Yoshifumi Horita

Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat

Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Several hypotheses to account for these therapeutic effects have been suggested, and current thinking is that neuroprotection rather than neurogenesis is responsible. To enhance the therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial cell line‐derived neurotrophic factor (GDNF) gene using a fiber‐mutant F/RGD adenovirus vector and investigated whether GDNF gene‐modified hMSCs (GDNF‐hMSCs) could contribute to functional recovery in a rat permanent middle cerebral artery occlusion (MCAO) model. We induced MCAO by using intraluminal vascular occlusion, and GDNF‐hMSCs were intravenously infused into the rats 3 hr later. MRI and behavioral analyses revealed that rats receiving GDNF‐hMSCs or hMSCs exhibited increased recovery from ischemia compared with the control group, but the effect was greater in the GDNF‐hMSC group. Thus, these results suggest that intravenous administration of hMSCs transfected with the GDNF gene using a fiber‐mutant adenovirus vector may be useful in the cerebral ischemia and may represent a new strategy for the treatment of stroke.

Dotlike Hemosiderin Spots Are Associated With Past Hemorrhagic Strokes in Patients With Lacunar Infarcts

Background and Purpose. Dotlike hemosiderin spots ongradient‐echo T2*‐weighted magnetic resonance imaging of the brain have been histologically diagnosed as old microbleeds associated with small vessel disease (SVD). The authors hypothesize that the presence of many dotHSs may be correlated with the fragility of small vessels and the recurrence of SVD, including lacunar infarction and deep intracerebral hemorrhage (ICH). Methods. To investigate how dotHSs are related to past history of SVD, the number of subcortical or deep dotHSs was investigated in 146 patients with lacunar infarctions (95men, 51 women, age 38 to 90 [66.6 ± 9.4] years). They were divided into 2 subgroups according to history of deep ICHs or lacunar infarctions. The odds ratio (OR) for past history was estimated from logistic regression analyses with the number of subcortical or deep dotHSs as well as other factors. Results. Of 146 patients with lacunar infarctions, 11 had past symptomatic ICHs and 19 had past symptomatic lacunar infarctions. An elevated rate of history of ICH was found for lacunar infarction patients with many deep dotHSs (≥3; OR, 9.1; 95% confidence interval, 1.6–51, P= .015). However, history of lacunar infarction was not significantly associated with the number of subcortical or deep dotHSs. Conclusions. Our findings suggest that many deep dotHSs on T2*‐weighted magnetic resonance imaging may be correlated with deep ICH—lacunar infarction type of SVD recurrence but not lacunar infarction—lacunar infarction type.

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.

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.

Cerebral aneurysms associated with segmental dilative arteriopathy of the circle of Willis.

Background: Dilative arteriopathy is a form of dolichoectasia. It is sometimes observed in the posterior circulation, and it may be associated with various type of stroke. Herein, we report two unusual cases of saccular aneurysms associated with a segmental dilative arteriopathy located in the anterior circulation. Case Descriptions: The first case is a 39-year-old woman with irregular tortuosity and coiling of the left internal cerebral artery along with saccular aneurysms in this artery. The second case is a 45-year-old woman presenting with a ruptured saccular aneurysm in the coiling of the anterior cerebral artery. In both cases, the aneurysm was clipped successfully, and the patients recovered uneventfully with no neurological deficits. Conclusion: Dilative arteriopathy of the circle of Willis is an unusual anomaly and is characterized by tortuous and elongated arteries, which are sometimes observed in patients with a congenital anomaly. This report describes two cases of saccular aneurysm associated with dilative arteriopathy of the circle of Willis with no medical history, which to the best of our knowledge has not previously been described.

Exophytic glioblastoma multiforme originating from the medulla oblongata

Glioblastoma multiforme (GBM) is most frequently located in the supratentorial region of the brain. In this paper, we report the case of a 25-year-old man who presented with a heterogeneous tumor with exophytic features and located in the caudal fourth ventricle. The tumor was subtotally resected and the patient underwent radiotherapy at a dosage of 50 Gy and concurrent chemotherapy with temozolomide. Histopathological examination revealed the typical features of conventional GBM. The patient independently performed the activities of daily living for 11 months. However, after identifying a recurrence of the tumor in the dorsal medulla oblongata, the patient suddenly died at home 12 months after diagnosis, likely due to respiratory arrest. To the best of our knowledge, it is extremely rare for GBM to occur in the medulla oblongata and only eight cases have been described in detail. Patients with intrinsic GBM of the medulla oblongata died within three months. In contrast, patients with exophytic GBMs of the medulla oblongata survived for more than one year. Patients with GBMs that occurred in the medulla oblongata and exhibited exophytic growth patterns had a better prognosis than patients with intrinsic GBMs because the tumors could be more radically and safely resected. Correspondence to: Masahiko Wanibuchi, M.D, Department of Neurosurgery, Sapporo Medical University, Minami 1 Jo Nishi 16 Chome, Chuo-ku, Sapporo, Hokkaido 060-8543 (Japan), Tel: +81-11-611-2111, Fax: +81-11-614-1662; E-mail: wanibuti@sapmed.ac.jp