Shu Sogabe, HABOSHI Tatsuya, Izumi Yamaguchi, Masaaki Korai, Nobuaki Yamamoto, Kenji Shimada, Yasuhisa Kanematsu and Yasushi Takagi : Experience of using coronary perfusion balloon catheter for acute middle cerebral artery occlusion, Surgical Neurology International, Vol.14, No.365, 365, 2023.
(要約)
We present the case of an individual with acute occlusion of the middle cerebral artery caused by atherosclerosis. The patient underwent angioplasty using a coronary perfusion balloon, which resulted in a favorable clinical outcome. A 66-year-old male patient presented with an acute onset of right hemiplegia and dysarthria. Magnetic resonance imaging revealed an occlusion of the left middle cerebral artery, and alteplase was administered, followed by a mechanical thrombectomy and intracranial balloon catheter angioplasty. Due to restenosis, a coronary perfusion balloon catheter was used for a 15-minute angioplasty procedure while maintaining the perfusion. This treatment approach led to the recanalization of the artery and favorable clinical outcomes. The coronary perfusion balloon may represent a viable therapeutic alternative for the management of refractory intracranial atherosclerotic large vessel occlusion.
Yuki Yamamoto, Nobuaki Yamamoto, Tomohiro Matsuda, Kazutaka Kuroda, Izumi Yamaguchi, Shu Sogabe, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi and Yuishin Izumi : Stent retrieval for free-floating thrombus attached to carotid artery stenosis: A report of two cases., Surgical Neurology International, Vol.14, 274, 2023.
(要約)
In cases of carotid artery stenosis with FFT, it is technically possible to retrieve a thrombus with a stent retriever. Although thrombus removal may help reduce the risk of ischemic complications in a series of urgent CAS procedures, there are concerns such as mechanical irritation to the carotid artery plaque, and its indications and alternative treatments should be carefully considered.
Joji Fujikawa, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama, Teruo Oda, Nobuaki Yamamoto, Yuishin Izumi, Hideo Mure, Satoshi Goto and Yasushi Takagi : Cranial geometry in patients with dystonia and Parkinson's disease., Scientific Reports, Vol.13, No.1, 2023.
(要約)
Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.
Nobuaki Yamamoto, Kazutaka Kuroda, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Kenji Shimada, Ryoma Morigaki, Yasuhisa Kanematsu, Yuishin Izumi and Yasushi Takagi : Long-sheath Introducer-assisted Revascularization (L-SHARE) Technique for Treating Large-vessel Occlusion by a Giant Clot, Internal Medicine, Vol.62, No.6, 909-913, 2023.
(要約)
Revascularization for common carotid artery (CCA) occlusion might be difficult. We reported our strategy for revascularizing CCA occlusion by giant clots. A 94-year-old woman was transferred to our hospital because of right hemiparesis and aphasia. CCA occlusion and giant clots were detected on ultrasonography. We performed mechanical thrombectomy using a 9-Fr balloon-guiding catheter, stent retriever, and aspiration catheter through a 9-Fr long-sheath introducer [long-sheath introducer-assisted revascularization (L-SHARE) technique]. We successfully recanalized CCA occlusion using this method. The L-SHARE technique might be useful for recanalization of CCA occlusion.
Manabu Ishihara, Yasuhisa Kanematsu, Nobuaki Yamamoto, Kenji Shimada, Takeshi Miyamoto, Izumi Yamaguchi, Shu Sogabe, Yuki Yamamoto, Jun Oto and Yasushi Takagi : Prognostic factors for acute large vessel occlusion with NIHSS 5 or lower., The Journal of Medical Investigation : JMI, Vol.70, No.1.2, 22-27, 2023.
(要約)
MCA occlusion is associated with poor prognosis, even with NIHSS score ??5, and d-IAS may provide a predictor. J. Med. Invest. 70 : 22-27, February, 2023.
Yuki Kanazawa, Tosiaki Miyati, Masafumi Harada, Mitsuharu Miyoshi, Yuki Matsumoto, Hiroaki Hayashi, Yasuhisa Kanematsu and Yasushi Takagi : Evaluation of Biological Metabolic Activity within an Atherosclerotic Plaque using Chemical Exchange Saturation Transfer Imaging, Proceedings of ISMRM, Vol.32, No.2982, 2023.
Cerebrovascular and cardiovascular disease are the main causes of death in Japan. The leading causes of the need for long-term care in Japan are also cerebrovascular and cardiovascular disease, which together account for more than one-fourth of the total. The Cerebrovascular and Cardiovascular Disease Control Act, of Japanese national law, was promulgated by a legislative act in 2018. On the basis of the Cerebrovascular and Cardiovascular Disease Control Act, the Ministry of Health, Labour and Welfare, Japan, published the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease (Japanese National Plan) in 2020. By the example of the Japanese National Plan, Tokushima prefecture established a cerebrovascular and cardiovascular disease countermeasure promotion plan to progress cerebrovascular and cardiovascular disease measures according to their own circumstances. One of the important measures of the plan is improving emergency transportation systems. Patients with intracranial large vessel occlusion strokes should be served by direct transfer to endovascular capable centers avoiding delays by misguided transfer to primary stroke centers. Considering the limited availability of endovascular capable centers, accurate identification of patients with high probability of having large vessel occlusion strokes in the prehospital setting is importance. To address this problem, we introduced prehospital scale called Field Assessment Stroke Triage for Emergency Destination (FAST-ED) on emergency transportation systems in Tokushima city.
(キーワード)
Cerebrovascular and cardiovascular disease / emergency transportation systems / prehospital scale
Yoshitaka Kurashiki, Hiroshi Kagusa, Kenji Yagi, Tomoya Kinouchi, Manabu Sumiyoshi, Takeshi Miyamoto, Kenji Shimada, Keiko T Kitazato, Yoshihiro Uto and Yasushi Takagi : Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage, Journal of Cerebral Blood Flow and Metabolism, 2022.
(要約)
Cerebral ischemia triggers inflammatory changes, and early complications and unfavorable outcomes of endovascular thrombectomy for brain occlusion promote the recruitment of various cell types to the ischemic area. Although anti-inflammatory M2-type macrophages are thought to exert protective effects against cerebral ischemia, little has been clarified regarding the significance of post-ischemic phase-dependent modulation of M2-type macrophages. To test our hypothesis that post-ischemic phase-dependent modulation of macrophages represents a potential therapy against ischemic brain damage, the effects on rats of an M2-type macrophage-specific activator, Gc-protein macrophage-activating factor (GcMAF), were compared with vehicle-treated control rats in the acute (day 0-6) or subacute (day 7-13) phase after ischemia induction. Acute-phase GcMAF treatment augmented both anti-inflammatory CD163 M2-type- and pro-inflammatory CD16 M1-type macrophages, resulting in no beneficial effects. Conversely, subacute-phase GcMAF injection increased only CD163 M2-type macrophages accompanied by elevated mRNA levels of arginase-1 and interleukin-4. M2-type macrophages co-localized with CD36 phagocytic cells led to clearance of the infarct area, which were abrogated by clodronate-liposomes. Expression of survival-related molecules on day 28 at the infarct border was augmented by GcMAF. These data provide new and important insights into the significance of M2-type macrophage-specific activation as post-ischemic phase-dependent therapy.
Taku Matsuda, Ryoma Morigaki, Yuki Matsumoto, Hideo Mure, Kazuhisa Miyake, Masahito Nakataki, Masafumi Harada and Yasushi Takagi : Obsessivecompulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia, Scientific Reports, Vol.12, No.1, 20350, 2022.
(要約)
We aimed to clarify the correlations between motor symptoms and obsessive-compulsive symptoms and between the volumes of basal ganglia components and obsessive-compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive-compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers' scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). "Checking" rituals had a strong and significant negative correlation with the Burke-Fahn-Marsden Dystonia Rating Scale (ϱ = - 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ϱ = 0.72, p = 0.023; left: ϱ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive-compulsive disorder and dystonia.
Kenji Shimada, Kazuhisa Miyake, Izumi Yamaguchi, Shu Sogabe, Masaaki Korai, Yasuhisa Kanematsu and Yasushi Takagi : Efficacy of Utilizing Both 3-Dimensional Multimodal Fusion Image and Intra-Arterial Indocyanine Green Videoangiography in Cerebral Arteriovenous Malformation Surgery, World Neurosurgery, Vol.169, e260-e269, 2022.
(要約)
An understanding of the complex morphology of an arteriovenous malformation (AVM) is important for successful resection. We have previously reported the utility of intra-arterial indocyanine green (ICG) videoangiography for this purpose, but that method cannot detect the angioarchitecture covered by brain tissue. 3-dimensional (3D) multimodal fusion imaging is reportedly useful for this same purpose, but cannot always visualize the exact angioarchitecture due to poor source images and processing techniques. This study examined the results of utilizing both techniques in patients with AVMs. Both techniques were applied in 12 patients with AVMs. Both images were compared with surgical views and evaluated by surgeons. Although evaluations for identifying superficial feeders by ICG videoangiography were high in all cases, the more complicated the AVM, the lower the evaluation by 3D multimodal fusion imaging. Conversely, evaluation of the estimated range of the nidus was high in all cases by 3D multimodal fusion imaging, but low in all but one case by ICG videoangiography. Nidus flow reduction was recognized by Flow 800 analysis obtained after ICG videoangiography. These results showed that utilizing both techniques together was more useful than each modality alone in AVM surgery. This was particularly effective in identifying superficial feeders and estimating the range of the nidus. This technique is expected to offer an optimal tool for AVM surgery.
J Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, H Nakanishi, T Oda, Yuishin Izumi and Yasushi Takagi : Diagnosis and Treatment of Tremor in Parkinson's Disease Using Mechanical Devices, Life, Vol.13, No.1, 78, 2022.
(要約)
Parkinsonian tremors are sometimes confused with essential tremors or other conditions. Recently, researchers conducted several studies on tremor evaluation using wearable sensors and devices, which may support accurate diagnosis. Mechanical devices are also commonly used to treat tremors and have been actively researched and developed. Here, we aimed to review recent progress and the efficacy of the devices related to Parkinsonian tremors. The PubMed and Scopus databases were searched for articles. We searched for "Parkinson disease" and "tremor" and "device". Eighty-six articles were selected by our systematic approach. Many studies demonstrated that the diagnosis and evaluation of tremors in patients with PD can be done accurately by machine learning algorithms. Mechanical devices for tremor suppression include deep brain stimulation (DBS), electrical muscle stimulation, and orthosis. In recent years, adaptive DBS and optimization of stimulation parameters have been studied to further improve treatment efficacy. Due to developments using state-of-the-art techniques, effectiveness in diagnosing and evaluating tremor and suppressing it using these devices is satisfactorily high in many studies. However, other than DBS, no devices are in practical use. To acquire high-level evidence, large-scale studies and randomized controlled trials are needed for these devices.
Eiji Shikata, Takeshi Miyamoto, Tadashi Yamaguchi, Izumi Yamaguchi, Hiroshi Kagusa, Daiki Gotoh, Kenji Shimada, Yoshiteru Tada, Kenji Yagi, 北里 慶子, Yasuhisa Kanematsu and Yasushi Takagi : An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with infammatory changes in rat brain harboring cerebral aneurysms prone to rupture, Journal of Neuroinflammation, Vol.19, No.161, 161, 2022.
(要約)
An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na/K-ATPase (ATP1α3). Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet. Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05). Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.
Kenji Shimada, Izumi Yamaguchi, Takeshi Miyamoto, Shu Sogabe, Kazuhisa Miyake, Yasuhisa Kanematsu and Yasushi Takagi : Efficacy of intraarterial indocyanine green videoangiography in surgery for arteriovenous fistula at the craniocervical junction in a hybrid operating room: illustrative cases, Journal of Neurosurgery. Case Lessons, Vol.3, No.23, 1-6, 2022.
(要約)
Sufficient understanding of the angioarchitecture of an arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is crucial to surgical treatment but is often difficult because of the complex vascular anatomy. Intraarterial indocyanine green (ICG) videoangiography has emerged as a more useful option for understanding the vascular anatomy than intravenous ICG videoangiography. This report describes two cases of CCJ AVFs successfully treated by surgery using intraarterial ICG videoangiography and describes the efficacy of this technique. Case 1 involved a 71-year-old man presenting with tetraparesis after sudden onset of severe headache due to subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) demonstrated CCJ epidural AVF. Intraarterial ICG videoangiography revealed the drainer, which had been difficult to identify. The AVF disappeared after disconnection of the drainer. Case 2 involved a 68-year-old man presenting with severe headache due to SAH. DSA showed multiple AVFs at the CCJ and cerebellar tentorium. Intraarterial ICG videoangiography demonstrated concomitant perimedullary AVF and dural AVF at the CCJ. All AVFs disappeared postoperatively. Intraarterial ICG videoangiography was useful for definitive diagnosis of CCJ AVF, facilitating identification of feeders and drainers with bright and high phase contrast and allowing repeated testing to confirm flow direction.
Izumi Yamaguchi, Yasuhisa Kanematsu, Kenji Shimada, Nobuaki Yamamoto, Kazuhisa Miyake, Takeshi Miyamoto, Shu Sogabe, Eiji Shikata, Manabu Ishihara, 山本 陽子, Kazutaka Kuroda and Yasushi Takagi : Single-session hematoma removal and transcortical venous approach for coil embolization of an isolated transverse-sigmoid sinus dural arteriovenous fistula in a hybrid operating room: illustrative case, Journal of Neurosurgery. Case Lessons, Vol.3, No.21, CASE2267, 2022.
(要約)
Dural arteriovenous fistula (DAVF) can present with massive hematoma, which sometimes requires emergent removal. Therefore, a surgical strategy for single-session hematoma removal and shunt occlusion in the same surgical field is important. A 73-year-old man was transferred to the authors' hospital with a headache. Brain computed tomography (CT) revealed an intracerebral hematoma in the right temporoparietal lobe (hematoma volume 12 ml). A cerebral angiogram revealed a right isolated transverse-sigmoid sinus (TSS)-DAVF fed by the occipital artery and middle meningeal artery. There was cortical venous reflux into the Labbé vein and posterior parietal vein. Percutaneous transarterial and transvenous embolization were unsuccessful. The following day, his consciousness level acutely declined with a headache, and brain CT showed hematoma expansion (hematoma volume 41 ml) with a midline shift. Therefore, the authors performed single-session hematoma removal and a transcortical venous approach for coil embolization of an isolated TSS-DAVF in a hybrid operating room. His postoperative course was uneventful. No recurrence was observed 3 months postoperatively on cerebral angiography. Single-session hematoma removal and a transcortical venous approach for coil embolization of an isolated TSS-DAVF is considered in cases with massive hematoma. This strategy is useful, considering recent developments in hybrid operating rooms.
Tadashi Yamaguchi, Takeshi Miyamoto, Eiji Shikata, Izumi Yamaguchi, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Masaaki Korai, Keiko T. Kitazato, Yasuhisa Kanematsu and Yasushi Takagi : Activation of the NLRP3/IL-1β/MMP-9 pathway and intracranial aneurysm rupture associated with the depletion of ERα and Sirt1 in oophorectomized rats, Journal of Neurosurgery, 1-8, 2022.
(要約)
Subarachnoid hemorrhage (SAH) due to intracranial aneurysm (IA) rupture is often a devastating event. Since the incidence of SAH increases especially in menopause, it is crucial to clarify the detailed pathogenesis of these events. The activation of vascular nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes has been studied in ischemic stroke and cardiovascular disease. However, the role of NLRP3 in IA rupture still needs to be explained. The authors sought to test their hypothesis that, under estrogen-deficient conditions, activation of NLRP3 inflammasomes via downregulation of the estrogen receptor (ER) facilitates IA rupture. Ten-week-old female Sprague Dawley rats with and without oophorectomy were subjected to hemodynamic changes and hypertension (OVX+/HT and OVX-/HT, respectively) and fed a high-salt diet. Separately, using human brain endothelial cells (HBECs) and human brain smooth muscle cells (HBSMCs), the authors tested the effect of NLRP3 under estrogen-free conditions and in the presence of estradiol or of ER agonists. In OVX+/HT rats, the frequency of IA rupture was significantly higher than in OVX-/HT rats (p = 0.03). In the left posterior cerebral artery prone to rupture in OVX+/HT rats, the levels of the mRNAs encoding ERα and Sirt1, but not of that encoding ERβ, were decreased, and the levels of the mRNAs encoding NLRP3, interleukin-1β (IL-1β), and matrix metalloproteinase 9 (MMP-9) were elevated. Immunohistochemical analysis demonstrated that the expression profiles of these proteins correlated with their mRNA levels. Treatment with an ER modulator, bazedoxifene, normalized the expression profiles of these proteins and improved SAH-free survival. In HBECs and HBSMCs under estrogen-free conditions, the depletion of ERα and Sirt1 and the accumulation of NLRP3 were counteracted by exposure to estradiol or to an ERα agonist but not to an ERβ agonist. To the authors' knowledge, this work represents the first demonstration that, in an aneurysm model under estrogen-deficient conditions, the depletion of ERα and Sirt1 may contribute to activation of the NLRP3/IL-1β/MMP-9 pathway, facilitating the rupture of IAs in the estrogen-deficient rat IA rupture model.
Shinji Nagahiro, Yoshifumi Mizobuchi, Kohhei Nakajima and Yasushi Takagi : A Novel Approach to Microvascular Decompression for Hemifacial Spasm: Method Description and Associated Outcome, Operative Neurosurgery, Vol.00, 1-7, 2022.
(要約)
Microvascular decompression (MVD) is the only potential cure for hemifacial spasm (HFS). However, traditional techniques such as the interposition method may have limited effect in some cases. Alternative techniques have been proposed; however, they can be more complex or difficult to perform than the standard approach. To describe a safe decompression technique-the "shelter method"-which involves creating a shelter-like space around the facial nerve root exit zone and present associated outcomes. Medical records and intraoperative findings of 92 patients with HFS who underwent MVD using the shelter method between April 1997 and March 2017 were retrospectively reviewed. As a historical control group, we included 53 patients who had undergone MVD by the traditional interposition method before March 1989. The patients were divided into 3 subgroups according to the arteries involved and degree or direction of arterial compression to the seventh nerve. Patient outcomes were assessed as excellent, good, fair, and poor according to the MVD scoring system of the Japan Society for MVD Surgery. In the shelter method group, complete disappearance of HFS was achieved in 87 patients (94.6%). The curative rate of the shelter method group was significantly higher than that of the interposition method group. The overall complication rates were significantly lower in the shelter method group than in the interposition method group. Our findings indicate high curative and low complication rates of the shelter method, suggesting that it helps treat HFS caused by various types of arterial compression.
Joji Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, Teruo Oda, Hiroshi Nakanishi, Yuishin Izumi and Yasushi Takagi : Therapeutic Devices for Motor Symptoms in Parkinson's Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials., Frontiers in Aging Neuroscience, Vol.14, 2022.
(要約)
Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.
Yoshiteru Tada, Toshitaka Fujihara, Kenji Shimada, Nobuaki Yamamoto, Hiroki Yamazaki, Yuishin Izumi, Masafumi Harada, Yasuhisa Kanematsu and Yasushi Takagi : Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging, Journal of the Neurological Sciences, Vol.436, 1-8, 2022.
(要約)
Arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures. Overall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment. Of the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028). A diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.
Yuki Yamamoto, Nobuaki Yamamoto, Yasuhisa Kanematsu, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Shu Sogabe, Kenji Shimada, Yasushi Takagi and Yuishin Izumi : The claw sign predicts first-pass effect in mechanical thrombectomy for cerebral large vessel occlusion in the anterior circulation, Surgical Neurology International, Vol.13, No.72, 1-7, 2022.
(要約)
Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the "claw sign," was examined as candidate preoperative imaging factor for predicting the FPE. We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE. FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01-7.06; = 0.047). The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke.
Yoshifumi Mizobuchi, Kohhei Nakajima, Toshitaka Fujihara, Mai Azumi and Yasushi Takagi : Development of a Navigation-guided Fence-post Catheter for Brain Tumor Resection, The Journal of Medical Investigation : JMI, Vol.69, No.1,2, 117-119, 2022.
(要約)
Navigation system devices have been developed to allow precise resection of brain tumor. The fence-post catheter techniques that use a navigation system have been used in many neurosurgery centers. However, an exclusive catheter for the fence-post catheter techniques have not been made, and substituted silicon tube of the cerebral ventricle drainage or a Nelaton catheter is widely used. In this brief technical note, we describe a new fence-post catheter with steel tip device that was designed for more precise tissue resection and is useful in tumor resection. The newly designed fence-post catheter helps to visually gauge the accurate depth from the tumor bottom during tumor resection. Furthermore, the catheter tip has moderate weight and is made of a non-magnetic material. Using our fence-post catheter, which has a metal part at the tip of the tube (length, 13 mm), operators can clearly notice that they are getting closer to base of the tumor by checking the metal part during the resection of deep tumors. Our newly developed fence-post tube enables easy confirmation of the distance to deep-tissue regions and improves the degree of safety during tumor removal. J. Med. Invest. 69 : 117-119, February, 2022.
Kenya Kusunose, Hironori Takahashi, Susumu Nishio, Yukina Hirata, Robert Zheng, Takayuki Ise, Koji Yamaguchi, Shusuke Yagi, Daiju Fukuda, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi and Masataka Sata : Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source, Journal of Cardiology, Vol.78, No.5, 355-361, 2021.
(要約)
In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission. Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF. We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05). LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF.
Kenji Shimada, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Shu Sogabe, Kazuhisa Miyake, Yoshiteru Tada, 北里 慶子, Yasuhisa Kanematsu and Yasushi Takagi : Involvement of Neutrophil Extracellular Traps in Cerebral Arteriovenous Malformations, World Neurosurgery, E1-E7, 2021.
(要約)
Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs. We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients. Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus. Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs.
Masaaki Korai, Yasuhisa Kanematsu, Izumi Yamaguchi, Tadashi Yamaguchi, Yuki Yamamoto, Nobuaki Yamamoto, Takeshi Miyamoto, Kenji Shimada, Junichiro Satomi, Mami Hanaoka, Kazuhito Matsuzaki, Koichi Satoh and Yasushi Takagi : Subarachnoid Hemorrhage Due to Rupture of Vertebral Artery Dissecting Aneurysms: Treatments, Outcomes, and Prognostic Factors, World Neurosurgery, Vol.152, e86-e93, 2021.
(要約)
Mortality rate after subarachnoid hemorrhage due to rupture of vertebral artery dissecting aneurysms (VADAs) is high; endovascular coil trapping is the first-line therapy to prevent rerupture. To select optimal treatments, the positional relationship between the VADA and posterior inferior cerebellar artery (PICA) and the morphology of the contralateral vertebral artery must be considered, and outcome predictors of different treatment methods and their possible complications must be identified. We retrospectively studied 44 patients with ruptured VADAs who had undergone endovascular or surgical treatment. VADA morphology was assessed on conventional preoperative angiograms, and VADAs were categorized based on their site in relation to the PICA. VADA site, treatment method, and complications were used to identify prognostic factors. The sites of the 44 VADAs were PICA-proximal (n = 3), PICA-distal (n = 22), PICA-absent (n = 7), and PICA-involved (n = 12). Treatments included internal coil trapping (n = 30), proximal coil occlusion (n = 5), and stent placement (n = 3); surgical flow alteration via an occipital artery-PICA bypass and ligation at the proximal vertebral artery and the PICA origin was performed in 6 patients. Periprocedural rebleeding was associated with a poor outcome. Internal coil trapping prevented the rerupture of PICA-proximal and PICA-absent VADAs, and flow alteration prevented rerupture of PICA-involved VADAs; there were no complications directly attributable to these procedures. Periprocedural rebleeding was a poor prognostic factor. Internal trapping of PICA-proximal and PICA-absent VADAs and flow alteration in PICA-involved VADAs prevented rerupture.
Kenji Shono, Yoshifumi Mizobuchi, Izumi Yamaguchi, Kohhei Nakajima, Yuri Fujiwara, Toshitaka Fujihara, Keiko Kitazato, Kazuhito Matsuzaki, Yoshihiro Uto, Oltea Sampetrean, Hideyuki Saya and Yasushi Takagi : Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway., Scientific Reports, Vol.11, No.1, 2021.
(要約)
Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.
Yasuhisa Kanematsu, Kenji Shimada, Yoshiteru Tada, Masaaki Korai, Takeshi Miyamoto, Shu Sogabe, Izumi Yamaguchi, Yoko Ymamoto, Nobuaki Yamamoto, Yuki Yamamoto, Koichi Satoh and Yasushi Takagi : Coil embolization with overlapping horizontal low-profile stents to treat a giant thrombosed fetal posterior cerebral aneurysm using contralateral approach through anterior communicating artery: Case report., Surgical Neurology International, Vol.12, No.347, 2021.
(要約)
The treatment of internal carotid artery (ICA) - posterior communicating artery aneurysms (ICPC aneurysms) is challenging when a fetal posterior cerebral artery (PCA) arises from the saccular neck. This complex angioarchitecture renders endovascular approaches difficult. Giant thrombosed IC-PC aneurysms are also hard to treat by endovascular coiling because its flow-diversion effect is insufficient. We report the first case of a ruptured giant thrombosed IC-PC aneurysm associated with a fetal PCA that was successfully treated by coil embolization with retrograde overlap horizontal stenting using low-profile stents introduced through the contralateral ICA. The aneurysm was completely occluded and follow-up MRI scans demonstrated the reduction of the aneurysmal size. Our technique is advantageous because low-profile stents can be used to treat lesions not accessible with flow-diverter stents due their presence in complex angioarchitectures, and overlap stenting may have flow-diversion effects that can result in the complete occlusion of giant thrombosed aneurysms.
Pham Tran Phuong, Daiju Fukuda, Sachiko Nishimoto, JR Kim-Kaneyama, XF Lei, Yutaka Takahashi, Tomohito Sato, Kimie Tanaka, Kumiko Suto, Yutaka Kawabata, Koji Yamaguchi, Shusuke Yagi, Kenya Kusunose, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi, Michio Shimabukuro, Mitsutoshi Setou, Glen N Barber and Masataka Sata : STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases, European Heart Journal, Vol.42, No.42, 4336-4348, 2021.
(要約)
Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis. Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP. Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.
Kenji Shimada, Yoko Yamamoto, Takeshi Miyamoto, Shu Sogabe, Toshitaka Fujihara, Kohhei Nakajima, Yoshifumi Mizobuchi, Yasuhisa Kanematsu and Yasushi Takagi : Efficacy of Intra-arterial Indocyanine Green Videoangiography in Hemangioblastoma Surgery: A Case Report., NMC Case Report Journal, Vol.8, No.1, 295-300, 2021.
(要約)
Intravenous indocyanine green (ICG) videoangiography is reportedly useful for vascular neurosurgery, and for treating hemangioblastoma due to its high vascularity. Videoangiography obtained after intra-arterial ICG injection has emerged as a more useful option than that after intravenous injection. This report offers the first description of a case of hemangioblastoma successfully treated using intra-arterial ICG videoangiography, and describes the efficacy of this technique. A 20-year-old man presented with progressive cerebellar ataxia and dysphagia. Magnetic resonance imaging (MRI) revealed an enhanced solid tumor in the medulla oblongata. Digital subtraction angiography (DSA) showed a highly vascularized tumor. Surgery was performed to remove the tumor in a hybrid operating room. A catheter was introduced into the vertebral artery (VA) for intra-arterial ICG videoangiography. Superficial feeders and drainers were identified and flow dynamic changes in the tumor were assessed by intra-arterial ICG videoangiography. The tumor was removed after confirming lack of flow in the drainer. Intra-arterial ICG videoangiography was more useful than intravenous ICG videoangiography in hemangioblastoma surgery for identifying feeders and drainers and assessing flow dynamics in the tumor. Use of Flow 800 made these findings simpler and easier to evaluate.
Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki, Yuishin Izumi and Yasushi Takagi : Percutaneous Transluminal Angioplasty and Stenting Using an Aspiration Catheter, Journal of Neuroendovascular Therapy, Vol.16, No.5, 277-282, 2021.
(要約)
<p><b>Objective</b>: During percutaneous transluminal angioplasty (PTA) for the vertebral artery, occlusion of the subclavian artery using a balloon guiding catheter may be useful to prevent embolism of clots and/or debris distal to an atherosclerotic lesion. However, when placing a balloon guiding catheter at the intended vessels is difficult, it may be useful to use an aspiration catheter (AC) for mechanical thrombectomy as an intermediate catheter to suction way clots and/or debris. We report two cases in which PTA was performed for an atherosclerotic lesion at the intracranial vertebral artery using an AC, which ended without complications.</p><p><b>Case Presentations</b>: Case 1: A 74-year-old man presented with dysarthria and was admitted to our hospital. MRI revealed severe left vertebral artery stenosis and diffuse cerebral infarct areas at the territory of the posterior circulation. The patient had an abdominal aortic aneurysm and abnormally shaped left tortuous subclavian artery. Therefore, we performed PTA and stenting via the left brachial artery. We guided a 6-Fr long sheath to the left subclavian artery, and a 6-Fr AC for thrombectomy was guided through the long sheath to the V4 portion of the left vertebral artery. Thereafter, PTA was carried out under manual aspiration from the AC. As restenosis at the atherosclerotic lesion occurred after PTA, we performed stenting using a coronary stent system for this lesion under manual aspiration from the AC. No new infarct areas were observed on post-procedural MRI. Case 2: A 74-year-old woman presented with dysarthria and was admitted to our hospital. MRI demonstrated basilar artery occlusion and diffuse cerebral infarct areas at the territory of the posterior circulation. As her symptom worsened after admission, we performed urgent mechanical thrombectomy. We first performed thrombectomy using a stent retriever and then performed PTA and stenting (PTAS) for residual basilar artery stenosis via the AC under manual aspiration.</p><p><b>Conclusion</b>: When it is difficult to place a guiding catheter at the intended vessels during PTA, an AC may be useful to prevent distal embolization.</p>
Hiroshi Koyama, Hideo Mure, Ryoma Morigaki, Ryosuke Miyamoto, Kazuhisa Miyake, Taku Matsuda, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Satoshi Goto and Yasushi Takagi : Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia, Life, Vol.11, No.6, 477, 2021.
(要約)
Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% ( < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.
Yoshifumi Mizobuchi, Aki Shimada, Kohhei Nakajima, Hiroshi Kagusa and Yasushi Takagi : Reversible Hearing Impairment Due to Inferior Colliculi Compression by a Pineal Glial Cyst, NMC Case Report Journal, Vol.8, No.1, 79-84, 2021.
Manabu Ishihara, Nobuto Nakanishi, Rie Tsutsumi, Kanako Hara, Kyoka Machida, Nobuaki Yamamoto, Yasuhisa Kanematsu, Hiroshi Sakaue, Jun Oto and Yasushi Takagi : Elevated Urinary Titin and its Associated Clinical Outcomes after Acute Stroke., Journal of Stroke & Cerebrovascular Diseases, Vol.30, No.3, 2021.
(要約)
Forty-one patients were included (29 male; age, 68 ± 15 years), 29 had ischemic stroke, 8 had intracerebral hemorrhage, and 4 had subarachnoid hemorrhage. The levels of urinary titin on days 1, 3, 5, and 7 were 9.9 (4.7-21.1), 16.2 (8.6-22.0), 8.9 (4.8-15.2), and 8.7 (3.6-16.2) pmol/mg Cr, respectively. The peak urinary titin level was associated with the mRS score (r = 0.55, p < 0.01), the NIHSS score (r = 0.72, p < 0.01), and the BI (r = -0.59, p < 0.01) upon hospital discharge. In multivariate analysis, the peak urinary titin was associated with poor outcome (p = 0.03).
(キーワード)
Aged / Aged, 80 and over / Biomarkers / Connectin / Disability Evaluation / Female / Functional Status / Humans / Male / Middle Aged / Patient Discharge / Predictive Value of Tests / Prospective Studies / Recovery of Function / Stroke / Time Factors / Treatment Outcome / Up-Regulation / Urinalysis
Kohhei Nakajima, Yoshifumi Mizobuchi, Toshitaka Fujihara, Mai Azumi and Yasushi Takagi : Continued-Maintenance Therapy with High-dose Methotrexate Improves Overall Survival of Patients with Primary Central Nervous System Lymphoma., The Journal of Medical Investigation : JMI, Vol.68, No.3.4, 286-291, 2021.
(要約)
In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021.
(キーワード)
Aged / Antineoplastic Combined Chemotherapy Protocols / Central Nervous System / Central Nervous System Neoplasms / Humans / Lymphoma, Non-Hodgkin / Methotrexate / Retrospective Studies
Daisy Ma Tabuena, Ryoma Morigaki, Ryosuke Miyamoto, Hideo Mure, Nobuaki Yamamoto, Kazuhisa Miyake, Taku Matsuda, Yuishin Izumi, Yasushi Takagi, P Rollin Tabuena and Toshitaka Kawarai : Ataxia with vitamin E deficiency in the Philippines: A case report of two siblings., The Journal of Medical Investigation : JMI, Vol.68, No.3.4, 400-403, 2021.
(要約)
Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.
Nobuaki Yamamoto, Yuishin Izumi, Yuki Yamamoto, K Kuroda, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki and Yasushi Takagi : Factors associated with DWI-ASPECTS score in patients with acute ischemic stroke due to cerebral large vessel occlusion, Clinical Neurology and Neurosurgery, Vol.199, 106316, 2020.
(要約)
The Alberta Stroke Program Early CT score (ASPECTS) of patients with acute ischemic stroke at the time of admission varies. It is crucial to select appropriate methods of treatment, such as recombinant tissue-plasminogen activator, and/or endovascular thrombectomy. According to the recent guidelines, endovascular thrombectomy for patients with large vessel occlusion (LVO) and lesion of ischemic tissue that was not yet infarcted is effective. This result demonstrates the importance of patient selection based on neuroradiological imaging. However, there are many patients who are judged as ineligibility for recanalization therapy because of presence of large ischemic core, indicating unfavorable ASPECTS, at the time of admission. We investigated the factors associated with favorable diffusion-weighted image (DWI)-ASPECTS score at the time of admission. We studies patients with LVO within 24 h from onset who were admitted into our hospital. We divided them into two groups, with favorable DWI-ASPECTS (≥6), and unfavorable DWI-ASPECTS (<6) at the time of admission. We investigated factors associated with favorable DWI-ASPECTS by evaluation of our patients' severity of clinical symptom, etiology, and radiological findings. This study showed that mild white matter lesion (Fazekas scale ≤1), absence of internal carotid artery (ICA) occlusion and cardioembolic stroke were independent factor of favorable DWI-ASPECTS at the time of admission. (odds ratio 12.92, p < 0.001, odds ratio 0.31, p = 0.001, odds ratio 0.16, p = 0.001, respectively) CONCLUSIONS: Absence of severe white matter lesion, cardioembolic stroke, and ICA occlusion might be associated with favorable DWI-ASPECTS at the time of admission.
(キーワード)
Aged / Aged, 80 and over / Brain Ischemia / Cerebrovascular Disorders / Diffusion Magnetic Resonance Imaging / Female / Humans / Ischemic Stroke / Male / Middle Aged / Patient Admission / Prospective Studies / Retrospective Studies / Severity of Illness Index
Kenji Shono, Izumi Yamaguchi, Yoshifumi Mizobuchi, Hiroshi Kagusa, Akiko Sumi, Toshitaka Fujihara, Kohhei Nakajima, T Keiko Kitazato, Kazuhito Matsuzaki, Hideyuki Saya and Yasushi Takagi : Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma., Scientific Reports, Vol.10, No.1, 2020.
(要約)
Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin
Ryoma Morigaki, Ryosuke Miyamoto, Hideo Mure, Koji Fujita, Taku Matsuda, Yoko Yamamoto, Masahito Nakataki, Tetsuya Okahisa, Yuki Matsumoto, Kazuhisa Miyake, Nobuaki Yamamoto, Ryuji Kaji, Yasushi Takagi and Satoshi Goto : Can Pallidal Deep Brain Stimulation Rescue Borderline Dystonia? Possible Coexistence of Functional (Psychogenic) and Organic Components., Brain Sciences, Vol.10, No.9, 636, 2020.
(要約)
The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.
Hideo Mure, Naoto Toyoda, Ryoma Morigaki, Koji Fujita and Yasushi Takagi : Clinical Outcome and Intraoperative Neurophysiology of the Lance-Adams Syndrome Treated with Bilateral Deep Brain Stimulation of the Globus Pallidus Internus: A Case Report and Review of the Literature., Stereotactic and Functional Neurosurgery, Vol.98, No.6, 399-403, 2020.
(要約)
Our results show that impairment in the basal ganglion circuitry might be involved in the pathogenesis of myoclonus in patients with LAS.
Yuki Kanazawa, Masafumi Harada, Mitsuharu Miyoshi, Takashi Abe, Yuki Matsumoto and Yasushi Takagi : Characterization of Brain Tumors using Amide Proton and Nuclear Overhauser Effect at 3 Tesla MR Scanner, Proceedings of the 28th Virtual Conference of ISMRM, No.1697, 2020.
48.
Yuki Kanazawa, Masafumi Harada, Tosiaki Miyati, Takashi Abe, Mitsuharu Miyoshi, Yuki Matsumoto, Hiroaki Hayashi, Yasuhisa Kanematsu and Yasushi Takagi : Chemical Exchange Saturation Transfer Imaging for Atherosclerotic Plaques, Proceedings of 28th Virtual Meeting of ISMRM, No.2128, 2020.
49.
Shotaroh Yoshioka, Takeshi Miyamoto, Junichiro Satomi, Yoshiteru Tada, Kenji Yagi, Kenji Shimada, Koji Naruishi, Eiji Shikata, Izumi Yamaguchi, Tadashi Yamaguchi, Masaaki Korai, Yoshihiro Okayama, Masafumi Harada, Keiko Kitazato, Yasuhisa Kanematsu, Shinji Nagahiro and Yasushi Takagi : Disequilibrium of Plasma Protease/Anti-Protease Due to Severe Periodontal Disease Contributes to Human Subarachnoid Hemorrhage, Neurosurgery Open, Vol.1, No.3, 1-9, 2020.
Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; >0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.
Akemi Hioka, Yoshiteru Tada, Keiko Kitazato, Naoki Akazawa, Yasushi Takagi and Shinji Nagahiro : Action observation treatment improves gait ability in subacute to convalescent stroke patients., Journal of Clinical Neuroscience, Vol.75, 55-61, 2020.
(要約)
The aim of this study was to investigate the effects of action observation treatment (AOT) on gait ability in patients with subacute to convalescent stroke. Sixteen patients with subacute stroke were divided into a control group (n = 8) and AOT group (n = 8) when admitted to the convalescent ward. The control group received a conventional rehabilitation only. In addition to conventional rehabilitation, the AOT received AOT for 3 months (30 min per day 5 times per week). The AOT involved observing the action of another subject in a comfortable gait situation from the front, sides, and back via video and conducting the actual action. All participants were assessed during the main-assessment period, which included a baseline (i.e., when admitted to the convalescent ward) and 1, 2, and 3 months after baseline. The sub-assessment period at 2 and 3 months after baseline was conducted with participants who could walk independently. The main outcomes of the main-assessment and sub-assessment periods were Functional Ambulation Classification (FAC) and the 10-m walk test (10MWT), respectively. With respect to the FAC, we used a split plot design analysis of covariance to test the interaction between assessment time and group. There was no significant interaction between assessment time and group in FAC. However, a significant improvement of the 10MWT in the sub-assessment period was observed in the AOT group, but not the control group. Our results indicate that AOT may be an effective therapy for patients with subacute to convalescent stroke who can walk independently.
Yamamoto Yuki, Nobuaki Yamamoto, Koji Fujita, Fukumoto Tatsuya, Murakami Nagahisa, Hideo Mure, Yasuhisa Kanematsu, Yasushi Takagi and Yuishin Izumi : Cerebral Venous Thrombosis: An Unexpected Complication with Cerebrospinal Fluid Leaks after a Fall in a Patient with Spinocerebellar Ataxia Type 6., Internal Medicine, Vol.59, No.14, 1749-1753, 2020.
Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yuishin Izumi and Yasushi Takagi : Cone beam-computed tomography angiography by intravenous contrast injection is reliable to evaluate patients with large vessel occlusion, Journal of Clinical Neuroscience, Vol.70, 67-71, 2019.
(要約)
Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients due to emergent large vessel occlusion (ELVO) is standard treatment, the benefits, however, are highly time-sensitive. After patient eligibility for reperfusion therapy is determined by conventional radiological examinations, the time to be transferred from the department of radiological examination to angiography-suites is critical. We speculated that the time required for the diagnosis of AIS might be reduced if we could determine MT eligibility in patients with ELVO at angiography-suites. Modern angiography-suites with flat panel detectors can perform cone beam (CB)-CT. We performed CB-CTA using intravenous injection of contrast agent to evaluate occlusion sites, collateral score, and construction of vessels distal to occlusion sites and determined if CB-CTA could be useful to evaluate patients with ELVO. We included 15 patients with ELVO diagnosed by conventional MRI or CT/CTA, and investigated whether CB-CTA was reliable to diagnose occlusion sites. We also studied if collateral score on CB-CTA was associated with prognosis after successful reperfusion by MT by comparison between favorable (modified Rankin scale (mRS) 0-2), and unfavorable outcome group (mRS 3-6). There was strong agreement of occlusion sites between CB-CTA and conventional radiological examination (κ = 0.80). Collateral score determined by CB-CTA was significantly different between favorable outcome and unfavorable outcome group (median collateral score 2.3 v.s. 1.3, p = 0.040). Although prospective study of AIS patients at a radiography department is indispensable, CB-CTA performed in an angiography-suite might be useful to evaluate patients with ELVO.
Izumi Yamaguchi, Yasuhisa Kanematsu, Kenji Shimada, Masaaki Korai, Takeshi Miyamoto, Eiji Shikata, Tadashi Yamaguchi, Nobuaki Yamamoto, Yuki Yamamoto, Keiko Kitazato, Yoshihiro Okayama and Yasushi Takagi : Active Cancer and Elevated D-Dimer Are Risk Factors for In-Hospital Ischemic Stroke, Cerebrovascular Diseases Extra, Vol.9, No.3, 129-138, 2019.
(要約)
Little attention has been paid to the pathogenesis of in-hospital stroke, despite poor outcomes and a longer time from stroke onset to treatment. We studied the pathophysiology and biomarkers for detecting patients who progress to in-hospital ischemic stroke (IHS). Seventy-nine patients with IHS were sequentially recruited in the period 2011-2017. Their characteristics, care, and outcomes were compared with 933 patients who had an out-of-hospital ischemic stroke (OHS) using a prospectively collected database of the Tokushima University Stroke Registry. Active cancer and coronary artery disease were more prevalent in patients with IHS than in those with OHS (53.2 and 27.8% vs. 2.0 and 10.9%, respectively; p < 0.001), the median onset-to-evaluation time was longer (300 vs. 240 min; p = 0.015), and the undetermined etiology was significantly higher (36.7 vs. 2.4%; p < 0.001). Although there was no significant difference in stroke severity at onset between the groups, patients with IHS had higher modified Rankin Scale (mRS) scores (3-6) at discharge (67.1 vs. 50.3%; p = 0.004) and rates of death during hospitalization (16.5 vs. 2.9%; p < 0.001). D-dimer (5.8 vs. 0.8 µg/mL; p < 0.001) and fibrinogen (532 vs. 430 mg/dL; p = 0.014) plasma levels at the time of onset were significantly higher in patients with IHS after propensity score matching. Multivariate logistic regression analysis revealed that active cancer (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.26-4.20), prestroke mRS scores 3-5 (OR 6.78; 95% CI 3.96-11.61), female sex (OR 1.57; 95% CI 1.19-2.08), and age ≥75 years (OR 2.36; 95% CI 1.80-3.08) were associated with poor outcomes. Patients with IHS had poorer outcomes than those with OHS because of a higher prevalence of active cancer and functional dependence before stroke onset. Elevated plasma levels of D-dimer and fibrinogen, especially with active cancer, can help identify patients who are at a higher risk of progression to IHS.
Tanaka Hiroki, Nankaku Manabu, Nishikawa Toru, Yonezawa Honami, Mori Hiroki, Kikuchi Takayuki, Nishi Hidehisa, Yasushi Takagi, Miyamoto Susumu, Ikeguchi Ryosuke and Matsuda Shuichi : A follow-up study of the effect of training using the Hybrid Assistive Limb on Gait ability in chronic stroke patients., Topics in Stroke Rehabilitation, Vol.26, No.7, 491-496, 2019.
(要約)
: Recently, use of the Hybrid Assistive Limb (HAL) that is effective for improvement of gait ability in chronic stroke patients has been reported. However, how long the effects are maintained remains unknown. The purpose of the present study was to investigate whether the effect of gait training using the HAL on gait ability was maintained for 3 months after the intervention. : A longitudinal, observational study with an intervention for a single group that adhered to the STROBE guidelines was performed. Nine chronic stroke patients were enrolled in this study. The patients performed gait training sessions using the HAL, 2-5 sessions/week for 3 weeks. Gait speed, stride length, cadence, and 2-minute walk distance (2MWD) were measured before and after intervention and at 3-month follow-up. The clinical trial registration number of this study is UMIN000012764 R000014756. : Compared to the initial status, gait speed ( = .02), stride length ( = .03), cadence ( = .01), and 2MWD ( < .05) were significantly increased immediately after the intervention. Moreover, gait speed ( < .01), cadence ( = .03), and 2MWD ( = .02) remained significantly higher 3 months after the intervention. There were no significant changes in all outcome measures between after intervention and at 3-month follow-up. : This study showed that gait training using the HAL resulted in significant improvement of gait ability after the intervention and the effect was maintained for 3 months after the training.
Yoshinori Maki, Takayuki Kikuchi, Katsuya Komatsu, Yasushi Takagi and Susumu Miyamoto : Rare Case of Concurrent Glossopharyngeal and Trigeminal Neuralgia, in Which Glossopharyngeal Neuralgia was Possibly Induced by Postoperative Changes Following Microvascular Decompression for Trigeminal Neuralgia., World Neurosurgery, Vol.130, 150-153, 2019.
(要約)
Glossopharyngeal neuralgia (GPN) and trigeminal neuralgia (TN) can result from mechanical stimulation of the glossopharyngeal nerve (GPNv) and trigeminal nerve (TNv) by blood vessels. TN can cause severe pain in the orofacial region, whereas GPN manifests as pain in the tongue, throat, tonsil, and ear. Although these 2 neuralgias can occur concurrently, concurrence of recurrent TN and GPN that develops postoperatively has not been previously described. A 68-year-old male complained of right glossalgia and pain in the pharynx radiating to the right auricular area. The patient had previously undergone microvascular decompression (MVD) for right TN. Medication and intraoral xylocaine spray did not relieve the symptoms. An oral surgeon was unable to find any disease related to the glossalgia. The anesthesiologist pointed out that the symptoms could be from partial recurrence of the TN because the patient also complained of pain in the inferior alveolus. Magnetic resonance angiography indicated that the right GPNv seemed to be compressed by the right posterior inferior cerebellar artery (PICA); hence, MVD for both GPN and TN was performed. Intraoperatively, the right PICA was found to be adherent to the GPNv because of the thickened arachnoid membrane and was subsequently detached. The TNv was also examined, but only a Teflon ball was found, which was detached from the TNv. The GPN disappeared postoperatively, although TN persisted after the second operation. GPN can result from adhesions between the GPNv and arachnoid membrane following previous MVD.
(キーワード)
Aged / Glossopharyngeal Nerve / Glossopharyngeal Nerve Diseases / Humans / Male / Microvascular Decompression Surgery / Pain / Postoperative Period / Trigeminal Nerve / Trigeminal Neuralgia / Vertebral Artery
Tadashi Yamaguchi, Takeshi Miyamoto, keiko Kitazato, Eiji Shikata, Izumi Yamaguchi, Masaaki Korai, Kenji Shimada, Kenji Yagi, Yoshiteru Tada, Yoshihito Matsuzaki, Yasuhisa Kanematsu and Yasushi Takagi : Time-dependent and site-dependent morphological changes in rupture-prone arteries: ovariectomized rat intracranial aneurysm model, Journal of Neurosurgery, 2019.
(要約)
The pathogenesis of intracranial aneurysm rupture remains unclear. Because it is difficult to study the time course of human aneurysms and most unruptured aneurysms are stable, animal models are used to investigate the characteristics of intracranial aneurysms. The authors have newly established a rat intracranial aneurysm rupture model that features site-specific ruptured and unruptured aneurysms. In the present study the authors examined the time course of changes in the vascular morphology to clarify the mechanisms leading to rupture. Ten-week-old female Sprague-Dawley rats were subjected to hemodynamic changes, hypertension, and ovariectomy. Morphological changes in rupture-prone intracranial arteries were examined under a scanning electron microscope and the association with vascular degradation molecules was investigated. At 2-6 weeks after aneurysm induction, morphological changes and rupture were mainly observed at the posterior cerebral artery; at 7-12 weeks they were seen at the anterior Willis circle including the anterior communicating artery. No aneurysms at the anterior cerebral artery-olfactory artery bifurcation ruptured, suggesting that the inception of morphological changes is site dependent. On week 6, the messenger RNA level of matrix metalloproteinase-9, interleukin-1β, and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of metalloproteinase-2 was significantly higher at the posterior cerebral artery, but not at the anterior communicating artery, of rats with aneurysms than in sham-operated rats. These findings suggest that aneurysm rupture is attributable to significant morphological changes and an increase in degradation molecules. Time-dependent and site-dependent morphological changes and the level of degradation molecules may be indicative of the vulnerability of aneurysms to rupture.
Eiji Shikata, Tetsuya Tamura, Kiyohito Shinno, Yoshihiro Okayama, Naoki Shinohara, Kenji Shimada, Yasuhisa Kanematsu, Keiko T Kitazato, Shinji Nagahiro and Yasushi Takagi : Importance of Managing the Water-Electrolyte Balance by Delivering the Optimal Minimum Amount of Water and Sodium After Subarachnoid Hemorrhage., World Neurosurgery, Vol.129, e352-e360, 2019.
(要約)
After aneurysmal subarachnoid hemorrhage (aSAH), crystalloid fluids with a relatively high sodium concentration have been used to maintain the cerebral blood flow. However, the prophylactic delivery of water and sodium by intravenous (IV) infusion will not necessarily improve the prognosis of patients after aSAH, and the excessive supply of water and sodium can negatively affect the outcome. We hypothesized that the delivery of an optimal amount of water and sodium separately might improve the outcome after aSAH. We recruited 55 consecutive patients who had undergone clipping or endovascular coil embolization after aSAH. Group 1 (n = 33) received conventional therapy (i.e., prophylactic IV sodium and water [protocol 1]). Group 2 (n = 22) received the optimal amount of water and sodium separately (protocol 2). The median total of water and sodium chloride supplied in group 1 was significantly greater than that supplied in group 2 (P < 0.01). The modified Rankin scale score at discharge was 0-2 in 15 patients (95%) in group 2 and 23 patients (55%) in group 1 (P < 0.001). On multivariate logistic regression analysis, the odds ratio for a discharge modified Rankin scale score of 0-2 or 3-6 was significantly associated with the treatment protocol (P < 0.05) and the net fluid balance on days 4-8 (P < 0.05). The separate delivery of optimal amounts of water and sodium could be a promising therapeutic strategy to improve the prognosis after aSAH.
Hermanto Yulius, Takakuni Maki, Yasushi Takagi, Susumu Miyamoto and Jun Takahashi : Xeno-free culture for generation of forebrain oligodendrocyte precursor cells from human pluripotent stem cells, Journal of Neuroscience Research, Vol.97, No.7, 828-845, 2019.
(要約)
Oligodendrocytes (OLs) show heterogeneous properties that depend on their location in the central nervous system (CNS). In this regard, the investigation of oligodendrocyte precursor cells (OPCs) derived from human pluripotent stem cells (hPSCs) should be reconsidered, particularly in cases of brain-predominant disorders for which brain-derived OPCs are more appropriate than spinal cord-derived OPCs. Furthermore, animal-derived components are responsible for culture variability in the derivation and complicate clinical translation. In the present study, we established a xeno-free system to induce forebrain OPCs from hPSCs. We induced human forebrain neural stem cells (NSCs) on Laminin 511-E8 and directed the differentiation to the developmental pathway for forebrain OLs with SHH and FGF signaling. OPCs were characterized by the expression of OLIG2, NKX2.2, SOX10, and PDGFRA, and subsequent maturation into O4 cells. In vitro characterization showed that >85% of the forebrain OPCs (O4 ) underwent maturation into OLs (MBP ) 3 weeks after mitogen removal. Upon intracranial transplantation, the OPCs survived, dispersed in the corpus callosum, and matured into (GSTϖ ) OLs in the host brains 3 months after transplantation. These findings suggest our xeno-free induction of forebrain OPCs from hPSCs could accelerate clinical translation for brain-specific disorders.
Toshiyuki Okazaki, Yasuhisa Kanematsu, Kenji Shimada, Masaaki Korai, Junichiro Satomi, Masaaki Uno, Shinji Nagahiro and Yasushi Takagi : A Single-center Retrospective Study with 5- and 10-year Follow-up of Carotid Endarterectomy with Patch Graft., Neurologia Medico-Chirurgica, Vol.59, No.6, 231-237, 2019.
(要約)
Carotid endarterectomy (CEA) is widely used for cervical artery stenosis. In Japan, primary closure after endarterectomy has been a standard technique. Recently, the patch closure has been shown to be superior to the primary suture for the prevention of restenosis and ipsilateral stroke. This study evaluated the 5- and 10-year outcomes following CEA with patch graft closure in our institution. Between January 2000 and March 2013, 134 patients, who underwent CEA with patch graft closure were investigated in the current retrospective study. Among these patients, 102 CEAs in 97 patients were followed up for 5 years and 66 CEAs in 61 patients were for 10 years after the procedure. Restenosis was defined as >50% recurrent luminal narrowing at the endarterectomy site. In 5 years, symptomatic restenosis exhibited minor stroke in one patient at 58 months after CEA (restenosis rate 1.0%). The ipsilateral minor stroke occurred in three patients including the above case (2.9%). In 10 years, asymptomatic restenosis occurred in three patients in addition to the above symptomatic case (restenosis rate 6.1%), and the ipsilateral minor stroke occurred in four patients (6.1%). Carotid endarterectomy with patch graft exerted a high protective effect from restenosis up to 5 and 10 years in our institution. The number of carotid artery stenting is increasing all over the world but we speculated that the established surgical procedure of patched CEA prevented restenosis and ipsilateral stroke.
Mieko Oka, Mika Kushamae, Tomohiro Aoki, Tadashi Yamaguchi, Keiko Kitazato, Yu Abekura, Takakazu Kawamata, Tohru Mizutani, Miyamoto Susumu and Yasushi Takagi : KRAS G12D or G12V Mutation in Human Brain Arteriovenous Malformations, World Neurosurgery, Vol.126, e1365-e1373, 2019.
(要約)
Brain arteriovenous malformations (BAVMs) are vascular malformations composed of tangles of abnormally developed vasculature without capillaries. Abnormal shunting of arteries and veins is formed, resulting in high-pressure vascular channels, which potentially lead to rupture. BAVMs are generally considered a congenital disorder. But clinical evidence regarding involution, regrowth, and de novo formation argue against the static condition of this disease. Recently, the presence of the somatic activating KRAS mutations in more than half of BAVM cases was reported, suggesting the role of KRAS function in the pathogenesis. KRAS mutation in codon35 (G→A, G12D; G→T, G12V) was examined by a digital polymerase chain reaction analysis using genome purified from paraffin-embedded slides of human BAVMs. We also examined protein expression of KRAS G12D in lesions to corroborate results from digital polymerase chain reaction analysis. We detected codon35 G→A mutation in 15 (39.5%) among 38 samples and codon35 G→T mutation in 10 (27.0%) among 37 samples we could assess mutations. There were no samples positive for both codon35 G→A and G→T mutation. The ratio of codon35 G→A mutation ranged from 0.60% to 12.28% and that of G→T was from 1.20% to 8.99%. We next examined protein expression of KRAS G12D in BAVM lesions in immunohistochemistry. A KRAS G12D mutant was detected mainly in endothelial cells of dilated vessels in lesions. KRAS mutations in codon35 were detected in about two thirds of specimens examined. KRAS function may actively contribute to the pathobiology of BAVM and can become a therapeutic target.
(キーワード)
Adult / Arteriovenous Fistula / Child / Female / Genetic Predisposition to Disease / Humans / Intracranial Arteriovenous Malformations / Male / Point Mutation / Proto-Oncogene Proteins p21(ras)
Natsue Kishida, Takakuni Maki, Yasushi Takagi, Ken Yasuda, Hisanori Kinoshita, Takashi Ayaki, Takayuki Noro, Yusuke Kinoshita, Yuichi Ono, Hiroharu Kataoka, Kazumichi Yoshida, Eng H. Lo, Ken Arai, Susumu Miyamoto and Ryosuke Takahashi : Role of Perivascular Oligodendrocyte Precursor Cells in Angiogenesis After Brain Ischemia., Journal of the American Heart Association, Vol.8, No.9, e011824, 2019.
(要約)
Background Oligodendrocyte precursor cells ( OPC s) regulate neuronal, glial, and vascular systems in diverse ways and display phenotypic heterogeneity beyond their established role as a reservoir for mature oligodendrocytes. However, the detailed phenotypic changes of OPC s after cerebral ischemia remain largely unknown. Here, we aimed to investigate the roles of reactive OPC s in the ischemic brain. Methods and Results The behavior of OPC s was evaluated in a mouse model of ischemic stroke produced by transient middle cerebral artery occlusion in vivo. For in vitro experiments, the phenotypic change of OPC s after oxygen glucose derivation was examined using a primary rat OPC culture. Furthermore, the therapeutic potential of hypoxic OPC s was evaluated in a mouse model of middle cerebral artery occlusion in vivo. Perivascular OPC s in the cerebral cortex were increased alongside poststroke angiogenesis in a mouse model of middle cerebral artery occlusion. In vitro RNA -seq analysis revealed that primary cultured OPC s increased the gene expression of numerous pro-angiogenic factors after oxygen glucose derivation. Hypoxic OPC s secreted a greater amount of pro-angiogenic factors, such as vascular endothelial growth factor and angiopoietin-1, compared with normoxic OPC s. Hypoxic OPC -derived conditioned media increased the viability and tube formation of endothelial cells. In vivo studies also demonstrated that 5 consecutive daily treatments with hypoxic OPC -conditioned media, beginning 2 days after middle cerebral artery occlusion, facilitated poststroke angiogenesis, alleviated infarct volume, and improved functional disabilities. Conclusions Following cerebral ischemia, the phenotype of OPC s in the cerebral cortex shifts from the parenchymal subtype to the perivascular subtype, which can promote angiogenesis. The optimal use of hypoxic OPC s secretome would provide a novel therapeutic option for stroke.
Akinori Miyakoshi, Takeshi Funaki, C Jun Takahashi, Yasushi Takagi, Takayuki Kikuchi, Kazumichi Yoshida, Hiroharu Kataoka, Yohei Mineharu, Masakazu Okawa, Yukihiro Yamao, Yasutaka Fushimi, Tomohisa Okada, Kaori Togashi and Susumu Miyamoto : Restoration of Periventricular Vasculature After Direct Bypass for Moyamoya Disease: Intra-Individual Comparison, Acta Neurochirurgica, Vol.161, No.5, 947-954, 2019.
(要約)
While periventricular anastomosis, a unique abnormal vasculature in moyamoya disease, has been studied in relation to intracranial hemorrhage, no study has addressed its change after bypass surgery. The authors sought to test whether direct bypass surgery could restore normal periventricular vasculature. Patients who had undergone direct bypass surgery for moyamoya disease at a single institution were eligible for the study. Baseline, postoperative, and follow-up magnetic resonance angiography (MRA) scans were scheduled before surgery, after the first surgery, and 3 to 6 months after contralateral second surgery, respectively. Sliding-thin-slab maximum-intensity-projection coronal MRA images of periventricular anastomoses were scored according to the three subtypes (lenticulostriate, thalamic, and choroidal anastomosis). Baseline and postoperative MRA images were compared to obtain a matched comparison of score changes in the surgical and nonsurgical hemispheres within individuals (intra-individual comparison). Of 110 patients, 42 were identified for intra-individual comparisons. The periventricular anastomosis score decreased significantly in the surgical hemispheres (median, 2 versus 1; p < 0.001), whereas the score remained unchanged in the nonsurgical hemispheres (median, 2 versus 2; p = 0.57); the score change varied significantly between the surgical and nonsurgical hemispheres (p < 0.001). Of the 104 periventricular-anastomosis-positive hemispheres undergoing surgery, 47 (45.2%) were assessed as negative in the follow-up MRA. Among the subtypes, choroidal anastomosis was most likely to be assessed as negative (79.7% of positive hemispheres). Periventricular vasculature can be restored after direct bypass. The likelihood of correction of choroidal anastomosis is a subject requiring further studies.
Toshihiro Munemitsu, Akira Ishii, Eiji Okada, Hideo Chihara, Kazumichi Yoshida, Jun C Takahashi, Yasushi Takagi and Susumu Miyamoto : Ex Vivo Assessment of Various Histological Differentiation in Human Carotid Plaque with Near-infrared Spectroscopy Using Multiple Wavelengths., Neurologia Medico-Chirurgica, Vol.59, No.5, 163-171, 2019.
(要約)
We previously reported that near-infrared hyperspectral imaging enabled the localization of atherosclerotic plaques from outside the vessels, but not the optical characteristics of each histological component. Therefore, the near-infrared spectrum of each component was collected from the sliced section of the human carotid plaque obtained with endarterectomy and the optical characteristics were confirmed in several wavelengths. Based on this information, we assessed the diagnostic accuracy for ex vivo chemogram in each plaque component created with near-infrared spectroscopy (NIRS), using multiple wavelengths. The chemogram projected on the actual image of plaque was created based on light intensity and transmittance change at three wavelengths. The wavelengths that were mainly were 1440, 1620, 1730, and 1930 nm. We evaluated the accuracy of histological diagnosis in chemogram compared with pathological findings, analyzing interobserver agreement with κ-statistics. The chemograms that we created depicted the components of fibrous tissue, smooth muscle, lipid tissue, intraplaque hemorrhage, and calcification. Diagnostic odds ratio in each component was as follows: 259.6 in fibrous tissue, 144 in smooth muscle, 1123.5 in lipid tissue, 29.3 in intraplaque hemorrhage, and 136.3 in calcification. The κ-statistics revealed that four components, excluding intraplaque hemorrhage, had substantial or almost perfect agreement. Thus, this study demonstrated the feasibility of using chemogram focused on specific component during the histological assessment of atherosclerotic plaques, highlighting its potential diagnostic ability. Chemograms of various target components can be created by combining multiple wavelengths. This technology may prove to be useful in improving the histological assessment of plaque using NIRS.
Yamamoto Yuki, Nobuaki Yamamoto, Yasuhisa Kanematsu, Masaaki Korai, Kenji Shimada, Yuishin Izumi and Yasushi Takagi : The Claw Sign: An angiographic Predictor of Recanalization After Mechanical Thrombectomy for Cerebral Large Vessel Occlusion., Journal of Stroke & Cerebrovascular Diseases, Vol.28, No.6, 1555-1560, 2019.
(要約)
Mechanical thrombectomy undoubtedly improves functional outcomes for patients with acute ischemic stroke. Although we have observed occlusion sites that protrude proximally into the vessel on angiography, termed the "claw sign," we have been unable to state its clinical significance. In this study, we aimed to determine whether the presence of a claw sign was related to recanalization success after mechanical thrombectomy. We retrospectively included 73 consecutive patients treated for acute cerebral large vessel occlusion by mechanical thrombectomy between January 2014 and December 2017. The angiographic claw sign was defined as a thrombus that protruded proximally by more than half the diameter of the parent artery. Claw sign positivity, clinical and etiological features, and outcomes were compared between groups with and without recanalization. The claw sign was observed in 29 of 73 (40%) patients and was positive significantly more frequently in those with recanalization (50.0%) than in those without recanalization (5.9%) (P < .01). By multivariate analysis, the claw sign was the only pretreatment parameter to predict successful recanalization (odds ratio, 12.50; 95% confidence interval, 1.50-103.00; P = .019). The presence of the claw sign might predict successful recanalization in patients undergoing mechanical thrombectomy for large vessel occlusion.
(キーワード)
Aged / Aged, 80 and over / Angiography, Digital Subtraction / Cerebral Angiography / Cerebral Arteries / Cerebrovascular Circulation / Constriction, Pathologic / Female / Humans / Intracranial Thrombosis / Male / Middle Aged / Predictive Value of Tests / Retrospective Studies / Thrombectomy / Thrombolytic Therapy / Treatment Outcome / Vascular Patency
Akemi Hioka, Yoshiteru Tada, Keiko Kitazato, Yasuhisa Kanematsu, Yoshifumi Mizobuchi, Hideo Mure, Kenji Shimada, Toshiyuki Okazaki, Masaaki Korai, Noki Akazawa, Yuki Matsumoto, Yuki Matsumoto, Yasushi Takagi and Shinji Nagahiro : Activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons., Journal of Clinical Neuroscience, Vol.60, 79-83, 2019.
(要約)
The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training.
Hiroshi Kagusa, Yoshifumi Mizobuchi, Kohhei Nakajima, Toshitaka Fujihara, Yoshimi Bando and Yasushi Takagi : Metastatic tumor to the orbital cavity from a primary carcinoma of the uterine cervix : a case report., The Journal of Medical Investigation : JMI, Vol.66, No.3,4, 355-357, 2019.
(要約)
Metastatic tumors to the orbit of the eye, especially from primary carcinomas of the uterine cervix are very rare. A 64-year-old woman with a history of carcinoma of the uterine cervix presented with right eye pain and blepharoptosis for 2 weeks. Magnetic resonance imaging revealed a mass at the right orbital apex. Surgical extirpation was performed due to severe pain. Postoperative pathology demonstrated a poorly differentiated squamous cell carcinoma. The origin was ultimately considered to be the carcinoma of the uterine cervix. In conclusion, this report describes a rare case of a metastatic tumor at the orbital apex derived from the cervix of the uterus. J. Med. Invest. 66 : 355-357, August, 2019.
Yoshifumi Mizobuchi, Kohhei Nakajima, Toshitaka Fujihara, Kazuhito Matsuzaki, Hideo Mure, Shinji Nagahiro and Yasushi Takagi : The risk of hemorrhage in stereotactic biopsy for brain tumors., The Journal of Medical Investigation : JMI, Vol.66, No.3,4, 314-318, 2019.
(要約)
Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy. J. Med. Invest. 66 : 314-318, August, 2019.
(キーワード)
Adolescent / Adult / Aged / Aged, 80 and over / Biopsy / Brain / Brain Neoplasms / Cerebral Hemorrhage / Female / Humans / Male / Middle Aged / Stereotaxic Techniques / Young Adult
K Komatsu, Yasushi Takagi, T Kikuchi, Y Yamao, Y Fushimi, J Grinstead, S Ahn and S Miyamoto : Ruptured intranidal aneurysm of an arteriovenous malformation diagnosed by delay alternating with nutation for tailored excitation (DANTE)-prepared contrast-enhanced magnetic resonance imaging, Acta Neurochirurgica, Vol.160, No.12, 2435-2438, 2018.
(要約)
This case report describes the usefulness of delay alternating with nutation for tailored excitation (DANTE)-prepared, contrast-enhanced magnetic resonance imaging (CE-MRI) for detecting the rupture site of an arteriovenous malformation (AVM). A ruptured intranidal aneurysm was confirmed histopathologically. Accurate non-invasive information about the possible rupture site of an AVM is critical for optimal treatment and evaluation. Vessel wall enhancement visualized by DANTE-prepared CE-MRI may be a useful tool for providing information about changes in inflammatory status and vulnerability to further developments.
Toshiyuki Okazaki, H Nakagawa, Hideo Mure, Kenji Yagi, H Hayase, Yasushi Takagi and K Saito : Microdiscectomy and Foraminotomy in Cervical Spondylotic Myelopathy and Radiculopathy, Neurologia Medico-Chirurgica, Vol.58, No.11, 468-476, 2018.
(要約)
This study was to assess the efficacy of microdiscectomy, cage fixation, and right tranuncal foramintomy for the patients suffering from right radiulo-myelopathy. Anterior cervical foraminotomy was reported to be an effective option for the treatment of cervical degenerative radiculopathy but with the problem of recurrence. Since Hakuba reported the method of trans-unco-discal approach in 1976, it was designed as keyhole foraminotomy which was called transuncal approach, transpedicular approach or transvertebral approach. In the anterior approach, we usually use the right-sided approach because most of us are right-handed surgeons. We retrospectively investigated our patients who had the right foraminal stenosis causing radiculopathy and were treated with microdiscectomy, cage fixation, and right keyhole transuncal foraminotomy. Since 2011, 23 patients were treated with the manner. All of the 23 patients who had central canal stenosis and among the 23 patients, 8 patients showed only right radiculopathy and 15 patients showed radiculo-myelopathy. In all patients, the radiculopathy disappeared or significantly improved without any complications postoperatively. The average of VAS scores was 7.6 ± 2.2 in preoperative state, 2.8 ± 2.2 at discharge, and 1.1 ± 1.6 in 1 month after surgery. The average of follow-up time was 38.3 months and they had no recurrence of radiculopathy. We showed that this manner is effective and one option for the combined disease of right foraminal and canal stenosis and we believe that this manner is not complex and safe if we can understand the anatomy.
N Enomoto, Hideo Mure, Toshiyuki Okazaki, M Azumi, S Okita, Shinji Nagahiro and Yasushi Takagi : Posttraumatic Cerebrospinal Fluid Leak Associated with an Upper Cervical Meningeal Diverticulum, World Neurosurgery, Vol.116, 50-55, 2018.
(要約)
Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear. We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved. Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak.
Yasuhisa Kanematsu, Junichiro Satomi, Masaaki Korai, Toshiyuki Okazaki, Idumi Yamaguchi, Yoshiteru Tada, Masaaki Uno, Shinji Nagahiro and Yasushi Takagi : Flow Alteration Therapy for Ruptured Vertebral Artery Dissecting Aneurysms Involving the Posterior Inferior Cerebellar Artery, Neurologia Medico-Chirurgica, Vol.58, 341-349, 2018.
(要約)
Surgery for- and endovascular treatment of vertebral artery (VA) dissecting aneurysms involving the origin of the posterior inferior cerebellar artery (PICA) remain challenging. Their ideal treatment is complete isolation of the aneurysm by surgical or endovascular trapping plus PICA reconstruction. However, postoperative lower cranial nerve palsy and medullary infarction are potential complications. We report four patients with VA dissecting aneurysms involving the PICA origin who were treated by occipital artery (OA)-PICA bypass followed by proximal occlusion of the VA and clip ligation of the PICA origin instead of trapping. There were no procedural or ischemic complications. In all patients, angiography performed 2-3 weeks later showed good patency of the bypass graft and complete obliteration of the aneurysm. During the follow-up period ranging from 1 to 14 years, none experienced bleeding. Although retrograde blood flow to the dissecting aneurysm persisted in the absence of trapping, iatrogenic lower cranial nerve injury could be avoided. The decrease in aneurysmal flow might elicit spontaneous thrombosis and prevent aneurysmal rerupture. Our technique might be less invasive than aneurysmal trapping and help to prevent rebleeding.
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohhei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, KT Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro and Yasushi Takagi : Down-regulation of MDR1 by Ad-DKK3 via Akt/NFB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model, Journal of Neuro-Oncology, Vol.139, No.2, 323-332, 2018.
(要約)
Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.
Yuki Yamamoto, Nobuaki Yamamoto, Junichiro Satomi, Idumi Yamaguchi, Masaaki Korai, Yasuhisa Kanematsu, Yasushi Takagi and Ryuji Kaji : Dural arteriovenous fistula in the superior orbital fissure, Surgical Neurology International, Vol.9, No.1, 95, 2018.
(要約)
Dural arteriovenous fistulas (dAVFs) are extremely rare in the superior orbital fissure, and they exhibit ocular symptoms similar to the dAVF in the cavernous sinus because of the intraorbital venous congestion. Hence, the distinction of these conditions is imperative because of some inherent differences in endovascular treatment techniques. A 58-year-old woman presented with a gradually worsening left eyeball protrusion and conjunctival congestion. The digital subtraction angiography revealed a dAVF with a shunting point in the left superior orbital fissure. Moreover, the inferolateral trunk of the left internal carotid artery and the left middle meningeal artery were involved as feeding arteries. Shunting blood flow drained into the facial vein through the superior ophthalmic vein (SOV) but not into the cavernous sinus, which was located just posterior to the superior orbital fissure. We performed transvenous coil embolization in the SOV through the facial vein, and the symptoms disappeared completely. We experienced a case of a dAVF in the superior orbital fissure. This case presented a possibility of the presence of one subtype of the dAVF in the part of the cavernous sinus separated at the superior orbital fissure in front. Transvenous coil embolization in the SOV through the facial vein efficiently occluded the fistula.
Y Helmanto, T Sunohara, A Faried, Yasushi Takagi, J Takahashi, T Maki and S Miyamoto : Transplantation of feeder-free human induced pluripotent stem cell-derived cortical neuron progenitors in adult male Wistar rats with focal brain ischemia, Journal of Neuroscience Research, Vol.96, No.5, 863-874, 2018.
(要約)
The use of human induced pluripotent stem cells (hiPSCs) eliminates the ethical issues associated with fetal or embryonic materials, thus allowing progress in cell therapy research for ischemic stroke. Strict regulation of cell therapy development requires the xeno-free condition to eliminate clinical complications. Maintenance of hiPSCs with feeder-free condition presents a higher degree of spontaneous differentiation in comparison with conventional cultures. Therefore, feeder-free derivation might be not ideal for developing transplantable hiPSC derivatives. We developed the feeder-free condition for differentiation of cortical neurons from hiPSCs. Then, we evaluated the cells' characteristics upon transplantation into the sham and focal brain ischemia on adult male Wistar rats. Grafts in lesioned brains demonstrated polarized reactivity toward the ischemic border, indicated by directional preferences in axonal outgrowth and cellular migration, with no influence on graft survival. Following the transplantation, forelimb asymmetry was better restored compared with controls. Herein, we provide evidence to support the use of the xeno-free condition for the development of cell therapy for ischemic stroke.
Yasushi Takagi, H Hadeishi, Y Mineharu, K Yoshida, K Ogasawara, A Ogawa and S Miyamamoto : Initially Missed or Delayed Diagnosis of Subarachnoid Hemorrhage: A Nationwide Survey of Contributing Factors and Outcomes in Japan., Journal of Stroke & Cerebrovascular Diseases, Vol.27, No.4, 871-877, 2018.
(要約)
Subarachnoid hemorrhage (SAH) remains a significant cause of mortality in Japan. The Japan Stroke Society set out to conduct a nationwide survey to identify contributing factors and outcomes of SAH misdiagnosis. We initially surveyed 737 training institutes and 1259 departments in Japan between April 2012 and March 2014 for the presence of misdiagnosed SAH. Clinical information was then sought from respondents with a positive misdiagnosis. Information on 579 misdiagnosed cases was collected. Most initial misdiagnoses occurred in nonteaching hospitals (72%). Of those presenting with headache, 55% did not undergo a computed tomography (CT) scan. In addition, SAH was missed in the patients who underwent CT scans. The clinically diagnosed rerupture rate was 27%. Mortality among all cases was 11%. Institutes achieving a final diagnosis were staffed by neurologists or neurosurgeons. Multivariate logistic regression analysis indicated that age (≥65), consciousness level (Japan Coma Scale score at correct diagnosis), rerupture of an aneurysm, and no treatment by clipping or coiling were significantly associated with poor clinical outcome. The prognosis of misdiagnosis of SAH is severe. Neuroradiological assessment and correct diagnosis can prevent SAH misdiagnosis. When there is a possible diagnosis of SAH, consultation with a specialist is important.
(キーワード)
Age Factors / Aged / Delayed Diagnosis / Diagnostic Errors / Embolization, Therapeutic / Female / Health Care Surveys / Humans / Japan / Logistic Models / Magnetic Resonance Imaging / Male / Middle Aged / Multivariate Analysis / Neurosurgical Procedures / Odds Ratio / Predictive Value of Tests / Reproducibility of Results / Risk Factors / Subarachnoid Hemorrhage / Time Factors / Tomography, X-Ray Computed / Treatment Outcome
RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.
Takayuki Kikuchi, Akira Ishii, Hideo Chihara, Daisuke Arai, Mitsushige Ando, Yohei Takenobu, Tomohisa Okada, Yasushi Takagi and Susumu Miyamoto : Occlusion Status on Magnetic Resonance Angiography Is Associated with Risk of Delayed Ischemic Events in Cerebral Aneurysms Treated with Stent-Assisted Coiling., World Neurosurgery, Vol.107, 226-232, 2017.
(要約)
Management after stent-assisted coiling (SAC) for unruptured intracranial aneurysm is sometimes difficult because close monitoring for ischemic events for a long period of time after the procedure is necessary. The purpose of this study was to clarify the usefulness of magnetic resonance angiography (MRA) at follow-up after SAC. Sixty-six consecutive cases of SAC for unruptured intracranial aneurysm in our institute and affiliated hospitals were retrospectively reviewed for a delayed ischemic event. Occlusion status of the aneurysm and stent apposition on time-of-flight (TOF)-MRA, patient demographics, and characteristics of the aneurysms were analyzed for a possible relationship to delayed ischemic events. Over a median follow-up of 755 days, 14 patients had delayed ischemic events after a median follow-up of 230.5 days. All of the ischemic events were transient or asymptomatic. Univariate analysis revealed that the history of hypertension (P = 0.042) and the occlusion status of the aneurysm (P = 0.006) were significantly associated with delayed ischemic events. Multivariate analysis indicated that dome filling had a hazard ratio of 4.96 (95% confidence interval [CI], 1.30-23.60) and 3.74 (95% CI, 1.10-13.34), compared with neck remnant and complete obliteration, respectively. Six of 7 patients who had persistent dome filling during follow-up developed a delayed ischemic event. In this preliminary study, dome filling on follow-up TOF-MRA is a possible risk factor for delayed ischemic events. TOF-MRA could be a modality for tailored management after SAC.
Yoshio Araki, Yasushi Takagi, Yohei Mineharu, Hatasu Kobayashi, Susumu Miyamoto and Toshihiko Wakabayashi : Rapid contralateral progression of focal cerebral arteriopathy distinguished from RNF213-related moyamoya disease and fibromuscular dysplasia., Child's Nervous System, Vol.33, No.8, 1405-1409, 2017.
(要約)
Focal cerebral arteriopathy includes unifocal or multifocal lesions that are unilateral or bilateral. Large- and/or medium-sized vessels are involved and can be visualized on angiography. We report a case of cerebral infarction in a 9-year-old Japanese female who presented with a transient ischemic attack. Steno-occlusion involving the distal part of the internal carotid artery, proximal middle cerebral artery, and anterior cerebral artery was observed. Digital subtraction angiography demonstrated a beaded appearance in the cervical portion of the diseased internal carotid artery. Revascularization surgery was performed 45 days after the onset. A new infarction appeared on the other side of the anterior cerebral artery territory 7 months after the first onset. Antiplatelets and vasodilators were administered, and no progression was observed during 18 months of follow-up. Genetic analysis did not show ring finger protein 213 (RNF213)-related moyamoya disease, and pathological examination revealed no characteristics of fibromuscular dysplasia. The radiological and genetic features coincided with focal cerebral arteriopathy, which is a distinct entity from fibromuscular dysplasia and RNF213-related moyamoya disease.
Yoshiko Matsuda, Yohei Mineharu, Mitsuru Kimura, Yasushi Takagi, Hatasu Kobayashi, Toshiaki Hitomi, Kouji H. Harada, Yoshito Uchihashi, Takeshi Funaki, Susumu Miyamoto and Akio Koizumi : RNF213 p.R4810K Variant and Intracranial Arterial Stenosis or Occlusion in Relatives of Patients with Moyamoya Disease., Journal of Stroke & Cerebrovascular Diseases, Vol.26, No.8, 1841-1847, 2017.
(要約)
This study aimed to determine the effectiveness of genetic testing for the p.R4810K variant (rs112735431) of the Mysterin/RNF213 gene, which is associated with moyamoya disease and other intracranial vascular diseases, in the family members of patients with moyamoya disease. We performed genotyping of the RNF213 p.R4810K polymorphism and magnetic resonance angiography on 59 relatives of 18 index patients with moyamoya disease. Nineteen individuals had follow-up magnetic resonance angiography with a mean follow-up period of 7.2 years. Six of the 34 individuals with the GA genotype (heterozygotes for p.R4810K) showed intracranial steno-occlusive lesions in the magnetic resonance angiography, whereas none of the 25 individuals with the GG genotype (wild type) showed any abnormalities. Follow-up magnetic resonance angiography revealed de novo lesions in 2 and disease progression in 1 of the 11 individuals with the GA genotype, despite none of the 8 individuals with the GG genotype showing any changes. Accordingly, 8 individuals had steno-occlusive lesions at the last follow-up, and all had the p.R4810K risk variant. The prevalence of steno-occlusive intracranial arterial diseases in family members with the p.R4810K variant was 23.5% (95% confidence interval: 9.27%-37.78%), which was significantly higher than in those without the variant (0%, P = .0160). Genotyping of the p.R4810K missense variant is useful for identifying individuals with an elevated risk for steno-occlusive intracranial arterial diseases in the family members of patients with moyamoya disease.
(キーワード)
Adenosine Triphosphatases / Adolescent / Adult / Aged / Aged, 80 and over / Constriction, Pathologic / Disease Progression / Female / Gene Frequency / Genetic Association Studies / Genetic Predisposition to Disease / Heredity / Heterozygote / Homozygote / Humans / Intracranial Arteriosclerosis / 日本 (Japan) / Magnetic Resonance Angiography / Male / Middle Aged / Moyamoya Disease / Pedigree / Phenotype / Polymorphism, Genetic / Prevalence / Risk Factors / Time Factors / Ubiquitin-Protein Ligases / Young Adult
Takaaki Morimoto, Yohei Mineharu, Koh Ono, Masahiro Nakatochi, Sahoko Ichihara, Risako Kabata, Yasushi Takagi, Yang Cao, Lanying Zhao, Hatasu Kobayashi, Kouji H. Harada, Katsunobu Takenaka, Takeshi Funaki, Mitsuhiro Yokota, Tatsuaki Matsubara, Ken Yamamoto, Hideo Izawa, Takeshi Kimura, Susumu Miyamoto and Akio Koizumi : Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease., PLoS ONE, Vol.12, No.4, e0175649, 2017.
(要約)
The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.
(キーワード)
Adenosine Triphosphatases / Aged / Aged, 80 and over / Amino Acid Substitution / Asian Continental Ancestry Group / Case-Control Studies / Coronary Artery Disease / Female / Genetic Predisposition to Disease / Humans / Japan / Male / Middle Aged / Moyamoya Disease / Polymorphism, Single Nucleotide / Risk Factors / Ubiquitin-Protein Ligases
Toshinari Kawasaki, Kazumichi Yoshida, Takayuki Kikuchi, Akira Ishii, Yasushi Takagi and Susumu Miyamoto : Ruptured Aneurysms of the Occipital Artery Associated with Congenital Occipital Bone Defect., World Neurosurgery, Vol.97, 759.e13-759.e15, 2017.
(要約)
Traumatic aneurysms of the superficial temporal artery have been frequently reported in the literature, whereas traumatic aneurysms of the occipital artery (OA) are extremely rare. A 30-year-old man had been followed at another hospital for meningoencephalocele associated with his congenital occipital bone defect. He was admitted to our hospital with a chief complaint of neck swelling and pain during a football game. Computed tomography and magnetic resonance imaging showed a hematoma in his right neck along with the meningoencephalocele. In addition, it showed an atrophic cerebellum with a cyst protruding from his occipital bone defect. Digital subtraction angiography of the right OA showed 3 aneurysms responsible for the large hematoma in his neck. Endovascular embolization with 20% N-butyl-2-cyanoacrylate was performed for treatment of the ruptured aneurysms followed by emergent surgical evacuation of the hematoma. An occipital cranioplasty with titanium mesh was performed 10 months after the emergent intervention. In this patient, the congenital occipital bone defect with meningoencephalocele might have been the remote source of risk for traumatic pseudoaneurysms along the muscle branches of the OA.
(キーワード)
Adult / Aneurysm, Ruptured / Cerebral Arteries / Humans / Intracranial Aneurysm / Male / Occipital Bone
Yoichi Nakayama, Yohei Mineharu, Yoshiki Arawaka, Sei Nishida, Hirofumi Tsuji, Hidehiko Miyake, Maki Yamaguchi, Sachiko Minamiguchi, Yasushi Takagi and Susumu Miyamoto : Cerebral amyloid angiopathy in a young man with a history of traumatic brain injury: a case report and review of the literature., Acta Neurochirurgica, Vol.159, No.1, 15-18, 2017.
(要約)
Cerebral amyloid angiopathy (CAA), a cause of recurrent and multiple lobar hemorrhages, characteristically occurs in persons aged ≥55 years. We report a case of a 32-year-old male who had recurrent hemorrhage in the left multiple lobes, with a history of traumatic brain injury and hematoma evacuation at the age of 1 year. He underwent surgical treatment and was histopathologically diagnosed as having CAA. The literature review yielded six CAA cases, including ours, aged less than 55 years. All were male and four had histories of severe TBI, suggesting that male sex and TBI may be associated with CAA in young persons.
Izumi Yamaguchi, Yasuhisa Kanematsu, Kenji Shimada, Nobuaki Yamamoto, Masaaki Korai, Kazuhisa Miyake, Takeshi Miyamoto, Shu Sogabe, Eiji Shikata, Manabu Ishihara, Yuki Yamamoto, Kazutaka KURODA and Yasushi Takagi : Evaluation of Serial Intra-Arterial Indocyanine Green Videoangiography in the Surgical Treatment of Cranial and Craniocervical Junction Arteriovenous Fistulae: A Case Series, Operative Neurosurgery, Vol.25, No.3, 292-300, 2023.
(要約)
Intravenous indocyanine green (IV-ICG) videoangiography is commonly performed to detect blood flow in the microscopic view. However, intra-arterial ICG (IA-ICG) videoangiography provides high-contrast imaging, repeatability within a short period of time, and clear-cut separation of the arterial and venous phases compared with IV-ICG. These features are useful for detecting retrograde venous drainage (RVD) and shunt occlusion in arteriovenous fistulae (AVF) surgery. This study aimed to investigate whether IA-ICG videoangiography can be repeatable within a short period of time and be useful for detecting RVD and shunt occlusion in cranial- and craniocervical junction (CCJ)-AVF surgery. Between January 2012 and December 2022, 50 patients were treated with endovascular or surgical intervention for cranial- and CCJ-AVF at Tokushima University Hospital. Of these, 5 patients (6 lesions) underwent open surgery with IA-ICG videoangiography in a hybrid operating room. We analyzed the data of these 5 patients (6 lesions). There were 4/patient (median, range 2-12) and 3.5/lesion (median, range 2-10) intraoperative IA-ICG runs. IA-ICG videoangiography detected RVD in all patients. Clearance of IA-ICG-induced fluorescence was achieved within 30 seconds in all patients at each region of interest. After the disconnection of the fistulae, IA-ICG videoangiography and intraoperative digital subtraction angiography (DSA) confirmed the disappearance of RVD in all patients. There were no complications associated with IA-ICG videoangiography. This study showed that IA-ICG videoangiography is repeatable within a short period of time before and after obliteration and can be useful for detecting RVD and shunt occlusion in cranial- and CCJ-AVF surgery. IA-ICG videoangiography also allows intraoperative DSA studies in a hybrid operating room. Considering the recent advancements in hybrid operating rooms, combining IA-ICG videoangiography with intraoperative DSA is a useful strategy for cranial- and CCJ-AVF surgery.
Yuki Kanazawa, Tosiaki Miyati, Masafumi Harada, Mitsuharu Miyoshi, Mayuka Seguchi, Hiroaki Hayashi, Yuki Matsumoto, Yasuhisa Kanematsu and Yasushi Takagi : Metabolic Analysis Within an Atherosclerotic Plaque Using Chemical Exchange Saturation Transfer Imaging, The 109th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA2023), Chicago, Nov. 2023.
2.
Yasushi Takagi : AVM surgery using intra-arterial ICG videoangiography in hybrid operating room, The 16th Korea-Japan Joint Conference on Surgery for Cerebral Stroke, Gifu, Sep. 2023.
3.
Yuki Kanazawa, Tosiaki Miyati, Masafumi Harada, Mitsuharu Miyoshi, Yuki Matsumoto, Hiroaki Hayashi, Yasuhisa Kanematsu and Yasushi Takagi : Evaluation of Biological Metabolic Activity within an Atherosclerotic Plaque using Chemical Exchange Saturation Transfer Imaging, The 32st Annual Meeting of ISMRM, Toronto, Jun. 2023.
4.
Mayuka Seguchi, Yuki Kanazawa, Tosiaki Miyati, Masafumi Harada, Mitsuharu Miyoshi, Yuki Matsumoto, Hiroaki Hayashi, Yasuhisa Kanematsu and Yasushi Takagi : Diffusion weighted-viscosity imaging for atherosclerotic plaques, The 32st Annual Meeting of ISMRM, Toronto, Jun. 2023.
5.
Joji Fujikawa, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama, Teruo Oda, Nobuaki Yamamoto, Yuishin Izumi, Hideo Mure, Satoshi Goto and Yasushi Takagi : Cranial geometry in patients with dystonia, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
6.
NAKANISHI Hiroshi, Ryoma Morigaki, Nobuaki Yamamoto, Joji Fujikawa, Teruo Oda, OMAE Hiroshi, Yuishin Izumi and Yasushi Takagi : The effect of Rikaba, a hybrid physical exercise salon for Parkinson's disease patients, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
7.
Hideo Mure, Ryoma Morigaki, Ryosuke Miyamoto, Kazuhisa Miyake, Matsuda Taku, Hiroshi Koyama and Yasushi Takagi : Long-term follow-up of 12 patients treated with bilateral pallidal stimulation for tardive dystonia, 13th Scientific meeting of Asian Australasian Society for Streotactic and Functional Neurosurgery, Osaka, Apr. 2023.
8.
OMAE Hiroshi, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, 中野渡 友香, Megumi Kuno, Tetsuya Matsuura and Yasushi Takagi : Cognitive changes due to subthalamic nucleus deep brain stimulation in elderly Parkinson's Disease, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
9.
Ryoma Morigaki, Maya Anzai, Joji Fujikawa, Teruo Oda, Hayasawa Hiroaki, Matsuda Taku, Jiro Kasahara and Yasushi Takagi : Changes in phosphodiesterase 10A in mice model of levodopa-induced dyskinesia, The 13th Scientific meeting of Asian Australasian Society for Stereotactic and Functional Neurosurgery (AASSFN 2023), Osaka, Apr. 2023.
10.
Yasushi Takagi : AVM surgery using intra-arterial ICG videoangiography in hybrid operating room, 10th European Japanese Cerebrovascular Congress, Kyoto, Nov. 2022.
11.
Yuki Matsumoto, Yuki Kanazawa, Yuki Kinjo, Masafumi Harada, Toshiaki Miyati, Hiroaki Hayashi, Mitsuharu Miyoshi, Naoki Maeda, Yasuhisa Kanematsu, Yasushi Takagi and Akihiro Haga : Evaluation of Blood Flow and Plaque Vulnerability in Carotid Artery Stenosis Focusing on Morphological and Component Characteristics, ISMRM 30th Annual Meeting, London, May 2022.
12.
Naoki Maeda, Yuki Kanazawa, Yuki Kinjo, Yuki Matsumoto, Masafumi Harada, Tosiaki Miyati, Hiroaki Hayashi, Mitsuharu Miyoshi, Yasuhisa Kanematsu, Yasushi Takagi and Akihiro Haga : Is it possible to evaluate morphological carotid artery stenosis information using NASCET criteria?, RSNA2021 (Radiological Society of North America), Chicago, Nov. 2021.
13.
Yoshiteru Tada, Toshitaka Fujihara, Kenji Shimada, Nobuaki Yamamoto, Hiroki Yamazaki, Yuishin Izumi, Masafumi Harada, Yasuhisa Kanematsu and Yasushi Takagi : Peri-ictal normal arterial spin labeling imaging in patients with seizures, 13 回アジア・オセアニアてんかん学会(13th AOEC), Jun. 2021.
14.
Ryoma Morigaki, Masatoshi Ogawa, Shinya Ohkita, Taku Matsuda, Yasushi Takagi and Satoshi Goto : Phospho-serine 276 of nuclear factor kappa b is involved in the genesis of l-dopa-induced dyskinesia, The Journal of Neuroscience, 2021.
15.
Yuki Kanazawa, Masafumi Harada, Mitsuharu Miyoshi, Takashi Abe, Yuki Matsumoto and Yasushi Takagi : Characterization of Brain Tumors using Amide Proton and Nuclear Overhauser Effect at 3 Tesla MR Scanner, ISMRM Virtual Conference, Aug. 2020.
16.
Yuki Kanazawa, Masafumi Harada, Tosiaki Miyati, Takashi Abe, Mitsuharu Miyoshi, Yuki Matsumoto, Hiroaki Hayashi, Yasuhisa Kanematsu and Yasushi Takagi : Chemical Exchange Saturation Transfer Imaging for Atherosclerotic Plaques, ISMRM Virtual Conference, Aug. 2020.
17.
Idumi Yamaguchi, Tadashi Yamaguchi, Eiji Shikata, 北里 慶子 and Yasushi Takagi : Down-regulation of PD-L1 via FKBP5 lowered by a cyclooxygenase-2 inhibtor in GSCs and GBM cells may be attributable to enhance antitumor effects of immunotherapy, Society for NeuroOncology 2019, Nov. 2019.
18.
Ryoma Morigaki, S Okita, Hideo Mure, Yasushi Takagi and S Goto : Olfactory type g-protein alfa subunit related changes in the striatum underlie the genesis of L-DOPA induced dyskinesiaBrain and Brain PET2019, Brain and Brain PET2019, Jul. 2019.
19.
Tadashi Yamaguchi, Keiko T Kitazato, Eiji Shikata, Idumi Yamaguchi, Takeshi Miyamoto, Masaaki Korai, Kenji Shimada, Yoshiteru Tada, Yasuhisa Kanematsu and Yasushi Takagi : Pro-inflammatory response promoted by Porphyromonas gingivalis lipopolysaccharide enhances the rupture of experimental intracranial aneurysms., Brain and Brain PET2019, Yokohama, Jul. 2019.
20.
Ryoma Morigaki, Shinya Ohkita, Hideo Mure, Yasushi Takagi and Satoshi Goto : Olfactory type G-protein alfa subunit related changes in the striatum underlie the genesis of L-dopa-induced dyskinesia, Journal of Cerebral Blood Flow and Metabolism, Yokohama, Jun. 2019.
21.
Yuki Yamamoto, Nobuaki Yamamoto, K Kuroda, Yasuhisa Kanematsu, Masaaki Korai, Kenji Shimada, Yuishin Izumi and Yasushi Takagi : High White Blood Cell Count is a Risk Factor for Contrast-Induced Nephropathy following Mechanical Thrombectomy, The 5th European Stroke Organization Conference, ESOC 2019, Milan, May 2019.
22.
Nobuaki Yamamoto, Yuki Yamamoto, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yuishin Izumi, Yasushi Takagi and Ryuji Kaji : Hyperintense Signals on Arterial Spin-Labeled Imaging as a predictor for favorable outcome after Late Time Window Thrombectomy, The 5th European Stroke Organization Conference, ESOC 2019, Milan, May 2019.
Eiji Shikata, Tetsuya Tamura, Kiyohito Shinnno, N Shinohara, Y Okayama, Yasuhisa Kanematsu and Yasushi Takagi : Separate management of water-electrolyte balance using maintenance fluid and salt leads to a favorable prognosis after aneurysmal subarachnoid hemorrhage, 11th World Stroke Congress 2018, Oct. 2018.
25.
Kyoko Nishi, Yasushi Takagi, Yasuhisa Kanematsu, Ryuji Kaji, Y Hamada, T Takagi, S Katoh and Shinji Nagahiro : Development and future prospects of Tokushima University Hospital stroke care unit (SCU), 11th World Stroke Congress 2018, Montreal, Oct. 2018.
26.
山口 泉, 四方 英二, 高麗 雅章, 兼松 康久, 里見 淳一郎, 北里 慶子, 永廣 信治, 髙木 康志 : Retrospective study of patients with in-hospital stroke, 11th World Stroke Congress 2018, モントリオール, 2018年10月.
27.
Tadashi Yamaguchi, Takeshi Miyamoto, Masaaki Korai, Kenji Shimada, Yoshiteru Tada, Yasuhisa Kanematsu, Junichiro Satomi, Shinji Nagahiro and Yasushi Takagi : Estrogen deficiency activates inflammasome in a rat model of intracranial aneurysms, 11th World Stroke Congress 2018, Montreal, Oct. 2018.
28.
Masaaki Korai, Yasuhisa Kanematsu, Idumi Yamaguchi, Nobuaki Yamamoto, Yuki Yamamoto, Junichiro Satomi and Yasushi Takagi : Treatment strategy and outcom of ruptured vertebral artry dissecting aneurysms, World Live Neurovascular Conference 2018, 神戸市, Apr. 2018.
29.
Kenji Shono, Izumi Yamaguchi, Toshitaka Fujihara, Keiko Kitazato, Kohhei Nakajima, Yoshifumi Mizobuchi, Hideo Mure, Kohhei Nakajima, Junichiro Satomi, Shinji Nagahiro and Yasushi Takagi : Celecoxib inhibits proliferation and induces apoptosis in glioma stem cells and an animal model of glioblastoma., 22ND ANNUAL SCIENTIFIC MEETING AND EDUCATION DAY OF THE SOCIETY FOR NEURO-ONCOLOGY, San Francisco, Nov. 2017.
Yuka Hiroshima, Takayoshi Shinya, Hitoshi Ikushima, Youichi Otomi, Hideki Otsuka, Chisato Tonoiso, Akiko Kubo, Takashi Kawanaka, Yasushi Takagi and Masafumi Harada : Multi-modality Imaging for the Patients with Metastatic Brain Tumors After Stereotactic Irradiation, The 82nd Annual Meeting of the Japan Radiological Society, Apr. 2023.
庄野 健児, 里見 淳一郎, 多田 恵曜, 兼松 康久, 山本 伸昭, 和泉 唯信, 梶 龍兒, 原田 雅史, 永廣 信治, 髙木 康志 : Optimal timing of DWI to avoid false-negative findings in patients with TIA, 第41回日本脳神経CI学会総会, 2018年3月.
191.
Yasushi Takagi : Microvascular anastomosis for moyamoya disease, 4th Winter Seminar on Cerebrovascular Diseases(CVD), Feb. 2018.
192.
Yasushi Takagi : Current status of surgical treatment against brain arteriovenous malformations, 4th Winter Seminar on Cerebrovascular Diseases(CVD), Feb. 2018.