Kei Miyata

Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia.

Although intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat middle cerebral artery occlusion models, there are few reports of MSC treatment in global cerebral ischemia. We utilized a global cerebral ischemia model induced by arresting the heart with a combination of hypovolemia and intracardiac injections of a cold potassium chloride solution in order to study the potential therapeutic benefits of human mesenchymal stem cells (hMSCs) on global cerebral ischemia. hMSCs were intravenously injected into the rats 3 h after resuscitation from cardiac arrest. The effects on structural and functional outcome of hMSC were assessed at 5 h and 1, 3, and 7 days using magnetic resonance spectroscopy (MRS), histology, and cognitive functional analysis. Intravenous delivery of hMSCs reduced the Lac/Cr ratios, nuclear DNA fragmentation, neuronal loss, and elicited functional improvement compared with the control sham group. Enzyme-linked immunosorbent assay (ELISA) of the hippocampus revealed an increase in BDNF in hMSC-treated group. These data suggest that intravenous delivery of hMSC may have a therapeutic effect in global cerebral ischemia.

Arterial Spin-Labeling Magnetic Resonance Imaging After Revascularization of Moyamoya Disease

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a technique for depicting cerebral perfusion without contrast medium. The purpose of this study was to determine whether ASL can be used to detect hyperperfusion after revascularization for moyamoya disease as effectively as N-isopropyl-[123I]β-iodoamphetamine ((123)I-IMP) single-photon emission computed tomography (SPECT). Fifteen consecutive patients with moyamoya disease were included in the study. All patients underwent surgical revascularization. Postoperatively, regional cerebral blood flow (rCBF) was measured by flow-sensitive alternating inversion recovery (FAIR) ASL and (123)I-IMP SPECT during the acute stage, and rCBF of the operative side was compared with the other side. The asymmetry ratio (AR) was then calculated from the rCBF as measured using each modality. The postoperative AR of ASL was moderately correlated with that of (123)I-IMP SPECT (y = 0.180x + 0.819; R = 0.80; P = .0003). In this series, 2 patients (13.3%) suffered symptomatic hyperperfusion after revascularization and accordingly exhibited increased AR of ASL. Our data indicate that early increases in rCBF in patients with hyperperfusion could be detected using FAIR ASL supplemental to (123)I-IMP SPECT after revascularization. Our data indicate that FAIR ASL is a convenient method for evaluating hyperperfusion that can be performed repeatedly without the use of contrast medium or radioisotopes.

The Difference in Location between Traumatic Cerebral Microbleeds and Microangiopathic Microbleeds Associated with Stroke

Microbleeds (MBs) are low‐intensity spots on gradient echo T2*‐weighted MRI frequently associated with cerebral microangiopathies resulting in stroke. MBs can also be caused by cerebral axonal injuries. We compared the location of MBs associated with cerebral microangiopathies with those associated with trauma.

The Number of Microbleeds on Gradient T2∗-weighted Magnetic Resonance Image at the Onset of Intracerebral Hemorrhage

OBJECTIVE Deep intracerebral hematoma (ICH) is frequently associated with microbleed (MB) arising from degenerated MB. Increased numbers of MB are correlated with increased age, and we examined a possible relationship between MB number and ICH onset in younger patients. METHODS Excluding patients with ICH and a history of ICH, we examined the number of MB and other risk factors in 195 patients with deep ICH (97 male, 98 female) consecutively admitted to our hospital. The patients were equally divided into 3 subgroups according to age (groups A, B, and C). Odds ratios were estimated from logistic regression analyses. RESULTS The number (percentage) of MB in group A (< or =60 years old, n = 64) 5.0 +/- 9.6 (65.6%) was less than group B (61-69 years old, n = 63) 6.6 +/- 9.1 (79.4%) or group C (> or =70 years old, n = 68) 6.0 +/- 7.0 (86.8%). Multivariate analyses demonstrated that MB greater than or equal to 3 was significantly associated with higher age in group A versus B (odds ratio: 2.3; 95% confidence interval: 1.01-5.3; P = .046) and in group A versus C (odds ratio: 2.6; 95% confidence interval: 1.1-6.2; P =.030). CONCLUSIONS Our findings suggest that risk factors for the development of ICH may differ with age, and younger patients with deep ICH have fewer MB.

Dynamics of Dot‐Like Hemosiderin Spots on T2*‐Weighted MRIs Associated with Stroke Recurrence

Background and Purpose. Dot‐like low‐intensity spots (dot‐like hemosiderin spots: dotHSs) on gradient echo T2*‐weighted (‐w) brain magnetic resonance imaging (MRIs) are frequently associated with cerebral small vessel disease (SVD), including deep intracerebral hemorrhages and lacunar infarctions. This study investigated how numbers of newly appeared dotHSs contribute to recurrent SVD. Methods. We prospectively analyzed numbers of newly appeared dotHSs in 12 patients with prior SVD (8 males, 4 females; mean 67.6 ± 10.7 years old) readmitted with recurring SVD between October 2001 and March 2003. Numbers of appeared dotHSs per year were counted on T2*‐w MRI scans after SVD recurrence and compared to previous MRIs. Seventy‐one outpatients (35 males, 36 females; mean 64.3 ± 9.6 years old) with histories of intracerebral hemorrhages (ICH) that came to the hospital during the study period served as controls. The hazard ratio (HR) for recurrence was estimated from a multivariate logistic regression model, using the number of appeared dotHSs (per year) and other risk factors. Results. Multivariate analyses revealed that an elevated rate of recurrence was found in patients with substantial numbers of appeared dotHSs (≥5/year) (HR, 7.34; P= 0.0008). We also analyzed factors associated with the numbers of appeared dotHSs. A number of appeared dotHSs (≥5/year) was significantly and independently associated with the initial number of dotHSs (≥10) on T2*‐w MRIs following the first SVD (HR, 18.6; P= 0.0001). Conclusions. Though a small sample size limited the power of our analyses, our findings suggest that a number of newly appeared dotHSs may be associated with SVD recurrence.

Hematoma Size in Deep Intracerebral Hemorrhage and its Correlation with Dot-Like Hemosiderin Spots on Gradient Echo T2*-Weighted MRI

Background and Purpose. Dot‐like low intensity spots (dot‐like hemosiderin spots: dotHSs) on gradient echo T2*‐weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large‐sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size.

Dot‐Like Hemosiderin Deposition on T2*‐Weighted MR Imaging Associated with Nonhypertensive Intracerebral Hemorrhage

Background and Purpose. Microangiopathy, a disorder often related to hypertension, is an important cause of deep intracerebral hematoma (ICH). The microangiopathy is associated with dot‐like low‐intensity spots (a dot‐like hemosiderin spot: dotHS) on gradient‐echo T2*‐weighted MR images that have been histologically diagnosed as old microbleeds. The locations of dotHS are consistent with deep ICH. Methods. To investigate how dotHS or other risk factors contribute to nonhypertensive deep ICH, the number and location of dotHSs, as well as other risk factors were examined in 213 deep ICH patients (106 males, 107 females, age: 37‐94 (65.8 ± 11.2) years) consecutively admitted to Hakodate Municipal Hospital. Patients were divided into two subgroups according to the presence or absence of hypertension. DotHSs were also divided into deep and subcortical dotHS and investigated independently. Odds ratios (ORs) were estimated from logistic regression analyses. Furthermore, nonhypertensive ICH patients were compared with nonhypertensive healthy volunteers matched for age and sex. Results. No risk factors were identified in the 31 nonhypertensive deep ICH patients that differed from those found in the 182 hypertensive deep ICH patients. Deep dotHS ≥ 1 (OR: 25.5; 95% CI: 4.76‐137; P= .0002), subcortical dotHS ≥ 1 (OR: 9.0; 95% CI: 1.79‐44.9; P= .046), diabetes mellitus (OR: 9.0; 95% CI: 1.53‐52.3; P= .015), and smoking (OR, 9.6; 95% CI; 1.8‐49.8, P= .007) significantly elevated the risk of nonhypertensive ICH, compared to the healthy volunteers. Conclusions. Our findings suggest that deep and subcortical dotHSs may be risk factors for the development of non‐hypertensive deep ICH.

Reversibility of White Matter Hyperintensity by Revascularization Surgery in Moyamoya Disease

BACKGROUND White matter lesions (WMLs) indicate progressive cerebral small vessel disease and are frequently observed in aging people and stroke patients. The purpose of this study was to evaluate WMLs and the influence of revascularization surgery for WMLs in patients with moyamoya disease. METHODS A total of 42 hemispheres in 21 patients with moyamoya disease were included in this analysis. WMLs were detected on fluid-attenuated inversion recovery (FLAIR) imaging in 24 hemispheres. The distribution pattern of WMLs was categorized. WMLs were measured by manually creating a region of interest, and the total WML volume in the hemisphere was estimated and compared with the control group. Clinical features of patients with WMLs and postoperative changes were analyzed. RESULTS The total WML volume in moyamoya disease was significantly higher than that of controls (P = .014). WMLs were observed in the internal watershed zone, especially in the watershed zone between the anterior cerebral artery and the middle cerebral artery. Patients with WMLs had significantly higher magnetic resonance angiography scores compared with controls (P = .015). A given patients total WML volume per hemisphere was significantly decreased after surgery (P = .001). CONCLUSIONS WMLs on FLAIR imaging increase in patients with moyamoya disease and are reversible by revascularization surgery. Improvement of cerebral blood flow is partly related to the decrease in WMLs. The present results provide insight into the potential role of revascularization surgery.

Radical Removal of Recurrent Malignant Meningeal Tumors of the Cavernous Sinus in Combination with High-Flow Bypass

BACKGROUND Meningiomas or solitary fibrous tumors arising from the cavernous sinus (CS) are usually treated with radiosurgery to control growth. Surgical removal of cavernous tumors is indicated only for tumors extending outside the CS. However, even after adequate treatment, the tumor may exhibit recurrence or malignant transformation. We report a treatment option for recurrent meningeal tumors of the CS. METHODS In 4 patients with CS tumors that exhibited regrowth after multiple operations and radiosurgery, radical removal in combination with high-flow bypass was performed, and a vascularized muscle flap was used for reconstruction. One patient had a radiation-induced atypical meningioma, 2 patients had transformed atypical meningiomas, and 1 patient had a frequently recurring solitary fibrous tumor. RESULTS No local recurrence was observed in any patients during a follow-up period of 13-41 months. In all patients, a Karnofsky performance scale score of >80 on admission was maintained at >70 at the final follow-up evaluation. CONCLUSIONS Radical removal in combination with high-flow bypass provides favorable results and maintains quality of life in patients with recurrent CS meningeal tumors.

Vascular remodeling of the circle of Willis in moyamoya disease

Abstract Objectives: A positive (outward) remodelling pattern in patients with typical atherosclerotic disease was recognised using magnetic resonance imaging (MRI). In this report, the outer diameter of the circle of Willis was evaluated in patients with moyamoya disease, and its remodelling pattern was verified. Methods: A total of 18 consecutive patients with moyamoya disease were included in this analysis. The diameter of the terminal portion of the internal carotid artery (ICA) (C1), proximal portion of the middle cerebral artery (MCA) (M1) and proximal portion of the anterior cerebral artery (A1) was evaluated using fast imaging employing steady-state acquisition (FIESTA) imaging. The outer diameter was estimated using these images, and compared with the control group, and the correlation with magnetic resonance angiography (MRA) scores was calculated for patients with moyamoya disease. Results: The mean diameter of the moyamoya patient group on FIESTA was significantly lower than that of the control group in the C1, M1 and A1 (P < 0.0001). The M1 diameter on the FIESTA image showed a strong correlation with the moyamoya disease MRA score (y = (0.53x+2.31; R = 0.72), whereas the C1 diameter on the FIESTA image showed only a weak correlation (y = (0.16x+2.47; R = 0.21). Conclusion: We found that the outer diameter of all the vessels around the C1 was generally reduced in patients with moyamoya disease. Diameter of the MCA especially decreases as the disease progresses, similar to the negative (constrictive) remodelling pattern.