研究者詳細 - 秋山　幸功

論文 - 秋山　幸功

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Combined endoscopic endonasal and transcranial approach for internal carotid artery aneurysms: usefulness and safety of endonasal proximal control.

Ryota Sato, Yukinori Akiyama, Takeshi Mikami, Yuka Kawata, Chie Kamada, Yusuke Kimura, Katsuya Komatsu, Nobuhiro Mikuni

Neurosurgical review 46 ( 1 ) 283 - 283 2023年10月 [国際誌]

It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion.

Microbleeds Due to Reperfusion Enhance Early Seizures after Carotid Ligation in a Rat Ischemic Model.

Takuro Saito, Takeshi Mikami, Tsukasa Hirano, Hiroshi Nagahama, Rei Enatsu, Katsuya Komatsu, Satoshi Okawa, Yukinori Akiyama, Nobuhiro Mikuni

Neurologia medico-chirurgica 63 ( 6 ) 228 - 235 2023年06月 [国内誌]

Impaired reperfusion in ischemic brain disease is a condition that we are increasingly confronted with owing to recent advances in reperfusion therapy. In the present study, rat models of reperfusion were investigated to determine the causes of acute seizures using magnetic resonance imaging (MRI) and histopathological specimens. Rat models of bilateral common carotid artery ligation followed by reperfusion and complete occlusion were created. We compared the incidence of seizures, mortality within 24 h, MRI, and magnetic resonance spectroscopy (MRS) to evaluate ischemic or hemorrhagic changes and metabolites in the brain parenchyma. In addition, the histopathological specimens were compared with those observed on MRI. In multivariate analysis, the predictive factors of mortality were seizure (odds ratios (OR), 106.572), reperfusion or occlusion (OR, 0.056), and the apparent diffusion coefficient value of the striatum (OR, 0.396). The predictive factors of a convulsive seizure were reperfusion or occlusion (OR, 0.007) and the number of round-shaped hyposignals (RHS) on susceptibility-weighted imaging (SWI) (OR, 2.072). The incidence of convulsive seizures was significantly correlated with the number of RHS in the reperfusion model. RHS on SWI was confirmed pathologically as microbleeds in the extravasation of the brain parenchyma and was distributed around the hippocampus and cingulum bundle. MRS analysis showed that the N-acetyl aspartate level was significantly lower in the reperfusion group than in the occlusion group. In the reperfusion model, RHS on SWI was a risk factor for convulsive seizures. The location of the RHS also influenced the incidence of convulsive seizures.

Computational Fluid Dynamics Analysis Features in Aneurysm Development in Rats.

Shoichi Komura, Katsuya Komatsu, Takeshi Mikami, Yukinori Akiyama, Sangnyon Kim, Rei Enatsu, Hiroshi Nagahama, Nobuhiro Mikuni

Neurologia medico-chirurgica 63 ( 6 ) 250 - 257 2023年06月 [国内誌]

The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

Transcranial electrical stimulation technique for induction of unilateral motor evoked potentials.

Shoto Yamada, Rei Enatsu, Shu Ishikawa, Yusuke Kimura, Katsuya Komatsu, Tomohiro Chaki, Yukinori Akiyama, Takeshi Mikami, Nobuhiro Mikuni

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 150 194 - 196 2023年06月 [国際誌]

OBJECTIVE: Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses. METHODS: The stimulation of C1(+)-C4(-) or C2(+)-C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed. RESULTS: The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 μV, respectively. CONCLUSIONS: The C1(+)-C4/C2(+)-C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses. SIGNIFICANCE: Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery.

Correction to: The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.

Shoto Yamada, Yukinori Akiyama, Shunsuke Tachibana, Kengo Hayamizu, Yusuke Kimura, Shuichi Hashimoto, Michiaki Yamakage, Nobuhiro Mikuni

Journal of anesthesia 37 ( 1 ) 160 - 160 2023年02月 [国内誌]

The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.

Shoto Yamada, Yukinori Akiyama, Shunsuke Tachibana, Kengo Hayamizu, Yusuke Kimura, Shuichi Hashimoto, Michiaki Yamakage, Nobuhiro Mikuni

Journal of anesthesia 37 ( 1 ) 154 - 159 2023年02月 [国内誌]

Remimazolam is a short-acting benzodiazepine that was approved for clinical use in 2020. We report three patients who underwent surgery for cerebral and spinal cord tumors, in whom transcranial electrical stimulation-motor-evoked potential (TES-MEP) was successfully monitored under general anesthesia with remimazolam. During total intravenous anesthesia with propofol at a target concentration of 2.7 - 3.5 µg/mL and 0.1 - 0.35 µg/kg/min of remifentanil, delayed awakening, bradycardia, and hypotension during propofol anesthesia were expected in all three cases. With patient safety as the top priority, we considered changing the anesthetic agent. Propofol was replaced with remimazolam at a loading dose of 12 mg/kg/h for a few seconds (case 3), followed by 1 mg/kg/h for maintenance (cases 1-3). TES-MEP was recorded during propofol and remimazolam administration in all three patients. Amplitudes of TES-MEP during anesthesia with propofol and remimazolam were 461.5 ± 150 µV and 590.5 ± 100.9 µV, 1542 ± 127 µV and 1698 ± 211 µV, and 581.5 ± 91.3 µV and 634 ± 82.7 µV sequentially from Case 1. Our findings suggest that intraoperative TES-MEP could be measured when anesthesia was managed with remimazolam at 1 mg/kg/h.

Effect of remimazolam on intraoperative neurophysiology monitoring of visual-evoked potential: a case series.

Shoto Yamada, Kengo Hayamizu, Yukinori Akiyama, Yusuke Kimura, Shuichi Hashimoto, Nobuhiro Mikuni, Michiaki Yamakage

Journal of anesthesia 2023年01月 [国内誌]

There are very few reports on the effects of benzodiazepines such as midazolam and diazepam on intraoperative visual-evoked potential (VEP), and there is no report on the effect of remimazolam at all. Five patients underwent neurosurgery using VEP monitoring for avoiding surgical injury to the optic nerve. In all cases, drug administration was based on actual body weight. General anesthesia was induced with propofol and remifentanil, and then maintained with propofol at target concentrations of 2.7-3.5 µg/ml for maintaining bispectral index (BIS) between 40 and 60. After resection of the tumor under stable VEP, we discontinued propofol immediately followed by infusion of remimazolam at 12 mg/kg/h for a few seconds, then reduced to 1 mg/kg/h. After a time, when blood levels of remimazolam appeared to be stable, VEP was monitored again and compared to controls. In all cases, we were able to confirm that there was reproducibility. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for VEP in neurosurgery.

Impact of BRAF/MEK inhibitor on BRAF V600E-mutated pilocytic astrocytoma.

Ryo Hamada, Yusuke Akane, Yukinori Akiyama, Kohichi Takada, Masaki Yamamoto

Pediatrics international : official journal of the Japan Pediatric Society 65 ( 1 ) e15653 2023年 [国際誌]

Deep learning for the diagnosis of mesial temporal lobe epilepsy.

Kyoya Sakashita, Yukinori Akiyama, Tsukasa Hirano, Ayaka Sasagawa, Masayasu Arihara, Tomoyoshi Kuribara, Satoko Ochi, Rei Enatsu, Takeshi Mikami, Nobuhiro Mikuni

PloS one 18 ( 2 ) e0282082 2023年 [国際誌]

OBJECTIVE: This study aimed to enable the automatic detection of the hippocampus and diagnose mesial temporal lobe epilepsy (MTLE) with the hippocampus as the epileptogenic area using artificial intelligence (AI). We compared the diagnostic accuracies of AI and neurosurgical physicians for MTLE with the hippocampus as the epileptogenic area. METHOD: In this study, we used an AI program to diagnose MTLE. The image sets were processed using a code written in Python 3.7.4. and analyzed using Open Computer Vision 4.5.1. The deep learning model, which was a fine-tuned VGG16 model, consisted of several layers. The diagnostic accuracies of AI and board-certified neurosurgeons were compared. RESULTS: AI detected the hippocampi automatically and diagnosed MTLE with the hippocampus as the epileptogenic area on both T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) images. The diagnostic accuracies of AI based on T2WI and FLAIR data were 99% and 89%, respectively, and those of neurosurgeons based on T2WI and FLAIR data were 94% and 95%, respectively. The diagnostic accuracy of AI was statistically higher than that of board-certified neurosurgeons based on T2WI data (p = 0.00129). CONCLUSION: The deep learning-based AI program is highly accurate and can diagnose MTLE better than some board-certified neurosurgeons. AI can maintain a certain level of output accuracy and can be a reliable assistant to doctors.

Male sex and presence of preoperative symptoms are associated with early recurrence of WHO grade I meningiomas after surgical resection: analysis from the nationwide Brain Tumor Registry of Japan.

Soichi Oya, Fusao Ikawa, Nao Ichihara, Masahiko Wanibuchi, Yukinori Akiyama, Hirofumi Nakatomi, Nobuhiro Mikuni, Yoshitaka Narita

Neurosurgical review 46 ( 1 ) 10 - 10 2022年12月 [国際誌]

This study aimed to assess the risk factors for the recurrence of WHO grade I intracranial meningiomas using the Brain Tumor Registry of Japan (BTRJ) database. We extracted the data of 4641 patients with intracranial WHO grade I meningiomas treated only by surgical resection between 2001 and 2008. We conducted complete data analysis (n = 3690) and multiple imputation analysis (n = 4641) to adjust for missing data on tumor size. The influence of factors including age, sex, size, extent of resection, location, and preoperative symptoms on PFS was assessed. Univariate analyses of the complete data set showed that age did not affect PFS; however, male sex (p < 0.001), tumor size ≥ 30 mm (p < 0.001), low extent of resection, tumor location at the skull base (p < 0.001), and the presence of preoperative symptoms (p < 0.001) were risk factors for a significantly shorter PFS. Multivariate analysis demonstrated that male sex (p < 0.001) and presence of preoperative symptoms (p = 0.027) were independent risk factors for shorter PFS alongside large tumor size (p < 0.001) and non-gross total resection (p < 0.001). These results were confirmed for the imputed dataset. While most previous large nationwide studies of meningiomas have evaluated overall survival, progression-free survival has yet to be thoroughly examined. This study suggests that even histologically benign meningiomas may have a sex difference in postoperative behavior. This observation may provide clues to understanding the mechanism of meningioma cell proliferation.

Validity of Preoperative Screening Before Open-Heart Surgery in Reduction of Perioperative Ischemic Stroke.

Katsuya Komatsu, Takeshi Mikami, Yusuke Kimura, Yukinori Akiyama, Nobuyoshi Kawaharada, Nobuhiro Mikuni

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 31 ( 8 ) 106584 - 106584 2022年08月 [国際誌]

OBJECTIVES: Cerebrovascular event after open-heart surgery is a critical complication and contributes to poor prognosis, including increased mortality. The purpose of this study is to investigate the appropriate preoperative risk assessment and monitoring for reducing the risk of ischemic stroke after open-heart surgery. MATERIALS AND METHODS: 184 patients who underwent surgery for valvular heart disease were included in this study. Near-infrared oxygen saturation monitoring (INVOS system) was performed during open-heart surgery. For the purpose of perioperative stroke risk assessment, we evaluated the clinical and radiological factors of the group that underwent preoperative consultation and the group that did not, and of the patients with and without postoperative ischemic stroke. RESULTS: Preoperative consultation was performed in 60 cases. Large vessel steno-occlusive disease was found in nine cases, of which three had undergone revascularization surgery. Cerebral infarction developed in four cases, all of which had no large vessel steno-occlusive disease. There was no significant association between the development of postoperative ischemic stroke and presence of large vessel steno-occlusive disease. Preoperative baseline INVOS value was significantly low in the ischemic stroke group (49.5 ± 12.5) compared to the non-ischemic stroke group (66.8 ± 10.0), (P = 0.012). CONCLUSIONS: In open-heart surgery for valvular heart disease, low preoperative baseline INVOS values were associated with cerebral ischemic stroke after surgery. The combination of appropriate preoperative screening for large vessel steno-occlusive disease and measurement of INVOS could be used as a simple and useful method in screening for the risk of ischemic stroke after open-heart surgery.

Prognostic usefulness of a modified risk model for solitary fibrous tumor that includes the Ki-67 labeling index.

Shintaro Sugita, Keiko Segawa, Noriaki Kikuchi, Tomoko Takenami, Tomomi Kido, Makoto Emori, Yukinori Akiyama, Kohichi Takada, Shiro Hinotsu, Tadashi Hasegawa

World journal of surgical oncology 20 ( 1 ) 29 - 29 2022年02月 [国際誌]

BACKGROUND: Predicting the prognosis of patients with solitary fibrous tumor (SFT) is often difficult. The prognostic risk models developed by Demicco et al. are now the standard for evaluating the risk of SFT metastasis in the current World Health Organization classification of soft tissue and bone tumors. METHODS: In this study, we examined the prognostic usefulness of a modified version of the Demicco risk models that replaces the mitotic count with the Ki-67 labeling index. We compared the three-variable and four-variable Demicco risk models with our modified risk models using Kaplan-Meier curves based on data for 43 patients with SFT. RESULTS: We found a significant difference in metastasis-free survival when patients were classified into low-risk and intermediate/high-risk groups using the three-variable (P = 0.022) and four-variable (P = 0.046) Demicco models. There was also a significant difference in metastasis-free survival between the low-risk and intermediate/high-risk groups when the modified three-variable (P = 0.006) and four-variable (P = 0.022) models were used. CONCLUSION: Modified risk models that include the Ki-67 labeling index are effective for prediction of the prognosis in patients with SFT.

Macrohistory of Moyamoya Disease Analyzed Using Artificial Intelligence.

Tomoyoshi Kuribara, Yukinori Akiyama, Takeshi Mikami, Katsuya Komatsu, Yusuke Kimura, Yasuhiro Takahashi, Kyoya Sakashita, Ryohei Chiba, Nobuhiro Mikuni

Cerebrovascular diseases (Basel, Switzerland) 51 ( 4 ) 413 - 426 2022年 [国際誌]

INTRODUCTION: Moyamoya disease is characterized by progressive stenotic changes in the terminal segment of the internal carotid artery and the development of abnormal vascular networks called moyamoya vessels. The objective of this review was to provide a holistic view of the epidemiology, etiology, clinical findings, treatment, and pathogenesis of moyamoya disease. A literature search was performed in PubMed using the term "moyamoya disease," for articles published until 2021. RESULTS: Artificial intelligence (AI) clustering was used to classify the articles into 5 clusters: (1) pathophysiology (23.5%); (2) clinical background (37.3%); (3) imaging (13.2%); (4) treatment (17.3%); and (5) genetics (8.7%). Many articles in the "clinical background" cluster were published from the 1970s. However, in the "treatment" and "genetics" clusters, the articles were published from the 2010s through 2021. In 2011, it was confirmed that a gene called Ringin protein 213 (RNF213) is a susceptibility gene for moyamoya disease. Since then, tremendous progress in genomic, transcriptomic, and epigenetic profiling (e.g., methylation profiling) has resulted in new concepts for classifying moyamoya disease. Our literature survey revealed that the pathogenesis involves aberrations of multiple signaling pathways through genetic mutations and altered gene expression. CONCLUSION: We analyzed the content vectors in abstracts using AI, and reviewed the pathophysiology, clinical background, radiological features, treatments, and genetic peculiarity of moyamoya disease.

Effects of polarity of bipolar sensorimotor direct cortical stimulation on intraoperative motor evoked potentials.

Shoto Yamada, Rei Enatsu, Yusuke Kimura, Katsuya Komatsu, Yukinori Akiyama, Takeshi Mikami, Satoko Ochi, Nobuhiro Mikuni

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 132 ( 10 ) 2351 - 2356 2021年10月 [国際誌]

OBJECTIVE: The present study investigated the effects of the stimulus polarity and location of motor evoked potential (MEP) to establish a stimulation protocol. METHODS: Nineteen patients who intraoperatively underwent MEP in bipolar direct cortical stimulation were enrolled in the present study. Somatosensory evoked potentials (SEP) of the contralateral median nerve stimulation were recorded to determine stimulation sites. MEP was performed under two settings in all patients: 1. Anodal bipolar stimulation: an anode on the precentral gyrus and a cathode on the postcentral gyrus, 2. Cathodal bipolar stimulation: a cathode on the precentral gyrus and an anode on the postcentral gyrus. MEP amplitudes and the coefficient of variation (CV) at a stimulation intensity of 25 mA and the thresholds of induced MEP were compared between the two settings. RESULTS: An electrical stimulation at 25 mA induced a significantly higher amplitude in cathodal bipolar stimulation than in anodal bipolar stimulation. Cathodal bipolar stimulation also showed significantly lower thresholds than anodal stimulation. CV did not significantly differ between the two groups. CONCLUSIONS: These results indicate that cathodal bipolar stimulation is superior to anodal bipolar stimulation for intraoperative MEP monitoring. SIGNIFICANCE: MEP in cathodal bipolar cortical stimulation may be used in a safe and useful evaluation method of motor fiber damage that combines sensitivity and specificity.

Preserved arachnoid membrane acts as a predictor of postoperative visual improvement in clinoidal meningioma.

Yusuke Kimura, Masahiko Wanibuchi, Yukinori Akiyama, Takeshi Mikami, Nobuhiro Mikuni

Clinical neurology and neurosurgery 208 106874 - 106874 2021年09月 [国際誌]

OBJECTIVES: Improvement of patient visual outcome is very important in the treatment of clinoidal meningioma (CLM). The purpose of this study is to determine the association between arachnoid preservation and visual outcome. PATIENTS: Fifteen patients with CLMs that caused visual impairment underwent surgery in our hospital. The patients included 4 men and 11 women, and the mean age was 53.3 years. METHODS: The clinical findings of these patients were retrospectively reviewed. We divided the patients into two groups based on the presence or absence of the arachnoid membrane. Group 1 comprised cases in which arachnoid preservation was intraoperatively confirmed. Group 2 comprised cases in which the arachnoid membrane was not preserved. The Landolt C chart was used to evaluate visual acuity, and dynamic visual field tests using Goldmann perimetry were used to evaluate the visual field. Results were compared before and after surgery. RESULTS: The visual acuity of the ipsilateral eye was significantly improved in Group 1 (p = 0.038). There were no other significant differences between the two groups in terms of tumor volume, patient age, and symptom duration. CONCLUSIONS: Patients in which arachnoid preservation could be intraoperatively confirmed had good improvement in visual acuity. Further research with an increased number of cases is needed to confirm these findings.

Additional Revascularization Using Multiple Burr Holes for PCA Involvement in Moyamoya Disease.

Chie Kamada, Tsukasa Hirano, Takeshi Mikami, Katsuya Komatsu, Hime Suzuki, Syuichi Tsushima, Yukinori Akiyama, Nobuhiro Mikuni

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 30 ( 8 ) 105852 - 105852 2021年08月 [国際誌]

In specific cases of moyamoya disease (MMD), posterior cerebral artery (PCA) stenosis can develop after treatment of the anterior circulation and require additional revascularization. Here, we report two cases that underwent additional posterior indirect revascularization with multiple burr holes for PCA involvement after bilateral revascularization treatment of the anterior circulation. They presented with transient ischemic attack even after bilateral superficial temporal artery-middle cerebral artery bypass, and magnetic resonance angiography (MRA) showed that PCA stenosis had worsened. Indirect revascularization with multiple burr holes using Benz-marked skin incisions was performed. After surgery, the symptoms improved without perioperative complications, and cerebral angiography showed collateral circulation via the burr hole. Indirect revascularization for MMD is often combined with direct revascularization, and there are only a few reports on the use of multiple burr hole surgery alone. In addition, there are few reports of posterior circulation, despite the emphasis on the importance of PCA involvement in MMD. Indirect revascularization with multiple burr holes alone can be performed in multiple areas and applied to patients who cannot undergo direct revascularization using the occipital artery. The procedure is simple and less invasive than traditional direct revascularization procedures. Therefore, it can be effective, especially in pediatric cases of MMD with PCA involvement.

Effect of adjuvant radiotherapy after subtotal resection for WHO grade I meningioma: a propensity score matching analysis of the Brain Tumor Registry of Japan.

Soichi Oya, Fusao Ikawa, Nao Ichihara, Masahiko Wanibuchi, Yukinori Akiyama, Hirofumi Nakatomi, Nobuhiro Mikuni, Yoshitaka Narita

Journal of neuro-oncology 153 ( 2 ) 351 - 360 2021年06月 [国際誌]

PURPOSE: This study aimed to improve the understanding of the role of adjuvant radiotherapy (AR) after subtotal resection (STR) of World Health Organization (WHO) grade I meningiomas. METHODS: We retrospectively reviewed the Brain Tumor Registry of Japan database. Among 7341 patients diagnosed with intracranial meningioma during 2001-2008, we identified 406 patients with WHO grade I meningioma treated with STR as initial treatment. Data on progression-free survival (PFS) were assessed for their relevance to clinical factors including age, sex, tumor location and size, presence of preoperative symptoms, and AR. RESULTS: AR was administered for 73 patients (18.0%). Regrowth occurred in 90 cases (22.2%) during the median follow-up period of 6.0 years (interquartile range, 2.7-7.7 years). Multivariate Cox regression analysis of the entire cohort showed that no AR was associated with significantly shorter PFS (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.33-5.42, p = 0.004). The therapeutic effect of AR was confirmed for skull base, but not non-skull base, meningiomas (p = 0.003 and 0.69, respectively). Propensity score matching analysis balanced the influence of confounding factors to generate AR+ and AR- cohorts of 73 patients each. PFS was significantly longer in the AR+ cohort than in the AR- cohort (HR 3.46, 95% CI 1.53-8.59, p = 0.003). Subgroup analysis demonstrated the favorable effect of AR only for skull base meningiomas. CONCLUSIONS: Our study revealed that AR improves tumor control after STR in WHO grade I meningiomas. However, this beneficial effect might be limited to skull base meningiomas.

Pitfalls of Commonly Used Ischemic and Dementia Models Due to Early Seizure by Carotid Ligation.

Tsukasa Hirano, Takeshi Mikami, Shoto Yamada, Hiroshi Nagahama, Rei Enatsu, Satoshi Ookawa, Yukinori Akiyama, Nobuhiro Mikuni

Neurologia medico-chirurgica 61 ( 5 ) 312 - 320 2021年05月 [国内誌]

While the bilateral common carotid artery (CCA) ligation model is widely used in cerebrovascular disease and dementia studies, it can frequently cause seizures. We examined the validity of seizure as an experimental model of ischemia. Eight-week-old male Wistar and Sprague-Dawley (SD) rats were implanted with electrocorticography (ECoG) electrodes and bilateral CCA ligation was performed and compared to the sham groups. ECoG monitoring was used to confirm the seizure discharge and count the number of spikes in the interictal phase 2 h after ligation, followed by power spectral analysis. Magnetic resonance imaging (MRI) was performed 6 h after bilateral CCA ligation to assess fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) values. Magnetic resonance spectroscopy (MRS) was also performed and the ischemic parameters and electrophysiological changes were compared. The Wistar rat group had significantly higher mortality, frequency of seizures, incidence of non-convulsive seizures, and number of spikes in the interictal period compared to those in the SD rat group. Power spectral analysis showed increased power in the delta band in both Wistar and SD rat groups. MRI, after CCA ligation, showed significantly lower ADC values, lower glutamine and glutamate levels, and higher lactate values in Wistar rats, although there was no difference in FA values. Metabolic and electrophysiological changes after CCA ligation differed according to the rat strain. Wistar rats were prone to increased lactate and decreased glutamine and glutamate levels and the development of status epilepticus. Seizures can affect the results of ischemic experiments.

Aging-associated inflammation and fibrosis in arachnoid membrane.

Hime Suzuki, Takeshi Mikami, Naotoshi Iwahara, Yukinori Akiyama, Masahiko Wanibuchi, Katsuya Komatsu, Rintaro Yokoyama, Tsukasa Hirano, Ryusuke Hosoda, Yoshiyuki Horio, Atsushi Kuno, Nobuhiro Mikuni

BMC neurology 21 ( 1 ) 169 - 169 2021年04月 [査読有り] [国際誌]

BACKGROUND: The physiological and pathological significance of the arachnoid membrane (AM) is still unknown. In this study, we investigated various characteristics of the AM, focusing on the influence of inflammation and fibrosis. METHODS: Small pieces of AM sample were obtained during neurosurgical procedures from 74 cases. The clinical and pathological characteristics of the hyperplastic AM group (≥ 50 μm) and the non-hyperplastic AM group (< 50 μm) were compared. Then, potential correlations between AM thickness and clinical characteristics were analyzed. Moreover, VEGFα, TGFβ, and TGFα levels were quantitated by real time PCR. Then, the potential correlations between AM thickness and these inflammatory or anti-inflammatory markers, and the influence of the original disease were calculated. RESULTS: The median age of the patients in hyperplastic AM group was significantly older than that of the non-hyperplastic AM group. Moreover, the number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells in the hyperplastic AM group was significantly higher than that in the non-hyperplastic AM group. The AM thickness was significantly correlated to age and number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells. The thickness of the AM was significantly correlated to the messenger RNA expression levels of VEGFα (ρ = 0.337), and the VEGFα expression levels were significantly correlated with TGFβ and TNFα. CONCLUSIONS: The AM hyperplasia was influenced by aging and could be a result of inflammation and fibrosis through cytokine secretion from the inflammatory cells and fibroblasts in the AM.

Accumulation of Macromolecules in Idiopathic Normal Pressure Hydrocephalus.

Yukinori Akiyama, Rintaro Yokoyama, Hiroyuki Takashima, Yuka Kawata, Masayasu Arihara, Ryohei Chiba, Yusuke Kimura, Takeshi Mikami, Nobuhiro Mikuni

Neurologia medico-chirurgica 61 ( 3 ) 211 - 218 2021年03月 [国内誌]

The clearance system in the brain is not completely understood. The aim of this study was to prove the presence of the "glymphatic system" in the human brain using magnetic resonance spectroscopy (MRS).Spectral data of the brain white matter were obtained from healthy volunteers and patients with hydrocephalic dementia and used to measure intracerebral metabolites, including macromolecules (MMs) and lipids. Data were transferred from the MRS scanners to a workstation, and metabolites were quantified with the spectrogram-based eddy current method and water scaling.MM levels were significantly higher in patients with a slow gait and executive dysfunction due to normal pressure hydrocephalus (NPH) than in asymptomatic volunteers (p <0.01). In contrast, the N-acetyl aspartate (NAA) level was significantly lower in patients with executive dysfunction than in asymptomatic volunteers (p <0.01). There were no statistically significant differences in metabolites, including alanine, aspartate, creatine, γ-amino butyric acid, D-glucose, glutamine, glutamate, glycerophosphorylcholine, phosphorylcholine, lactate, myoinositol, N-acetyl-aspartyl-glutamate, scyllo-inositol, taurine, creatine methylene, and guanine, in the centrum semiovale between patients with NPH and asymptomatic volunteers.We quantitatively evaluated cerebral metabolites, particularly in the centrum semiovale, with MRS. In the brain of patients with a slow gait and executive dysfunction due to NPH, MRS revealed significantly higher MM levels and lower NAA levels compared to healthy volunteers. Therefore, it may be concluded that the patients have a dysfunctional glymphatic system in the brain.

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