川合 謙介

Aims. Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug-resistant epilepsy, however, evidence for long-term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan.Methods. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug-resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices.Results. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow-up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family-accessed QOL which improved over time. No new safety issues were identified.Conclusions. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug-resistant epilepsy, with >90% follow-up rate, indicates long-term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow-up and difficulties in seizure counting are also discussed.

てんかんの三次診療施設に紹介された18歳以上のてんかん患者48名(男24例、女24例)を対象として、6ヵ月間におけるてんかん発作の状態およびQOLを調査した。紹介理由は発作コントロールのための治療調整に次いで確定診断および手術適応の評価が多く、三次施設で行われた介入方法は薬剤調整に次いで教育と外科的治療が多かった。三次施設受診により、発作頻度および覚醒時の発作回数は有意に減少し、てんかん特異的健康関連QOL調査尺度の総得点と精神活動を除くすべての下位項目で有意な改善がみられたほか、社会生活に支障をきたし日数は減少し、患者の治療満足度は改善した。発作が抑制されない患者をより専門の診療施設に紹介し、適切な治療後に紹介元に戻すという循環的な診療連携システムが患者のQOLを高め、社会生活の不利益の改善につながると考えられた。

Vagus nerve stimulation (VNS) causes neuromodulatory effects in the cerebral cortex, which are useful not only for therapy on intractable epilepsy but also for enhancement of higher brain functions such as cognition and memory. Recently, it has been reported that VNS may also affect auditory-evoked neutral activities. However, it remains to be elucidated how and where VNS modulates neutral activities in the auditory cortex. Here, we examined effects of VNS on adaptation of neutral activities in response to repeated stimuli in the rat auditory cortex. Both a surface and depth microelectrode array recorded auditory-evoked potentials in response to click train and oddball stimuli. We quantified a repetition rate transfer function and common stimulus-specific adaptation (SSA) index from the amplitude of middle-latency response (PI). Consequently, VNS affected temporal response property and increased SSA in the layer 1 and 5/6 of auditory cortex. This result suggests that VNS strengthens adaptation in the auditory cortex in a layer-specific manner. (C) 2017 Wiley Periodicals, Inc.

Introduction: Although Ommaya reservoir implantation is effective in reducing the target volume of cystic brain metastases preceding stereotactic radiosurgery, adequate volume reduction cannot be achieved in some cases, and the factors leading to failure in volume reduction have not been clearly identified. In this study, we investigated the factors leading to failure in volume reduction after use of the Ommaya reservoir. Materials and methods: Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively. Results: The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p = 0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction. Conclusion: For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst. (C) 2016 Elsevier Ltd. All rights reserved.

Objective: Cortico-cortical evoked potential (CCEP) has been utilized to evaluate connectivity between cortices. However, previous reports have rarely referred to the impact of volume-conducted potential (VCP) which must be a confounding factor of large potential around the stimulation site. To address this issue, we challenged the null hypothesis that VCP accounts for the majority of the recorded potential, particularly around the stimulation site. Methods: CCEP was recorded with high-density intracranial electrodes in 8 patients with intractable epilepsy. First, we performed regression analysis for describing the relationship between the distance and potential of each electrode. Second, we performed principal component analysis (PCA) to reveal the temporal features of recorded waveforms. Results: The regression curve, declining by the inverse square of the distance, fitted tightly to the plots (R-2: 0.878-0.991) with outliers. PCA suggested the responses around the stimulation site had the same temporal features. We also observed the continuous declination over the anatomical gap and the phase reversal phenomena around the stimulation site. Conclusions: These results were consistent with the null hypothesis. Significance: This study highlighted the risk of misinterpreting CCEP mapping, and proposed mathematical removal of VCP, which could lead to more reliable mapping based on CCEP. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

We report a case of dural arteriovenous fistula (DAVF) of the isolated superior sagittal sinus (SSS) that was successfully treated with transcranial transvenous embolization. The transcranial approach has only been reported in small case series, and its technical details have yet to be discussed.<br>A 53-year-old man who underwent five craniotomies for an occipitoparietal hemangiopericytoma presented with dizziness and mild cognitive dysfunction 2 months after the last craniotomy. The patient's MRI showed venous congestion of the deep medullary veins of the bilateral cerebral hemispheres. Cerebral angiography revealed a DAVF of the SSS with cortical reflux. As the posterior part of the SSS had been removed in the previous surgery, the transcranial approach was applied for embolization of the fistula. An oval craniectomy above the SSS was prepared anteriorly to the DAVF in the operating room. The SSS was punctured by an 18-gauge cannula under fluoroscopic guidance in the angiography room on the following day. Through the outer sheath of this cannula, the fistula was embolized with platinum coils. The venous congestion showed significant improvement on postoperative imaging, along with improvements in cognitive impairment and dizziness.<br>Thus, direct sinus puncture can be a useful option for transvenous embolization of DAVF when the typical transjugular approach is difficult.

Purpose: The purpose of this study was to determine the optimal duration of long-term videoEEG monitoring (VEEG) in patients with epilepsy. The response time of medical staff to seizures was also evaluated from the viewpoint of safety of the monitoring. Methods: We estimated the optimal duration of VEEG from the seizure onset pattern. We retrospectively investigated all VEEG sessions performed in our department during the period between June 2005 and July 2016. Sessions with no seizures and with only non-epileptic seizures were excluded. Using 91 sessions from 69 patients, information on the onset time and response time of medical staff to seizures was collected. Results: The median duration from the start of VEEG to the first seizure was 2 days. Seventy-seven percent of first seizures occurred within 3 days of VEEG. The median duration from the first seizure to the third seizure was 2 days. Eighty percent of third seizures occurred within 3 days of the first seizure. There was no significant diurnal distribution of seizure occurrence. Medical staff did not respond to 20% of generalized seizures and 69% of focal seizures. The overlooking of generalized seizures occurred mainly during the hours of 1-2 pm and 8-9 pm but there was no significant diurnal pattern in overlooking generalized and focal seizures. Conclusion Based on these findings, we suggest that VEEG can be terminated when no seizure occurs within 4 days after onset. In our VEEG protocol, in which all antiepileptic drugs were discontinued before the start of a session, there was no diurnal pattern of seizure occurrence. This is the first study investigating the diurnal pattern of overlooking seizures by medical staff during VEEG. Since there was no diurnal pattern to the overlooking, medical staff should pay equal, 24- hour attention to patients on VEEG.

Patient-specific vascular replicas are essential to the simulation of endovascular treatment or for vascular research. The inside of silicone replica is required to be smooth for manipulating interventional devices without resistance. In this report, we demonstrate the fabrication of patient-specific silicone vessels with a low-cost desktop 3D printer. We show that the surface of an acrylonitrile butadiene styrene (ABS) model printed by the 3D printer can be smoothed by a single dipping in ABS solvent in a time-dependent manner, where a short dip has less effect on the shape of the model. The vascular mold is coated with transparent silicone and then the ABS mold is dissolved after the silicone is cured. Interventional devices can pass through the inside of the smoothed silicone vessel with lower pushing force compared to the vessel without smoothing. The material cost and time required to fabricate the silicone vessel is about USD $2 and 24 h, which is much lower than the current fabrication methods. This fast and low-cost method offers the possibility of testing strategies before attempting particularly difficult cases, while improving the training of endovascular therapy, enabling the trialing of new devices, and broadening the scope of vascular research.

We report two extremely rare cases involving the development of transient selective retrograde amnesia for simple machine operation lasting for several hours. A 61-year-old male taxi driver suddenly became unable to operate a taximeter, and a 66-year-old female janitor suddenly became unable to use a fax machine. They could precisely recount their episodes to others both during and after the attacks, and their memories during their attacks corresponded to the memory of the witness and the medical records of the doctor, respectively. Therefore, it appears that these individuals remained alert and did not develop anterograde amnesia during their attacks. On day 4, they underwent high-resolution magnetic resonance imaging (MRI), and diffusion-weighted MRI with 2-mm section thickness revealed small high-intensity signal lesions in the left hippocampal cornu ammonis area 1 (CA1) region. However, these lesions disappeared during the chronic phase. This is the first report describing lesions detected by MRI in patients with transient selective amnesia without anterograde amnesia. Reversible damage to the hippocampal CA1 region may cause transient selective amnesia by impairing the retrieval of relevant memories.

Objective: Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. Methods: Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) studies performed before and &gt;6 months after surgery. Results: Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. Significance: The long-termoutcome for complex partial seizures afterMHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

OBJECTIVE The microvascular anatomy of spinal perimedullary arteriovenous fistulas (AVFs) is more complicated than that of dural AVFs, and occlusion rates of AVF after open microsurgery or endovascular embolization are lower in patients with perimedullary AVFs (29%-70%) than they are in those with dural AVF (97%-98%). Reports of intraoperative blood flow assessment using indocyanine green (ICG) video angiography in spinal arteriovenous lesions have mostly been for spinal dural AVFs. No detailed reports on spinal perimedullary AVFs are available. METHODS Participants were 11 patients with spinal perimedullary AVFs (Type IVa in 5 patients, Type VIb in 4, and Type IVc in 2). Intraoperative ICG video angiography was assessed by measuring the number of cases in which this modality was judged essential by the surgeon to correctly occlude the fistula. RESULTS In all patients, arterial feeders were identified and intravenous ICG video angiography was performed before and after blocking the feeders. In one patient, selective intraarterial ICG video angiography was also performed. The findings provided by ICG video angiography significantly changed the surgical procedure in 4 of 11 patients (36%). Post-operatively, complete occlusion of the AVF was achieved in 10 of the 11 patients (91%). CONCLUSIONS Intraoperative ICG video angiography can have a significant impact on deciding surgical strategy in the microsurgical treatment of spinal perimedullary AVF.

A 45-year-old woman had a 6-month history of progressive amnesia and diplopia. At age 34, a pineal germinoma was diagnosed; whole-brain radiation induced tumor regression for 10 years. The tumor had recurred and at surgery it was detached from the fornix and resected through an occipital transtentorial approach (figure 1). The fornix was decompressed and amnesia was remarkably recovered (figure 2A).

Vagus nerve stimulation (VNS) is a therapy on medically refractory epilepsy, and recently reported to improve cognitive function including learning and memory. The thalamo-cortical system may underlie such VNS-induced cognitive improvements. Thus, the present study targeted the auditory cortex and thalamus in rats, and investigated whether and how VNS modulates stimulus-specific adaptation (SSA) of the neural activity in these nuclei. A depth electrode array recorded auditory evoked potentials from the auditory thalamus and cortex under an oddball paradigm either with or without VNS. Consequently, VNS weakened SSA in the cortex, but did not affect that in the thalamus, indicating that VNS has neuromodulatory effects on the cortical inhibitory system and the thalamo-cortical projections, but not on the feedforward projections from the auditory periphery up to thalamus.

Background and Purpose: We analyzed the ability of a machine learning approach that uses diffusion tensor imaging (DTI) structural connectomes to determine lateralization of epileptogenicity in temporal lobe epilepsy (TLE). Materials and Methods: We analyzed diffusion tensor and 3-dimensional (3D) T-1-weighted images of 44 patients with TLE (right, 15, left, 29; mean age, 33.0 +/- 11.6 years) and 14 age-matched controls. We constructed a whole brain structural connectome for each subject, calculated graph theoretical network measures, and used a support vector machine (SVM) for classification among 3 groups (right TLE versus controls, left TLE versus controls, and right TLE versus left TLE) following a feature reduction process with sparse linear regression. Results: In left TLE, we found a significant decrease in local efficiency and the clustering coefficient in several brain regions, including the left posterior cingulate gyrus, left cuneus, and both hippocampi. In right TLE, the right hippocampus showed reduced nodal degree, clustering coefficient, and local efficiency. With use of the leave-one-out cross-validation strategy, the SVM classifier achieved accuracy of 75.9 to 89.7% for right TLE versus controls, 74.4 to 86.0% for left TLE versus controls, and 72.7 to 86.4% for left TLE versus right TLE. Conclusion: Machine learning of graph theoretical measures from the DTI structural connectome may give support to lateralization of the TLE focus. The present good discrimination between left and right TLE suggests that, with further refinement, the classifier should improve presurgical diagnostic confidence.

BACKGROUND: Refractory temporal lobe epilepsy due to spontaneous temporal pole encephalocele is a rare but increasingly recognized condition. Optimal surgical management is complicated by the lack of knowledge regarding both the extent of the epileptogenic area and the need for repair of the encephalocele. CASE DESCRIPTION: We report two cases that add significant information to these issues. In Case 1, with a 5-year history of refractory seizures, implantation of diagnostic subdural electrodes into the anterior temporal base happened to abolish the seizures completely. No structural changes were evident on postoperative magnetic resonance imaging. In Case 2, with a large encephalocele and a 5-year history of refractory seizures, surgical disconnection of the temporal pole successfully abolished seizures without any need for encephalocele repair. CONCLUSIONS: These two cases support the view that the epileptogenic area is confined to within the temporal pole for spontaneous temporal pole encephalocele. Temporopolar disconnection represents one surgical option for this entity that achieves seizure cessation without requiring extra repair procedures.

Background. ICG videoangiography (ICG-VAG) is widely used in neurovascular surgery. In carotid artery disease, it has been used to assess the extent of the plaque and to confirm the removal of the plaque and patency of the artery. We introduce a novel usage of the ICG-VAG to confirm the patency of the external carotid artery (ECA) and superior thyroid artery (STA), which should work as a drainage system of possible debris in the lumen. Method. Consecutive 27 patients with severe internal carotid artery stenosis were employed. Carotid endarterectomy (CEA) was done in the usual fashion. After suturing the arteriotomy, ICG was injected intravenously before reperfusion. Before declamping procedure, ICG-VAG mode was started. As the declamping procedure went on, the assistant judged whether the STA and the ECA were patent by watching the ICG flow on the monitor. After confirming the patency of the ECA-CCA system, the ICA was reperfused. Result. The back flow from the STA was not confirmed in two cases. The back flow from the ECA was confirmed in all 27 cases. In four cases, the ICG-VAG showed air bubbles in the lumen; these bubbles were washed away to the ECA or STA. Conclusion. Using ICG-VAG during the reperfusion procedure of CEA, the patency of the ECA and the STA can be confirmed. It may contribute to reduce embolic complication during reperfusion procedure.

Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270-330 g) were used. Each rat underwent implantation of a VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same anesthesia as previously. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and the LFP was recorded with a sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. The PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased the PLV in a normal state, particularly in the high- band. In an epileptic state, on the other hand, VNS increased the PLV in the high- band and decreased the PLV in the and low- bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state. (C) 2015 Wiley Periodicals, Inc.

This prospective, nationwide, specified drug use-results survey investigated the effects of levetiracetam (LEV) in elderly individuals with partial-onset seizures of advanced-age onset in a practical setting. Participants comprised LEV-naïve patients with onset of focal epilepsy at ≥50 years old and management by at least one antiepileptic drug. Efficacy measures were the physician-rated global improvement scale (GIS), and proportions of patients showing 50% and 100% seizure reduction by comparing seizure frequency during the 4-week pre-treatment period and the last 4 weeks of the 25-week treatment period. Adverse drug reactions (ADRs) and retention rate were also evaluated. Data for safety, GIS evaluation, and seizure frequency analyses were available from 105, 78, and 76, respectively, of 116 enrolled patients, 83 (71.55%) of whom were enrolled by neurosurgeons. Improvement rate (improved or markedly improved) as determined by GIS was 98.72% (77/78). Seventy-four (97.37%) and 64 patients (84.21%) showed 50% and 100% seizure reduction, respectively. Incidence of ADRs was 12.38%, including one serious ADR (mania). LEV retention rate remained high at the end of the 25-week treatment period (96.00%). LEV appears efficacious and well-tolerated in elderly patients with focal epilepsy. Including LEV in the treatment regimen may allow elderly patients to achieve freedom from seizures.

Recognition of faces and written words is associated with category-specific brain activation in the ventral occipitotemporal cortex (vOT). However, topological and functional relationships between face-selective and word-selective vOT regions remain unclear. In this study, we collected data from patients with intractable epilepsy who underwent high-density recording of surface field potentials in the vOT. "Faces" and "letterstrings" induced outstanding category-selective responses among the 24 visual categories tested, particularly in high-gamma band powers. Strikingly, within-hemispheric analysis revealed alternation of face-selective and letterstring-selective zones within the vOT. Two distinct face-selective zones located anterior and posterior portions of the mid-fusiform sulcus whereas letterstring-selective zones alternated between and outside of these 2 face-selective zones. Further, a classification analysis indicated that activity patterns of these zones mostly represent dedicated categories. Functional connectivity analysis using Granger causality indicated asymmetrically directed causal influences from face-selective to letterstring-selective regions. These results challenge the prevailing view that different categories are represented in distinct contiguous regions in the vOT.

This article reviews the current status of surgical treatment of epilepsy and introduces the ongoing challenges. Seizure outcome of resective surgery for focal seizures associated with focal lesions is satisfactory. Particularly for mesial temporal lobe epilepsy, surgical treatment should be considered from the earlier stage of the disease. Meanwhile, surgical outcome in nonlesional extratemporal lobe epilepsy is still to be improved using various approaches. Disconnective surgeries reduce surgical complications of extensive resections while achieving equivalent or better seizure outcomes. Multiple subpial transection is still being modified expecting a better outcome by transection to the vertical cortices along the sulci- and multi-directional transection from a single entry point. Hippocampal transection is expected to preserve memory function while interrupting the abnormal epileptic synchronization. Proper selection or combination of subdural and depth electrodes and a wide-band analysis of electroencephalography may improve the accurate localization of epileptogenic region. Patients for whom curative resective surgery is not indicated because of generalized or bilateral multiple nature of their epilepsies, neuromodulation therapies are options of treatment which palliate their seizures.

Vagus nerve stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has been used to treat more than 60,000 patients, the precise therapeutic mechanism of action has not been elucidated. Here, we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits seizures. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high-spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS-induced phase modulation at the local network level. VNS significantly increased the phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA delivered at 10 Hz. This PLV modulation was most effective when the interelectrode distance was about 1.6 mm. Gamma-band PLVs within the auditory cortex increased more significantly than those between the auditory and nonauditory cortices, while alpha- and low-beta PLV exhibited more synchronization between the auditory and nonauditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and has some implications for the mechanism of action of VNS.

Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.

Although immaturity of neointimal smooth muscle cells (SMCs) in coronary arteries has recently been demonstrated to be associated with acute coronary syndrome, the carotid arterial counterpart has not been investigated. We hypothesized that the same investigation of carotid endarterectomy specimens might contribute to living patients. Carotid endarterectomy specimens from 33 Asian males who underwent a 5-year follow-up were examined. Age, atherosclerotic risk factors, and percentage stenosis were investigated. Histologically, the fibrous cap/lipid core ratio was measured. Maturation of SMCs was assessed by the h-caldesmon/smooth muscle actin (SMA) ratio by immunohistochemistry in 3 different regions (luminal, medial, and opposite side of lipid core) in the neointima. Associations of these factors with preoperative symptoms along with postoperative systemic atherogenic cardiovascular events were analyzed. It was revealed that fibrous cap/lipid core ratio was significantly lower in symptomatic than in asymptomatic patients, while the h-caldesmon/SMA ratio was significantly lower in patients with than without postoperative systemic atherogenic cardiovascular events by the Student's t-test (P&lt;0.05). Logistic regression model demonstrated that younger age and a lower h-caldesmon/SMA ratio were associated with postoperative systemic atherogenic cardiovascular events (P&lt;0.05). This result was not different when 3 different regions were each analyzed instead. Immaturity of neointimal SMCs shown by a lower h-caldesmon/SMA ratio by immunohistochemistry was associated with systemic atherogenic cardiovascular events. Thus, this finding may be predictive of these events after carotid endarterectomy. Uniform results among different neointimal regions suggest that immaturity of neointimal SMCs causes plaque instability and does not occur secondarily to plaque instability.

A large basilar trunk aneurysm was incidentally found in a 77-year-old woman in examination for headache. Though it was asymptomatic, high signal intensity was noticed in the brainstem around the aneurysm on FLAIR image of MRI. As she was otherwise healthy, surgical clipping was performed through anterior temporal approach.

ObjectiveResective surgery for mesial temporal lobe epilepsy (MTLE) with a correspondent lesion has been established as an effective and safe procedure. Surgery for temporal lobe epilepsies with bilateral hippocampal sclerosis or without correspondent lesions, however, carries a higher risk of devastating memory decline, underscoring the importance of establishing the memory-dominant side preoperatively and adopting the most appropriate procedure. In this study, we focused on high gamma activities (HGAs) in the parahippocampal gyri and investigated the relationship between memory-related HGAs and memory outcomes after hippocampal transection (HT), a hippocampal counterpart to neocortical multiple subpial transection. The transient nature of memory worsening after HT provided us with a rare opportunity to compare HGAs and clinical outcomes without risking permanent memory disorders. MethodsWe recorded electrocorticography from parahippocampal gyri of 18 patients with temporal lobe epilepsy while they executed picture naming and recognition tasks. Memory-related HGA was quantified by calculating differences in power amplification of electrocorticography signals in a high gamma range (60-120Hz) between the two tasks. We compared memory-related HGAs from correctly recognized and rejected trials (hit-HGA and reject-HGA). Using hit-HGA, we determined HGA-dominant sides and compared them with memory outcomes after HT performed on seven patients. ResultsWe observed memory-related HGA mainly between 500 and 600msec poststimulus. Hit-HGA was significantly higher than reject-HGA. Three patients who had surgery on the HGA-dominant side experienced transient memory worsening postoperatively. The postoperative memory functions of the other four patients remained unchanged. SignificanceParahippocampal HGA was indicated to reflect different memory processes and be compatible with the outcomes of HT, suggesting that HGA could provide predictive information on whether the mesial temporal lobe can be resected without causing memory worsening. This preliminary study suggests a refined surgical strategy for atypical MTLE based on reliable memory lateralization.

Vagus nerve stimulation (VNS) reduces intractable epileptic seizures. VNS is also likely to improve higher brain functions such as cognition and memory, although the mechanisms of action remain speculative. In this study, we examined the effects of VNS on auditory perception. Using a depth microelectrode array, we investigated neural activities in the auditory cortex and thalamus of anesthetized rats in terms of reproducibility and temporal resolution of sound evoked responses. Consequently, we found that, in the auditory cortex, VNS improved reproducibility of neural activities in response to characteristic-frequency tones and strengthened adaptation to repetitive clicks. On the other hand, in the thalamus, VNS had no significant effect on reproducibility and temporal resolution of sound evoked responses. Thus, VNS may affect auditory perception.

How visual object categories are represented in the brain is one of the key questions in neuroscience. Studies on low-level visual features have shown that relative timings or phases of neural activity between multiple brain locations encode information. However, whether such temporal patterns of neural activity are used in the representation of visual objects is unknown. Here, we examined whether and how visual object categories could be predicted (or decoded) from temporal patterns of electrocorticographic (ECoG) signals from the temporal cortex in five patients with epilepsy. We used temporal correlations between electrodes as input features, and compared the decoding performance with features defined by spectral power and phase from individual electrodes. While using power or phase alone, the decoding accuracy was significantly better than chance, correlations alone or those combined with power outperformed other features. Decoding performance with correlations was degraded by shuffling the order of trials of the same category in each electrode, indicating that the relative time series between electrodes in each trial is critical. Analysis using a sliding time window revealed that decoding performance with correlations began to rise earlier than that with power. This earlier increase in performance was replicated by a model using phase differences to encode categories. These results suggest that activity patterns arising from interactions between multiple neuronal units carry additional information on visual object categories. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Delalande's vertical hemispherotomy is an innovative evolution of hemispherectomy in minimizing brain resection. We report our modification for this surgical procedure. We modified the original procedure in two aspects for the purpose of less brain resection and confirmation of the complete disconnection. Firstly, all procedures were done via an interhemispheric route instead of a transcortical route. Secondly, we set the anterior disconnection plane as the one that connects the anterior end of the choroidal fissure to the anterior end of the foramen of Monro, instead of the former to the subcallosal area. We applied this modified vertical hemispherotomy to 7 cases. Four cases were children with hemimegalencephaly and other 3 were adults with ulegyric hemisphere. Surgical procedure was completed without complication in all cases. There was no case that required CSF shunting. Seizure outcome was Engel's class I in 6 and class IV in 1. Postoperative MRI revealed complete disconnection of the affected hemisphere in all patients. We reported our modification of vertical hemispherotomy. Although these are minor modifications, they further minimized brain resection and may serve for less invasiveness of procedure and improvement in completeness of disconnection and its confirmation during surgery. (C) 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270 - 330 g) were used. Each rat underwent implantation of VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same as previous anesthesia. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and LFP was recorded with sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased PLV in a normal state, particularly in the high-? band. In an epileptic state, on the other hand, VNS increased PLV in high-? band, and decreased PLV in the d and low-β bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state. ©2014 The Institute of Electrical Engineers of Japan.

BACKGROUND: There has been growing interest in clinical single-neuron recording to better understand epileptogenicity and brain function. It is crucial to compare this new information, single-neuronal activity, with that obtained from conventional intracranial electroencephalography during simultaneous recording. However, it is difficult to implant microwires and subdural electrodes during a single surgical operation because the stereotactic frame hampers flexible craniotomy. OBJECTIVE: To describe newly designed electrodes and surgical techniques for implanting them with subdural electrodes that enable simultaneous recording from hippocampal neurons and broad areas of the cortical surface. METHODS: We designed a depth electrode that does not protrude into the dura and pulsates naturally with the brain. The length and tract of the depth electrode were determined preoperatively between the lateral subiculum and the lateral surface of the temporal lobe. A frameless navigation system was used to insert the depth electrode. Surface grids and ventral strips were placed before and after the insertion of the depth electrodes, respectively. Finally, a microwire bundle was inserted into the lumen of the depth electrode. We evaluated the precision of implantation, the recording stability, and the recording rate with microwire electrodes. RESULTS: Depth-microwire electrodes were placed with a precision of 3.6 mm. The mean successful recording rate of single-or multiple-unit activity was 14.8%, which was maintained throughout the entire recording period. CONCLUSION: We achieved simultaneous implantation of microwires, depth electrodes, and broad-area subdural electrodes. Our method enabled simultaneous and stable recording of hippocampal single-neuron activities and multichannel intracranial electroencephalography.

Object. Meningiomas treated by subtotal or partial resection are associated with significantly shorter recurrence-free survival than those treated by gross-total resection. The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection. Methods. This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. Retreatment was defined as reresection or stereotactic radiosurgery due to postoperative tumor growth. Results. A total of 38 patients were included in this study. Regrowth of residual tumor was observed in 22 patients with a mean follow-up period of 6.1 years. Retreatment was performed for 20 of these 22 tumors with regrowth. Risk factors related to significantly shorter retreatment-free survival were age younger than 50 years (p = 0.006), postresection tumor volume of 4 cm(3) or more (p = 0.016), no dural detachment (p = 0.001), and skull base location (p = 0.016). Multivariate analysis revealed that no dural detachment (hazard ratio [BR] 6.42,95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor. Conclusions. Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.

Background: Vagus nerve stimulation (VNS) is a palliative treatment for drug resistant epilepsy for which the efficacy and safety are well established. Accumulating evidence suggests that ascending vagal signals modulate abnormal cortical excitability via various pathways. However, there is no direct evidence for an ascending conduction of neural impulses in a clinical case of VNS. Objective: We recorded and analyzed the short-latency components of the vagus nerve (VN) evoked potential (EP) from the viewpoint of determining whether or not it is a marker for the ascending neural conduction. Methods: EPs within 20 ms were prospectively recorded simultaneously from a surgical wound in the neck and at multiple scalp sites during implantation surgery in 25 patients with drug-resistant epilepsy. Electrical stimulation was delivered using the clinical VNS Therapy system. A recording was made before and after a muscle relaxant was administered, when changing the rostrocaudal position of stimulation, or when stimulating the ansa cervicalis instead of the VN. Results: The short-latency components consisted of four peaks. The early component around 3 ms, which was most prominent in A1-Cz, remained unchanged after muscle relaxation while the later peaks disappeared. Rostral transition of the stimulation resulted in an earlier shift of the early component. The estimated conduction velocity was 27.4 +/- 10.2 m/s. Stimulation of the ansa cervicalis induced no EP. Conclusions: The early component was regarded as directly resulting from ascending neural conduction of A fibers of the VN, probably originating around the jugular foramen. Recording of VN-EP might document the cause of treatment failure in some patients. (C) 2013 Elsevier Inc. All rights reserved.

Vagus Nerve Stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has treated more than 60,000 patients, the precise therapeutic mechanism of action have not been elucidated. Here we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits a seizure. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high-spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS-induced phase modulation at a local network level. VNS significantly increased phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA and delivered at 10 Hz. This PLV modulation was most effective when the inter-electrode distance was about 1.6 mm. Gamma-band PLVs within the auditory cortex increased more significantly than those between the auditory and non-auditory cortices, while alpha- and low-beta PLV exhibited more synchronization between the auditory and non-auditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and have some implications for the mechanism of action of VNS. © 2013 The Institute of Electrical Engineers of Japan.

Objective: We developed a novel technique of spatial normalization of subdural electrode positions across subjects and assessed the spatial-temporal dynamics of high-gamma activity (HGA) in the dominant hemisphere elicited by three distinct language tasks. Methods: The normalization process was applied to 1512 subdural electrodes implanted in 21 patients with intractable epilepsy. We projected each task-related HGA profile onto a normalized brain. Results: The word interpretation task initially elicited HGA augmentation in the bilateral fusiform gyri at 100 ms after stimulus onsets, subsequently in the left posterior middle temporal gyrus, in the left ventral premotor cortex at 200 ms and in the left middle and left inferior frontal gyri at 300 ms and after. The picture naming task elicited HGA augmentation in few sites in the left frontal lobe. The verb generation task elicited HGA in the left superior temporal gyrus at 100-600 ms. Common HGA augmentation elicited by all three tasks was noted in the left posterior-middle temporal and left ventral premotor cortices. Conclusions: The spatial-temporal dynamics of language-related HGA were demonstrated on a spatially normalized brain template. Significance: This study externally validated the spatial and temporal dynamics of language processing suggested by previous neuroimaging and electrophysiological studies. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

High gamma activity (HGA) has been shown to be positively correlated with blood oxygenation level-dependent (BOLD) responses in the primary cortices with simple tasks. It is, however, an open question whether the correlation is simply applied to the association areas related to higher cognitive functions. The aim of this study is to investigate quantitative correlation between HGA and BOLD and their spatial and temporal profiles during semantic processing. Thirteen patients with intractable epilepsy underwent fMRI and electrocorticography (ECoG) with a word interpretation task to evoke language-related responses. Percent signal change of BOLD was calculated at each site of ECoG electrode, which has power amplification of high gamma band (60-120 Hz) activity. We transformed locations of individual electrodes and brains to a universal coordination using SPM8 and made the quantitative comparisons on a template brain. HGAs were increased in several language-related areas such as the inferior frontal and middle temporal gyri and were positively correlated with BOLD responses. The most striking finding was different temporal dynamics of HGAs in the different brain regions. Whereas the frontal lobe showed longer-lasting HGA, the HGA-intensity on the temporal lobe quickly declined. The different temporal dynamics of HGA might explain why routine language-fMRI hardly detected BOLD in the temporal lobe. This study clarified different neural oscillation and BOLD response in various brain regions during semantic processing and will facilitate practical utilization of fMRI for evaluating higher-order cognitive functions not only in basic neuroscience, but also in clinical practice. (C) 2012 Elsevier Inc. All rights reserved.

Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-evoked phase modulation at a local network level. Eight adult Wistar rats (270 - 330 g) were used. Each rat underwent implantation of VNS system (Cyberonics, Houston, TX., USA) under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same as previous anesthesia. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and LFP was recorded with sampling rate of 1000 Hz. Phase-locking value (PLV) between all pairs of electrodes in varied frequency bands was calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased PLV in a normal state, particularly in high-γ band. In an epileptic state, VNS increased PLV in high-γ band, and decreased in d and low-β bands. VNS modulates synchrony in a band-specific and state-dependent manner. VNS might keep cortical synchrony within the optimal state. © 2013 IEEE.

Accurate prediction of epileptic seizures will open novel therapeutic possibilities for patients with intractable epilepsy. We attempted to identify precursors of seizures in the functional networks of electrocorticograms by applying graph theory. Long-term electrocorticograms for periods of 39-76 h from three patients with temporal lobe epilepsy were investigated using pair-wise cross-correlations. Time-varying network properties suggested that there were several distinct brain states. Although functional networks during seizures could be characterized as having a regular topography, no consistent characteristics of functional networks were found immediately prior to seizure onsets. However, it was found that seizures under an identical state were followed by similar transients of the network properties. These results suggest that network properties themselves could not serve as reliable predictors of seizure onset. Yet, some significant pre-seizure changes in the parameters tested appear likely to depend on the brain state. To predict seizures, it may be necessary to take into consideration the states of the brain. In addition to stationary network properties we characterized in the present study, dynamic interactions of epileptic activities with the network might be taken into account to predict the spread of a seizure.