Satoshi Iihoshi

A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats.

The primary objective of this study was to test the hypothesis that intravenous administration of autologous bone marrow cells could improve functional recovery after middle cerebral artery occlusion (MCAO) for 45 min in the rat and to determine specific time windows for efficacy. Mononuclear cells from autologous bone marrow were transfected with the LacZ reporter gene, and injected intravenously into rats at 3-72 h after induction of MCAO. Histological analysis of the ischemic lesion at 14 days after transplantation revealed reduced ischemic lesion volume. Lesion volume was 250+/-45 mm(3) (n=6) after MCAO without cell transplantation. Lesions were minimally detected by absence of 2,3,5-triphenyltetrazolium chloride (TTC) staining when bone marrow cells were infused 3 h after lesion induction. Lesions were clearly detected beginning with the 6-h postlesion group and became progressively larger at 12, 24 and 72 h (80+/-25, 140+/-18, and 180+/-22 mm(3), respectively; n=6 for each group). Transplanted LacZ(+) bone marrow cells accumulated extensively in and around the ischemic lesions, and immunohistochemistry suggests some neuronal and glial lineage differentiation. Behavioral testing (Morris water maze and Treadmill stress test) indicated greater functional recovery in the treated group. These findings suggest that early intervention with intravenous administration of autologous mononuclear cells from bone marrow can reduce lesion size in the MCAO model in the rat, and improve functional outcome.

Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat

Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy in animal models of cerebral ischemia and spinal cord injury. We intravenously delivered human mesenchymal stem cells (SH2+, SH3+, CD34-, and CD45-) immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP or LacZ into rats 12 h after induction of transient middle cerebral artery occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were delivered at 12 h after lesion induction. Lesion size was assessed using MR imaging and spectroscopy, and histological methods. Functional outcome was assessed using the Morris water maze and a treadmill test. Intravenous delivery of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and functional improvement was positively correlated with the number of cells injected. The reduction of lesion size could be assessed in vivo with MRI and MRS and was correlated with subsequent histological examination of the brain. This work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction volume and improve functional outcome.

Intraoperative Indocyanine Green Videoangiography for Spinal Vascular Lesions: Case Report

BACKGROUND AND IMPORTANCE: In surgery of spinal vascular lesions such as spinal arteriovenous fistula or vascular tumors, assessment of feeding arteries and draining veins is important. Intraoperative digital subtraction angiography is useful but is invasive and sometimes technically demanding. Near-infrared indocyanine green (ICG) videoangiography is less invasive and has been reported as an intraoperative diagnosis of arterial patency during clipping surgery of cerebral aneurysms or bypass surgeries. We present our experience with intraoperative ICG videoangiography in 3 cases of spinal vascular lesions. CLINICAL PRESENTATION: Two patients had spinal arteriovenous fistula (perimedullary, n = 1; dural, n = 1), and 1 patient had spinal cord hemangioblastoma at the thoracic or thoracolumbar level. The surgical microscope was an OPMI Pentero (Carl Zeiss, Oberkochen, Germany). After laminectomy and opening of the dura, ICG (5 mg) was injected intravenously. The ICG angiography clearly demonstrated feeding and draining vessels. The ICG findings greatly helped successful interruption of arteriovenous fistula and total removal of the tumor. CONCLUSION: Intraoperative ICG videoangiography for spinal vascular lesions was useful by providing information on vascular dynamics directly. However, the diagnostic area is limited to the field of the surgical microscope. Although intraoperative digital subtraction angiography is still needed in cases of complex spinal vascular lesions, ICG videoangiography will be an important diagnostic modality in the field of spinal vascular surgeries.

Assessment of Moyamoya Disease Using Multidetector Row Computed Tomography

The recent introduction of multidetector row computed tomography (MDCT) scanners has enabled high-resolution 3-dimensional reconstruction. The purpose of this study was to establish a method to evaluate moyamoya disease using computed tomography angiography (CTA), specifically MDCT. Twenty-four patients (48 sides total) with moyamoya disease diagnosed by magnetic resonance angiography (MRA) were evaluated by means of CTA using MDCT by 3 independent observers, and the resulting 144 sides were analyzed. CTA and MRA were compared in terms of the steno-occlusive changes exhibited in each vessel. CTA and MRA scores were assigned on the basis of the severity of occlusive changes in the internal carotid artery, middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. CTA scores were significantly correlated with MRA scores (P < .0001), and the 2 scores were in complete agreement in 57 sides (39.6%). The mean CTA score was significantly lower than the mean MRA score (P < .0001). Compared with CTA, MRA overestimated occlusion in 115 of the 576 vessels assessed. The mean MRA score was significantly higher in the overestimation group than in the good correlation group (P < .0001). CTA had a significantly higher rate of detection of moyamoya-affected vessels (P = .0001). Our data indicate that CTA using MDCT is a more reliable technique than MRA for diagnosing moyamoya disease. The ability to perform CTA quickly is a significant benefit for patients with moyamoya disease, particularly in pediatric and emergency cases.

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.

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.

Therapeutic temperature modulation in severe or moderate traumatic brain injury: a propensity score analysis of data from the Nationwide Japan Neurotrauma Data Bank

OBJECTIVE In patients with severe traumatic brain injury (TBI), a randomized controlled trial revealed that outcomes did not significantly improve after therapeutic hypothermia (TH) or normothermia (TN). However, avoiding pyrexia, which is often associated with intracranial disorders, might improve clinical outcomes. The objective of this study was to compare neurological outcomes among patients with moderate and severe TBI after therapeutic temperature modulation (TTM) in the absence of other interventions. METHODS Data from 1091 patients were obtained from the Japan Neurotrauma Data Bank Project 2009, a cohort observational study. Patients with cardiac arrest, those with a Glasgow Coma Scale score of 3 and dilated fixed pupils, and those whose cause of death was injury to another area of the body were excluded, leaving 687 patients aged 16 years or older in this study. The patients were divided into 2 groups: the TTM group underwent TN (213 patients) or TH (82 patients), and the control group (392 patients) did not receive TTM. The primary end point for this study was the rate of poor outcome at hospital discharge, and the secondary end point was in-hospital death. Out of the 208 total items in the database, 29 variables that could potentially affect outcome were matched using the propensity score (PS) method in order to reduce selection bias and balance the baseline characteristics. RESULTS From each group, 141 patients were extracted using the PS-matching process. Among the patients in the TTM group, 29 had undergone TH and 112 had undergone TN. In a log-rank test using Kaplan-Meier survival curves, no significant differences in patient outcome or death were observed between the 2 groups (poor outcome, p = 0.83; death, p = 0.18). A Cox proportional-hazards regression analysis established the HR for poor outcome and mortality at 1.03 (95% CI 0.78-1.36, p = 0.83) and 1.34 (95% CI 0.87-2.07, p = 0.18), respectively. CONCLUSIONS There was no clear improvement in neurological outcomes after TTM in patients with moderate or severe TBI. To elucidate the role of TTM in patients with these injuries, a prospective study is needed with long-term follow-up using specific target temperatures.

Subarachnoid Hemorrhage after Resuscitation from Out-of-hospital Cardiac Arrest

BACKGROUND This study was undertaken to retrospectively investigate clinical features of subarachnoid hemorrhage (SAH) with cardiopulmonary arrest in patients achieving return of spontaneous circulation (ROSC) in order to explore the possibility of long-term survival. METHODS Of 143 SAH patients with cardiopulmonary arrest in our hospital between April 2004 and June 2012, data on 59 (41%) patients who attained ROSC were analyzed to determine the predictive factors for neurologic recovery and outcome. Recovery of brainstem reflexes and improvement of Glasgow Coma Scale (GCS) motor score were noted (postresuscitation neurologic restorative assessment, grade I) in 5, and 2 of these patients survived. RESULTS By-grade analysis of patient background characteristics revealed a significantly shorter duration of cardiac arrest (P = .001) and a significantly smaller adrenaline dose (P = .011) for grade I patients. A logistic analysis of 1-week survival data revealed significant differences in duration of cardiac arrest (P = .022) and adrenaline dose (P = .019), with odds ratios of 0.89 and 0.25, respectively. Cox regression analysis of mortality data revealed significant differences in the duration of cardiac arrest (P = .012), adrenaline dose (P < .0001), and location of ROSC (P = .016), with hazard ratios of 1.03, 1.43, and 1.98, respectively. CONCLUSIONS Cardiac arrest caused by SAH is a disease state with a grave prognosis, but there is the possibility of a good survival outcome when the administration of a small dose of adrenaline results in the rapid recovery of brainstem reflexes.

Quantitative Assessment of Flow Reduction After Feeder Embolization in Meningioma by Using Pseudocontinuous Arterial Spin Labeling.

BACKGROUND Meningioma is a hypervascular tumor of the central nervous system. Angiographic disappearance of tumor blush after preoperative feeder embolization allows qualitative, but not quantitative, assessment of flow reduction. Pseudocontinuous arterial spin labeling (PCASL), which has evolved from magnetic resonance imaging techniques, allows noninvasive measurement of cerebral blood flow (CBF) using water protons in the arterial blood flow. OBJECTIVE We applied PCASL for assessment of blood flow in meningioma and its reduction on preoperative embolization. METHODS Forty-one consecutive patients (11 males, 30 females) with histologically proven meningioma were evaluated by PCASL. Quantitative assessment by an absolute value of tumor blood flow (TBF) and a relative value of tumor vascular index (tVI; calculated as TBF divided by CBF) were calculated. In 8 cases, in which preoperative embolization was achieved, flow reduction rate was evaluated. RESULTS TBF of meningiomas, 155.8 mL/100 g·min(-1) on average, was 2.6 times higher than CBF, 59.9 mL/100 g·min(-1) (P < 0.001). Patients who underwent feeder embolization showed statistically greater flow reduction rate, which was calculated as 42.7% (P < 0.05). Mean tVI before embolization was 4.1, which was reduced to 2.1 after embolization. CONCLUSION PCASL could yield quantitative assessment of blood flow in meningioma including flow reduction rate in cases of feeder embolization.

Overview of Image Diagnosis of Moyamoya Disease

As mentioned in the Introduction, when the original concept of moyamoya disease is reviewed, digital subtraction angiography (DSA) is still the most reliable diagnostic modality. However, as mentioned in the following sections, as far as the depiction of the steno-occlusive change of the Willis ring is concerned, other modalities such as magnetic resonance angiography (MRA) and 3-dimensional computed tomography angiography (3D-CTA) with best quality is quite compatible with DSA. However, the depiction of the moyamoya vessels and the collateral circulation is not always clear in MRA and magnetic resonance imaging (MRI). In addition, 3D-CTA essen tially depicts the morphological aspect of vasculature that is not necessarily identical to the true circulation of the blood flow. In addition, the collateral circulation such as (1) basal moyamoya, and (2) transdural anastomosis of the meningeal artery including the vault moyamoya and ethmoidal moyamoya is not well demonstrated in other modalities (Figs.1 and 2).