Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity.

DOI： 10.18926/AMO/65980

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DOI： 10.1186/s13287-023-03362-z

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

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Language：Japanese   Publisher：(一社)日本脳神経外傷学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. METHODS: Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. RESULTS: SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). CONCLUSIONS: This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.

DOI： 10.1186/s13287-023-03236-4

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BACKGROUND: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. OBJECTIVE: To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. METHODS: Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. RESULTS: Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. CONCLUSION: Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

DOI： 10.1016/j.brs.2023.03.003

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Diffusely infiltrative midline gliomas are known to have a poor prognosis. The standard treatment for typical diffuse midline glioma in the pons is local radiotherapy as surgical resection is inappropriate. This case reports a brainstem glioma in which stereotactic biopsy and foramen magnum decompression were concomitantly performed to confirm the diagnosis and improve symptoms. A 23-year-old woman was referred to our department with a chief complaint of headache for six months. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintense swelling of the brainstem with the pons as the main locus. Enlargement of the lateral ventricles was observed because of cerebrospinal fluid obstruction out of the posterior fossa. This was atypical for a diffuse midline glioma in terms of the longstanding slow progression of symptoms and patient age. Stereotactic biopsy was performed for diagnosis, and foramen magnum decompression (FMD) was concomitantly performed to treat the obstructive hydrocephalus. The histological diagnosis was astrocytoma, IDH-mutant. Post-surgery, the patient's symptoms were relieved, and she was discharged on the fifth day after surgery. The hydrocephalus was resolved, and the patient returned to normal life without any symptoms. The tumor size follow-up with MRI demonstrated no marked change for 12 months. Even though diffuse midline glioma is considered to have a poor prognosis, clinicians should contemplate if it is atypical. In atypical cases like the one described herein, surgical treatment may contribute to pathological diagnosis and symptom improvement.

DOI： 10.2176/jns-nmc.2022-0159

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Functional neurosurgery for epilepsy, movement disorders, and spasticity includes some device-based surgeries such as deep brain stimulation, subdural electrode placement, vagus nerve stimulation, and baclofen pump implantation. These surgeries have a higher risk of surgical site infection(SSI)than other general neurological surgeries. Furthermore, because device removal after infection can significantly impair patients'activities of daily living and quality of life, SSI in functional neurosurgery is a worrisome surgical complication. In this study, we conducted a mini-review of the risk of infection in each device-based surgery and described associated surgical procedures and preparations performed at our institution, with a focus on infection prevention.

DOI： 10.11477/mf.1436204662

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AIMS: SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. METHODS: We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. RESULTS: In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. CONCLUSION: SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke.

DOI： 10.1111/cns.13947

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.

DOI： 10.18926/AMO/63742

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Drug-refractory essential tremors, especially those in the upper extremities, may benefit from surgical treatment. Currently, three main treatment methods are available: deep brain stimulation (DBS), radiofrequency coagulation (RF), and magnetic resonance -guided focused ultrasound surgery (MRgFUS). DBS is a device-based therapy, and its effects are reversible, whereas RF and FUS create irreversible coagulation lesions. DBS and RF require the direct puncturing of the target, whereas FUS focuses ultrasound from extracranial sources. The primary target is the ventralis intermedius of the thalamus (Vim); however, the posterior subthalamic area (PSA) is also reportedly an effective target site. In this article, we will summarize the features of the three treatments for essential tremors, and discuss the treatment strategies and methods for each symptom.

DOI： 10.11477/mf.1416202092

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

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Language：Japanese   Publisher：(一社)日本脳神経外傷学会  

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Language：English  

Early-onset isolated (DYT1) dystonia is one of the most common forms of primary dystonia in childhood, and deep brain stimulation of the globus pallidus internus (GPi-DBS) is a highly effective treatment for it. However, the effectiveness of GPi-DBS in monozygotic twins with DYT1 dystonia has never been reported globally. Here, we report the cases of monozygotic twins with DYT1 dystonia who were treated using GPi-DBS, and we include a literature review. The younger brother showed an abnormal gait, with external rotation of the right lower leg at 6 years old. The symptoms gradually became so severe that he had difficulty walking on his own at 9 years of age. Treatment with levodopa-carbidopa partially resolved his symptoms, but most of the symptoms remained. Meanwhile, the older brother developed dystonia in both upper limbs at 8 years of age, with gradual symptom progression. At 13 years of age, they were diagnosed with DYT1 dystonia. Bilateral GPi-DBS was performed in both patients at 16 years of age. Their symptoms remarkably improved after surgery. The Burke-Fahn-Marsden dystonia rating scale (BFMDRS) movement score was reduced from 52 to 2 points for the younger brother and from 35 to 1 point for the older brother. Even if monozygotic twins have the same genes, the onset and severity of symptoms might vary in accordance with differences in epigenomic profiles. However, GPi-DBS treatment was very effective for the two cases; thus, we should consider the surgical interventions for each patient.

DOI： 10.2176/jns-nmc.2022-0084

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In the management of patients with craniosynostosis, it is important to understand growth curve of the normal cranium. Although three-dimensional (3D) computed tomography (CT) images taken in thin slices are easily available nowadays, data on the growth curves of intracranial volume (ICV), cranial length, cranial width, and cranial height in the normal cranium are mainly based on older studies using radiography, and there are insufficient reports using CT images especially taken in thin slices. The purpose of this study was to establish growth curves in the normal cranium of Japanese children using thin-slice images. Cranial images of 106 subjects (57 males, 49 females; aged 0-83 months) without significant cranial abnormalities were retrospectively analyzed. Using thin-slice CT images, the ICV and two-dimensional parameters such as cranial length, cranial width, and cranial height were measured by iPlan, followed by generating growth curves and calculating cephalic index (CI). ICV calculated from thin-slice CT images was compared with that obtained by substituting two-dimensional parameters into Mackinnon formula. The ICV growth curves for males and females were similar in shape. As with the ICV, the two-dimensional parameters increased most rapidly in the first year after birth. There was no significant difference in CI between the sexes or among any age groups. ICV calculated from thin-slice 3D CT images was 60% of that obtained from Mackinnon formula. These data will enable us to compare these specific measurements in craniosynostosis patients directly with those of normal children, which will hopefully help in managing these patients.

DOI： 10.2176/nmc.oa.2021-0208

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Parkinson's disease (PD) patients often suffer from spinal diseases requiring surgeries, although the risk of complications is high. There are few reports on outcomes after spinal surgery for PD patients with deep brain stimulation (DBS). The objective of this study was to explore the data on spinal surgery for PD patients with precedent DBS. We evaluated 24 consecutive PD patients with 28 spinal surgeries from 2007 to 2017 who received at least a 2-year follow-up. The characteristics and outcomes of PD patients after spinal surgery were compared to those of 156 non-PD patients with degenerative spinal diseases treated in 2013-2017. Then, the characteristics, outcomes, and spinal alignment of PD patients receiving DBS were analyzed in degenerative spinal/lumbar diseases. The mean age at the time of spinal surgery was 68 years. The Hoehn and Yahr score regarding PD was stage 1 for 8 patients, stage 2 for 2 patients, stage 3 for 8 patients, stage 4 for 10 patients, and stage 5 for 0 patient. The median preoperative L-DOPA equivalent daily dose was 410 mg. Thirteen patients (46%) received precedent subthalamic nucleus (STN) DBS. Lumbar lesions with pain were common, and operation and anesthesia times were long in PD patients. Pain and functional improvement of PD patients persisted for 2 years after surgery with a higher complication rate than for non-PD patients. PD patients with STN DBS maintained better lumbar lordosis for 2 years after spinal surgery. STN DBS significantly maintained spinal alignment with subsequent pain and functional amelioration 2 years after surgery. The outcomes of spinal surgery for PD patients might be favorably affected by thorough treatment for PD including DBS.

DOI： 10.2176/nmc.oa.2021-0094

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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BACKGROUND: The major surgical treatment for Parkinson's disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. METHODS: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). RESULTS: VNS with 0.25-0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. CONCLUSIONS: VNS with 0.25-0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.

DOI： 10.3390/biomedicines9070789

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Deep brain stimulation(DBS)is an effective therapy for conditions involving drug-resistant involuntary movements, such as Parkinson's disease, tremor, and dystonia. Programming of DBS, as well as strict surgical indications, appropriate target selection, and accurate electrode placement, is one of the most important factors in the success of DBS. To obtain effective stimulation for a long period, it is important to expand the therapeutic window and reduce side effects. Recent advances in DBS devices have dramatically expanded the variety of stimulus settings. While the indication criteria of DBS and surgical techniques have been established, the details of the programming algorithm are not yet unified. In this paper, we describe the features of each device, basic programming methods, management of DBS-related side effects, and advanced stimulus methods.

DOI： 10.11477/mf.1436204461

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

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Despite the advances in pharmacological therapies, only the half of depressed patients respond to currently available treatment. Thus, the need for further investigation and development of effective therapies, especially those designed for treatment-resistant depression, has been sorely needed. Although antidepressant effects of mesenchymal stem cells (MSCs) have been reported, the potential benefit of this cell therapy on treatment-resistant depression is unknown. Cell encapsulation may enhance the survival rate of grafted cells, but the therapeutic effects and mechanisms mediating encapsulation of MSCs remain unexplored. Here, we showed that encapsulation enhanced the antidepressant effects of MSCs by attenuating depressive-like behavior of Wistar Kyoto (WKY) rats, which are considered as a promising animal model of treatment-resistant depression. The implantation of encapsulated MSCs (eMSCs) into the lateral ventricle counteracted depressive-like behavior and enhanced the endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus, whereas the implantation of MSCs without encapsulation or the implantation of eMSCs into the striatum did not show such ameliorative effects. eMSCs displayed robust and stable secretion of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, fibroblast growth factor-2, and ciliary neurotrophic factor (CNTF), and the implantation of eMSCs into the lateral ventricle activated relevant pathways associated with these growth factors. Additionally, eMSCs upregulated intrinsic expression of VEGF and CNTF and their receptors. This study suggests that the implantation of eMSCs into the lateral ventricle exerted antidepressant effects likely acting via neurogenic pathways, supporting their utility for depression treatment.

DOI： 10.1038/s41380-018-0208-0

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Cell therapy for disorders of the central nervous system has progressed to a new level of clinical application. Various clinical studies are underway for Parkinson's disease, stroke, traumatic brain injury, and various other neurological diseases. Recent biotechnological developments in cell therapy have taken advantage of the technology of induced pluripotent stem (iPS) cells. The advent of iPS cells has provided a robust stem cell donor source for neurorestoration via transplantation. Additionally, iPS cells have served as a platform for the discovery of therapeutics drugs, allowing breakthroughs in our understanding of the pathology and treatment of neurological diseases. Despite these recent advances in iPS, adult tissue-derived mesenchymal stem cells remain the widely used donor for cell transplantation. Mesenchymal stem cells are easily isolated and amplified toward the cells' unique trophic factor-secretion property. In this review article, the milestone achievements of cell therapy for central nervous system disorders, with equal consideration on the present translational obstacles for clinic application, are described.

DOI： 10.1111/cns.13247

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Malignant glioma is one of the most common brain cancers in humans, which is very devastating. The expression of reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is decreased in various human cancers. Lately, we have developed a novel second-generation adenoviral vector that expresses REIC/Dkk-3 (Ad-SGE-REIC) and revealed its antiglioma efficacy. The present investigator-initiated clinical trial is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed at Okayama University Hospital, Okayama, Japan. The primary end points are dose-limiting toxicities and the incidence of adverse events. The secondary end points are the objective response rate and immunological assessment. Use of Ad-SGE-REIC will help to improve the prognosis of patients with malignant brain tumors.

DOI： 10.2217/fon-2019-0743

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Background: Spinal cord stimulation (SCS) exerts neuroprotective effects in animal models of Parkinson's disease (PD). Conventional stimulation techniques entail limited stimulation time and restricted movement of animals, warranting the need for optimizing the SCS regimen to address the progressive nature of the disease and to improve its clinical translation to PD patients. Objective: Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats. Methods: We developed a small device that could deliver continuous SCS. At the start of the experiment, thirty female Sprague-Dawley rats received the dopamine (DA)-depleting neurotoxin, 6-hydroxydopamine, into the right striatum. The SCS device was fixed below the shoulder area of the back of the animal, and a line from this device was passed under the skin to an electrode that was then implanted epidurally over the dorsal column. The rats were divided into three groups: control, 8-h stimulation, and 24-h stimulation, and behaviorally tested then euthanized for immunohistochemical analysis. Results: The 8- and 24-h stimulation groups displayed significant behavioral improvement compared to the control group. Both SCS-stimulated groups exhibited significantly preserved tyrosine hydroxylase (TH)-positive fibers and neurons in the striatum and substantia nigra pars compacta (SNc), respectively, compared to the control group. Notably, the 24-h stimulation group showed significantly pronounced preservation of the striatal TH-positive fibers compared to the 8-h stimulation group. Moreover, the 24-h group demonstrated significantly reduced number of microglia in the striatum and SNc and increased laminin-positive area of the cerebral cortex compared to the control group. Conclusions: This study demonstrated the behavioral and histological benefits of continuous SCS in a time-dependent manner in freely moving PD animals, possibly mediated by anti-inflammatory and angiogenic mechanisms.

DOI： 10.3389/fnagi.2020.00164

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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BACKGROUND: Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease. OBJECTIVE: To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording. METHODS: STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed. RESULTS: The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and -0.45 ± 1.5, and -2.5 ± 1.1 and -3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position. CONCLUSION: Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.

DOI： 10.1093/ons/opy351

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Wistar Kyoto (WKY) rats are a useful animal model of treatment-resistant depression. Lithium is effective for treating recurrent mood disorders or treatment-resistant depression, and lithium augmentation treatment is also useful for treatment-resistant depression. However, the treatment effect of lithium on the depressive behavior of WKY rats remains poorly understood, and whether lithium augments the treatment effect of antidepressants in WKY rats is also unknown. In this study, we evaluated the treatment effect of lithium in WKY rats. We also sought to determine if lithium treatment augments the treatment effect of fluoxetine. Lithium was administered for 15 consecutive days and fluoxetine was administered 23.5, 5, and 1 h before the forced swim test (FST) day 2, based on previous studies. Lithium treatment counteracted depressive behavior in the FST and increased hippocampal neurogenesis. Additionally, co-administration of lithium and fluoxetine augmented the treatment effect observed in the FST and in hippocampal neurogenesis in WKY rats, although fluoxetine monotherapy showed no treatment effect. Lithium prevented an increase in body weight, similar to its effect in human patients. These results are consistent with those of lithium augmentation treatment for human patients with treatment-resistant depression. They suggest that WKY rats are a promising animal model for treatment-resistant depression. However, lithium treatment has various side effects. A new treatment with the same anti-depressive effect as fluoxetine + lithium treatment and fewer side effects compared with lithium would be desirable for patients with treatment-resistant depression.

DOI： 10.1016/j.brainres.2019.04.001

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OBJECTIVE: In Parkinson's disease (PD), abnormal postures are often accompanied, which interfere with rehabilitation and subsequent functional recovery. This study investigated the relationship between clinical characteristics and improvement in abnormal postures of PD patients who received subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: Seventy-four PD patients were included in this study. Clinical data were analyzed using the patients' functional status at pre- and post-STN-DBS, including anteflexion vs. non-anteflexion, scoliosis vs. non-scoliosis, improved anteflexion vs. non-improved anteflexion, and improved scoliosis vs. non-improved scoliosis. RESULTS: In patients with anteflexion, UPDRS III motor score at off medication was worse than that of patients with non-anteflexion. Patients with scoliosis presented with more comorbid spinal deformity and longer disease duration than those without scoliosis. Cobb angle of patients with asymmetrical psoas major and erector spinal muscles was more than that of patients without the asymmetry. Patients with improved anteflexion after STN-DBS had thicker abdominal oblique muscle and transverse abdominal muscle than those of patients without improved anteflexion. Patients with improved scoliosis were significantly younger at PD onset than those without improvement. CONCLUSIONS: There were only a few prognostic factors recognized in patients with improved postures. The thick abdominal muscle for anteflexion and younger PD onset for scoliosis were significant factors for improvement by STN-DBS. Rehabilitation designed to maintain muscle for correct postures may contribute to the amelioration of abnormal postures by STN-DBS, although multicenter trials are needed.

DOI： 10.1016/j.parkreldis.2018.07.014

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DOI： 10.1016/j.hrcr.2018.06.009

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DOI： 10.11477/mf.1436203809

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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OBJECTIVEOffending vessels at the site of neurovascular contact (NVC) in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS) may have specific hemodynamic features. The purpose of this study was to investigate the wall shear stress (WSS) of offending vessels at NVCs by conducting a computational fluid dynamics (CFD) analysis.METHODSThe authors retrospectively analyzed the cases of 20 patients (10 with TN and 10 with HFS) evaluated by 3D CT angiography and used the imaging findings for analysis of the hemodynamic parameters. The 3D CFD images were directly compared with the NVCs determined by simulated multifusion images of CT angiogram and MR cisternogram, and operative photos. The magnitudes of the WSS (WSSm) at the proximal (WSSm-p), just-beginning (WSSm-j), contact site (WSSm-s), and distal (WSSm-d) areas of each NVC were analyzed. The ratios of the WSSm-j, WSSm-s, and WSSm-d areas to the WSSm-p area were calculated individually. The direction of the WSS (WSSv) and its temporal variation (WSSvV) were depicted and morphologically compared with the NVC confirmed by simulated images and operative findings.RESULTSThe ratios of WSSm at the just-beginning and the contact site to the proximal area of the NVCs (WSSm-j/WSSm-p and WSSm-s/WSSm-p) were both significantly higher than that at the distal area (WSSm-d/WSSm-p) (p < 0.05). The WSSv and WSSvV at the NVCs showed small variation in a single cardiac cycle, especially along the areas that were in contact with the affected nerve.CONCLUSIONSAreas of relatively high WSSm and temporal variation of WSSm (WSSmV) were observed at the NVCs. Less mobility of the WSSv and WSSvV was detected along the side of the vessels in contact with the nerves. These findings may be consistent with the actual area of the NVC. Hemodynamic features of the site of NVC can be added to the preoperative simulation for MVD surgery, which may be useful for the diagnosis and treatment planning of TN and HFS.

DOI： 10.3171/2018.1.JNS172544

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The success of deep brain stimulation (DBS) depends heavily on surgical accuracy, and brain shift is recognized as a significant factor influencing accuracy. We investigated the factors associated with surgical accuracy and showed the effectiveness of a dural sealant system for preventing brain shift in 32 consecutive cases receiving DBS. Thirty-two patients receiving DBS between March 2014 and May 2015 were included in this study. We employed conventional burr hole techniques for the first 18 cases (Group I) and a dural sealant system (DuraSeal) for the subsequent 14 cases (Group II). We measured gaps between the actual positions of electrodes and the predetermined target positions. We then retrospectively evaluated the factors involved in surgical accuracy. The average gap between an electrode's actual and target positions was 1.55 ± 0.83 mm in all cases. Postoperative subdural air volume e, the only factor associated with surgical accuracy (r = 0.536, P < 0.0001), was significantly smaller in Group II (Group I: 43.9 ± 27.7, Group II: 12.1 ± 12.5 ml, P = 0.0006). The average electrode position gap was also significantly smaller in Group II (Group I: 1.77 ± 0.91, Group II: 1.27 ± 0.59 mm, P = 0.035). Use of a dural sealant system could significantly reduce intracranial air volume, which should improve surgical accuracy.

DOI： 10.2176/nmc.oa.2017-0242

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OBJECTIVE: Optimal placement of electrodes is important for spinal cord stimulation. Factors affecting the difficulty of percutaneous electrode placement are not well known. In this study, we retrospectively evaluated the factors affecting the difficulty of percutaneous electrode placement. METHODS: We performed a retrospective analysis of 90 consecutive procedures of percutaneous cylindrical electrode implantation at the first author's institution. Age, sex, smoking state, body mass index, the duration of time from the beginning of pain syndrome to operation, diagnosis, the number of previous electrode placements, the previous electrode implantation period, the presence of axial low back pain, the electrode tip level, the pattern of electrode placement, and the reason for reimplantation were selected as factors associated with the success of electrode placement or the operation time of electrode placement. RESULTS: The number of previous electrode placements and the electrode tip level were independently associated with the operation time of electrode placement. According to both univariable and multivariable regression analyses, 1 previous electrode placement lengthened the operation time by approximately 15 minutes. No factors were significantly associated with the success of electrode placement. The more frequently that previous electrode placement was performed, the more difficult electrode placement tended to be. However, electrode reimplantation can be successful given extra time. CONCLUSIONS: This is the first study to evaluate factors affecting the difficulty of percutaneous electrode placement. A history of percutaneous cylindrical electrode placement did not affect the success of current placement, although it lengthened the operation time.

DOI： 10.1016/j.wneu.2018.02.040

PubMed

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Language：Japanese   Publisher：(一社)日本脳神経外科コングレス  

症例は側頭葉てんかんを発症した13歳男児。頭部MRIで右側頭葉内広範囲、基底核、深部白質、側脳室内などに多発する病変を認め、さらに経時的に造影病変は変化した。Fluorodeoxyglucose-positron emission tomography(FDG-PET)で悪性を示唆する所見はなく、subtraction ictal single-photon emission computed tomography coregistered to MRI(SISCOM)と発作時脳波で右側頭葉が発作焦点であると判断し、一期的に右側頭葉切除を行った。病理学的診断はdysembryoplastic neuroepithelial tumorであった。現時点で術後半年経過したが、発作は消失し、残存病変についても増大していない。多発性DNTは非常にまれであり、変化に富む画像所見とあわせて、治療方針の決定に難渋した。本症例はてんかんの治療目的に手術を行ったが、複雑な病態であっても、治療目的を明確にし、それに応じた検査、手術を行うことが重要である。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02632&link_issn=&doc_id=20180403310006&doc_link_id=10.7887%2Fjcns.27.317&url=https%3A%2F%2Fdoi.org%2F10.7887%2Fjcns.27.317&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Several reports have shown that long-term potentiation (LTP) per se effectively enhances neurogenesis in the hippocampus of intact animals. If LTP can enhance neurogenesis in chronic hypoperfusion, this approach could potentially become a new therapeutic strategy for the restoration of cognitive function and for prevention from deterioration of mild cognitive impairment (MCI). Using an in vivo LTP model of rats, we examined whether LTP per se can enhance neurogenesis in hypoperfusion rats that underwent permanent bilateral common carotid artery occlusion (permanent 2-vessel occlusion, P2VO). High frequency stimulation (HFS) in the subacute phase after P2VO enhanced hippocampal cell proliferation and neurogenesis. However, most enhanced cell proliferation and neurogenesis was seen in the hypoperfusion rats that received HFS and for which LTP could finally be induced. In contrast, the same effect was not seen in the LTP induction in the chronic phase. The present findings, which reveal that most enhanced neurogenesis was seen in hypoperfusion rats for which LTP could be finally induced, could explain the ability of LTP-like activities such as learning paradigms and environmental stimuli to increase the rate of neurogenesis in the hippocampus even under hypoperfusion conditions. Moreover, the present findings, which reveal that LTP induction in the chronic phase after P2VO could not effectively enhance neurogenesis in the hypoperfusion rats, could indicate that patients with MCI and even middle-aged healthy control individuals should start LTP-like activities as early as possible and continue with these activities to prevent age-related deterioration of hippocampal function.

DOI： 10.3389/fnagi.2018.00029

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BACKGROUND/AIMS: Bone marrow stromal cells (BMSCs) transplantation is an important strategy for the treatment of ischemic stroke. Currently, there are no effective methods to guide BMSCs toward the targeted site. In this study, we investigated the effect of electrical stimulation on BMSCs migration in an ischemic model of rats. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. BMSCs (2.5×105 cells/ 4 µl PBS) were stereotaxically injected into the left corpus callosum at 1 day after MCAO. After BMSCs injection, a plate electrode with a diameter of 3 mm connected to an implantable electrical stimulator was placed on the right frontal epidural space and a counter electrode was placed in the extra-cranial space. Electrical stimulation at preset current (100 µA) and frequency (100 Hz) was performed for two weeks. Behavioral tests were performed at 1, 4, 8, and 15 days after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at 15 days after MCAO for evaluation of infarction area and the migration distance and area of BMSCs found in the brain tissue. After evaluating cell migration, we proceeded to explore the mechanisms guiding these observations. MCAO rats without BMSCs transplantation were stimulated with same current and frequency. At 1 and 2 weeks after MCAO, rats were euthanized to evaluate stromal cell-derived factor 1 alpha (SDF-1α) level of brain tissues in the bilateral cortex and striatum. RESULTS: Behavioral tests at 4, 8, and 15 days after MCAO revealed that stimulation group displayed significant amelioration in mNSS and cylinder test compared to control group (p<0.05). Similarly, the infarction areas of stroke rats in stimulation group were significantly decreased compared to control group (p<0.05). Migration distance and area of transplanted BMSCs were significantly longer and wider respectively in stimulation group. An increased concentration gradient of SDF-1α in stimulation group accompanied this enhanced migration of transplanted cells. CONCLUSIONS: These results suggest that electrical stimulation enhances migratory ability of transplanted BMSCs in ischemic stroke model of rats. If we can direct the implanted BMSCs to the site of interest, it may lead to a greater therapeutic effect.

DOI： 10.1159/000488409

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Congress of Neurological Surgeons  

Dysembryoplastic neuroepithelial tumor (DNT) is a type of brain tumor that causes refractory epilepsy. We present the case of a 13-year-old boy with temporal lobe epilepsy. Magnetic resonance imaging (MRI) revealed multiple lesions in the right temporal lobe, basal ganglia, deep white matter, and lateral ventricle. Serial MRI showed morphological changes of contrast-enhanced lesions, but fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed hypometabolic lesions. Subtraction ictal single-photon emission computed tomography coregistered to MRI (SISCOM) and ictal electroencephalography (EEG) suggested the seizure onset zone might be located in the right temporal lobe. We performed right temporal lobectomy, and pathological diagnosis confirmed DNT. At one year post-surgery, the patient has achieved seizure-free status, and the remaining lesions have not increased. Multifocal DNT is extremely rare, and treatment strategy was difficult to determine in this case. Surgery should be performed when appropriate after clarifying the treatment purpose.

DOI： 10.7887/jcns.27.317

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Cell therapy for Parkinson's disease (PD) began in 1979 with the transplantation of fetal rat dopamine-containing neurons that improved motor abnormalities in the PD rat model with good survival of grafts and axonal outgrowth. Thirty years have passed since the 2 clinical trials using cell transplantation for PD patients were first reported. Recently, cell therapy is expected to develop as a realistic treatment option for PD patients owing to the advancement of biotechnology represented by pluripotent stem cells. Medication using levodopa, surgery including deep brain stimulation, and rehabilitation have all been established as current therapeutic strategies. Strong therapeutic effects have been demonstrated by these treatment methods, but they have been unable to stop the progression of the disease. Fortunately, cell therapy might be a key for true neurorestoration. This review article describes the historical development of cell therapy for PD, the current status of cell therapy, and the future direction of this treatment method.

DOI： 10.1177/0963689717735411

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Several targets and targeting methods are utilized in stereotactic surgery to achieve tremor suppression for patients with intractable tremor. Recent developments in magnetic resonance imaging, including diffusion tensor imaging, have enabled the setting of appropriate targets in stereotactic surgery. In this retrospective study, the optimal target to suppress tremors in stereotactic surgery was explored using diffusion tensor image-based fiber tractography. Four tracts were focused on in this study, namely: the cerebello-thalamo-premotor cortical fiber tract, cerebello-thalamo-primary motor cortical fiber tract, spino-thalamo-somatosensory cortical fiber tract, and pyramidal tract. In 10 patients with essential tremor, we evaluated the thalamotomy lesions and active contacts of the lead in thalamic stimulation by diffusion tensor image-based fiber tractography to reveal which part of the cerebral cortex is most affected by stereotactic surgery. Tremor suppression and adverse events were also evaluated in the patients involved in this study. Consequently, the good tremor suppression was achieved in all patients. There had been no permanent adverse events 3 months after surgery. Twelve lesions in thalamotomy patients or active contacts of the lead in thalamic stimulation patients were on the cerebello-thalamo-premotor cortical fiber tract (12/14 lesions or active contacts: 86%). In conclusion, the cerebello-thalamo-premotor cortical fiber tract may be an optimal target for tremor suppression. Diffusion tensor image-based fiber tractography may enable us to both determine the optimal target to achieve strong tremor suppression and to reduce the number of adverse events by keeping lesions or electrodes away from important fiber tracts, such as the pyramidal tract and spinothalamic fibers.

DOI： 10.2176/nmc.oa.2016-0277

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The hippocampus is thought to be an important region for depression. However, the relationship between hippocampal neurogenesis and depression is still controversial. Wistar Kyoto (WKY) rats are frequently used as a depression model. WKY rats are known to show physiologically abnormal features, and these features resemble abnormalities seen in depressed patients. However, the neurogenesis of WKY rats is still unknown. In this study, we first evaluated the neurogenesis of WKY rats and compared it to that of Wistar (WIS) rats. No strain effect was observed in the number of cells positive for 5-bromo-2'-deoxyuridine (BrdU) and BrdU/Doublecortin (Dcx) in the subventricular zone (SVZ). However, the number of BrdU- and BrdU/Dcx-positive cells in the dentate gyrus (DG) of the hippocampus was significantly lower in WKY rats than in WIS rats. Next, we evaluated the correlation between neurogenesis and behavior tests. Behavior tests did not affect neurogenesis in either strain. Hippocampal neurogenesis correlated negatively with the results of a forced swim test (FST) on day 2 in each strain. That is, rats with a lower level of native neurogenesis in the DG showed a higher level of learned helplessness induced by the inescapable stress of the FST on day 1. Our findings indicate that hippocampal neurogenesis in WKY rats is congenitally impaired in contrast to that in WIS rats. Native cell proliferation and neurogenesis in the DG are correlated with stress resistance. These findings may be useful for developing new targets for depression treatment.

DOI： 10.1016/j.bbr.2017.04.046

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Electroencephalogram (EEG) data include broadband electrical brain activity ranging from infra-slow bands (< 0.1 Hz) to traditional frequency bands (e.g., the approx. 10 Hz alpha rhythm) to high-frequency bands of up to 500 Hz. High-frequency oscillations (HFOs) including ripple and fast ripple oscillations (80-200 Hz and>200 / 250 Hz, respectively) are particularly of note due to their very close relationship to epileptogenicity, with the possibility that they could function as a surrogate biomarker of epileptogenicity. In contrast, physiological high-frequency activity plays an important role in higher brain functions, and the differentiation between pathological / epileptic and physiological HFOs is a critical issue, especially in epilepsy surgery. HFOs were initially recorded with intracranial electrodes in patients with intractable epilepsy as part of a long-term invasive seizure monitoring study. However, fast oscillations (FOs) in the ripple and gamma bands (40-80 Hz) are now noninvasively detected by scalp EEG and magnetoencephalography, and thus the scope of studies on HFOs /FOs is rapidly expanding.

DOI： 10.18926/AMO/55201

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Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.11477/mf.1436203479

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The high mobility group box-1 (HMGB1) exists as an architectural nuclear protein in the normal state, but displays an inflammatory cytokine-like activity in the extracellular space under pathological condition. Inflammation in the pathogenesis of Parkinson's disease (PD) has been documented. In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6-hydroxydopmaine (6-OHDA, 20 μg/4 μl) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 h after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic terminals inherent in the striatum, and attenuated PD behavioral symptoms compared to the control mAb-treated group. HMGB1 was retained in the nucleus of neurons and astrocytes by inhibiting the proinflammation-induced oxidative stress in the anti-HMGB1 mAb-treated group, whereas HMGB1 translocation was observed in neurons at 1 day and astrocytes at 7 days after 6-OHDA injection in the control mAb-treated group. Anti-HMGB1 mAb inhibited the activation of microglia, disruption of blood-brain-barrier (BBB), and the expression of inflammation cytokines such as IL-1β and IL-6. These results suggested that HMGB1 released from neurons and astrocytes was at least partly involved in the mechanism and pathway of degeneration of dopaminergic neurons induced by 6-OHDA exposure. Intravenous administration of anti-HMGB1 mAb stands as a novel therapy for PD possibly acting through the suppression of neuroinflammation and the attenuation of disruption of BBB associated with the disease.

DOI： 10.1016/j.expneurol.2015.11.003

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Dissecting aneurysms of the posterior cerebral artery (PCA) are rare, especially those at the P1 segment. Here, we describe the case of a 57-year-old woman with a subarachnoid hemorrhage (SAH). Computed tomography angiography (CTA) and digital subtraction angiography (DSA) revealed a small (3 mm) dissecting aneurysm with the typical pearl-and-string sign at the right P1 segment. Fourteen days after onset, the patient developed aphasia. DSA revealed vasospasm of the right middle cerebral artery, and we performed endovascular treatment by the intra-arterial injection of 1-(5-isoquinolinesulfonyl) homopiperazine. After this treatment, the patient's symptoms recovered immediately. Vertebral angiography revealed enlargement of the dissecting aneurysm (up to 7 mm diameter). We started a loading dose of 300 mg aspirin and 400 mg clopidogrel after observing growth of the aneurysm. Fifteen days after onset, we performed a stent-assisted coil embolization, and obtained nearly complete obliteration of the aneurysm with preserved patency of the parent artery. Six-month follow-up DSA demonstrated complete occlusion of the aneurysm with good patency of the stented PCA; the patient was at modified Rankin Scale 1. In the treatment of ruptured dissecting aneurysms, parent vessel occlusion (PVO) with aneurysm is common. However, PVO may cause both cerebral infarction of the distal area and perforator occlusion of the occluded vessel. Stent-assisted coil embolization can preserve parent vessel flow and obliterate the aneurysm. Stents offer a therapeutic alternative for PCA dissecting aneurysms, especially when PVO cannot be tolerated.

DOI： 10.11477/mf.1436203187

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Spinal dural arteriovenous fistulas(S-dAVFs)are rare vascular malformations of the spine. We experienced a case that presented with rapidly progressive brainstem dysfunction due to venous congestion of cervical dAVFs. A 56-year-old man diagnosed with cervical dAVF four years prior presented with gait disturbance and abnormal thermal nociception on his right side. In addition to the high-intensity lesion from the lower pons to the medulla oblongata on T2-weighted magnetic resonance imaging, diffusion-weighted imaging demonstrated cerebral infarction of the left ventrolateral medulla oblongata. Left vertebral angiography revealed that a feeding artery supplied by the radicular artery at the C4 level formed a fistula with the dilated ascending anterior perimedullary vein. We made a diagnosis of venous congestion due to cervical dAVFs. Numbness on the left upper limb occurred five days after the first symptom. Subsequently, hemiparesis on the left upper limb and swallowing disturbance occurred two weeks after the first symptom. The patient underwent surgical ligation of the dilated abnormal vein, with gradual improvement of his symptoms. Myelopathy due to venous congestion of S-dAVFs usually progresses slowly for several years. However, this case report warns about the possibility that some cases of S-dAVF with rapidly exacerbated symptoms may require prompt therapy.

DOI： 10.11477/mf.1436202944

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OBJECTIVE: Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays. RESULTS: Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p's<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p's<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p's<0.05). CONCLUSIONS: These results suggest that intra-arterial allogeneic transplantation of MSCs provides post-stroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical trials of cell transplantation for stroke patients.

DOI： 10.1371/journal.pone.0127302

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DOI： 10.1016/j.parkreldis.2014.01.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

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

DOI： 10.3390/ijms141121513

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Pyoktanin blue is an agent that is often used during STA-MCA anastomosis. In this report, we inject it into a cystic tumor for complete resection, and we report its usefulness. The patient was a 57-year-old female. She suffered from progressive cerebellar ataxia. CT and MR showed a cystic metastatic tumor at the right cerebellar hemisphere, 40mm in diameter. Craniotomy was performed, 5cm in diameter, using the right suboccipital approach. After peeling off the tumor from the surface layer of the brain, we injected diluted pyoktanin blue into the tumor to dye the inside wall. After that, the tumor was peeled off completely without exposing the dyed inside wall. We sometimes find it difficult to distinguish tumor from brain if there is tearing of the tumor wall. Tearing of the tumor can be prevented by injecting pyoktanin blue into it, and making the inside wall visible. Using this procedure, we think a tumor can be resected without residual tumor or damage to the brain. Although we have used this method only a few times, we think it is an easy and useful technique to inject pyoktanin blue into a cystic tumor during its resection.

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Intracranial cavernous sinus dural arteriovenous fistula (CS-dAVF) rarely causes intracranial hemorrhage. We report a case of CS-dAVF presenting with intracranial hemorrhage. A 62-year-old man presented tonic clonic convulsion with consciousness disturbance and was transferred to our hospital. CT scan revealed subarachnoid hemorrhage and right frontal subcortical hemorrhage. Angiography revealed right CS-dAVF which drained only into the vein of the right sylvian fissure. Transvenous embolization was performed using detachable coils. After embolization, CS-dAVF had completely disappeared and the patient was discharged without any symptom. We summarized the fourteen reported cases, including ours, of CS-dAVF with intracranial hemorrhage. All of them had retrograde drainage through cerebral veins.

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A 61-year-old woman suffered cisternal coil migration in the follow-up period after endovascular coil embolization for a ruptured cerebral aneurysm. She presented with sudden onset of headache. Computed tomography demonstrated diffuse subarachnoid hemorrhage, and cerebral angiography disclosed a left anterior choroidal artery aneurysm. The aneurysm was treated by endovascular embolization with Guglielmi detachable coils. During the embolization procedure, the microcatheter perforated the aneurysm. For direct closure of the perforation site with coils, the microcatheter was withdrawn and coils were deployed partially in the subarachnoid space and partially in the aneurysm sac. The coil mass was spread in the subarachnoid space around the aneurysm immediately after embolization. The patient was discharged with no neurological deficit. Three months later, follow-up radiography demonstrated obvious reduction in the size and compaction of the coil mass. Magnetic resonance angiography and digital subtraction angiography demonstrated stable occlusion of the aneurysm. The coil mass probably spread in the cistern around the aneurysm and was compacted by the shape memory of the coils and pulsation of the brain and vessels, as the subarachnoid clots around the aneurysm had disappeared. This case suggests that cisternal coil migration should be considered in the follow up of intracranial aneurysm treated with detachable coils.

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The authors report a case of 74-year-old woman suffering thrombosis of the confluence of sinuses after the left occipital transtentorial removal of a pineal region epidermoid cyst. Four days after the operation, the patient developed left homonymous hemianopsia. Magnetic resonance imaging revealed a venous infarct in the right occipital lobe and magnetic resonance venography disclosed a signal defect of the posterior part of the confluence of sinuses. The patients' neurological symptom recovered soon after anticoagulation treatment, and magnetic resonance venography after the sixth week showed recanalization of the confluence of sinuses. Although it might be rare, thrombosis of the dural sinus should be recognized as a complication of craniotomy.

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A case of arterial stenosis after coil migration in intracranial aneurysm embolization is presented. A 51-year-old woman suffered sudden onset of headache and unconsciousness. Computed tomography demonstrated diffuse subarachnoid hemorrhage and cerebral angiography disclosed a right internal carotid artery (ICA) bifurcation aneurysm and a right ICA-anterior choroidal artery aneurysm. The aneurysms were treated by endovascular embolization with Guglielmi detachable coils. During the embolization procedure of the ICA bifurcation aneurysm, a coil strand detached in the sac had migrated into the ICA. We did not retrieve the migrated coil, because the free coil strand was stable in the ICA and did not cause distal flow reduction. The patient suffered vasospasm of the right ICA and underwent intra-arterial infusion of fasudil hydrochloride and percutaneous transluminal angioplasty of the ICA on day 9. The patient experienced infarction in the territory of the right anterior cerebral artery area and needed a ventriculo-peritoneal shunt for hydrocephalus. The patient was discharged with mild right hemiparesis. Follow-up angiography after six months revealed right ICA and middle cerebral artery stenosis, but the free strand of the migrated coil had not moved in the right ICA. We suspect that the coil strand might have induced thrombosis or intimal hyperplasia of the proximal M1 segment and right ICA. Although late stenosis of the parent artery might be rare, it should be recognized as a long term complication of a migrated free coil strand in the endovascular treatment of intracranial aneurysms.

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A catheter-assisted technique is a technical option that has been developed to allow the endovascular treatment of wide-neck aneurysms. We report our experience of the catheter-assisted technique in treating a wide-neck aneurysm in the posterior inferior cerebellar artery.

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本脳神経外傷学会  

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Language：Japanese   Publisher：(一社)日本小児神経学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：日本生物学的精神医学会・日本神経精神薬理学会  

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Language：Japanese   Publisher：日本生物学的精神医学会・日本神経精神薬理学会  

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DOI： 10.2531/spinalsurg.31.53

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Language：Japanese   Publisher：(一社)日本脳神経外傷学会  

62歳男。作業中、ヘルメットを着用せずに2mの高さから200kgの鉄板が落下し、頭部を強打した。意識レベルはJCS I-3、前頭部に裂傷および右不全片麻痺を認めた。頭部CTでは前頭部正中右寄りに開放骨折、矢状縫合の離開、左急性硬膜外血腫を認めた。徐々に意識レベルが低下し、緊急開頭手術を施行した。硬膜外血腫を除去したが、骨片を残した正中部からの出血が続くため、頭部を軽度挙上し出血を低減させた。次いで上矢状静脈洞を露出するよう追加開頭すると、静脈洞が2cm程度裂けており、大量出血を認めた。1.5×5cm程度のファブリン添付コラーゲンシートで静脈洞の壁を作るように圧迫止血すると、硬膜外への出血は収まった。しかし、硬膜内の硬膜下血腫を認め、上矢状静脈洞内側壁が裂けていたため、内側からもフィブリン添付コラーゲンシートで挟みこむように止血した。止血確認後、外減圧術を終えた。術後は軽度の右麻痺のみが残り、見守り歩行可能な状態で、リハビリ病院へ転院した。受傷から3ヵ月後にチタンプレートによる頭蓋骨形成術を行い、その後は神経脱落症状なく、受傷4ヵ月後より事故前の生活に戻った。

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Other Link： http://search.jamas.or.jp/link/ui/2017004125

Language：Japanese   Publisher：(一社)日本小児神経外科学会  

分子生物学的発達により、様々な難治性の中枢神経系疾患に対する再生医療が可能になる日を想像することができるようになった。てんかんに対しては、抗けいれん剤を用いた内科的治療を軸として、海馬扁桃体切除・焦点切除・脳梁離断・迷走神経刺激を始めとする外科的治療が行われている。しかし治療抵抗性を有する一部の難治性てんかんが存在する。本稿では、てんかん治療の現状に続き、てんかん動物モデルについて概説する。その後、細胞療法、神経保護作用を有する薬物治療、および電気刺激について述べる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

【背景】最近、ventro oralis posterior nucleus(VOP)やposterior subthalamic area(PSA)を標的にした難治性振戦に対する治療の有効性が報告されている。当科でも、難治性振戦に対してPSAを標的とした手術を行っており、この部位の手術に関するdiffusion tensor imaging based fiber tractography(DTI-FT)による解析を試みた。【目的】PSAにおける神経線維の走行を解析し、難治性振戦に対する最適な標的について検討する。【方法】2013年7月から2014年10月までに難治性振戦に対する脳深部刺激療法を行った患者を対象とした。男性2名、女性2名、平均年齢は69.8歳(66〜75歳)であった。術前に3T-MRIでナビゲーション用の画像と共にDTIも撮像した。術中にVIM(ventro intermedial neucleus)、PSA刺激を行い、振戦抑制効果の高い部位に電極を留置した。Stealth Navigation StealthViz上で術前MRI、fiber tractography、術後MRIのfusion画像を作成し、視床VL(ventro lateral)核、PSA(posterior subthalamic area)周囲を走行する神経線維と活動電極の位置関係について検討を行った。【結果】全例で良好な振戦の抑制が得られた。DTI-FTで、視床VL核、PSAを通過する神経線維を明瞭に描出することが可能であった。活動電極はDTI-FTから想定される視床VL核およびPSAを走行する神経線維上にあった。【結論】難治性振戦に対する定位脳手術の標的決定において、DTI-FTは有用であることが示唆された。(著者抄録)

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

【はじめに】パーキンソン病(PD)に対する視床下核刺激療法(STN-DBS)において、体部位局在を解明することは精度の高い手技を行う上で重要である。STN-DBSを施行したPD患者における視床下核内の体部位局在の同定を試みた。【対象と方法】2010年3月から2014年3月までにSTN-DBSを行ったPD患者77人を対象とした。微小電極記録(microelectrode recording;MER)の際、他動的単関節運動による単一神経活動の変調が、再現性を有し認められた場合に、これを運動関連神経細胞とした。運動関連神経細胞の局在を間接的評価として、mid-commissural point(MCP)からの3次元座標を算出した。直接的評価として、術後CTと術前MRIの合成画像上でDBS電極を描出させ、STN内における位置を評価した。【結果】DBS電極は152個留置し、MERは169回行った。捕捉できた運動関連神経細胞の総数は258個(単関節に反応した神経細胞:151個)であり、その内訳は肩102(45)、肘61(15)、手27(5)、指3(0)、股113(45)、膝96(39)、足9(2)であった。各関節は、電極進入方向からターゲットまで指、手、肘、肩、足、膝、股の順で局在していた。上肢と下肢の運動関連神経細胞の出現部位の平均座標はX:13.1±1.1、12.7±1.2mm(p=0.033)、Y:0.22±1.3、-0.45±1.5mm(p=0.0068)、Z:-2.5±1.1、-3.0±1.4(p=0.019)であった。MRI上で運動関連神経細胞はすべてSTN内に存在しており、その多くは上外側に局在していた。【結論】PD症例におけるSTNの体部位局在を示した。上肢の運動関連神経細胞は下肢と比較し、より外側、前方、上方に位置していた。多くの運動関連神経細胞はSTNの上外側に存在していた。(著者抄録)

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Other Link： https://search.jamas.or.jp/link/ui/2016123797

Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

Diffusion tensor imagingによるfiber tractography(DTI-FT)は解剖学的構造物とその他の部位へのconnectivityを解析するために広く使用されている。我々は、視床手術の際にFT上での治療部位の解析を行い、振戦抑制効果の高い治療部位は小脳-視床外側核-運動前野の神経線維束上であったことを報告した。そこで、FT上での標的決定による定位脳手術を実施し、手術手技および治療効果を評価し、手術計画におけるFTの有用性について検討を行った。振戦評価にはFahn-Tolosa-Marin tremor scaleを使用した。術前にStealth Navigation StealthViz上でFTを作成し、小脳-視床外側核-運動前野の神経線維束が最も収束する部位を標的として、手術計画を立てた。いずれの症例も75%以上のtremor scaleの改善を示し、良好な振戦抑制が得られた。従来の間接的標的決定に基づく手術での振戦抑制効果と同等であった。手術による有害事象に関しても従来の手術手技と差はなかった。高い振戦抑制効果を得るために標的とすべき神経線維束に関しては、未だ統一された見解はないが、当科で経験した10例のDBS(4例)、thalamotomy(6例)では、小脳-視床外側核-運動前野を走行する神経線維束上に標的を置いており、高い振戦抑制効果が得られた。FTは、難治性振戦に対する定位脳手術の計画作成に有用であると考えられた。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2015166907

Language：English   Publisher：PUBLIC LIBRARY SCIENCE  

In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson's disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness and safety.

DOI： 10.1371/journal.pone.0101468

Web of Science

PubMed

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Language：Japanese   Publisher：(一社)日本定位・機能神経外科学会  

【目的】パーキンソン病(PD)患者の認知機能低下は非運動症状の中でも出現頻度が高く、状態把握が重要である。視床下核刺激療法を施行するPD患者の認知機能について検討を行った。【対象と方法】PD患者51名(男性21名、女性30名)を対象とした。平均年齢は63.9±7.3歳、平均罹病期間は12.2±5.8年であった。認知機能評価にMini-Mental State Examination(MMSE)とWechsler Adult Intelligence Scale-III(WAIS-III)、脳血流SPECTを行った後、three-dimensional stereotaxic ROI template(3DSRT)とStatistical Parametric Mapping(SPM)8を用いて脳血流評価を行った。【結果】MMSEの平均得点は27.1±2.5点、カットオフ以下の患者は51名中5名(9.8%)であった。WAIS-IIIでは全検査IQ、言語性IQ、動作性IQにおいて重症度が増すごとに有意な認知機能低下がみられた。3DSRTではPD患者は一般平均値と比較して前頭葉、側頭葉、頭頂葉、後頭葉の脳血流が低下していた。SPM8ではPD患者の認知機能は視床、帯状回部位の脳血流と相関した。【結語】PD患者の認知機能低下はヤール重症度と相関した。ヤール重症度がIIのPD患者の認知機能は保たれていたが、重症度がIIIとIVのPD患者の言語機能、作動記憶、視空間認知機能は著しく低下していた。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2014281140

Language：English  

Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data.

DOI： 10.3390/ijms141223390

PubMed

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Language：Japanese   Publisher：日本脳循環代謝学会  

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Language：Japanese   Publisher：(株)金芳堂  

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Language：Japanese   Publisher：日本定位・機能神経外科学会事務局  

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Other Link： https://search.jamas.or.jp/link/ui/2014281148

Language：Japanese   Publisher：日本定位・機能神経外科学会事務局  

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Other Link： https://search.jamas.or.jp/link/ui/2014281139

Language：Japanese   Publisher：日本定位・機能神経外科学会事務局  

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Other Link： https://search.jamas.or.jp/link/ui/2014281138

Event date： 2022.9.28 - 2022.10.1

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Venue：横浜  

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Venue：和歌山  

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Venue：Web  

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Event date： 2022.3.17 - 2022.3.19

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Event date： 2022.1.28 - 2022.1.29

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Venue：大阪  

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Venue：大阪  

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Venue：大阪  

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Venue：大阪  

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Event date： 2022.1.28 - 2022.1.29

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Venue：大阪  

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Venue：大阪  

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Venue：大阪  

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Event date： 2022.1.27 - 2022.1.28

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Venue：大阪  

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Event date： 2022.1.27 - 2022.1.28

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Venue：大阪  

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Event date： 2022.1.27 - 2022.1.28

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Venue：大阪  

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Event date： 2022.1.25

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Event date： 2021.12.22

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Venue：Web  

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Event date： 2021.12.5 - 2021.12.7

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Venue：神戸  

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Event date： 2021.12.5

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Event date： 2021.10.27 - 2021.10.30

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Event date： 2021.10.8

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Event date： 2021.9.24 - 2021.9.25

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Venue：京都  

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Event date： 2021.1.22 - 2021.1.23

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Venue：新潟  

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Venue：新潟  

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Venue：岡山  

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Event date： 2020.8.23

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Event date： 2019.9.9 - 2019.9.12

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Venue：Beijing  

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Event date： 2019.8.22

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Event date： 2019.8.9 - 2019.8.10

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Venue：東京  

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Event date： 2019.7.20 - 2019.7.21

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Event date： 2019.3.8 - 2019.3.9

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Venue：淡路  

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Venue：下関  

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Event date： 2019.2.16

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Venue：下関  

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Venue：東京  

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Venue：東京  

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Venue：東京  

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Venue：東京  

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Venue：東京  

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Venue：横浜（Web併催）  

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Venue：岡山  

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Venue：岡山  

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Venue：岡山  

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Venue：岡山  

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Venue：岡山  

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Venue：岡山  

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Venue：浜松  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：浜松  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：浜松  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜  

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Language：Japanese   Presentation type：Oral presentation (keynote)  

Venue：岡山  

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Language：Japanese   Presentation type：Poster presentation  

Venue：神戸  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

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Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：大阪  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：神戸  

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