Katsuya Komatsu

Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia

Intravenous transplantation of mesenchymal stem cells (MSCs) prepared from bone marrow ameliorates functional deficits in rat cerebral infarction models. Although several hypotheses to account for these therapeutic effects have been suggested, angiogenesis is thought to be largely responsible. MSCs were intravenously infused into rats in the relatively later time points after permanent middle cerebral artery occlusion (MCAO) to determine if they could contribute to neovascularization and functional recovery. Although MRI analysis revealed that only rats receiving MSCs 7days after MCAO exhibited decreased ischemic lesion volume than the control group, all MSCs treated rats receiving MSCs up to 1month after MCAO had greater angiogenesis near the border of the ischemic lesions and showed greater functional recovery in the treadmill stress test than did control rats. Thus, these results suggest that the time window of MSC therapy is at least over 1 month after cerebral infarction in the rat permanent MCAO model, and systemic delivery of MSCs in the later phase after cerebral ischemia may have beneficial effect through an angiogenic mechanism.

Nascent deep microbleeds and stroke recurrences.

BACKGROUND Cerebral microbleeds (MBs) on gradient echo T2*-weighted magnetic resonance imaging (MRI) scans are associated with the severity of cerebral microangiopathies. This study investigated the contributions of nascent deep MBs to stroke recurrence. METHODS We prospectively analyzed nascent deep MBs in patients admitted to our hospital who were treated for index strokes between April 2004 and November 2009. The number of nascent deep MBs was counted on T2*-weighted MRI scans around 1 year after the index strokes, and compared to previous MRIs on admission. Stroke recurrence-free rate curves were generated using the Kaplan-Meier method using the log-rank test. The odds ratio for nascent deep MBs was derived using a multivariate logistic regression model that was based on recurrent strokes and other risk factors. RESULTS We evaluated the MRIs (interval between MRIs 14.6 ± 5.9 months) of 508 patients (207 women; 68.9 ± 11.5 years), with a follow-up period of 44.1 ± 15.4 months. Repeated T2*-weighted MRI scans revealed 256 nascent deep MBs in 116 of 508 patients. The incidence of deep intracerebral hemorrhage was significantly greater in patients with nascent deep MBs than those without (2.0% vs 0.4% per year, respectively; P < .0001). Multivariate analyses revealed that the rate of nascent deep MBs was significantly elevated in patients whose stroke recurrences took the form of deep intracerebral hemorrhages (odds ratio 5.41; P = .007), when adjusted for hypertension, preexisting MBs, and other risk factors. CONCLUSIONS Our findings suggested that nascent deep MBs might be associated with stroke recurrence, in particular with deep intracerebral hemorrhage.

Antithrombotic Drug Uses and Deep Intracerebral Hemorrhages in Stroke Patients With Deep Cerebral Microbleeds

BACKGROUND It has been suggested that antiplatelet or anticoagulant drugs elevate the rate of intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (MBs). To investigate the mechanism by which antiplatelet drugs or warfarin may contribute to deep ICH occurrences in patients with deep MBs, we prospectively analyzed deep ICH occurrences in 807 consecutive patients (351 females and 456 males; mean age ± standard deviation 69.8 ± 12.0 years) who were admitted to our hospital with strokes. METHODS Occurrence-free rate curves were generated using the Kaplan-Meier method; deep ICH occurrence-free rates were compared using the log-rank test. The follow-up period was 0.5 to 71 months (mean ± standard deviation 31.6 ± 22.2 months). RESULTS In patients with deep MBs, the rates (1.0%/year; 6 ICHs in 180 patients) of deep ICH occurrence associated with antiplatelet drugs were not significantly greater than that without the drugs (1.0%/year; 6 ICHs in 167 patients; P = .977). The incidence of deep ICHs associated with warfarin use was not significantly greater than that without warfarin use. CONCLUSIONS Multivariate analysis revealed that the use of antiplatelet drugs or warfarin did not significantly influence the occurrence of deep ICH in patients with deep MBs. Antiplatelet drugs or warfarin did not significantly elevate the rate of deep ICHs in stroke patients with pre-existing deep MBs.

Nascent Lobar Microbleeds and Stroke Recurrences

BACKGROUND Lobar microbleeds (MBs) are occasionally visible on gradient-echo T2*-weighted (T2*-w) magnetic resonance imagings (MRIs) in patients with deep intracerebral hemorrhages (ICHs). This study investigated the contribution of nascent lobar MBs to occurrences of deep ICHs. METHODS We prospectively analyzed nascent lobar MBs in patients admitted to our hospital who were treated with index strokes between April 2004 and November 2009. Numbers of nascent lobar MBs were counted on T2*-w MRI scans around 1 year after index strokes and compared with previous MRIs on admission. Deep ICH occurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. The odds ratio (OR) for deep ICH occurrence was derived from a multivariate logistic regression model using nascent lobar MBs and risk factors. RESULTS We investigated MRIs (interscan interval: 14.6 ± 5.9 months) of 508 patients (207 women, 68.9 ± 11.5 years), with a follow-up period of 44.1 ± 15.4 months. Repeated T2*-w MRIs demonstrated 157 nascent lobar MBs in 62 of 508 patients. The occurrence rate of deep ICHs (1.9% per year) was significantly higher in patients with nascent lobar MBs than in those without (.5% per year, P = .012). Multivariate analyses revealed that the rate of nascent lobar MBs was significantly elevated in patients with deep ICH-type stroke recurrences (OR: 3.85, P = .020), adjusted by the presence of hypertension, diabetes mellitus, use of antithrombotic drugs, severity of white matter lesions, age, and gender. CONCLUSIONS Though a cohort study limited the power of analyses, our findings suggested that lobar MBs might be associated with 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.

Rigid endoscopic resection of deep-seated or intraventricular brain tumors

Abstract Rigid endoscopic resection using a thick sheath (ViewSite) may be a viable method for the resection or biopsy of selected deep-seated brain tumors, such as thalamic gliomas and malignant lymphomas. Neuroendoscopic biopsy is one technique used for the histological verification of suspected brain tumors. There are a number of advantages to using this technique. For example, under direct vision, it is possible to carefully observe the tumor surface and avoid vessels during tumor resections. It is also possible to collect enough specimens for a pathological diagnosis. Eighteen consecutive patients safely underwent rigid endoscopic resection or biopsy using a thick sheath (ViewSite). The two-handed endoscopic technique that utilized a mounted rigid endoscope proved very useful and safe, since it enabled easy stanching of hemorrhages. The aim of this study was to demonstrate how to use a thick sheath for deep-seated or intraventricular tumors. The rigid endoscopic approach with a thick sheath provides an alternative medial approach with improved visualization and a wider working space.

Assessment of Hemodynamic Compromise Using Computed Tomography Perfusion in Combination with 123I-IMP Single-Photon Emission Computed Tomography without Acetazolamide Challenge Test

OBJECTIVES The acetazolamide challenge test in conjunction with 123I-IMP single-photon emission computed tomography (SPECT) is a known method of assessing cerebrovascular reserve capacity. In this study, we investigated whether CT perfusion in combination with resting state 123I-IMP SPECT could be used instead of the acetazolamide challenge test to evaluate hemodynamic compromise in patients with atherosclerotic occlusive disease. METHODS Twenty consecutive patients with unilateral internal carotid artery or middle cerebral artery steno-occlusive disease were enrolled. 123I-IMP SPECT was performed with and without the acetazolamide challenge test, and with CT perfusion. Cerebral blood flow (CBF), cerebral blood volume, and mean transit time (MTT) obtained by CT perfusion were compared with CBF and cerebrovascular reactivity (CVR) obtained by 123I-IMP SPECT. RESULTS The asymmetry ratio of MTT as measured by CT perfusion showed a strong correlation with the CVR to acetazolamide as measured by 123I-IMP SPECT (ρ = -.780, P <.001). Based on the CBF obtained through 123I-IMP SPECT and the MTT obtained through CT perfusion, hemodynamic compromise was detected with high sensitivity (1.000) and specificity (.929), and a cutoff value of 30% was found to be suitable for the asymmetry ratio of MTT. MTT prolongation was significantly improved after revascularization surgery in hemodynamic compromise (P = .028). CONCLUSION MTT as measured by CT perfusion in combination with CBF as measured by resting state 123I-IMP SPECT may be useful for evaluating hemodynamic compromise as an alternative to the acetazolamide challenge test.

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.

Cortical and subcortical vascular hypointensity on T2* weighted imaging in moyamoya disease

Objectives: Decreased cortical and subcortical vascular signals in gradient echo T2* weighted imaging have been reported in acute stroke due to major artery occlusion. The purpose of this study was to evaluate this cortical and subcortical vascular hypointensity (CSVH) in patients with moyamoya disease. Methods: Subjects were 20 consecutive patients with moyamoya disease. The numbers of CSVH in each hemisphere were counted and the numbers were compared between patients with moyamoya disease and controls. The distribution of CSVH, clinical features of cases exhibiting large numbers of CSVH and post-operative changes were analysed. Results: Patients with moyamoya disease had significantly more CSVH in the middle cerebral artery territory (p < 0.001) and the anterior cerebral artery territory (p < 0.001) compared with controls. The number of CSVH was correlated significantly with regional cerebral blood flow, as shown through simple regression analysis (R = 0.461, p = 0.006), and the numbers of CSVH were significantly higher in patients with higher magnetic resonance angiography scores (p = 0.017). A given patient’s total number of CSVH per hemisphere was significantly decreased after surgery (p = 0.018). Conclusion: CSVH on T2* WI may be a useful tool for diagnosing and evaluating the extent of moyamoya disease. Our small series study shows that revascularization surgery can decrease the number of CSVH.