Mitsunori Matsumae

Computer-assisted Interactive Three-dimensional Planning for Neurosurgical Procedures

We have used three-dimensional reconstruction magnetic resonance imaging techniques to understand the anatomic complexity of operative brain lesions and to improve preoperative surgical planning. We report our experience with 14 cases, including intra- and extra-axial tumors and a vascular malformation. In each case, preoperative planning was performed using magnetic resonance imaging-based three-dimensional renderings of surgically critical structures, such as eloquent cortices, gray matter nuclei, white matter tracts, and blood vessels. Simulations, using the interactive manipulation of three-dimensional data, provided an efficient and comprehensive way to appreciate the anatomic relationships. Interactive three-dimensional computer-assisted preoperative simulations provided otherwise inaccessible information that was useful for the surgical removal of brain lesions.

Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway

Background and Purpose— Neuroprotective effects of electric stimulation have been recently shown in ischemic stroke, but the underlying mechanisms remain poorly understood. Methods— Adult Wistar rats weighing 200 to 250 g received occlusion of the right middle cerebral artery for 90 minutes. At 1 hour after reperfusion, electrodes were implanted to rats on the right frontal epidural space. Electric stimulation, at preset current (0 to 200 &mgr;A) and frequency (0 to 50 Hz), was performed for 1 week. Stroke animals were subjected to behavioral tests at 3 days and 1 week postmiddle cerebral artery and then immediately euthanized for protein and immunohistochemical assays. After demonstration of behavioral and histological benefits, subsequent experiments pursued the mechanistic hypothesis that electric stimulation exerted antiapoptotic effects through the phosphoinositide 3-kinase-dependent pathway; thus, cortical stimulation was performed in the presence or absence of specific inhibitors of phosphoinositide 3-kinase (LY294002) in stroke rats. Results— Cortical stimulation abrogated the ischemia-associated increase in apoptotic cells in the injured cortex by activating antiapoptotic cascades, which was reversed by the phosphoinositide 3-kinase inhibitor LY294002 as reflected behaviorally and immunohistochemically. Furthermore, brain levels of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor) were upregulated, which coincided with enhanced angiogenesis and suppressed proliferation of inflammatory cells in the ischemic cortex. Conclusions— These results suggest that electric stimulation prevents apoptosis through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain might have been rendered as a nurturing microenvironment characterized by robust angiogenesis and diminished microglial/astrocytic proliferation, resulting in the reduction of infarct volumes and behavioral recovery. Electric stimulation is a novel and potent therapeutic tool for cerebral ischemia.

Impact of the Combination of 5-Aminolevulinic Acid-Induced Fluorescence with Intraoperative Magnetic Resonance Imaging-Guided Surgery for Glioma

OBJECTIVE To compare intraoperative magnetic resonance imaging (MRI)-guided resection with resection guided by 5-aminolevulinic acid (5-ALA)-induced fluorescence in patients with gliomas and to evaluate the impact of intraoperative MRI in glioma surgery. METHODS From January 2005 to February 2009, 33 patients with gliomas (6 with World Health Organization [WHO] grade II, 7 with WHO grade III, 20 with WHO grade IV) who underwent craniotomy with neuronavigation and received 5-ALA by the same neurosurgeon were investigated retrospectively. In 19 patients, operations were performed using a combination of 5-ALA with intraoperative 1.5-T MRI. All patients were subjected to postoperative 1.5-T MRI to confirm the extent of resection. RESULTS Of 33 patients with gliomas, 21 (4 with WHO grade III and 17 with WHO grade IV) were 5-ALA-induced fluorescence-positive (5-ALA (+)). Surgery with intraoperative MRI was performed in 10 of the 21 patients, and the average resection rate was 92.6%. The average resection rate of patients who underwent surgery without intraoperative MRI was 91.8%. 5-ALA-induced fluorescence was not detected in 12 patients (6 with WHO grade II, 3 with WHO grade III, and 3 with WHO grade IV) with gliomas. Surgery with intraoperative MRI was performed in 9 of 12 patients, and the average resection rate was 89.2%. The average resection rate of patients who underwent surgery without intraoperative MRI was 68.7%. Intraoperative MRI-guided tumor resection resulted in a better resection rate in patients with 5-ALA-induced fluorescence-negative (5-ALA (-)) gliomas than in patients with 5-ALA (+) gliomas (20.5% vs 0.8%). CONCLUSIONS Intraoperative MRI-guided resection is a powerful tool to treat 5-ALA (-) gliomas (mostly low grade), and 5-ALA is useful for high-grade gliomas. The combination of intraoperative MRI and 5-ALA has a synergistic effect in glioma surgery. Additionally, precise tumor grading in preoperative imaging studies can be difficult. Surgery for gliomas should be performed using both 5-ALA-induced fluorescence and intraoperative MRI-guided resection.

Neuroprotective effects of liraglutide for stroke model of rats

The number of diabetes mellitus (DM) patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1) are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson’s test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF). The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

Delayed accumulation of activated macrophages and inhibition of remyelination after spinal cord injury in an adult rodent model

OBJECT Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin debris. The object of this study was to investigate the mechanisms underlying the failure of significant remyelination after SCI. METHODS The authors investigated macrophage recruitment and related factors in rats by comparing a contusion model (representing contusive SCI with residual myelin debris and failure of remyelination) with a model consisting of chemical demyelination by lysophosphatidylcholine (representing multiple sclerosis with early clearance of myelin debris and remyelination). The origin of infiltrating macrophages was investigated using mice transplanted with bone marrow cells from green fluorescent protein-transfected mice. The changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining at 2, 4, and 7 days postinjury. To investigate various factors that might be involved, the authors also investigated gene expression of macrophage chemotactic factors and adhesion factors. RESULTS Activated macrophages coexpressing green fluorescent protein constituted the major cell population in the lesions, indicating that the macrophages in both models were mainly derived from the bone marrow, and that very few were derived from the intrinsic microglia. Immunostaining showed that in the contusion model, myelin debris persisted for a long period, and the infiltration of macrophages was significantly delayed. Among the chemotactic factors, the levels of monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor were lower in the contusion model at 2 and 4 days postinjury. CONCLUSIONS The results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination.

Spontaneous cervical epidural hematoma.

The authors report a case of spontaneous cervical epidural hematoma in a 13-year-old boy who exhibited hematoma recurrence 3 years after the first incidence. A review of the literature indicates very few reports of the recurrence of spinal epidural hematoma.

Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time

Background and Purpose— Hematoma expansion after acute intracerebral hemorrhage is common and is associated with early deterioration and poor clinical outcome. The computed tomographic angiography (CTA) spot sign is a promising predictor of expansion; however, frequency and predictive values are variable across studies, possibly because of differences in onset-to-CTA time. We performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and frequency and predictive ability of the spot sign. Methods— We completed a systematic review for studies of CTA spot sign and hematoma expansion. We subsequently pooled patient-level data on the frequency and predictive values for significant hematoma expansion according to 5 predefined categorized onset-to-CTA times. We calculated spot-sign frequency both as raw and frequency-adjusted rates. Results— Among 2051 studies identified, 12 met our inclusion criteria. Baseline hematoma volume, spot-sign status, and time-to-CTA were available for 1176 patients, and 1039 patients had follow-up computed tomographies for hematoma expansion analysis. The overall spot sign frequency was 26%, decreasing from 39% within 2 hours of onset to 13% beyond 8 hours (P<0.001). There was a significant decrease in hematoma expansion in spot-positive patients as onset-to-CTA time increased (P=0.004), with positive predictive values decreasing from 53% to 33%. Conclusions— The frequency of the CTA spot sign is inversely related to intracerebral hemorrhage onset-to-CTA time. Furthermore, the positive predictive value of the spot sign for significant hematoma expansion decreases as time-to-CTA increases. Our results offer more precise risk stratification for patients with acute intracerebral hemorrhage and will help refine clinical prediction rules for intracerebral hemorrhage expansion.

Quantification of cerebrospinal fluid shunt flow rates

Shunt placement diverting cerebrospinal fluid (CSF) has been the treatment of choice for hydrocephalus for the past several decades. However, the procedure often requires revisions owing to excessive drainage, low CSF flow rates, or infections within the system. With regard to valve pressure, selection of an appropriate valve for a specific patient prior to surgery is not always a simple task. Further, an optimal valve selected at the time of implantation may no longer be appropriate given changing pathophysiological conditions as time passes. It is thus desirable to provide a single valve in which the pressure may be modified when necessary without revision. A programmable pressure valve (designed by Sophysa of France) comes in one model which accommodates different pressure settings obviating revision when pressure changes are needed. Pressure changes can be achieved externally by means of a special magnet which allows precise adjustments in valve pressure to be made through the scalp. The authors introduce the mechanism and describe the cases treated using this valve.

Efficacy of the coadministration of granulocyte colony-stimulating factor and stem cell factor in the activation of intrinsic cells after spinal cord injury in mice

OBJECT Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that induces undifferentiated stem cells from the bone marrow (BM) into the peripheral blood. Stem cell factor (SCF) is also a hematopoietic cytokine that stimulates the differentiation and proliferation of neural stem cells and has neuroprotective effects. In cerebrally infarcted mice, the combination of G-CSF and SCF promotes the differentiation of BM-derived cells into neural cells, stimulates the proliferation of intrinsic neural stem cells, and improves motor function. The object of this study was to investigate the effects of these cytokines on BM stem cells, intrinsic cells, and motor function recovery in spinal cord-injured mice. METHODS For marking BM-derived cells, the authors induced contusive spinal cord injury in mice transplanted with BM cells from green fluorescent protein (GFP)-transgenic mice after whole-body irradiation. These mice were treated with G-CSF and SCF in the subacute injury phase. Bromodeoxyuridine (BrdU) was injected into these mice to label proliferating cells. The cell numbers and phenotype of the BM-derived cells were evaluated, and the change in intrinsic cells (proliferation, accumulation, and differentiation) was noted using immunohistological analysis at 4 weeks postinjury (wpi). A behavior analysis was conducted until 12 wpi using the Basso, Beattie, Bresnahan locomotor rating scale. RESULTS In the SCF + G-CSF group, improvement in hindlimb motor function was significantly greater than in the SCF group, G-CSF group, and sham-treatment (vehicle) group after 8 wpi. At 4 wpi, the number of GFP+ BM-derived cells induced in the lesion did not significantly differ between groups. At 4 wpi, the authors evaluated perilesional GFP− intrinsic spinal cord cells. The number of GFP− and F4/80+ cells was significantly greater in the SCF + G-CSF group than in the other 3 groups. As compared with the sham group, the number of NG2+/BrdU+ cells was significantly increased in the SCF + G-CSF group. CONCLUSIONS In this study, the combined administration of SCF and G-CSF in traumatic spinal cord injury not only improved motor function, but also induced the accumulation of intrinsic microglia and the active proliferation of intrinsic oligodendrocyte precursor cells.

Sequential changes in MR water proton relaxation time detect the process of rat brain myelination during maturation.

For better understanding of the behavior of water molecules in the animal brain, changes in magnetic resonance water proton relaxation processes were studied in the rat during maturation. Midbrains of male Wistar rats were removed at various time points ranging from 2 to 70 days after birth. Changes in relaxation time (water proton longitudinal relaxation time by the inversion recovery, and water proton transverse relaxation time by the spin echo and the Carr-Purcell-Meiboom-Gill pulse sequence (CPMG)) and water content were then determined for various stages of brain development. During maturation both water proton longitudinal relaxation time and water proton transverse relaxation time values decreased and this finding paralleled the decline in water content. Using the CPMG pulse sequence, the transverse relaxation time values were observed to separate into two components after 21 days. Morphologically, the most prominent change at the matured stage of midbrain development in the rat is myelination. Water proton relaxation time, which can be estimated using the CPMG pulse sequence, showed a close correlation with myelination in the central nervous system.