Yoshiaki Kumon

Evaluation of risk of hemorrhagic transformation in local intra-arterial thrombolysis in acute ischemic stroke by initial SPECT.

BACKGROUND AND PURPOSE Thrombolytic therapy was carried out on patients with acute ischemic stroke, and the risk of hemorrhagic transformation was evaluated from the residual cerebral blood flow (CBF) by pretherapeutic single-photon emission-computed tomography (SPECT). METHODS Local intra-arterial thrombolytic therapy was carried out using urokinase or recombinant tissue plasminogen activator (rt-PA) within 6 hours from the onset in 34 patients in whom no hypodensity areas were observed on the initial computed tomography examination. In the 20 patients with carotid territory occlusion who underwent 99mTc-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT, the residual CBF of the ischemic region was evaluated semiquantitatively by calculating two parameters: the ischemic regional activity to cerebellar activity ratio (R/CE ratio) and asymmetry index (AI). RESULTS The occluded vessels could be recanalized in 22 (92%) of the 24 patients in the urokinase group and in all 10 of the patients in the rt-PA group. Hemorrhagic transformation appeared in 4 patients in the urokinase group and 3 patients in the rt-PA group. Among the 20 patients who underwent SPECT before the treatment, the residual CBF was lower in the 5 patients who developed hemorrhagic transformation than in the 15 who did not (P < .05). Hemorrhagic transformation occurred in all patients with R/CE ratio of less than 0.35 and AI of more than 1.5. CONCLUSIONS The risk of hemorrhagic transformation after recanalization of occluded vessels by local intra-arterial thrombolytic therapy was considered to be high when the pretherapeutic residual CBF was markedly reduced.

Evaluation of prognostic factors following expansive laminoplasty for cervical spinal stenotic myelopathy

BACKGROUND Expansive laminoplasty of several types has been proposed for patients with cervical multisegmental stenotic myelopathy to reduce postlaminectomy complications. Its effectiveness has not been fully explored by evaluating long-term results and magnetic resonance imaging (MRI) findings before and after surgery. METHODS We conducted a 5-year follow-up study of 22 patients with cervical spondylotic myelopathy and/or ossification of the posterior longitudinal ligament surgically treated with expansive laminoplasty. The operative results were examined using the Japanese Orthopedic Association (JOA) disability scale, with reference to the findings of MRI, computed tomography, and radiography. RESULTS Postoperative improvement was observed in 18 (81.8%) of the 22 patients. In 11 patients the percentage recovery of the JOA score was higher than 50% (average: 83.1%), while in the remaining 11 patients it was lower than 50% (average: 20.1%). Factors contributing to incomplete recovery appear to be related mainly to cord degeneration with atrophy (depicted as a T2-high intensity area) and to specific factors such as long symptom duration, age higher than 70 years, deterioration due to trauma, severe cord compression, radiculopathy, and kyphotic cervical curvature. CONCLUSIONS In cervical myelopathy, patients with multisegmental stenosis, expansive laminoplasty can be expected to provide a favorable outcome by providing sufficient cord decompression and stabilization of the cervical spine, when the stenotic cervical canal is enlarged to the normal range (over 12 mm residual anteroposterior diameter and 200 mm2 residual canal area). The efficacy can be restricted by various factors, especially irreparable cord degeneration.

Angioplasty after Intra-Arterial Thrombolysis for Acute Occlusion of Intracranial Arteries

BACKGROUND AND PURPOSE The purpose of this study was to report our experience with percutaneous transluminal angioplasty (PTA) of intracranial arteries in acute stroke patients who were resistant to intra-arterial thrombolysis alone. METHODS PTA was performed within 6 hours from symptom onset in 13 acute stroke patients in whom no hypodensity areas were observed on initial CT. PTA was classified into 3 categories: immediate (3 patients), delayed (3 patients), and rescue (7 patients) angioplasty. Treatment results in the PTA group for 9 cases of middle cerebral artery (MCA) occlusion were compared with those in the thrombolysis alone group for 12 cases of thrombotic MCA occlusion. RESULTS Technical success rates for immediate, delayed, and rescue angioplasty were 100%, 100%, and 71%, respectively, and that of angioplasty for the MCA was 100%. Ten patients (77%) showed improvement in the National Institutes of Health (NIH) stroke score after treatment. Improvement in NIH stroke scores in the PTA group for MCA occlusion was greater than that in the thrombolysis alone group (P<0.01). Nine patients (69%) had an excellent, good, or fair outcome 3 months after treatment. In 9 patients who had follow-up angiography 1 month after treatment, no restenosis or reocclusion was demonstrated. There were no symptomatic complications during or after treatment. CONCLUSIONS This limited study demonstrates the technical feasibility of angioplasty for intracranial arteries in acute ischemic stroke and suggests that angioplasty may be an effective option for improving the success rate of recanalization and preventing reocclusion of the MCA. The present results encourage us to perform further clinical trials in a larger number of patients to assess the efficacy of this procedure.

Suppression of Stat3 promotes neurogenesis in cultured neural stem cells.

To investigate the effects of signal transducer and activator of transcription 3 (Stat3) on neural stem cell fate, stem cells were inoculated with an adenovirus vector expressing dominant negative form of Stat3 (Stat3F). One day later, a promoter assay revealed significant reduction of the transcriptional level in the transfected cells. Three days later, Western blot analysis and immunocytochemical analysis revealed that the protein level of microtubule‐associated protein (MAP)2 and the number of MAP2‐positive cells were increased significantly in the transfected cells whereas the protein level of glial fibrillary acidic protein (GFAP) and the number of GFAP‐positive cells were decreased significantly. In addition, mRNA levels of Notch family members (Notch1, 2, and 3) and of inhibitory basic helix‐loop‐helix (bHLH) factors (Hes5, Id2, and Id3) were significantly downregulated at 3 days after viral inoculation with Stat3F; however, mRNA levels of bHLH determination factors (Math1 and Neurogenin3) and bHLH differentiation factors (NeuroD1 and NeuroD2) were significantly upregulated. These data indicated that suppression of Stat3 directly induced neurogenesis and inhibited astrogliogenesis in neural stem cells.

Multivariable Analysis of Predictive Factors Related to Outcome at 6 Months After Intra-Arterial Thrombolysis for Acute Ischemic Stroke

BACKGROUND AND PURPOSE Recent reports have suggested that a rapid assessment of pretreatment residual cerebral blood flow (CBF) could be used to optimize selection criteria for thrombolysis in patients with acute ischemic stroke to improve clinical outcome. We investigated retrospectively residual CBF and other clinical factors related to outcome at 6 months after intra-arterial thrombolysis by using multivariable analysis. METHODS Seventy-six patients received intra-arterial thrombolysis within 6 hours of symptom onset. The multiple regression method was used to analyze associations between the modified Rankin scale (MRS) at 6 months after treatment and clinical factors including age, infarction type, duration of ischemia, dose of urokinase, degree of recanalization, hemorrhage, National Institutes of Health Stroke Scale score (NIHSSS), and residual CBF evaluated by pretreatment single-photon emission-computed tomography; these values were assessed with the use of the regional-to-cerebellar activity (R/CE) ratio of ischemic region to cerebellum and asymmetry index. RESULTS MRS at 6 months was good (0 to 3) in 65% and poor (4 to 6) in 35%. Factors significantly related to MRS at 6 months were R/CE ratio (P<0.0001), NIHSSS at baseline and the following day (P<0.0001), cardioembolic infarction (P=0.0014), age (P=0.0074), and recanalization grade (P=0. 007). NIHSSS of >20, R/CE ratio of <0.35, cardioembolic infarction, incomplete recanalization (grade <3), and older age (>75 years) were determined to be significant independent predictors of poor outcome. CONCLUSIONS The residual CBF, neurological score at baseline and the following day, age, and recanalization grade correlated significantly with long-term outcome. The NIHSSS of >20 and R/CE ratio of <0.35 were determined to be significant independent predictors of poor outcome by multivariable analysis.

Neuroprotective nitric oxide synthase inhibitor reduces intracellular calcium accumulation following transient global ischemia in the gerbil

By observing the ultrastructural intracellular Ca2+ distribution with Ca(2+)-oxalate-pyroantimonate method, we examined whether the protective mechanism of the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (LNNA), involves change of the intracellular Ca2+ movement in delayed neuronal death (DND) in gerbil hippocampal CA1 neurons following 5-min forebrain ischemia. In the group intraventricularly administered 5.0 mg/ml LNNA, 15 min after reperfusion the intracellular Ca2+ deposits and the mitochondrial Ca2+ uptake index increased to levels similar to those in the control group administered only artificial cerebro-spinal fluid, but by 180 min after reperfusion they had returned to the preischemic level. By 15 min after reperfusion Ca2+ deposits in the endoplasmic reticulum (ER) had almost disappeared in both groups, but at 180 min of reperfusion, the ER in only the LNNA group showed Ca2+ deposits. It is suggested that the neuronal toxicity of NO involves the dysfunction of the intracellular Ca2+ transport system including the mitochondria and ER.

Accuracy of diffusion tensor magnetic resonance imaging-based tractography for surgery of gliomas near the pyramidal tract: a significant correlation between subcortical electrical stimulation and postoperative tractography.

BACKGROUND: Diffusion tensor (DT) imaging-based fiber tracking is a noninvasive magnetic resonance technique that can delineate the course of white matter fibers. OBJECTIVE: To evaluate the accuracy and usefulness of this DT imaging-based fiber tracking for surgery in patients with gliomas near the pyramidal tract (PT). METHODS: Subjects comprised 32 patients with gliomas near the PT. DT imaging-based fiber tracks of the PT were generated before and within 3 days after surgery in all patients. A tractography-integrated navigation system was used during the operation. Cortical and subcortical motor-evoked potentials (MEPs) were also monitored during resection to maximize the preservation of motor function. The threshold intensity for subcortical MEPs was examined by searching the stimulus points and changing the stimulus intensity. Minimum distance between the resection border and the illustrated PT was measured on postoperative tractography. RESULTS: In all subjects, DT imaging-based tractography of the PT was successfully performed, preoperatively demonstrating the relationship between tumors and the PT. With the use of the tractography-integrated navigation system and intraoperative MEPs, motor function was preserved postoperatively in all patients. A significant correlation was seen between threshold intensity for subcortical MEPs and the distance between the resection border and PT on postoperative DT imaging. CONCLUSION: DT imaging-based fiber tracking is a reliable and accurate method for mapping the course of subcortical PTs. Fiber tracking and intraoperative MEPs were useful for preserving motor function in patients with gliomas near the PT.

Accumulation of macrophage-like cells expressing NG2 proteoglycan and Iba1 in ischemic core of rat brain after transient middle cerebral artery occlusion.

Although neurons and glia inevitably undergo degeneration in the core of ischemic lesions, many cells, particularly immune cells, infiltrate the core and survive in it. Such infiltrating cells may play certain roles in the regeneration and repair of damaged brain tissues. In this study, we characterized macrophage-like cells that accumulated in the ischemic core of a rat brain whose right middle cerebral artery was transiently occluded for 90 mins. Many of the accumulated macrophage-like cells expressed Iba1, a marker of macrophages/microglia, as well as NG2 chondroitin sulfate proteoglycan (NG2), which has been recognized as a marker of oligodendrocyte progenitor cells. Such macrophage-like cells were termed BINCs (brain Iba1+/NG2+ cells) to distinguish them from NG2/Iba1+ or NG2+/Iba1− cells that were also present in the perilesion and the contralateral hemisphere. Electron microscopy showed the localization of NG2 along the plasma membrane of cells that had many phagosomes and irregular-shaped or reniform heterochromatin-rich nuclei, which are characteristics of monocytes/macrophages. Brain Iba1+/NG2+ cells were highly proliferative and their number peaked at 7 days post-reperfusion. An immunoblot analysis of NG2 revealed the presence of two NG2s: one expressed by BINCs with a molecular weight of 300 kDa, and the other found in the contralateral hemisphere with a molecular weight of 290 kDa. Taken the various functions of NG2, BINCs may be involved in not only phagocytosis of degenerated cells but also the healing and regeneration of lesion cores.

Calcium Movement in Ischemia-Tolerant Hippocampal CA1 Neurons After Transient Forebrain Ischemia in Gerbils

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracelluar Ca2+ movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca2+ distribution and the Ca2+ adenosine triphosphatase (Ca2+-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca2+ from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca2+ deposits in these mitochondria were rapidly decreased. Plasma membrane Ca2+-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca2+ distribution and Ca2+-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca2+ sequestration and plasma membrane Ca2+-ATPase reduced Ca2+ toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.

Endovascular treatment for acute thrombotic occlusion of the middle cerebral artery: local intra-arterial thrombolysis combined with percutaneous transluminal angioplasty

Abstract We report our experience in treating 15 patients with acute thrombotic occlusion of the M1 or M2 segment of the middle cerebral artery who underwent intra-arterial thrombolytic therapy alone or in combination with percutaneous transluminal angioplasty (PTA). The results were compared with those of 30 patients with acute embolic occlusion of the same artery. Intra-arterial thrombolysis was performed in 10 patients and thrombolysis combined with PTA in 5 in whom symptoms reappeared due to restenosis or reocclusion, or in whom recanalisation was not successfully accomplished by thrombolysis alone. In the patients with embolism recanalisation was observed in 28 (93 %) and there was no patient with reocclusion. In the patients with thrombosis recanalisation immediately after thrombolysis alone was observed in 9 of 15 (60 %). Restenosis, with reappearance of symptoms, occurred in 2 of these (22 %). In the patients who also underwent PTA, angiography after 1 month did not demonstrate any restenosis or reocclusion. Thrombolysis combined with PTA for acute thrombotic stroke may provide an effective procedure for restoring patency and preventing reocclusion of the occluded artery.