Katsumi Irie

A New Method to Improve In-Bore Middle Cerebral Artery Occlusion in Rats Demonstration With Diffusion- and Perfusion-Weighted Imaging

BACKGROUND AND PURPOSE In-bore middle cerebral artery occlusion (MCAO) enables investigators to acquire preischemic MRI data and to image ischemic changes immediately after occlusion. We have developed a highly successful in-bore MCAO method. This study describes the methods and pertinent techniques. METHODS Sixty-seven Sprague-Dawley rats were subjected to temporary (n=36) or permanent (n=31) MCAO. The occluding device consisted of a supporting tubing, a driving line, and a silicone-coated 4-0 nylon suture occluder. Outside the magnet, the occluder was positioned in the carotid canal. MCAO was achieved in the magnet bore by remotely advancing the driving line until resistance was felt. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were acquired before and immediately after occlusion and were used to document the presence of MCAO. RESULTS Fifty-nine (88.1%) rats were successfully occluded, demonstrating hyperintensity on DWI, perfusion deficits on PWI, and no subarachnoid hemorrhage at postmortem examination. The average values of the apparent diffusion coefficient in both the frontoparietal cortex and the lateral caudoputamen significantly decreased as early as 3 minutes after the onset of ischemia. The failures included preocclusion damage (1/67), sliding out of the occluder during occlusion (1/67), no occlusion (2/67), and arterial perforation (4/67). CONCLUSIONS Our in-bore MCAO method is easily performed and is as successful as MCAO induced outside the magnet.

Cerebral hemodynamics in hypertensive patients compared with normotensive volunteers. A transcranial Doppler study.

Background and Purpose The present study was designed to examine cerebral hemodynamics in early and chronic stages of hypertension using transcranial Doppler sonography. Methods Our study population consisted of 16 chronic hypertensive patients with chronic and small deep brain infarction, 10 young early‐stage hypertensive subjects, and 16 young normotensive healthy volunteers. Using three‐dimensional mapping techniques, we identified the M1 portion of the middle cerebral arteries and measured mean blood flow velocity, and we calculated the Gosling pulsatility index (PI), Fourier PI of the first harmonic (Fourier PI1), and cerebrovascular resistance. Results Mean blood flow velocity in the young hypertensive group was statistically higher (71.7±11.7 cm/s [mean±SD]) than among chronic hypertensive subjects (56.9±21.4 cm/s, P<.01) and normotensive subjects (63.2±11.8 cm/s, P<.05). Gosling PI presented a mirror image of mean blood flow velocity in both hypertensive and normotensive subjects. Chronic hypertensive subjects showed significantly higher Fourier PI1 (0.32±0.05) and cerebrovascular resistance (2.08±0.82 mm Hg/cm per second) than normotensive subjects (0.25±0.03 and 1.31±0.23 mm Hg/cm per second [P<.005], respectively) or early‐stage hypertensive subjects (0.25±0.04 and 1.44±0.26 mm Hg/cm per second [P<.02], respectively). Conclusions Early‐stage hypertensive subjects demonstrated higher velocity, normal Fourier PI1, and near normal vascular resistance, whereas chronic hypertensive subjects showed near normal velocity, higher Fourier PI1, and greater vascular resistance. Results may indicate different degrees of cerebral arteriopathy and arteriolopathy between early and late stages of hypertension. (Stroke. 1994;25:1384‐1389.)

ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack

Background and Purpose— Several risk scores have been developed to predict the stroke risk after transient ischemic attack (TIA). However, the validation of these scores in different cohorts is still limited. The objective of this study was to elucidate whether these scores were able to predict short-term and long-term risks of stroke in patients with TIA. Methods— From the Fukuoka Stroke Registry, 693 patients with TIA were followed up for 3 years. Multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke. The discriminatory ability of each risk score for incident stroke was estimated by using C-statistics and continuous net reclassification improvement. Results— The multivariable-adjusted Cox proportional hazards model revealed that dual TIA and carotid stenosis were both significant predictors for stroke after TIA, whereas abnormal diffusion-weighted image was not. ABCD3 (C-statistics 0.61) and ABCD3-I (C-statistics 0.66) scores improved the short-term predictive ability for stroke (at 7 days) compared with the ABCD2 score (C-statistics 0.54). Addition of intracranial arterial stenosis (at 3 years, continuous net reclassification improvement 30.5%; P<0.01) and exclusion of abnormal diffusion-weighted imaging (at 3 years, continuous net reclassification improvement 24.0%; P<0.05) further improved the predictive ability for stroke risk until 3 years after TIA. Conclusions— The present study demonstrates that ABCD3 and ABCD3-I scores are superior to the ABCD2 score for the prediction of subsequent stroke in patients with TIA. Addition of neuroimaging in the ABCD3 score may enable prediction of long-term stroke risk after TIA.

Sex Differences in Short-Term Outcomes After Acute Ischemic Stroke The Fukuoka Stroke Registry

Background and Purpose— Variable sex differences in clinical outcomes after stroke have been reported worldwide. This study aimed to elucidate whether sex is an independent risk factor of poor functional outcome after acute ischemic stroke. Methods— Using the database of patients with acute stroke registered in the Fukuoka Stroke Registry in Japan from 1999 to 2013, 6236 previously independent patients with first-ever ischemic stroke who were admitted within 24 hours of onset were included in this study. Baseline characteristics were assessed on admission. Study outcomes included neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin Scale score, 3–6 at discharge). Logistic regression analyses were performed to evaluate the association between sex and clinical outcomes. Results— Overall, 2398 patients (38.5%) were women. Severe stroke (National Institutes of Health Stroke Scale score, ≥8) on admission was more prevalent in women than in men. The frequency of neurological improvement or deterioration during hospitalization was not different between the sexes. After adjusting for possible confounders, including age, stroke subtype and severity, risk factors, and poststroke treatments, it was found that female sex was independently associated with poor functional outcome at discharge (odds ratio, 1.30; 95% confidence interval, 1.08–1.57). There was heterogeneity of the association between sex and poor outcome according to age: women had higher risk of poor outcome than men among patients aged ≥70 years, but no clear sex difference was found in patients aged <70 years. Conclusions— Female sex was associated with the risk of poor functional outcome at discharge after acute ischemic stroke.

Cerebral blood flow and metabolism in patients with silent brain infarction: occult misery perfusion in the cerebral cortex

OBJECTIVES Silent brain infarction (SBI) is of growing interest as a possible risk factor for symptomatic stroke. Although morphological characteristics of SBI have been well defined, their characteristic patterns of cerebral blood flow (CBF) and metabolism are in dispute. The purpose of this study was to elucidate CBF and metabolism in patients with SBI in relation to symptomatic stroke. METHODS The patients underwent PET and were separated into three groups; control group (C group), with no lesions on CT (n=9, mean age 57), SBI group, with no neurological signs or history of stroke, but with ischaemic lesions on CT (n=9, mean age 63), and brain infarction group (BI group), with neurological deficits and compatible CT lesions in the area supplied by perforating arteries (n=19, mean age 56). Regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral blood volume (CBV) were measured by PET. RESULTS Mean values for CBF to the cerebral cortex and deep grey matter were lower in the SBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively) and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) than in the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively). Although mean CMRO2 of deep grey matter (2.36 (SD 0.52) ml/100 g/min) was significantly decreased in the SBI group compared with the C group (2.76 (SD 0.480), p<0.01), CMRO2 of the cortical area was as well preserved in the SBI patients (2.36 (SD 0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increase of mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively). CONCLUSIONS Patients with SBI showed decreased CBF and CMRO2 in deep grey matter. On the other hand, decreased CBF with milder increased OEF, resulting in preserved CMRO2 in the cerebral cortex indicates the presence of occult misery perfusion, suggesting that patients with SBI have reduced cerebral perfusional reserves.

Cerebral blood flow and metabolism in hypertensive patients with cerebral infarction.

The authors investigated, by positron emission tomography, the effect of long-standing hypertension on cerebral blood flow (CBF) and oxygen metabolism in patients with chronic atherothrombotic brain infarction. In the nonbrain infarct (non-BI) group (n=13, mean age: sixty-two years), the regional CBF (rCBF) was decreased significantly with a rise in the mean arterial blood pressure (MABP) in the cerebral cortexes (r=-0.575) and the deep gray matter (r=-0.451), whereas the regional cerebral metabolic rate for oxygen (rCMRO2) remained unchanged. In the brain infarct (BI) group (n=22, mean age: fifty-eight years), however, the rCBF as well as the rCMRO2 were reduced even in the normotensive patients and thus did not correlate with the MABP. These results suggest that long-standing hypertension per se causes a reduction in the rCBF but not in the oxygen metabolism with a compensatory increase in the oxygen extraction fraction. On the other hand, patients with brain infarction, even normotensives, show a diffuse decrease in cerebral circulation and metabolism, which is probably due to the more severe sclerotic changes that take place in the cerebral vessels.

Temporal evolution of average apparent diffusion coefficient threshold to define ischemic abnormalities in a rat permanent occlusion model

We examined average apparent diffusion coefficient (ADCav) thresholds to define ischemic lesion size and characterized the temporal evolution of the ADCav thresholds. Thirteen Sprague-Dawley rats underwent permanent middle cerebral artery occlusion in the magnetic resonance imaging unit. Diffusion-weighted imaging was acquired before occlusion and 25, 60, 90, 150, 210, and 270 minutes after occlusion. Absolute ADCav values from 0.46 to 0.62×10−3 mm2/s and the percentage of the decline of ADCav values from −32 to −16 compared with the baseline values were used to define the percentage of hemispheric lesion volume (HLV) at each time point. Twenty-four hours after occlusion, the rats were killed, and 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to calculate the percentage of hemispheric infarction volume (HIV), which was then used as the “gold standard” to determine ADCav thresholds. The ADCav-derived HLV was identical to and best correlated with the TTC-derived HIV when the absolute ADCav threshold was 0.62, 0.60, 0.54, 0.52, 0.50, and 0.50×10−3 mm2/s and the percentage of ADCav threshold was −16, −18, −24, −28, −30, and −30 at 25, 60, 90, 150, 210, and 270 minutes after occlusion, respectively. Our results suggest that both the absolute values and the percentage of ADCav thresholds can define the final lesion volume as early as 25 minutes and that these thresholds decrease over time and become constant 210 minutes after occlusion throughout the observation period.

Efficacy of Upper Extremity Robotic Therapy in Subacute Poststroke Hemiplegia: An Exploratory Randomized Trial

Background and Purpose— Our aim was to study the efficacy of robotic therapy as an adjuvant to standard therapy during poststroke rehabilitation. Methods— Prospective, open, blinded end point, randomized, multicenter exploratory clinical trial in Japan of 60 individuals with mild to moderate hemiplegia 4 to 8 weeks post stroke randomized to receive standard therapy plus 40 minutes of either robotic or self-guided therapy for 6 weeks (7 days/week). Upper extremity impairment before and after intervention was measured using the Fugl–Meyer assessment, Wolf Motor Function Test, and Motor Activity Log. Results— Robotic therapy significantly improved Fugl–Meyer assessment flexor synergy (2.1±2.7 versus −0.1±2.4; P<0.01) and proximal upper extremity (4.8±5.0 versus 1.9±5.5; P<0.05) compared with self-guided therapy. No significant changes in Wolf Motor Function Test or Motor Activity Log were observed. Robotic therapy also significantly improved Fugl–Meyer assessment proximal upper extremity among low-functioning patients (baseline Fugl–Meyer assessment score <30) and among patients with Wolf Motor Function Test ≥120 at baseline compared with self-guided therapy (P<0.05 for both). Conclusions— Robotic therapy as an adjuvant to standard rehabilitation may improve upper extremity recovery in moderately impaired poststroke patients. Results of this exploratory study should be interpreted with caution. Clinical Trial Registration— URL: http://www.umin.ac.jp/. Unique identifier: UMIN000001619.

Multiple Brain Infarction and Hemorrhage by Nonbacterial Thrombotic Endocarditis in Occult Lung Cancer— A Case Report

A fifty-four-year-old woman died from multiple brain infarction and hemor rhage in the bilateral cerebrum, cerebellum, and brainstem, with renal infarc tion. She developed hematuria and transient blindness sixteen days before admission. Low-grade fever, heart murmur, and aortic valve vegetation on ul trasonic cardiography suggested infectious endocarditis. Autopsy study re vealed occult adenocarcinoma in the lung and nonbacterial thrombotic endocarditis, but infective endocarditis was not histologically confirmed. The patient was considered to be a rare case of nonbacterial thrombotic endocarditis who developed multiple small infarctions mainly in the brainstem and cerebel lum. Nonbacterial thrombotic endocarditis seems to be still an important dis ease as the embolic source, even if cryptic, of systemic thromboembolism.

Ischemic Brain Metabolism in Patients With Chronic Cerebrovascular Disease : Increased Oxygen Extraction Fraction and Cerebrospinal Fluid Lactate

The aim of the present study is to elucidate the existence of chronically ischemic metabolism concomitant with misery perfusion of the brain in patients with chronic cerebrovascular disease. For this purpose, we measured cerebral blood flow (CBF) and oxygen metabolism by positron emission tomography (PET) and also determined cerebrospinal fluid (CSF) lactate as an indicator of the ischemic brain metabolism. Twenty-eight patients with chronic ischemic stroke and transient ischemic attack (TIA), who had angiographically occlusive (n = 11), stenotic (n = 10), and nonstenotic changes (n = 7) of the carotid artery and/or the intracranial major artery, were selected for this study. CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral blood volume (CBV) were determined by PET, and CSF lactate and pyruvate were determined by enzymatic method in the patients with various grades of stenotic changes of the carotid artery. There were no significant differences in PET parameters and CSF variables among the groups of the occlusive, stenotic, and nonstenotic carotid artery. However, CSF lactate was correlated negatively with mean bilateral hemispheric (m)CBF (R(2) = 0.229, P<.01), positively with mOEF (R(2) = 0.278, P<.005) and more highly with mCMRO2/CBF (absolute extraction of oxygen content to the brain) (R(2) = 0.473, P<.0001) in all patients. There was no correlation between CSF lactate and mCMRO2 or mCBV. None of the cases in the nonstenotic group showed mOEF greater than 0.45, or mCMRO2/CBF greater than 7.9 vol%, while 80% of the cases in the stenotic group and 82% of the cases in the occlusive group showed mOEF and mCMRO2/CBF exceeding the above-mentioned values, respectively. The present findings, that increased mOEF and mCMRO2/CBF were significantly correlated with increased CSF lactate, indicate the brain to be in a metabolically ischemic state or increased anaerobic glycolysis with oxygen metabolism maintained in patients with chronic ischemic stroke.