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Background We previously reported that glioma stemlike cells (GSCs) exist in the area of the tumor periphery showing no gadolinium enhancement on magnetic resonance imaging. In the present work, we analyzed glucose metabolism to investigate whether lactate could be predictive of tumor invasiveness and of use in detection of the tumor invasion area in glioblastoma multiforme (GBM). Methods The expression of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase (PDH) was investigated in 20 patients. In GSC lines, LDH-A and PDH expression also was examined in parallel to assessments of mitochondrial respiration. We then investigated the relationship between lactate/creatine ratios in the tumor periphery measured by magnetic resonance spectroscopy, using learning-compression-model algorithms and phenotypes of GBMs. Results In 20 GBMs, high-invasive GBM expressed LDH-A at significantly higher expression than did low-invasive GBM, whereas low-invasive GBM showed significantly higher expression of PDH than did high-invasive GBM. The highly invasive GSC line showed higher expression of LDH-A and lower expression of PDH compared with low-invasive GSC lines. The highly invasive GSC line also showed the lowest consumption of oxygen and the lowest production of adenosine triphosphate. Lactate levels, as measured by magnetic resonance spectroscopy, showed a significant positive correlation with LDH-A transcript levels, permitting classification of the GBMs into high-invasive and low-invasive phenotypes based on a cutoff value of 0.66 in the lactate/creatine ratio. Conclusions In the tumor periphery area of the highly invasive GBM, aerobic glycolysis was the predominant pathway for glucose metabolism, resulting in the accumulation of lactate. The level of lactate may facilitate prediction of the tumor-infiltrating area on GBM.

Objective In order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico–cortical evoked potentials (CCEPs). Methods We analyzed 14 patients’ data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs. Results The distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions. Conclusions We demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition. Significance The CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia.

Objective Cortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs. Methods We retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures. Results Out of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18–82 pairs per patient, ADs and clinical seizures were induced in 0–4 and 0–3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058). Conclusion Although caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation. Significance CCEP is safe under the established protocol.

Antiangiogenic therapy with bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is a common treatment for recurrent glioblastoma (GBM), but its survival benefit is limited. Resistance to Bev is thought to be a major cause of ineffectiveness on Bev therapy. To optimize Bev therapy, identification of a predictive biomarker for responsiveness to Bev is required. Based on our previous study, we focused on the expression and functions of CD44 and VEGF in the Bev therapy. Here, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti‐VEGF therapy. CD44 and VEGF expression in the tumor core and periphery of 22 GBMs was examined, and the relationship between expression of these molecules and progression‐free time on Bev therapy was analyzed. The degree of CD44 expression in the tumor periphery was evaluated by the ratio of the mRNA expression in the tumor periphery to that in the tumor core (P/C ratio). VEGF expression was evaluated by the amount of the mRNA expression in the tumor periphery. To elucidate the roles of CD44 in the Bev therapy, in vitro and in vivo studies were performed using glioma stem‐like cells (GSCs) and a GSC‐transplanted mouse xenograft model, respectively. GBMs expressing high P/C ratio of CD44 were much more refractory to Bev than those expressing low P/C ratio of CD44, and the survival time of the former was much shorter than that of the latter. In vitro inhibition of VEGF with siRNA or Bev‐activated CD44 expression and increased invasion of GSCs. Bev showed no antitumor effects in mice transplanted with CD44‐overexpressing GSCs. The P/C ratio of CD44 expression may become a useful biomarker predicting responsiveness to Bev in GBM. CD44 reduces the antitumor effect of Bev, resulting in much more highly invasive tumors., In this research, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti‐VEGF therapy. These results indicate CD44 will be a useful biomarker for predicting responsiveness to bevacizumab and may serve as a therapeutic target in both primary and recurrent GBMs.

To evaluate the effects on cognitive function of deep white matter hyperintensities (DWMHs) on magnetic resonance imaging (MRI) in patients treated surgically for unruptured intracranial aneurysms (UIAs). The subjects were 106 patients in whom a Wechsler adult intelligence scale-revised (WAIS-R) examination was performed 1 week before and 1 month after clipping surgery for asymptomatic UIAs. DWMH severity was evaluated on preoperative MR images by Fazekas scale, as follows: none (absence), mild (punctate foci), moderate (beginning confluence of foci), or severe (large confluent areas). A decrease of 7 or more points in intelligence quotient (IQ) postoperatively was considered deterioration. Fazekas score was none in 41 (none group), mild in 42 (mild group), moderate in 21, and severe in 2 patients (moderate/severe group). Patient characteristics, surgical factors, IQ change, and abnormal findings on postoperative MRI were compared among the groups. Although there was no statistically significant deterioration in IQ postoperatively in any group, the percentage of deteriorated patients was significantly higher in the moderate/severe group (34.8%) than in the other groups (4.9% in the none group, 7.1% in the mild group; p

Intracranial anaplastic hemangiopericytoma (AHPC) is a rare and malignant subset of solitary fibrous tumor/hemangiopericytoma (SFT/HPC) as per the WHO 2016 Classification of Tumors of the Central Nervous System. AHPC portends a poor prognosis and is associated with higher rates of recurrence/metastasis in comparison with SFT/HPC. Accordingly, it is critical to continue to define the clinical course of patients with AHPC and in so doing further refine clinicopathologic/immunohistochemical (IHC) criteria needed for definitive diagnosis. Herein, we describe clinical/histological characteristics of six patients with AHPC. In addition, we reviewed and analyzed the expression of various IHC markers reported within the literature (i.e., a total of 354 intracranial SFT/HPCs and 460 meningiomas). Histologically, tumors from our six patients were characterized by a staghorn-like vascular pattern, mitotic cells, and strong nuclear atypia. Immunohistochemically, all tumors displayed positive nuclear staining for STAT6; other markers, including CD34 and Bcl-2, were expressed only in three patients. Analysis of IHC expression patterns for SFT/HPC and meningioma within the literature revealed that nuclear expression of STAT6 had the highest specificity (100%) for SFT/HPC, followed by ALDH1 (97.2%) and CD34 (93.6%). Of note, SSTR2A (95.2%) and EMA (85%) displayed a high specificity for meningioma. Anaplastic SFT/HPC is a tumor with poor prognosis that is associated with higher rates of recurrence and metastasis in comparison with SFT/HPC. Given that anaplastic SFT/HPC requires more aggressive treatment than meningioma despite of a similar presentation on imaging, it is crucial to be able to distinguish between these tumors.

Objective To propose a method for intraoperative mapping and monitoring of the medial frontal motor areas (MFMA). Methods We estimated the location of the MFMA using the corticocortical evoked potential (CCEP) provoked by electric stimuli to the primary motor area (M1) of the upper limb. We localized or defined the MFMA by recording the motor evoked potentials (MEPs) provoked by electric stimuli to the medial frontal cortex around the estimated area. We monitored the patients' motor function during awake craniotomy and sequentially recorded the MEPs of the upper and/or lower limbs. This method was applied to 8 patients. Results Four patients who had part of the areas identified as the MFMA removed showed transient hemiparesis postoperatively (supplementary motor area [SMA] syndrome). The MEP from the M1 was preserved in the 4 patients. The resection of the identified MFMA might have caused their SMA syndrome. The CCEP showed a strong connection between the M1 and the SMA of the upper limb. Our method did not provoke any seizures. Conclusions This is a safe and sensitive method for intraoperative mapping and monitoring of the MFMA by combining electrophysiologic monitoring and awake craniotomy. It is clinically useful for mapping the MFMA and can prevent permanent motor deficits.

Funder: European Research Council; FundRef: http://dx.doi.org/10.13039/501100000781; Grant(s): GAP: 502670428 - BRAIN2MIND_NEUROCOMP, How does the human brain encode semantic information about objects? This paper reconciles two seemingly contradictory views. The first proposes that local neural populations independently encode semantic features; the second, that semantic representations arise as a dynamic distributed code that changes radically with stimulus processing. Combining simulations with a well-known neural network model of semantic memory, multivariate pattern classification, and human electrocorticography, we find that both views are partially correct: information about the animacy of a depicted stimulus is distributed across ventral temporal cortex in a dynamic code possessing feature-like elements posteriorly but with elements that change rapidly and nonlinearly in anterior regions. This pattern is consistent with the view that anterior temporal lobes serve as a deep cross-modal 'hub' in an interactive semantic network, and more generally suggests that tertiary association cortices may adopt dynamic distributed codes difficult to detect with common brain imaging methods.

Convergent evidence has demonstrated that semantics are represented by the interaction between a multimodal semantic hub at the anterior temporal lobe (ATL) and other modality-specific association cortical areas. Electrocorticogram (ECoG) recording with high spatiotemporal resolutions is efficient in evaluating such cortical interactions; however, this has not been a focus of preceding studies. The present study evaluated cortical interactions during picture naming using a novel ECoG cross-spectrum analysis, which was formulated from a computational simulation of neuronal networks and combined with a vector space model of semantics. The results clarified three types of frequency-dependent cortical networks: 1) an earlier-period (0.2–0.8 s from stimulus onset) high-gamma-band (90–150 Hz) network with a hub at the posterior fusiform gyrus, 2) a later-period (0.4–1.0 s) beta-band (15–40 Hz) network with multiple hubs at the ventral ATL and posterior middle temporal gyrus, and 3) a pre-articulation theta-band (4–7 Hz) network distributed over widely located cortical regions. These results suggest that frequency-dependent cortical interactions can characterize the underlying processes of semantic cognition, and the beta-band network with a hub at the ventral ATL is especially associated with the formation of semantic representation.

In the dual-stream model of language processing, the exact connectivity of the ventral stream to the anterior temporal lobe remains elusive. To investigate the connectivity between the inferior frontal gyrus (IFG) and the lateral part of the temporal and parietal lobes, we integrated spatiotemporal profiles of cortico-cortical evoked potentials (CCEPs) recorded intraoperatively in 14 patients who had undergone surgical resection for a brain tumor or epileptic focus. Four-dimensional visualization of the combined CCEP data showed that the pars opercularis (Broca’s area) is connected to the posterior temporal cortices and the supramarginal gyrus, whereas the pars orbitalis is connected to the anterior lateral temporal cortices and angular gyrus. Quantitative topographical analysis of CCEP connectivity confirmed an anterior–posterior gradient of connectivity from IFG stimulus sites to the temporal response sites. Reciprocality analysis indicated that the anterior part of the IFG is bidirectionally connected to the temporal or parietal area. This study shows that each IFG subdivision has different connectivity to the temporal lobe with an anterior–posterior gradient and supports the classical connectivity concept of Dejerine; that is, the frontal lobe is connected to the temporal lobe through the arcuate fasciculus and also a double fan-shaped structure anchored at the limen insulae.

OBJECTIVE For future artificial intelligence-based brain mapping, development of a rational and safe scoring system for a brain motor mapping algorithm using electrocorticography (ECoG score), which contains various spectral, purely intrinsic brain activities, is necessary for either before or in the absence of electrical cortical stimulation (ECS). METHODS We evaluated 1114 electrodes of 10 consecutive focal epilepsy patients who underwent subdural electrode implantation before epilepsy surgery at Kyoto University Hospital during 2011-2017. Data from ECoG-based mapping (bandpass filter of 0.016-300/600 Hz) to define the primary motor area (M1) localization were used to create an ECoG score (range = 0-4) by assigning 1 point each for the occurrence of ECoG components: very slow movement-related cortical potentials (

Background and Purpose: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. Methods: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. Results: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23–5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18–0.62; p < 0.01), independent of the 90-day mRS score. Conclusions: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.

Background The connection between the ventrolateral frontal and temporoparietal cortices has an important role in language function on the language-dominant side and spatial awareness on the nondominant side. However, the laterality of these pathways remains controversial. We investigated the laterality of this connection using corticocortical-evoked potentials (CCEPs). Methods From April 2014 to March 2016, 27 patients who had undergone frontotemporal craniotomy were enrolled. With the patients under general anesthesia, subdural electrodes were placed on both frontal and temporoparietal areas intraoperatively. Alternating 1-Hz electrical stimuli were delivered to the pars opercularis and pars triangularis with a stimulus intensity of 10 mA. CCEPs were obtained from temporoparietal areas by averaging the electrocorticogram time-locked to the stimulus onset. The amplitudes and latencies of the CCEP N1 components were compared between the dominant and nondominant sides. Results The median amplitudes of the CCEPs were 335.1 μV (range, 60.2–750) and 125.65 μV (range, 55.1–634) on the dominant and nondominant sides, respectively. The CCEP amplitudes were significantly larger on the dominant side than on the nondominant side (P = 0.013). In contrast, the median latency was 27.8 ms (range, 19.3–36.6) on the language-dominant side and 28.9 ms (range, 8.9–38.5) on the nondominant side. The latencies were not significantly different between the 2 sides (P = 0.604). Conclusions The CCEP amplitudes were significantly larger in the dominant hemisphere. These findings can lead to better hypotheses regarding the relationship between language functions and the development of the network connecting the frontal and temporoparietal cortices.

BACKGROUND The development of noninvasive approaches for identifying hypoperfused brain tissue at risk is of major interest. Recently, the temporal-shift (TS) maps estimated from resting-state blood oxygenation level-dependent (BOLD) signals have been proposed for determining hemodynamic state. OBJECTIVE To examine the equivalency of the TS map and the cerebrovascular reactivity (CVR) map derived from acetazolamide-challenged single-photon emission computed tomography (SPECT) in identifying hemodynamic impairment in patients with arterial occlusive diseases. METHODS Twenty-three patients with arterial occlusive diseases who underwent SPECT were studied. With a recursive TS analysis of low-frequency fluctuation of the BOLD signal, a TS map relative to the global signal was created for each patient. The voxel-by-voxel correlation coefficient was calculated to examine the image similarity between TS and SPECT-based cerebral blood flow (CBF) or CVR maps in each patient. Furthermore, simple linear regression analyses were performed to examine the quantitative relationship between the TS of BOLD signals and CVR in each cerebrovascular territory. RESULTS The within-patient, voxel-by-voxel comparison revealed that the TS map was more closely correlated with SPECT-CVR map ([Z(r)] = 0.42 ± 0.18) than SPECT-CBF map ([Z(r)] = 0.058 ± 0.11; P

Neuro-feedback (NFB) training by the self-regulation of slow potentials (SPs)0.5 Hz recorded from the vertex scalp has been applied for seizure suppression in patients with epilepsy. However, SP is highly susceptible to artifact contamination, such as the galvanic skin response (GSR). This study aimed to evaluate the correlation between SPs recorded from the scalp and intracranial electroencephalography (EEG) by event-related coherence analysis.The scalp and subdural SPs were simultaneously recorded during NFB training by the DC-EEG machine while undergoing invasive recordings before epilepsy surgery in 10 patients with refractory partial epilepsy. The SPs at the vertex electrode were used as a reference for coherence analysis.The coherence of SPs negatively correlated with the distance between the subdural and scalp electrodes. A significant negative correlation was noted between the linear subdural-scalp electrode distance and the coherence value (r = - 0.916, p 0.001).Scalp-recorded SPs from the vertex area primarily reflect the cortical activity of high lateral convexity.Our results strongly suggest that SPs in NFB recorded from the vertex scalp electrode is derived from the cortices of high lateral convexity but not from the artifacts, such as GSR.

Small and broad-necked aneurysms are generally very difficult to treat using endovascular therapy. The arrival of the low-profile stent (e.g., Low-profile Visualized Intraluminal Support; LVIS) has enabled reconstructive treatment for these aneurysms. In addition, the bulging technique using LVIS is an effective and attractive technique for performing stent-assisted coiling to preserve parent arteries and achieve neck coverage. We report here a patient with a small and wide-necked ruptured basilar artery (BA) top aneurysm, in whom successful treatment was achieved by stent-assisted coiling with LVIS Jr. using the bulging technique. A 74-year-old woman with moderate hypertension consulted for treatment of subarachnoid hemorrhage with a ruptured BA top aneurysm measuring 2.7 mm in height with a 4.3 mm neck. We initially tried emergency balloon-assisted coiling, but coiling proved difficult. We therefore performed stent-assisted coiling with LVIS Jr. using the bulging technique. The postoperative course was uneventful, with no aggravation of neurological symptoms, and the patient was discharged 14 days postoperatively. This treatment strategy with LVIS Jr. using the bulging technique may be very useful for patients with a ruptured aneurysm with a small and broad neck that would otherwise require treatment with intravascular devices or open surgery.

Background The frontal aslant tract is a deep frontal pathway connecting the superior frontal gyrus (SFG) to Broca area. This fiber is assumed to be associated with language functions, especially speech initiation and spontaneity. The aim of this study was to electrophysiologically investigate this network using corticocortical evoked potentials (CCEPs). Methods This study enrolled 8 patients with brain tumors or medically intractable focal epilepsies who underwent frontal craniotomy over the language-dominant side. All patients underwent CCEP recordings during tumor resection or during invasive evaluation for epilepsy surgery. Alternating 1-Hz electrical stimuli were delivered to pars opercularis (pO) and pars triangularis (pT), corresponding to Broca area, and SFG via the subdural grid electrodes with intensity of 10 mA. Electrocorticograms from SFG and pO/pT time-locked to 50 stimuli were averaged in each trial to obtain CCEP responses. Results In all patients, stimulation of pO/pT induced CCEP responses in SFG. CCEP responses were recorded in lateral SFG in 5 patients and in supplementary motor areas in 4 patients. Reciprocality was observed in 7 patients in the stimulation of SFG. CCEP responses were significantly faster at SFG from pO/pT than at pO/pT from SFG (Wilcoxon signed rank test, P = 0.028). Conclusions The present study demonstrated a corticocortical network connecting Broca areas and SFG in a reciprocal manner. Our findings might provide new insight into language and motor integration.

We investigated whether vagus nerve stimulation (VNS) induces a positive shift of slow cortical potentials (SCPs) in patients with50% seizure reduction (responders) but not in non-responders.We analyzed routine clinical electroencephalograms (EEGs) from 24 patients who were undergoing seizure treatment by VNS. The patients were divided into 2 groups by hardware time constant (TC) of EEG: the TC 10-s group (10 patients) and TC 2-s group (14 patients). We compared SCPs at 5 electrodes (Cz and adjacent ones) between the 2 states of VNS: during stimulation and between stimulations. Seizure reduction was independently judged. Correlation between SCP (positivity or not) and seizure reduction (50% or not) was estimated.In the TC 10-s group, the correlation between SCP and seizure reduction was significant (p0.05) (i.e., both good results in 4 and both negative results in 5). In TC 2-s group, the correlation between SCP and seizure reduction was not significant (p=0.209).A positive shift of SCP recorded by using a TC of 10s could be a surrogate marker for VNS response.SCP could be a biomarker of good responders to VNS.

Intracranial pure germinomas in children generally respond well to standard chemo-radiotherapy. However, some patients are refractory to standard therapy and require additional treatment. To investigate the characteristics of this subgroup, we retrospectively analyzed the clinical features and treatment outcomes of a cohort of 21 patients with intracranial pure germinomas who were diagnosed between April 2002 and December 2016 at Ehime University Hospital in Japan. Pure germinoma diagnosis was verified by histological examination of the tumor after surgery, and all patients received standard chemo-radiotherapy. A suite of clinical features, including neuroimaging, human chorionic gonadotropin-β subunit (HCG-β), and α-fetoprotein (AFP) in the cerebrospinal fluid (CSF), as well as immunohistochemical expression of HCG-β, AFP, and Ki-67 in the tumor tissue were analyzed. Nineteen of the 21 patients had a complete response to standard chemo-radiotherapy without early recurrence of the tumors. Of these 19 patients, 17 did not have elevated CSF HCG-β levels or express HCG-β in the tumor tissue. However, the two patients who were refractory to standard therapy had elevated CSF HCG-β levels and expressed HCG-β in the tumor cells. These data suggest that patients with pure germinoma presenting with both an elevation of HCG-β in the CSF and HCG-β expression in the tumor tissue may be refractory to frontline treatment. These markers may predict aggressive germinoma and may ultimately facilitate the development of more effective treatment options.

Glioblastoma multiforme (GBM) is largely due to glioma stem cells (GSCs) that escape from total resection of gadolinium (Gd)-enhanced tumor on MRI. The aim of this study is to identify the imaging requirements for maximum resection of GBM with infiltrating GSCs. We investigated the relationship of tumor imaging volume between MRI and

Objective We aimed at clarifying the clinical significance of the responses evoked by human entorhinal cortex (EC) electrical stimulation by means of cortico‐cortical evoked potentials (CCEPs). Methods We enrolled nine patients with medically intractable medial temporal lobe epilepsy who underwent invasive presurgical evaluations with subdural or depth electrodes. Single‐pulse electrical stimulation was delivered to the EC and fusiform gyrus (FG), and their evoked potentials were compared. The correlation between the evoked potentials and Wechsler Memory Scale‐Revised (WMS‐R) score was analyzed to investigate whether memory circuit was involved in the generation of the evoked potentials. Results In most electrodes placed on the neocortex, EC stimulation induced unique evoked potentials with positive polarity, termed as “widespread P1” (P1w). Compared with FG stimulation, P1w induced by EC stimulation were distinguished by their high occurrence rate, short peak latency (mean: 20.1 ms), small peak amplitude, and waveform uniformity among different recording sites. A stimulation of more posterior parts of the EC induced P1w with shorter latency and larger amplitude. P1w peak amplitude had a positive correlation (r = .69) with the visual memory score of the WMS‐R. In one patient, with depth electrode implanted into the hippocampus, the giant evoked potentials were recorded in the electrodes of the anterior hippocampus and EC near the stimulus site. Conclusions The human EC electrical stimulation evoked the short‐latency potentials in the broad neocortical regions. The origin of P1w remains unclear, although the limited evidence suggests that P1w is the far‐field potential by the volume conduction of giant evoked potential from the EC itself and hippocampus. The significance of the present study is that those evoked potentials may be a potential biomarker of memory impairment in various neurological diseases, and we provided direct evidence for the functional subdivisions along the anterior–posterior axis in the human EC.

OBJECTIVE Multispectrum electrocorticographic components are critical for mapping the nonprimary motor area (NPMA). The objective of this study was to derive and validate a reliable scoring system for electrocorticography-based NPMA mapping (NPMA score) to replace electrical cortical stimulation (ECS) during brain surgery. METHODS We analyzed 14 consecutive epilepsy patients with subdural electrodes implanted in the frontal lobe at Kyoto University Hospital. The NPMA score was retrospectively derived from multivariate analysis in the derivation group (patients = 7, electrodes = 713, during 2010-2013) and validated in the validation group (patients = 7, electrodes = 772, during 2014-2017). We assessed the accuracy and reliability of the score relative to ECS in determining the NPMA and predicting postoperative functional outcomes. RESULTS Multivariate analysis in the derivation group led to an 8-point score for predicting ECS-based NPMA (1 point for anatomical localization of the electrode and 1 or 2 points for movement-related electrocorticographic components regardless of somatotopy in very slow cortical potential shifts [

Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase ≥40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31+/CD45− endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis.

The aim of the study is to identify characteristic features of pineal germinoma that enhance preoperative accuracy in differentiating germinoma from other pineal region tumors. Twenty-one consecutive patients with pineal region tumors were enrolled. In all patients, tumor resection was performed to verify the histology. Clinical records including upward gaze palsy of Parinaud's syndrome and neuroimaging were analyzed. In addition, we evaluated the relationship between magnetic resonance imaging (MRI) findings and tumor progression patterns in pineal germinoma. Among 21 patients, 15 patients were diagnosed with germ cell tumor, 4 with pineal parenchymal cell tumor, and 2 with meningioma. Upward gaze palsy was seen in 11 patients; nine had pure germinomas and two had mixed germ cell tumors. These tumors occupied the pineal region with extension to the area of the mesodiencephalic junction (MDJ) and the bi-epithalamic area between the bilateral pulvinar and the third ventricle. Tumor involvement of the former area could cause upward gaze palsy by insulting the rostral interstitial nucleus of the medial longitudinal fasciculus located in the MDJ area. Tumor invasion into the latter area is commonly seen as a cardioid-shaped tumor as the tumor image on the axial MRI view. Upward gaze palsy and a cardioid-shaped tumor image on the axial MRI views were demonstrated to be specific features of pineal pure germinoma. It is suggested that combination of both features may become useful tools to preoperatively differentiate germinoma from other pineal tumors, resulting in achievement of the optimum treatment of pineal region tumors.

Electrocorticograms (ECoG) provide a unique opportunity to monitor neural activity directly at the cortical surface. Ten patients with subdural electrodes covering ventral and lateral anterior temporal regions (ATL) performed a picture naming task. Temporal representational similarity analysis (RSA) was used, for the first time, to compare spatio-temporal neural patterns from the ATL surface with pre-defined theoretical models. The results indicate that the neural activity in the ventral subregion of the ATL codes semantic representations from 250 msec after picture onset. The observed activation similarity was not related to the visual similarity of the pictures or the phonological similarity of their names. In keeping with convergent evidence for the importance of the ATL in semantic processing, these results provide the first direct evidence of semantic coding from the surface of the ventral ATL and its time-course.

Objectives To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). Methods We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. Results Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. Conclusion The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation.

Objective To evaluate infective complications with intracranial electroencephalography (EEG) recording so as to lessen them. Methods A database of intracranial monitoring cases with subdural electrodes at Kyoto University Hospital between May 1992 and March 2012 was retrospectively reviewed. Results This analysis included 46 EEG monitoring sessions. Infective complications related to intracranial electrodes occurred in 4 monitoring sessions (8.7%; 3 male patients). Causative agents were identified as Staphylococcus aureus in 3 monitoring sessions and Staphylococcus epidermidis in 1 session. In univariate analysis, the season of monitoring was identified as the sole significant risk factor. More infective complications occurred when monitoring occurred in autumn. More infective complications tended to occur in patients who had implantation in the right side or discontinuation of intravenously administered prophylactic antibiotics, although these factors were not statistically significant. Age, sex, duration of monitoring, number of electrodes, and pathologic diagnosis did not seem to be associated with an increased risk of infective complications. Infective complications had no significant influence on seizure outcome. Conclusions Invasive EEG monitoring during autumn might be a risk factor in terms of infective complications. S aureus was a common pathogen.

To assess the feasibility of multi-component electrocorticography (ECoG)-based mapping using "wide-spectrum, intrinsic-brain activities" for identifying the primary sensori-motor area (S1-M1).We evaluated 14 epilepsy patients with 1514 subdural electrodes implantation covering the perirolandic cortices at Kyoto University Hospital between 2011 and 2016. We performed multi-component, ECoG-based mapping (band-pass filter, 0.016-300/600 Hz) involving combined analyses of the single components: movement-related cortical potential (0.5-1 Hz), event-related synchronization (76-200 Hz), and event-related de-synchronization (8-24 Hz) to identify the S1-M1. The feasibility of multi-component mapping was assessed through comparisons with single-component mapping and electrical cortical stimulation (ECS).Among 54 functional areas evaluation, ECoG-based maps showed significantly higher rate of localization concordances with ECS maps when the three single-component maps were consistent than when those were inconsistent with each other (p 0.001 in motor, and p = 0.02 in sensory mappings). Multi-component mapping revealed high sensitivity (89-90%) and specificity (94-97%) as compared with ECS.Wide-spectrum, multi-component ECoG-based mapping is feasible, having high sensitivity/specificity relative to ECS.This safe (non-stimulus) mapping strategy, alternative to ECS, would allow clinicians to rule in/out the possibility of brain function prior to resection surgery.

Objective We assessed the temporal–spatial characteristics of ictal direct current (DC) shifts (or infraslow activity) and high frequency oscillations (HFOs) in 16 patients with intractable focal epilepsy. Methods The underlying etiology consisted of cortical dysplasia, glioma, hippocampal sclerosis, and low-grade neuroepithelial tumor in nine, four, two, and one patients, respectively. The median number of analyzed seizure events was 8.0 per patient (range: 2–10). Chronic electrocorticographic recording was performed with (1) a band-pass filter of 0.016–600 Hz (or 0.016–300 Hz) and a sampling rate of 2000 Hz (or 1000 Hz). Results Ictal DC shifts and a sustained form of ictal HFOs were observed in 75.0% and 50.0% of the patients, and 71.3% and 46.3% of the analyzed seizures. Visual assessment revealed that the onset of ictal DC shifts preceded that of ictal HFOs with statistical significance in 5/7 patients. The spatial extent of ictal DC shifts or HFOs was smaller than that of the conventionally defined seizure onset zone in 9/12 patients. Conclusion Both ictal DC shifts and HFOs might represent the core of tissue generating seizures. Significance The early occurrence of ictal DC shifts warrants further studies to determine the role of glia (possibly mediating ictal DC shifts) in seizure generation.

Study objectives To investigate the changes in cortical neural responses induced by external inputs during phasic rapid eye movement (p-REM) sleep. Methods Single-pulse electrical stimulation (SPES) was directly applied to the human cortex during REM sleep through subdural electrodes, in seven patients who underwent invasive presurgical evaluation for intractable partial epilepsy. SPES was applied to parts of the cortex through the subdural electrodes, and induced cortical responses were recorded from adjacent and remote cortical areas. Phase-locked corticocortical-evoked potentials (CCEPs) and nonphase-locked or induced CCEP-related high gamma activity (CCEP-HGA, 100-200 Hz), which are considered proxies for cortical connectivity and cortical excitability, respectively, were compared among wakefulness, p-REM (within ±2 seconds of significant bursts of REM), and tonic REM (t-REM) (periphasic REM) periods. Results During REM sleep, SPES elicited a transient increase in CCEP-HGA, followed by a subsequent decrease or suppression. The HGA suppression during both p-REM and t-REM was stronger than during wakefulness. However, its suppression during p-REM was weaker than during t-REM. On the other hand, the CCEP waveform did not show any significant difference between the two REM periods. Conclusions Cortical excitability to exogenous input was different between p-REM and t-REM. The change of the cortical excitability in p-REM was directed toward wakefulness, which may produce incomplete short bursts of consciousness, leading to dreams.

Objectives Recognizing the anatomical orientation surrounding the sellar floor is crucial in endoscopic endonasal transsphenoidal surgery (ETSS). Zero-echo-time (ZTE) sequences were recently suggested for a new bone identification technique on magnetic resonance imaging (MRI). This study aimed to evaluate the clinical usefulness of three-dimensional (3D)-ZTE-based MRI models in providing anatomical guidance for ETSS. Patients and Methods ZTE-based MRI and magnetic resonance angiography (MRA) data from 15 consecutive patients with pituitary tumor treated between September 2018 and May 2019 were used to create 3D-MRI models. From these, the architecture surrounding the sellar floor, particularly anatomical relationships between tumors and internal carotid arteries (ICAs), was visualized to preoperatively plan surgical procedures. In addition, 3D-ZTE-based MRI models were compared to actual surgical views during ETSS to evaluate model applicability. Results These 3D-ZTE-based MRI models clearly demonstrated the morphology of the sellar floor and matched well with intraoperative views, including pituitary tumor, by successively eliminating sphenoidal structures. The models also permitted determination of the maximum marginal line of the opening of the sellar floor by presenting vital structures such as ICAs and tumors. With such 3D-MRI models, the surgeon could access the intracranial area through the sellar floor more safely, and resect the pituitary tumor maximally without complications. Conclusion Our 3D-MRI models based on ZTE sequences allowed distinct visualization of vital structures and pituitary tumor around the sellar floor. This new method using 3D-ZTE-based MRI models showed low invasiveness for patients and was useful in preoperative planning for ETSS, facilitating maximum tumor resection without complications.

Synthetic artificial dura mater materials, such as expanded polytetrafluoroethylene sheets, are widely used in dura mater reconstruction in cases involving brain tumors or trauma surgery. In patients with postoperative infection related to the use of artificial dura mater, surgical debridement of the infected wound and removal of the artificial dura mater materials are necessary to control infection. In cases involving cerebrospinal fluid leakage, dura mater reconstruction must be performed immediately. Many useful techniques for performing dura mater reconstruction to treat postoperative infection have been reported; however, some have drawbacks with respect to the need for microvascular anastomosis or difficulties in obtaining watertight closure. We successfully treated 6 patients with postoperative artificial dura mater infection using free thigh fascia lata. Some surgeons believe that the use of free fascia in infected wounds is dangerous because free fascia is a non-vascularized tissue. However, performing complete debridement and covering such free fascia with well-vascularized tissue allow the fascia to become vascularized and tolerant of infection. Therefore, if the blood flow in the scalp is acceptable after a sufficient debridement, free fascia lata can be used for reconstruction in patients with postoperative infection of artificial dura mater. Furthermore, skull reconstruction can be performed safely and easily with solid-type artificial bone, sometimes combined with tissue expansion, thus resulting in good aesthetic outcomes.

Gliomas are the most common intra-axial primary brain tumour; therefore, predicting glioma grade would influence therapeutic strategies. Although several methods based on single or multiple parameters from diagnostic images exist, a definitive method for pre-operatively determining glioma grade remains unknown. We aimed to develop an unsupervised method using multiple parameters from pre-operative diffusion tensor images for obtaining a clustered image that could enable visual grading of gliomas. Fourteen patients with low-grade gliomas and 19 with high-grade gliomas underwent diffusion tensor imaging and three-dimensional T1-weighted magnetic resonance imaging before tumour resection. Seven features including diffusion-weighted imaging, fractional anisotropy, first eigenvalue, second eigenvalue, third eigenvalue, mean diffusivity and raw T2 signal with no diffusion weighting, were extracted as multiple parameters from diffusion tensor imaging. We developed a two-level clustering approach for a self-organizing map followed by the K-means algorithm to enable unsupervised clustering of a large number of input vectors with the seven features for the whole brain. The vectors were grouped by the self-organizing map as protoclusters, which were classified into the smaller number of clusters by K-means to make a voxel-based diffusion tensor-based clustered image. Furthermore, we also determined if the diffusion tensor-based clustered image was really helpful for predicting pre-operative glioma grade in a supervised manner. The ratio of each class in the diffusion tensor-based clustered images was calculated from the regions of interest manually traced on the diffusion tensor imaging space, and the common logarithmic ratio scales were calculated. We then applied support vector machine as a classifier for distinguishing between low- and high-grade gliomas. Consequently, the sensitivity, specificity, accuracy and area under the curve of receiver operating characteristic curves from the 16-class diffusion tensor-based clustered images that showed the best performance for differentiating high- and low-grade gliomas were 0.848, 0.745, 0.804 and 0.912, respectively. Furthermore, the log-ratio value of each class of the 16-class diffusion tensor-based clustered images was compared between low- and high-grade gliomas, and the log-ratio values of classes 14, 15 and 16 in the high-grade gliomas were significantly higher than those in the low-grade gliomas (p, Highlights • We have developed a novel unsupervised method for voxel-based clustered imaging. • Each class ratio in clustered images differentiated high from low-grade gliomas. • The 16-class clustered images showed the best performance for the differentiation. • Each class comprised different patterns of the seven diffusion tensor-based features. • Multiple parameters from diffusion tensor images are useful for glioma grading.

Surgical intervention is expected to improve the quality of life in patients with intractable epilepsy by providing adequate seizure control. Although many previous studies showed various rates of seizure freedom, definite conclusions have not yet been made regarding outcomes. In order to clarify the long-term postoperative outcome for a period up to 10 years, a retrospective review of our patients was performed longitudinally by using the survival analysis method. The postoperative state of epilepsy in 76 patients who underwent resection surgery was assessed based on Engel’s criteria. In addition, Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom. In this patient group, abnormal lesion were detected by MRI in 70 out of 76 cases, and the ictal onset zone was finally identified within temporal lobe in 51 cases. The most favorable outcome, defined as Engel Class Ia, was observed in 26 (37%), 24 (40%), and 18 (41%) cases at 2, 5, and 10 years after surgery, respectively. The Kaplan-Meier survival curve in the overall group estimated the probability of seizure freedom as 75% (95% confidence interval [CI] 70–80%), 67% (62–72%), and 51% (45–57%) at 2, 5, and 10 years follow up, respectively. Half of all seizure recurrences occurred within the first 2 postoperative years. In this study, we showed that long-term favorable outcome of seizure control following resection surgery can be achieved in more than half of the patients.

Bevacizumab has been reported to be effective for recurrent glioblastoma. In our hospital, ifosfamide, carboplatin, etoposide (ICE) is the second-line chemotherapy for first recurrence of glioblastoma after temozolomide failure. In the present analysis, we retrospectively investigated the feasibility and effectiveness of bevacizumab combined with ICE in patients with glioblastoma at second relapse during ICE treatment. Between 2010 and 2012, tumor progressions were diagnosed in consecutive 8 patients who were treated with ICE for the first recurrence of glioblastoma. These patients were administered 3 cycles of 10 mg/kg bevacizumab every two weeks in combination with ICE treatment. The objective response rate of bevacizumab combination was 75% in Neuro-Oncology Working Group (RANO criteria), including complete response and partial response. Median progression free survival (PFS) and median overall survival (OS) after second relapse were 3.7 months (95% confidence interval [CI], 2.5-18.5 months) and 6.0 months (95% CI, 3.2-19.7 months), respectively. The 6-month PFS rates were 25% (95% CI, 0-55.0%). The median OS after initial diagnosis was 23.3 months (95% CI, 16.2-55.8 months). The grade 2 or 3 hematologic adverse events were identified in 7 of 8 patients, most of which might be due to ICE chemotherapy. The results of our retrospective analysis suggest that combination treatment with bevacizumab and ICE may be safe and beneficial in patients with recurrent glioblastoma.

We aimed to clarify that high frequency activity (HFA) of cortico-cortical evoked potentials (CCEPs), elicited by single pulse electrical stimulation (SPES), reflects cortical excitability.We recruited 16 patients with refractory partial epilepsy who had chronic subdural electrode implantation for presurgical evaluation. A repetitive SPES was given to (1) the seizure onset zone (SOZ) and (2) the control cortices (non-seizure onset zone: nSOZ). CCEPs were recorded from the neighboring cortices within SOZ and nSOZ. We applied short-time Fourier transform to obtain the induced responses for the timing of early (50ms after SPES) and late CCEP components and analyzed the logarithmic power change for ripple (200Hz) and fast ripple (200Hz) bands.Twenty-one clear CCEPs were recorded for both the SOZ and nSOZ. The HFA power of early CCEPs in SOZ significantly increased compared to that in nSOZ in both frequency bands, particularly in mesial temporal lobe epilepsy (MTLE).Similar to the features of spontaneous pathological HFOs, the power of stimulus-induced HFAs in SOZ were greater than that outside SOZ, particularly in MTLE.HFA overriding CCEPs can be a surrogate marker of cortical excitability in epileptic focus.

To explore the relationship among parameters of magnetic resonance spectroscopy (MRS) and amide proton transfer (APT) imaging, and to assess the diagnostic performance of MRS and APT imaging for grading brain tumors in comparison with contrast enhancement of conventional MRI for preoperative grading in patients with brain tumor.Institutional Review Board approval and written informed consent were obtained. Forty-one patients with suspected brain tumors were enrolled in the study. Single-voxel MRS and 2D APT imaging of the same slice level were conducted using a 3T MRI scanner. Positive or negative contrast enhancement on TPositive correlations with statistical significance were found between total concentration of choline (Cho) and APTSignificant correlations were observed between metabolite concentrations and ratios on MRS and APT values. MRS and APT imaging showed comparable diagnostic capability for grading brain tumors, suggesting that both MRS and APT imaging offer potential for quantitatively assessing similar biological characteristics in brain tumors on noncontrast MRI.2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:732-739.

In order to preserve postoperative language function, we recently proposed a new intraoperative method to monitor the integrity of the dorsal language pathway (arcuate fasciculus; AF) using cortico–cortical evoked potentials (CCEPs). Based on further investigations (20 patients, 21 CCEP investigations), including patients who were not suitable for awake surgery (five CCEP investigations) or those without preoperative neuroimaging data (eight CCEP investigations including four with untraceable tractography due to brain edema), we attempted to clarify the clinical impact of this new intraoperative method. We monitored the integrity of AF by stimulating the anterior perisylvian language area (AL) by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. After tumor resection, single‐pulse electrical stimuli were also applied to the floor of the removal cavity to record subcortico‐cortical evoked potentials (SCEPs) at AL and PL in 12 patients (12 SCEP investigations). We demonstrated that (1) intraoperative dorsal language network monitoring was feasible even when patients were not suitable for awake surgery or without preoperative neuroimaging studies, (2) CCEP is a dynamic marker of functional connectivity or integrity of AF, and CCEP N1 amplitude could even become larger after reduction of brain edema, (3) a 50% CCEP N1 amplitude decline might be a cut‐off value to prevent permanent language dysfunction due to impairment of AF, (4) a correspondence (

Objective We describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG). Methods A three-dimensional grid of voxels covering the brain is created. The array-gain minimum-variance spatial filter is applied to an interictal spike to estimate the magnitude of the source and the time (Ta) when the magnitude exceeds a predefined threshold at each voxel. This calculation is performed through all spikes. Each voxel has the mean Ta ( ) and spike number (N sp ), which is the number of spikes whose source exceeds the threshold. Then, a random resampling method is used to determine the cutoff value of N sp for the statistically reproducible pattern of the activity. Finally, all the voxels where the source exceeds the threshold reproducibly shown on the MRI with a color scale representing . Results Four patients with intractable mesial temporal lobe epilepsy (MTLE) were analyzed. In three patients, the common pattern of the overlap between the propagation and the hypometabolism shown by fluorodeoxyglucose-positron emission tomography (FDG-PET) was identified. Conclusions TSI can visualize statistically reproducible patterns of the temporal and spatial spread of epileptic activity. Significance TSI can assess the statistical significance of the spatiotemporal pattern based on its reproducibility.

To investigate the diagnostic capability of anterior temporal lobe white matter abnormal signal (ATLAS) for determining seizure focus laterality in temporal lobe epilepsy (TLE) by comparing different MR sequences. This prospective study was approved by the institutional review board and written informed consent was obtained. Three 3D sequences (double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging (T2WI)) and two 2D sequences (FLAIR and T2WI) were acquired at 3 T. Signal changes in the anterior temporal white matter of 21 normal volunteers were evaluated. ATLAS laterality was evaluated in 21 TLE patients. Agreement of independent evaluations by two neuroradiologists was assessed using κ statistics. Differences in concordance between ATLAS laterality and clinically defined seizure focus laterality were analysed using McNemar’s test with multiple comparisons. Pre-amygdala high signals (PAHS) were detected in all volunteers only on 3D-DIR. Inter-evaluator agreement was moderate to almost perfect for each sequence. Correct diagnosis of seizure laterality was significantly more frequent on 3D-DIR than on any other sequences (P ≤ 0.031 for each evaluator). The most sensitive sequence for detecting ATLAS laterality was 3D-DIR. ATLAS laterality on 3D-DIR can be a good indicator for determining seizure focus localization in TLE. • Magnetic resonance imaging is widely used to investigate temporal lobe epilepsy. • Numerous MR sequences can show anterior temporal lobe white matter abnormal signal. • ATLAS on 3D-DIR can frequently indicate seizure focus laterality in TLE. • 3D-DIR is more sensitive about ATLAS laterality than T2WI or FLAIR.

Objective To describe a simple technique for preoperative surface localization of intracranial lesions. Methods 11 pills in total, including Alfarol (alfacalcidol) capsules, were affixed to a phantom with adhesive tape and a MRI scan was performed. The visibility of the pills and any spatial errors in determining their locations were evaluated. Between June 2006 and April 2009, we employed Alfarol capsules as a skin marker in MRI in clinical surgical cases. Results Alfarol capsules, whose actual size is 5.6 mm in diameter, were identified as a hyperintense spot at a size of 4.2, 4.2, and 4.5 mm in diameter in T1-weighted, T2-weighted, and FLAIR (fluid attenuated inversion recovery) sequence images, respectively. The size discrepancies were within 1.4 mm. The average spatial errors were 0.7, 0.6, and 0.7 mm in T1-weighted, T2-weighted, and FLAIR sequence images, respectively. Other pills were not identified in the MRI scans. During this 35-month period, 8 patients underwent preoperative MRI-guided localization at our institution. There were 5 men and 3 women in whom 8 biopsies were performed. In all cases, the result of the biopsy was positive and useful for the treatment that followed. No perioperative complications were encountered. Conclusion Alfarol capsule can be used as an external skin marker. Our simple and inexpensive method is a useful addition to preoperative evaluation of superficial intracranial lesions.

Here, we report three cases of moyamoya disease with a history of Kawasaki disease. A 33-year-old man was found to have stenotic lesions of the internal carotid arteries(ICAs)on both sides at a nearby hospital where he visited complaining of headache and lisping. He had received immunoglobulin therapy for Kawasaki disease at the ages of 1, 2, and 6 years. MRI showed only a chronic ischemic lesion in the white matter. Angiography showed occlusion at the terminal portion of the ICAs on both sides. He was diagnosed with moyamoya disease, but as he had no symptoms and preserved cerebral blood flow (CBF), he was kept under observation. An 8-year-old boy was diagnosed with moyamoya disease and underwent right encephaloduroarteriosynangiosis at a nearby hospital. He had received immunoglobulin therapy for Kawasaki disease at the age of 1 year. His ischemic symptoms worsened. Although MRI detected no apparent ischemic lesion, angiography revealed severe stenosis at the terminal portions of the ICAs on both sides, and 123I-IMP SPECT showed CBF impairment. Bilateral direct bypass was performed. His father was subsequently also diagnosed with moyamoya disease. A 4-year-old girl with epilepsy was diagnosed with moyamoya disease at a nearby hospital. She had been treated with aspirin for Kawasaki disease at the age of 1 year. MRI detected no remarkable ischemic lesions, but angiography revealed mild stenosis at the terminal portions of the ICAs on both sides. Five months later, her ischemic symptoms were worsening with progressing stenotic lesions, and she underwent bilateral direct bypass.

Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFA(SEP(N20)) and HFA(SEP(N80))) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFA(CCEP(N1)) and HFA(CCEP(N2))). HFA(SEP(N20)) showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1)) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1)) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

We analyzed ictal motor symptoms in 10 patients diagnosed to have supplementary motor area (SMA) seizures based on ictal encephalographic (EEG) findings and ictal clinical semiology. Inclusion criteria were (1) EEG seizure pattern in the vertex for the scalp recording or in the area over and/or adjacent to SMA for epicortical recording and (2) ictal motor semiology characterized, as previously reported, by sudden and a brief tonic posturing of extremities and trunk mainly occurring during sleep without loss of consciousness. In 50% (5/10) of the patients, tonic posturing began in one part of the body and moved to other part(s) in 5-10s. Unlike Jacksonian march seen in seizures involving the primary sensorimotor area (S1-M1), it spread in no accordance with the somatotopy in S1-M1. The sequential propagation of tonic posturing may represent the somatotopic organization within the SMA proper.

Summary: Purpose: Malformations of cortical development (MCDs) are a frequent cause of refractory epilepsy in humans. The in utero radiation model in rats shares many clinical and histopathologic characteristics with human MCDs. Previous studies reported the presence of clinical seizures in radiated rats, but also suggested a dose-dependent differential effect. Methods: Time-pregnant Sprague–Dawley rats were irradiated on embryonic day E17 with 100 cGy (low dose), 145 cGy (medium dose), 175 cGy (high dose), or were left untreated. Their adult litters were implanted with bifrontal epidural and hippocampal depth electrodes and underwent long-term video-EEG monitoring. After 2 weeks of monitoring, the animals were killed and their brains processed for histological studies. Results: Spikes were most frequently found in the rats that were subjected to low- and medium-dose radiation at E17 and were less frequently seen in the animals that were subjected to high-dose radiation. No interictal spikes were found in any of the control animals. Seizures were recorded in three of five animals of the medium-dose group. Histological studies showed a dose-dependent decrease in cortical thickness as well as an increase of cortical and hippocampal disorganization. Conclusions: In vivo epileptogenicity in radiated animals was present only in mild or moderate MCD. No in vivo epileptogenicity was seen in severe radiation-induced MCD.

In order to clarify the role of the lateral non-primary motor area in the control of voluntary movements, we studied movement-related cortical potentials (MRCPs) by direct epicortical recording from the lateral frontal lobe in nine patients with intractable partial epilepsy as a part of presurgical evaluation. We adopted movement tasks involving different body sites: eye closing, lip pursing, shoulder abduction, middle finger extension, thumb abduction, and foot dorsiflexion. We found that one or two small areas on the caudal lateral convexity of the frontal lobe generated pre-movement potential shifts regardless of the sites of movement (omni-Bereitschaftspotential; "omni-BP"). Such regions were located at or just rostral to the primary motor face area in six subjects, and at or rostral to the primary motor upper extremity area in three. Moreover, half of those areas were identified just adjacent (either rostral or caudal) to the primary negative motor area (PNMA), a cortical area of the lateral frontal lobe where negative motor responses were elicited by electric cortical stimulation. In conclusion, it is suggested that the lateral non-primary motor area plays a significant role, and has a close and direct relationship with other cortical areas in the frontal lobe, just like its counterpart on the mesial frontal cortex (supplementary negative motor area, SNMA).

Sleep‐induced changes in human brain connectivity/excitability and their physiologic basis remain unclear, especially in the frontal lobe. We investigated sleep‐induced connectivity and excitability changes in 11 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Single‐pulse electrical stimuli were directly injected to a part of the cortices, and cortico‐cortical evoked potentials (CCEPs) and CCEP‐related high‐gamma activities (HGA: 100–200 Hz) were recorded from adjacent and remote cortices as proxies of effective connectivity and induced neuronal activity, respectively. HGA power during the initial CCEP component (N1) correlated with the N1 size itself across all states investigated. The degree of cortical connectivity and excitability changed during sleep depending on sleep stage, approximately showing dichotomy of awake vs. non‐rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep partly had properties of both awake and NREM sleep, placing itself in the intermediate state between them. Compared with the awake state, single‐pulse stimulation especially during NREM sleep induced increased connectivity (N1 size) and neuronal excitability (HGA increase at N1), which was immediately followed by intense inhibition (HGA decrease). The HGA decrease was temporally followed by the N2 peak (the second CCEP component), and then by HGA re‐increase during sleep across all lobes. This HGA rebound or re‐increase of neuronal synchrony was largest in the frontal lobe compared with the other lobes. These properties of sleep‐induced changes of the cortex may be related to unconsciousness during sleep and frequent nocturnal seizures in frontal lobe epilepsy. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

“Formes frustes” of encephalopathy associated with anti-NMDAR antibody have been recently described in cases of chronic epilepsy. We report a young woman with a parietal lesion and anti-NMDAR antibody who acquired bilateral, secondary epileptogenesis in the temporal lobes within a period as short as six years. Removal of the primary epileptogenic lesion of oligoastrocytoma in the right parietal lobe resulted in seizure freedom, disappearance of secondary foci, and substantial decrease of the antibody titre. Chronic exposure to anti-NMDAR antibody, albeit at a low titre, may have resulted in a smoldering chronic course and relatively early acquisition of “reversible” secondary foci without development of a high degree of epileptogenicity and structural changes.

Summary: Purpose: The study goal was to evaluate the clinical usefulness of intravenous EEG recording by placing wire electrodes in the cavernous sinus (CS) and the superior petrosal sinus (SPS) in patients with intractable temporal lobe epilepsy (TLE), with special emphasis on the ictal recording. Methods: We placed Seeker Lite- 10 guide wire as electrodes in the bilateral CS, SPS, or both to simultaneously record both ictal and interictal EEGs with the scalp EEG in five patients with TLE. In addition, in one patient, we averaged interictal scalp and intravascular EEG time-locked to the epileptiform discharge recorded from the CS/SPS-EEG to further delineate the relationship of the spikes between scalp and intravenous recording. Results: In four of five patients, clinically useful recording was obtained to determine ictal focus. We recorded habitual seizures in three patients, and the detailed characteristics of ictal epileptiform discharges were shown. The averaged waveform of interictal epileptiform discharges clarified the spike distribution in the scalp EEGs, which was otherwise undetectable in the single trace. All of the patients completed the intravenous EEG monitoring without any neurological or psychological problems. Conclusions: The CS/SPS-EEG is a relatively noninvasive method that is useful for the detection of ictal focus and its spreading pattern and thus for the selection of surgical candidate among patients with intractable TLE. Although the number of seizures detected during the short monitoring period may be limited, due to the advantages of its safety and simplicity, it is worth trying for potential surgical candidates before more invasive examinations are applied. A further study with a larger number of patients is needed to estimate its practical risk.

To clarify the mechanism by which inhibitory motor responses such as cortical negative myoclonus are generated in humans, three patients with medically intractable partial epilepsy (two with frontal lobe epilepsy and one with parietal lobe epilepsy) were studied by means of direct cortical stimulation with a single electric pulse through subdural electrodes. All underwent chronic long-term video/EEG monitoring, cortical mapping by 50 Hz electric cortical stimulation and recording of cortical somatosensory evoked potentials with chronically implanted subdural grid electrodes (3 mm in diameter and centre-to-centre distance of 1 cm) to map both epileptogenic and functional zones. After these clinical evaluations, cortical stimulation by single electric pulse (0.3 ms duration, 1 Hz) was carried out through pairs of subdural electrodes located at the primary sensorimotor area (MI-SI), pre-supplementary motor area (pre-SMA) and lateral negative motor area (lateral NMA), while surface EMG was recorded from the muscles of the contralateral hand. The results showed that (i) in all subjects, single pulse stimulation of MI-SI elicited a motor evoked potential (MEP) followed by a silent period (SP) in the contralateral distal hand muscles, the latter lasting 300 ms after the stimulus. The duration of SP was proportional to the size of the preceding MEP. In one subject, SP without any preceding MEP was elicited, and, in another subject, there was a short SP immediately before MEP in the contralateral thenar muscle. (ii) Following the stimulation of either pre-SMA or lateral NMA, no SP was observed. It is concluded that the inhibitory mechanism within the MI-SI, but probably not in the non-primary motor areas, either closely linked to or completely independent of excitation, most likely plays an important role in eliciting brief negative motor phenomena such as cortical negative myoclonus or SP.