (69% versus 54%). At 3 months after the training, 56% of students answered the FAST (facial droop, arm weakness, speech disturbance, time to call for EMS) mnemonic correctly. CONCLUSIONS: Stroke education using these teaching aids of the animated cartoon and the Manga improved stroke knowledge in junior high school students.

Stroke education program of act FAST for junior high school students and their parents.

BACKGROUND: We produced a stroke education program using the FAST (facial droop, arm weakness, speech disturbance, time to call an ambulance) mnemonic. AIMS: The aim of this study is to examine efficacy of our education program for junior high school students and their parents. METHODS: One hundred ninety students of 3 junior high schools (aged 12-13 years) and their parents were enrolled. Students received a 45-minute lesson of stroke enlightenment using the FAST mnemonic. Enlightenment items, such as a magnet poster, were distributed. Parents were educated indirectly from their child. Surveys of stroke knowledge were examined at baseline, immediately after the lesson, and at 3 months after the lesson. RESULTS: For the students, correct answers at 3 months were significantly higher than those at baseline in questions of facial palsy (98% versus 33%), speech disturbance (98% versus 54%), numbness on one side (64% versus 42%), weakness on one side (80% versus 51%), calling an ambulance (88% versus 60%), alcohol drinking (85% versus 65%), smoking (70% versus 43%), dyslipidemia (58% versus 46%), hyperglycemia (59% versus 48%), and obesity (47% versus 23%). At 3 months, the parents answered more correctly questions of facial palsy (93% versus 66%), calling an ambulance (95% versus 88%), and alcohol drinking (65% versus 51%) than at baseline. At 3 months, 96% of students and 78% of parents answered the FAST mnemonic correctly. CONCLUSIONS: Our stroke education program improved stroke knowledge, especially the FAST message, for junior high school students and their parents.

Effects of 24-hour blood pressure and heart rate recorded with ambulatory blood pressure monitoring on recovery from acute ischemic stroke.

BACKGROUND AND PURPOSE: This study used ambulatory blood pressure (BP) monitoring to generate BP and heart rate (HR) profiles soon after stroke onset and evaluated the association between determined values and 3-month stroke outcomes. METHODS: We analyzed 24-hour ambulatory BP monitoring records from 104 patients with acute ischemic stroke. Ambulatory BP monitoring was attached at the second and eighth hospitalization days (Days 1 and 7). Both BP and HR were characterized using baseline, mean, maximum, and minimum values and coefficient of variation during 24-hour recording periods. Outcomes at 3 months were assessed as independence according to a modified Rankin Scale score of ≤2 and poor according to the score of ≥5. RESULTS: Sixty-six (63%) patients achieved independence and 12 (11%) had poor outcomes. Mean ambulatory BP monitoring values changed from 150.5±19.5/85.7±11.3 mm Hg on Day 1 to 139.6±19.3/80.0±11.7 mm Hg on Day 7. After multivariate adjustment, mean values of systolic BP (OR, 0.63; 95% CI, 0.45-0.85), diastolic BP (0.61; 0.37-0.98), pulse pressure (0.55; 0.33-0.85), and HR (0.61; 0.37-0.98) recorded on Day 1 as well as mean HR on Day 7 (0.47; 0.23-0.87) were inversely associated with independence and mean values of systolic BP (1.92; 1.15-3.68), diastolic BP (5.28; 1.92-22.85), and HR (4.07; 1.83-11.88) on Day 1 as well as mean HR on Day 7 (4.92; 1.36-36.99) were positively associated with a poor outcome. CONCLUSIONS: All of systolic BP, diastolic BP, pulse pressure, and HR on Day 1 and HR on Day 7 assessed using ambulatory BP monitoring were associated with outcomes of patients with stroke at 3 months.

[Cerebral deep vascular architectures and subcortical infarcts].

The lenticulostriate arteries (LSA) supply the lateral half of the head of the caudate nucleus, entire putamen, anterior limb, genu and the superior part of the internal capsule (IC) and a part of the corona radiata. The LSA consists with medial, intermediate and lateral branches. The medial branches perfuse the lateral segment of the globus pallidus, the head of the caudate nucleus and the anterior limb of the IC. The intermediate branches supply the anterior half of the LSA territory, while the lateral branches supply the posterior half. The anterior cerebral artery (ACA) perforators, predominantly Heubner's artery, perfuse the inferomedial part of the caudate head, the anteromedial part of putamen, the anterior part of the lateral segment of the globus pallidus and anterior limb of the internal capsule. Such territories can be represented by the anterior and ventral basal ganglions. The anterior choroidal artery (AChA) gives off three main groups of branches including the lateral branches that supply the medial temporal lobe, the medial branches that supply the cerebral peduncle and the superior branches that supply the internal capsule and the basal ganglia. The superior branches are further discriminated into proximal branches that supply the anterior one third of the posterior limb of internal capsule (PLIC) and the medial segment of the globus pallidus and distal branches that supply the posterior two-third of PLIC, retro-lenticular part of the internal capsule and the lateral thalamic nuclei. The superficial penetrating arteries, i.e. medullary arteries, arise from the cortical branches of the middle cerebral artery (MCA) and supply the deep white matter. Infarcts caused by the medullary artery occlusion are located in the centrum-semiovale and half of them were caused by embolic mechanism. The centrum-semiovale corresponds to cortical border-zone (BZ) while the corona radiate corresponds to internal BZ.

The anterior one third of the posterior limb of the internal capsule is also supplied by the anterior choroidal artery.

PURPOSE: It is universally recognized that the anterior choroidal artery (AChA) supplies the posterior two-third of the posterior limb of internal capsule (PLIC). On the other hand, the blood supply to the anterior one third of the PLIC has remained undetermined. We posit the anterior one third of the PLIC is also supplied by the AChA referring the previous microsurgical descriptions. METHODS: Ninety consecutive patients with isolated acute infarction in the PLIC were studied. We classified patients into 4 groups. 1. The anterior type that involved the anterior one-third part of the PLIC. 2. The posterior type that involved the caudal two-third part of the PLIC, 3. The combined type that located in the full length of the PLIC, 4. The dot type that restricted within PLIC up to10mm in diameter. RESULTS: Patient numbers in groups 1 through 4 were 7 (7.7%), 46 (51.1%), 9 (10.6%) and 28 (31.1%). The anterior type involved the medial part of pallidum (MPP) in 5 patients (71.4%) and none in the lateral thalamus (LT), while the posterior type involved MPP only in 6 patients (13.0%) and LT in 33 patients (71.7%). CONCLUSION: Corresponding to previous microsurgical descriptions, an occlusion of the proximal branches may cause anterior type infarct and that of the distal branches may cause posterior type infarcts. The anterior one third of the PLIC is also supplied by the branches of the AChA, albeit the low prevalence.

Stroke mechanisms and their correlation with functional outcome in medullary infarction.

PURPOSE: To study the stroke mechanism of medullary infarction (MI) and their correlation with prognosis. METHODS: We collected 81 consecutive patients with acute isolated MI including 50 patients with lateral MI (LMI), 30 with medial MI (MMI) and one with combined MI. The stroke mechanisms were defined as follows: 1. Large artery atherosclerotic occlusive disease (LAOD): with severe stenosis (>50%) or occlusion on the relevant arteries. 2. Penetrating artery disease (PAD): occlusion of penetrating arteries that arise from vertebral artery or basilar artery with no significant stenosis of the vertebro-basilar artery. 3. Dissection: angiographic findings met the criteria. 4. Cardiogenic embolism: abrupt onset with atrial fibrillation. The poor outcome was defined as a condition that includes the mRS ≥2 and/or dysphagia at one year after onset. RESULTS: There were 20 patients with PAD (40%), 18 with dissection (36.0%) and 11 with LAOD (22.0%) in LMI and 17 with PAD (56.6%), 10 with LAOD (33.3%) in MMI. LAOD and dissection compared with PAD were independently correlated with poor outcome in LMI (OR: 12.8, p = 0.029 and OR: 14.9, p = 0.035). LAOD was significantly correlated with poor outcome in MMI (OR: 13.4, p = 0.014). CONCLUSIONS: PAD was the most predominant stroke mechanism in MI and generally showed favorable outcome. Patients with LAOD and dissection showed worse outcome than those with PAD.

[Two cases of hippocampal infarction with persistent memory impairment in which diffusion-weighted magnetic resonance imaging was useful].

We present two patients (case 1: a 78-year-old right-handed woman, case 2: a 66-year-old right-handed woman) with suspected transient global amnesia. Both patients showed sudden onset amnesia that appeared to resolve within 24 hours, and they showed no abnormal findings on electroencephalography or single photon emission tomography. However, the results of the Wechsler Memory Scale-Revised (WMS-R) on the ninth (case2) or tenth day (case1) after the onset indicated memory impairment. And diffusion-weighted magnetic resonance imaging (DWI) revealed a unilateral high-intensity area in the hippocampus, leading to the diagnosis of hippocampal infarction in both patients. Case 1 had a left hippocampal lesion and exhibited impairment of predominantly verbal memory, while case 2 had a right hippocampal lesion and demonstrated impairment of predominantly visual memory. When evaluating a patient with suspected transient global amnesia, imaging of the hippocampus and tests on memory function after an appropriate interval from the onset are often helpful in establishing a correct diagnosis.

The relationship between progressive motor deficits and lesion location in patients with single infarction in the lenticulostriate artery territory.

As the corticospinal tracts cross the lenticulostriate artery (LSA) territory at the posterior segment, we hypothesized that posteriorly located infarctions of the LSA may be associated with progressive motor deficits. We prospectively studied 519 consecutive patients with LSA infarctions who entered our hospital within 24 h after onset. We categorized patients into two groups in terms of progress: no progress and progress. Progress was defined as worsening by 1 point or more in the National Institutes of Health Stroke Scale (NIHSS), some of which recovered afterward or thoroughly progressed. LSA infarctions on the first DWI were divided into proximal type and distal (group 1) type. The proximal type was further divided into anterior (group 2), intermediate (group 3) and posterior (group 4) type according to the middle point of antero-posterior diameter of the lateral ventricle. There were 109 patients who showed progress that accounted for 21.0% of all patients. The number of patients who progressed is as follows: distal type 65 (23.8%), anterior type 31 (36.0%), intermediate type 26 (56.5%) and posterior type 97 (85.0%). The Cochran-Armitage test showed a significant increase through group 1 to group 4 (p < 0.0001). Independent predictive factors for progress were male (OR 0.57, p = 0.0107), higher NIHSS on admission (≥4) (OR 3.02, p < 0.0001), intermediate proximal type (OR 3.3, p = 0.0007) and posterior proximal type (OR 16.4, p < 0.0001). The more posterior the infarct location, the more frequent was the progress that occurred, probably due to the anatomical fact that corticospinal tracts crossed the LSA territory at the posterosuperior quadrant.

New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan.

PURPOSE: Definite diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy (CADASIL) is mostly done by identification of NOTCH3 mutations. We aimed to develop criteria for selecting patients suspected for CADASIL to undergo genetic testing. SUBJECTS AND METHODS: All subjects were Japanese. We recruited CADASIL patients genetically diagnosed up until 2011 (n=37, Group 1) or after 2011 (n=65, Group 2), 67 young stroke patients (≤55 years old), and 53 NOTCH3-negative CADASIL-like patients. The members of Japanese research committee for hereditary cerebral small vessel disease discussed and generated the new criteria to maximize positive rate in Group 1 CADASIL patients, followed by validation of sensitivity and specificity. RESULTS: In Group 1 CADASIL patients, the ages at onset excluding migraine were distributed widely (37-74 years old) and bimodal (<55 and >55 years old). Frequencies of an autosomal dominant family history and vascular risk factor(s) were 73 and 65%, respectively. From these findings, the panel considered appropriate cut-off values and weighting for each item. In CADASIL Group 1 versus young stroke controls, the sensitivity and specificity of the new criteria were 97.3% and 80.6%, respectively. However, in CADASIL Group 2 versus NOTCH3-negative controls, the sensitivity and specificity were 96.9% and 7.5%, respectively. Forty mutations of NOTCH3 distributed in exons 2-8, 11, 14, 18, 19, and 21 were identified in this study. Ten mutations were unreported ones. CONCLUSION: We propose the new criteria of high sensitivity, which will help physicians to assess the need for genetic testing.

Ventricular Temperatures in Idiopathic Normal Pressure Hydrocephalus (iNPH) Measured with DWI-based MR Thermometry.

PURPOSE: The brain produces intense heat as a result of cerebral metabolism and cerebral blood flow, and the generated heat is removed mainly through circulation of the intracranial blood vessels and cerebrospinal fluid (CSF). Because magnetic resonance (MR) images are constructed from analysis of the spin of various molecules, the diffusion coefficient can be used as a parameter that reflects the temperature of water molecules. We used diffusion-weighted imaging (DWI)-based MR imaging to measure the temperature of the CSF around the lateral ventricles in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Our study included 33 cases of iNPH (Group N, mean age, 75.1 years) and 40 age-matched controls (Group C, mean age, 74.5 years). We calculated CSF temperature in the ventricular domain using the conversion formula to evaluate the feasibility of iNPH study. RESULTS: The mean temperatures were significantly higher in Group N (37.6°C ± 0.4°C) than Group C (36.7°C ± 0.5°C; P < 0.01). The cut-off value of 37.2°C (more than the mean + 2 standard deviations [SD] of the values in Group C) showed sensitivity of 72.4% and specificity of 77.5% for distinguishing the 2 groups. We confirmed improved CSF temperature in the lateral ventricles in all patients examined both before and after shunting. CONCLUSIONS: Elevated ventricular temperatures in patients with iNPH (Group N) may represent a disturbance in heat balance. Our results showed that thermometry using DWI-based MR imaging can help in the noninvasive and consistent evaluation of CSF temperature and may thus provide a useful supplementary brain biomarker for iNPH.

Effects of hyperacute blood pressure and heart rate on stroke outcomes after intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: The present study clarifies associations between stroke outcomes after intravenous tissue plasminogen activator (tPA) and blood pressure (BP) as well as heart rate (HR) profiles. METHODS: We assessed 125 patients with stroke who received tPA within 3 h of onset. We obtained baseline, mean, maximum, minimum, and coefficient of variation values for BP and HR during the initial 24 h. The primary outcome was independence at 3 months corresponding to a modified Rankin Scale score of 2 or less. The secondary outcomes were early neurological improvement at 24 h and intracerebral hemorrhage (ICH) within 36 h. RESULTS: Among the patients, 64 (51%) achieved independence, 66 (53%) early improvement, and 26 (21%) developed ICH. The 24-h time courses of SBP (P = 0.033), pulse pressure (PP, P = 0.007), and HR (P < 0.001) were lower among patients who reached independence than among those who did not. After multivariate adjustment, 24-h mean levels of SBP (odds ratio 0.69, 95% confidence interval 0.48-0.97, per 10-mmHg increase), PP (0.63, 0.41-0.94), and HR (0.59, 0.42-0.80, per 10-bpm increase) were inversely associated with independence, as were their maximum and minimum values. In particular, mean SBP values were inversely associated with independence at 8-16 and 16-24 h (0.73, 0.54-0.97 and 0.66, 0.47-0.91, respectively), but not at 0-8 h (0.79, 0.57-1.07). Baseline and maximum SBP were inversely associated with early improvement. Maximum and coefficient of variation of SBP were associated with ICH. CONCLUSION: Lower SBP, PP, and HR values during the initial 24 h after tPA, especially at 8 h thereafter, were associated with independence at 3 months.

Low levels of plasma soluble receptor for advanced glycation end products are associated with severe leukoaraiosis in acute stroke patients.

A secreted isoform of the receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE), can neutralize the adverse effects of RAGE signaling by acting as a decoy. RAGE signaling contributes to the development of diabetic microangiopathy, however few studies have addressed pivotal roles of RAGE signaling in acute stroke. We examined plasma sRAGE levels associated with clinical features in acute stroke patients. Plasma sRAGE was measured in 482 patients (318 men; mean age 71 years) admitted within three days of stroke onset. Median values of sRAGE were significantly different among stroke subtypes (p=0.001); 1010 pg/ml in atherothrombotic infarction, 933 pg/ml in lacunar, 1280pg/ml in cardioembolic infarction, 1050 pg/ml in other types of infarctions, and 943 pg/ml in primary intracerebral hemorrhage. Severe leukoaraiosis on brain MR images, high NIHSS scores on admission, cigarette smoking, and normal estimated glomerular filtration rate were significantly associated with low sRAGE levels (p<0.05). The low level of sRAGE was associated with severe leukoaraiosis, reflecting long-standing presence of hypertensive angiopathy. Kidneys play a role in the removal of sRAGE. RAGE signaling can contribute to the deterioration of neuronal damage under severe leukoaraiosis, result in a high NIHSS score on admission in acute stroke patients, especially those with smoking habits.