Publications by authors named "Takeharu Kunieda"

94 Publications

Hypoxia-induced phenotypic transition from highly invasive to less invasive tumors in glioma stem-like cells: Significance of CD44 and osteopontin as therapeutic targets in glioblastoma.

Transl Oncol 2021 May 27;14(8):101137. Epub 2021 May 27.

Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.

The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence, GSCs with highly invasive and highly migratory activities must assume a less-motile state and proliferate to regenerate tumor mass. Elucidating the molecular mechanism underlying this transition from a highly invasive phenotype to a less-invasive, proliferative tumor could facilitate the identification of effective molecular targets for treating GBM. Here, we demonstrate that severe hypoxia (1% O) upregulates CD44 expression via activation of hypoxia-inducible factor (HIF-1α), inducing GSCs to assume a highly invasive tumor. In contrast, moderate hypoxia (5% O) upregulates osteopontin expression via activation of HIF-2α. The upregulated osteopontin inhibits CD44-promoted GSC migration and invasion and stimulates GSC proliferation, inducing GSCs to assume a less-invasive, highly proliferative tumor. These data indicate that the GSC phenotype is determined by interaction between CD44 and osteopontin. The expression of both CD44 and osteopontin is regulated by differential hypoxia levels. We found that CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. Mouse brain tumors generated from CD44-knockdown GSCs exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene decreased GSC proliferation. These results suggest that interaction between CD44 and osteopontin plays a key role in tumor progression in GBM; inhibition of both CD44 and osteopontin may represent an effective therapeutic approach for suppressing tumor progression, thus resulting in a better prognosis for patients with GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2021.101137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175402PMC
May 2021

Frequency-Dependent Cortical Interactions during Semantic Processing: An Electrocorticogram Cross-spectrum Analysis Using a Semantic Space Model.

Cereb Cortex 2021 May 4. Epub 2021 May 4.

Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8507, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhab089DOI Listing
May 2021

Effects of a stable concentration of propofol on interictal high-frequency oscillations in drug-resistant epilepsy.

Epileptic Disord 2021 Apr;23(2):299-312

Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

The aim of this study was to clarify the effect of a stable concentration of propofol on interictal high-frequency oscillations (HFOs), which may contribute to identifying the epileptogenic zone intraoperatively for resection surgery. Nine patients with drug-resistant focal epilepsy who underwent invasive pre-surgical evaluation with chronic subdural electrodes were recruited. Five-minute electrocorticograms during wakefulness, slow-wave sleep, and under a stable brain concentration of propofol were recorded with the same electrodes. In each patient, 1-10 pairs of electrodes were selected for both electrodes with EEG changes within 5 seconds from the ictal onset (ictal pattern for 5 seconds [IP5]) and those outside the area of IP5 with no interictal epileptiform discharges (non-epileptiform [nEPI]). The numbers of ripples (80-250 Hz) and fast ripples (>250 Hz) were measured semi-automatically using an established algorithm. Statistical testing was performed with a mixed effect model. Thirty-seven pairs of electrodes from nine patients were analysed for IP5 and 29 pairs from seven patients were analysed for nEPI. The numbers of HFOs differed between the areas (IP5 and nEPI) and among the conditions (wakefulness, slow-wave sleep, propofol anaesthesia) (all p <0.01). The HFO occurrence rates were significantly higher for IP5 than those for nEPI in all conditions (for both ripples and fast ripples in all conditions; p <0.01). The occurrence rates of HFOs for IP5 were significantly higher than those for nEPI under propofol anaesthesia. These are fundamental findings for intraoperative HFO analysis, however, the following limitations should be considered: physiological HFOs could not be completely differentiated from pathological HFOs; in order to apply an HFO detector, an appropriate cut-off threshold is needed; an artefact of the impulse response filter appears as an HFO; and the series was comprised of a small number of heterogeneous patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1264DOI Listing
April 2021

Cortico-cortical evoked potential by single-pulse electrical stimulation is a generally safe procedure.

Clin Neurophysiol 2021 May 3;132(5):1033-1040. Epub 2021 Feb 3.

Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, Japan. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.12.022DOI Listing
May 2021

Intraoperative Brain Mapping by Cortico-Cortical Evoked Potential.

Front Hum Neurosci 2021 18;15:635453. Epub 2021 Feb 18.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

To preserve postoperative brain function, it is important for neurosurgeons to fully understand the brain's structure, vasculature, and function. Intraoperative high-frequency electrical stimulation during awake craniotomy is the gold standard for mapping the function of the cortices and white matter; however, this method can only map the "focal" functions and cannot monitor large-scale cortical networks in real-time. Recently, an electrophysiological method using cortico-cortical evoked potentials (CCEPs) induced by single-pulse electrical cortical stimulation has been developed in an extraoperative setting. By using the CCEP connectivity pattern intraoperatively, mapping and real-time monitoring of the dorsal language pathway is available. This intraoperative CCEP method also allows for mapping of the frontal aslant tract, another language pathway, and detection of connectivity between the primary and supplementary motor areas in the frontal lobe network. Intraoperative CCEP mapping has also demonstrated connectivity between the frontal and temporal lobes, likely the ventral language pathway. Establishing intraoperative electrophysiological monitoring is clinically useful for preserving brain function, even under general anesthesia. This CCEP technique demonstrates potential clinical applications for mapping and monitoring large-scale cortical networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2021.635453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930065PMC
February 2021

CD44 expression in the tumor periphery predicts the responsiveness to bevacizumab in the treatment of recurrent glioblastoma.

Cancer Med 2021 03 5;10(6):2013-2025. Epub 2021 Feb 5.

Department of Neurosurgery, Ehime University School of Medicine, Toon, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957167PMC
March 2021

Tumor edge-to-core transition promotes malignancy in primary-to-recurrent glioblastoma progression in a PLAGL1/CD109-mediated mechanism.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa163. Epub 2020 Nov 27.

Department of Neurosurgery, Ehime University, Japan.

Background: Glioblastoma remains highly lethal due to its inevitable recurrence. Most of this recurrence is found locally, indicating that postsurgical tumor-initiating cells (TICs) accumulate at the tumor edge. These edge-TICs then generate local recurrence harboring new core lesions. Here, we investigated the clinical significance of the edge-to-core (E-to-C) signature generating glioblastoma recurrence and sought to identify its central mediators.

Methods: First, we examined the association of E-to-C-related expression changes to patient outcome in matched primary and recurrent samples ( = 37). Specifically, we tested whether the combined decrease of the edge-TIC marker PROM1 (CD133) with the increase of the core-TIC marker CD109, representing E-to-C transition during the primary-to-recurrence progression, indicates poorer patient outcome. We then investigated the specific molecular mediators that trigger tumor recurrence driven by the E-to-C progression. Subsequently, the functional and translational significance of the identified molecule was validated with our patient-derived edge-TIC models in vitro and in vivo.

Results: Patients exhibiting the CD133/CD109 signature upon recurrence representing E-to-C transition displayed a strong association with poorer progression-free survival and overall survival among all tested patients. Differential gene expression identified that was tightly correlated with the core TIC marker and was linked to shorter patient survival. Experimentally, forced PLAGL1 overexpression enhanced, while its knockdown reduced, glioblastoma edge-derived tumor growth in vivo and subsequent mouse survival, suggesting its essential role in the E-to-C-mediated glioblastoma progression.

Conclusions: E-to-C axis represents an ongoing lethal process in primary glioblastoma contributing to its recurrence, partly in a PLAGL1/CD109-mediated mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/noajnl/vdaa163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764499PMC
November 2020

Relationship between Deep White Matter Hyperintensities on Magnetic Resonance Imaging and Postoperative Cognitive Function Following Clipping of Unruptured Intracranial Aneurysm.

Neurol Med Chir (Tokyo) 2021 Feb 30;61(2):152-161. Epub 2020 Dec 30.

Department of Neurosurgery, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.

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 <0.01, p <0.05, respectively). Brain injury was observed more frequently on postoperative MR images in the moderate/severe group (17.4%) compared with the none group (2.4%; p = 0.052). The presence of moderate/severe DWMHs was an independent prognostic factor for postoperative cognitive dysfunction. In conclusion, the presence of moderate/severe DWMHs was a prognostic factor for postoperative cognitive dysfunction after surgery for UIAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2176/nmc.oa.2020-0290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905299PMC
February 2021

A rare case of spinal dural arteriovenous fistula mimicking malignant glioma of the medulla oblongata: Significance of cerebral angiography for accurate diagnosis of brain stem region.

Surg Neurol Int 2020 12;11:287. Epub 2020 Sep 12.

Department of Neurosurgery, Ehime University School of Medicine, Toon, Ehime, Japan.

Background: The findings of a hyperintense sign on T2-weighted imaging (T2-WI) and gadolinium (Gd) contrast enhancement on magnetic resonance imaging (MRI) of the brain stem suggest malignant glioma. However, this pathological condition is probably uncommon, and it may be unknown that a dural arteriovenous fistula (DAVF) can imitate this radiological pattern. In addition, it is extremely rare to be caused by a spinal DAVF. Here, a rare case of spinal DAVF that mimicked malignant glioma of the medulla oblongata is presented.

Case Description: A 56-year-old woman was admitted with a progressive gait disturbance, vertigo, and dysphasia. MRI showed a hyperintense signal in the medulla oblongata on fluid-attenuated inversion recovery (FLAIR) and moderate contrast enhancement on Gd-enhanced MRI. Interestingly, Gd-enhanced MRI demonstrated abnormal dilated veins around the brain stem and cervical spinal cord. Cerebral angiography showed spinal DAVF at the left C4/C5 vertebral foramen fed by the C5 radicular artery. The fistula drained into spinal perimedullary veins and flowed out retrograde at the cortical vein of the posterior cranial fossa. Therefore, surgical disconnection of the spinal DAVF was performed by a posterior approach. The patient's postoperative course was uneventful. Cerebral angiography showed complete disappearance of the DAVF, with marked reductions of the hyperintense sign of the medulla oblongata on FLAIR.

Conclusion: This important case illustrates MRI findings mimicking brain stem glioma. In cases with the hyperintense sign-on T2-WI associated with contrast enhancement suspicious of brainstem glioma, careful checking for perimedullary abnormal vessels and additional cerebral angiography should be performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.25259/SNI_437_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538799PMC
September 2020

Tricks and traps of ICG endoscopy for effectively applying endoscopic transsphenoidal surgery to pituitary adenoma.

Neurosurg Rev 2020 Sep 5. Epub 2020 Sep 5.

Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

Differentiating tumor from normal pituitary gland is very important for achieving complete resection without complications in endoscopic endonasal transsphenoidal surgery (ETSS) for pituitary adenoma. To facilitate such surgery, we investigated the utility of indocyanine green (ICG) fluorescence endoscopy as a tool in ETSS. Twenty-four patients with pituitary adenoma were enrolled in the study and underwent ETSS using ICG endoscopy. After administering 12.5 mg of ICG twice an operation with an interval > 30 min, times from ICG administration to appearance of fluorescence on vital structures besides the tumor were measured. ICG endoscopy identified vital structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Elapsed times for internal carotid arteries did not differ according to tumor size. Conversely, as tumor size increased, elapsed times for normal pituitary gland were prolonged but those for the tumor were reduced. ICG endoscopy revealed a clear boundary between tumors and normal pituitary gland and enabled confirmation of no more tumor. ICG endoscopy could provide a useful tool for differentiating tumor from normal pituitary gland by evaluating elapsed times to fluorescence in each structure. This method enabled identification of the boundary between tumor and normal pituitary gland under conditions of a low-fluorescence background, resulting in complete tumor resection with ETSS. ICG endoscopy will contribute to improve the resection rate while preserving endocrinological functions in ETSS for pituitary adenoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-020-01382-4DOI Listing
September 2020

Engagement of cortico-cortical and cortico-subcortical networks in a patient with epileptic spasms: An integrated neurophysiological study.

Clin Neurophysiol 2020 09 29;131(9):2255-2264. Epub 2020 May 29.

Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, 54, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address:

Objective: We aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques.

Methods: Seventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks.

Results: Ictal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain.

Conclusions: In this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient.

Significance: Cortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.04.167DOI Listing
September 2020

Intracranial anaplastic solitary fibrous tumor/hemangiopericytoma: immunohistochemical markers for definitive diagnosis.

Neurosurg Rev 2021 Jun 15;44(3):1591-1600. Epub 2020 Jul 15.

Department of Neurosurgery, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-020-01348-6DOI Listing
June 2021

Electrical cortical stimulations modulate spike and post-spike slow-related high-frequency activities in human epileptic foci.

Clin Neurophysiol 2020 08 11;131(8):1741-1754. Epub 2020 May 11.

Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address:

Objective: Using interictal epileptiform discharges (IEDs), consisting of spikes and post-spike slow waves (PSSs), and IED-related high-frequency activities (HFAs), we elucidated inhibitory effects of electrical cortical stimulation (ECS) on human epileptic foci.

Methods: We recruited 8 patients with intractable focal epilepsy, and 50-Hz ECS was applied to the seizure-onset zone (SOZ) and non-SOZ. Before (5-min) and after (20-min) ECS, we evaluated the number of IED, the amplitudes of spikes and PSSs, spike-related HFA power, and PSS-related low gamma (30-50 Hz) activities.

Results: SOZ stimulation significantly decreased the number of IEDs and amplitude of spikes. Spike-related HFA power values in fast ripple (200-300 Hz) and ripple (80-150 Hz) bands were significantly suppressed only by SOZ stimulation in 4 and 3 patients, respectively. Among 4 patients with discrete PSSs, the amplitude ratio of spike/PSS decreased and the PSS-related low gamma activity power increased significantly in 2 patients and marginally in 1 patient.

Conclusions: ECS potentially modulates cortical excitability by reducing excitation and increasing inhibition, and monitoring IED-related HFAs may help achieve the optimal effects of ECS.

Significance: IED and IED-related HFAs are dynamic, potential surrogate markers for epileptic excitability during the interictal period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.03.042DOI Listing
August 2020

Clinical features and endoscopic findings of granular cell tumor of the sellar region: A case report and review of the literature.

Surg Neurol Int 2020 9;11:101. Epub 2020 May 9.

Departments of Neurosurgery, Ehime University School of Medicine, Shitsukawa, Toon, Ehime, Japan.

Background: Granular cell tumor (GCT) of the sellar region is a rare tumor of the sellar and suprasellar regions that originate from the neurohypophysis. This tumor is very difficult to differentiate from other pituitary neoplasms, such as pituitary adenoma, pituicytoma, and spindle cell oncocytoma. We report a rare case of GCT arising from the posterior pituitary of the sellar region and suggest a useful indicator for accurate diagnosis and pitfalls for surgical procedures.

Case Description: A 42-year-old woman was admitted to our hospital with bitemporal hemianopsia. Neuroimaging showed a large pituitary tumor in the sellar and suprasellar regions with a hypointense part on T2-weighted magnetic resonance imaging, and the enhanced anterior pituitary gland was displaced anteriorly. Laboratory findings showed mild hyperprolactinemia. Subtotal resection of the tumor was achieved using an endoscopic endonasal transsphenoidal approach. Histological findings showed round or polygonal cells with abundant granular eosinophilic cytoplasm staining strongly for thyroid transcription factor 1. The tumor was, therefore, diagnosed as a GCT of the sellar region, belonging to tumors of the posterior pituitary. After surgery, visual impairment and anterior pituitary function were improved. Follow-up neuroimaging after 1 year showed no signs of recurrence.

Conclusion: GCT of the sellar region is difficult to diagnose on routine neuroimaging. Therefore, accurate diagnosis requires careful identification of clinical signs, magnetic resonance imaging including hypointensity on T2-weighted imaging, and analysis of combined morphological and immunohistochemical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.25259/SNI_111_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265469PMC
May 2020

Connectivity Gradient in the Human Left Inferior Frontal Gyrus: Intraoperative Cortico-Cortical Evoked Potential Study.

Cereb Cortex 2020 06;30(8):4633-4650

Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325718PMC
June 2020

Intraoperative Electrophysiologic Mapping of Medial Frontal Motor Areas and Functional Outcomes.

World Neurosurg 2020 06 4;138:e389-e404. Epub 2020 Mar 4.

Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.02.129DOI Listing
June 2020

Clinical utility of new three-dimensional model using a zero-echo-time sequence in endoscopic endonasal transsphenoidal surgery.

Clin Neurol Neurosurg 2020 03 21;190:105743. Epub 2020 Feb 21.

Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clineuro.2020.105743DOI Listing
March 2020

Met-PET uptake index for total tumor resection: identification of C-methionine uptake index as a goal for total tumor resection including infiltrating tumor cells in glioblastoma.

Neurosurg Rev 2021 Feb 15;44(1):587-597. Epub 2020 Feb 15.

Department of Neurosurgery, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.

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 C-methionine (Met)-PET and also the relationship between Met uptake index and tumor activity. In ten patients, tumor-to-contralateral normal brain tissue ratio (TNR) was calculated to evaluate metabolic activity of Met uptake areas which were divided into five subareas by the degrees of TNR. In each GBM, tumor tissue was obtained from subareas showing the positive Met uptake. Immunohistochemistry was performed to examine the tumor proliferative activity and existence of GSCs. In all patients, the volume of Met uptake area at TNR ≦ 1.4 was larger than that of the Gd-enhanced area. The Met uptake area at TNR 1.4 beyond the Gd-enhanced tumor was much wider in high invasiveness-type GBMs than in those of low invasiveness type, and survival was much shorter in the former than the latter types. Immunohistochemistry revealed the existence of GSCs in the area showing Met uptake at TNR 1.4 and no Gd enhancement. Areas at TNR > 1.4 included active tumor cells with relatively high Ki-67 labeling index. In addition, it was demonstrated that GSCs could exist beyond the border of Gd-enhanced tumor. Therefore, to obtain maximum resection of GBMs, including infiltrating GSCs, aggressive surgical excision that includes the Met-positive area at TNR 1.4 should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-020-01258-7DOI Listing
February 2021

Active direct current (DC) shifts and "Red slow": two new concepts for seizure mechanisms and identification of the epileptogenic zone.

Neurosci Res 2020 Jul 8;156:95-101. Epub 2020 Feb 8.

Department of Neurology, Kyoto University Graduate School of Medicine, Japan.

An accurate identification of the epileptogenic zone is essential for patients with intractable epilepsy who are candidates to neurosurgery. EEG recordings can provide predictive biomarkers of the epileptogenic zone. Wide-band EEG makes it possible to record from infraslow (including DC shifts) to high frequency (HFO, over 300 Hz) oscillations for diagnostic purposes in patients with epilepsy. Although the presence of HFOs have been proposed to sign the epileptogenic zone, DC-like recordings demonstrate that DC shifts precede HFOs at seizure onset. This led to the proposal that "ictal active DC shifts" are causally related to seizure onset as opposed to "ictal passive DC shifts". Thus, active DC shifts may constitute predictive biomarkers of the epileptogenic zone in epilepsy. Since DC shift is commonly associated to a rise in extracellular potassium, potassium homeostasis regulated by Kir4.1 channels in astrocytes may play an key role at seizure onset. In addition, we hypothesize that, during the interictal period, the co-occurrence of slow events and interictal HFOs, so-called "Red slow", may also delineate an epileptogenic zone, even if a seizure would not be actually recorded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neures.2020.01.014DOI Listing
July 2020

Epithelioid glioblastoma presenting as multicentric glioma: A case report and review of the literature.

Surg Neurol Int 2020 17;11. Epub 2020 Jan 17.

Department of Neurosurgery, Ehime University School of Medicine.

Background: Epithelioid glioblastoma is a rare aggressive variant of glioblastoma multiforme (GBM), which was formally recognized by the World Health Organization classification of the central nervous system in 2016. Clinically, epithelioid GBMs are characterized by aggressive features, such as metastases and cerebrospinal fluid dissemination, and an extremely poor prognosis. A rare case of epithelioid GBM that was discovered as a multicentric glioma with different histopathology is reported.

Case Description: A 78-year-old man was admitted to our hospital with mild motor weakness of the right leg. Neuroimaging showed small masses in the left frontal and parietal lobes on magnetic resonance imaging. The abnormal lesion had been increasing rapidly for 3 weeks, and a new lesion appeared in the frontal lobe. 11C-methionine positron emission tomography (PET) showed abnormal uptake corresponding to the lesion. To reach a definitive diagnosis, surgical excision of the right frontal mass lesion was performed. Histological findings showed diffuse astrocytoma. Only radiotherapy was planned, but the left frontal and parietal tumors progressed further within a short period. Therefore, it was thought that these tumors were GBM, and a biopsy of the left parietal tumor was performed. The histological diagnosis was epithelioid GBM. Immunohistochemistry showed that most tumor cells were negatively stained for p53 and isocitrate dehydrogenase 1. V600E mutations were not identified, but promoter mutations were identified. Immediately after surgery, the patient was given chemotherapy using temozolomide, extended local radiotherapy and then bevacizumab. After 6 months, he showed no signs of recurrence.

Conclusion: Epithelioid GBM is one of the rarest morphologic subtypes of GBM and has a strongly infiltrative and aggressive nature. Therefore, careful identification of preoperative imaging studies and detailed evaluation of genetic studies are necessary to select the appropriate treatment for epithelioid GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.25259/SNI_544_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969379PMC
January 2020

Prognostic significance of immunohistochemical subtypes based on the stage of B-cell differentiation in primary CNS lymphoma.

Int J Clin Exp Pathol 2019 1;12(4):1457-1467. Epub 2019 Apr 1.

Department of Neurosurgery, Ehime University School of Medicine 454 Shitsukawa, Toon, Ehime 791-0295, Japan.

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947071PMC
April 2019

Mathematical structures for epilepsy: High-frequency oscillation and interictal epileptic slow (red slow).

Neurosci Res 2020 Jul 20;156:178-187. Epub 2019 Nov 20.

Department of Epilepsy, Movement Disorder and Physiology, Kyoto University, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

In the present study, we attempted to characterize two characteristic features within the dynamic behavior of wideband electrocorticography data, which were recorded as the brain waves of epilepsy, comprising high-frequency oscillations (HFOs) and interictal epileptic slow (red slow). The results of power spectrum and nonlinear time series analysis indicate that, on one hand, HFOs at epileptic focus are characterized by one-dimensional dynamical systems in ictal onset time segments at an epileptic focus for two patients' datasets; on the other hand, an interictal epileptic slow is characterized by the residue of power spectrum. The results suggest that the degree of freedom of the brain dynamics during epileptic seizure with HFO degenerates to low-dimensional dynamics; hence, the interictal epileptic slow as the precursors of the seizure onset can be detected simply from interictal brain wave data for the dataset of one patient. Therefore, our results are essential to understand the brain dynamics in epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neures.2019.11.008DOI Listing
July 2020

A score to map the lateral nonprimary motor area: Multispectrum intrinsic brain activity versus cortical stimulation.

Epilepsia 2019 11 15;60(11):2294-2305. Epub 2019 Oct 15.

Department of Epilepsy, Movement Disorders, and Physiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

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 [<0.5 Hz], 40-80-Hz band power increase, and 8-24-Hz band power decrease), which was validated in the validation group. The area under the receiver operating characteristic curve (AUC) was 0.89 in the derivation group. Good prediction (specificity = 94%, sensitivity = 100%) and discrimination (AUC = 0.87) were reproduced in the validation group. Overall, higher NPMA scores identified 2 patients with postoperative deficits after frontal lobe resection.

Significance: The NPMA score is reliable for NPMA mapping, potentially replacing ECS. It is a potential prognostic marker for postoperative functional deficits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16367DOI Listing
November 2019

Phagocytic elimination of synapses by microglia during sleep.

Glia 2020 01 19;68(1):44-59. Epub 2019 Aug 19.

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.

Synaptic strength reduces during sleep, but the underlying mechanisms of this process are unclear. This study showed reduction of synaptic proteins in rat prefrontal cortex (PFC) at AM7 or Zeitgeber Time (ZT0), when the light phase or sleeping period for rats started. At this time point, microglia were weakly activated, displaying larger and more granular somata with increased CD11b expression compared with those at ZT12, as revealed by flow cytometry. Expression of opsonins, such as complements or MFG-E8, matrix metalloproteinases, and microglial markers at ZT0 were increased compared with that at ZT12. Microglia at ZT0 phagocytosed synapses, as revealed by immunohistochemical staining. Immunoblotting detected more synapsin I in the isolated microglia at ZT0 than at ZT12. Complement C3- or MFG-E8-bound synapses were the most abundant at ZT0, some of which were phagocytosed by microglia. Systemic administration of synthetic glucocorticoid dexamethasone reduced microglial size, granularity and CD11b expression at ZT0, resembling microglia at ZT12, and increased synaptic proteins and decreased the sleeping period. Noradrenaline (NA) suppressed glutamate-induced phagocytosis in primary cultured microglia. Systemic administration of the brain monoamine-depleting agent reserpine decreased NA content and synapsin I expression in PFC, and increased expression of microglia markers, C3 and MFG-E8, while increasing the sleeping period. A NA precursor l-threo-dihydroxyphenylserine abolished the reserpine-induced changes. These results suggest that microglia may eliminate presumably weak synapses during every sleep phase. The circadian changes in concentrations of circulating glucocorticoids and brain NA might be correlated with the circadian changes of microglial phenotypes and synaptic strength.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/glia.23698DOI Listing
January 2020

Human entorhinal cortex electrical stimulation evoked short-latency potentials in the broad neocortical regions: Evidence from cortico-cortical evoked potential recordings.

Brain Behav 2019 09 30;9(9):e01366. Epub 2019 Jul 30.

Department of Epilepsy, Movement Disorders and Physiology, Kyoto University, Kyoto, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.1366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749511PMC
September 2019

Successful Reperfusion with Endovascular Therapy Has Beneficial Effects on Long-Term Outcome Beyond 90 Days.

Cerebrovasc Dis 2019 9;47(3-4):127-134. Epub 2019 Apr 9.

Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000499190DOI Listing
February 2020

Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions.

Tissue Barriers 2019 31;7(1):1593775. Epub 2019 Mar 31.

c Department of Molecular and Cellular Physiology, Graduate School of Medicine , Ehime University , Toon , Ehime , Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21688370.2019.1593775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592591PMC
August 2020

The neural tides of sleep and consciousness revealed by single-pulse electrical brain stimulation.

Sleep 2019 06;42(6)

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

Wakefulness and sleep arise from global changes in brain physiology that may also govern the flow of neural activity between cortical regions responsible for perceptual processing versus planning and action. To test whether and how the sleep/wake cycle affects the overall propagation of neural activity in large-scale brain networks, we applied single-pulse electrical stimulation (SPES) in patients implanted with intracranial EEG electrodes for epilepsy surgery. SPES elicited cortico-cortical spectral responses at high-gamma frequencies (CCSRHG, 80-150 Hz), which indexes changes in neuronal population firing rates. Using event-related causality (ERC) analysis, we found that the overall patterns of neural propagation among sites with CCSRHG were different during wakefulness and different sleep stages. For example, stimulation of frontal lobe elicited greater propagation toward parietal lobe during slow-wave sleep than during wakefulness. During REM sleep, we observed a decrease in propagation within frontal lobe, and an increase in propagation within parietal lobe, elicited by frontal and parietal stimulation, respectively. These biases in the directionality of large-scale cortical network dynamics during REM sleep could potentially account for some of the unique experiential aspects of this sleep stage. Together these findings suggest that the regulation of conscious awareness and sleep is associated with differences in the balance of neural propagation across large-scale frontal-parietal networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sleep/zsz050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559171PMC
June 2019

A rational, multispectral mapping algorithm for primary motor cortex: A primary step before cortical stimulation.

Epilepsia 2019 03 20;60(3):547-559. Epub 2019 Feb 20.

Department of Epilepsy, Movement Disorders, and Physiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

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 (<0.5-1.0 Hz), event-related synchronization (76-100 Hz or 100-200 Hz), and event-related desynchronization (8-12 Hz or 12-24 Hz). The ECoG score was assessed by calculating the sensitivity, specificity, and cutoff values of the score for localization concordance with M1 defined using only ECS as a reference.

Results: With an area under the receiver operating characteristic curve (AUC) of 0.76, cutoffs of scores of 4 and 1 showed high specificity (94%) and sensitivity (98%) in concordance with ECS-based mapping, respectively. The ECoG score for mapping M1 of the upper limb achieved greater accuracy (AUC = 0.85) compared to that of the face (AUC = 0.64).

Significance: The ECoG score proposed in the present study is rational, simple, and useful to define M1, and it is spatially concordant with ECS. Although ECS is still widely employed for presurgical examination, our proposed application of the ECoG score may be suitable for future brain M1 mapping, and possibly beyond M1 mapping, independently of ECS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.14669DOI Listing
March 2019

Interictal Slow and High-Frequency Oscillations: Is it an Epileptic Slow or Red Slow?

J Clin Neurophysiol 2019 Mar;36(2):166-170

Department of Epilepsy, Movement Disorders and Physiology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.

Purpose: We reported the presence of interictal slow and high-frequency oscillations (HFOs) (IIS + HFO) and its temporal change so as to elucidate its clinical usefulness as a surrogate marker of epileptogenic zone in a patient with intractable focal epilepsy.

Methods: We focused on one of the core electrodes of epileptogenicity, and investigated IIS + HFO in the pre- and post-segment of 30 minutes to all the 6 seizures. We adopted interictal slow in duration of 0.33 to 10 seconds, amplitude ≥50 μV and co-occurring with HFOs, and then divided into 5 groups depending on the amplitude of slow wave.

Results: Before and after all the 6 seizures, the number of IIS + HFO was 2,890 at one electrode in the core epileptogenic zone. The number of IIS + HFO significantly decreased for 30 minutes after seizures. Furthermore, the number of IIS + HFO with the amplitude of 200 to 399 μV significantly decreased after seizures.

Conclusions: IIS + HFO with the amplitude of 200 to 399 μV was influenced by and decreased after seizures. It may reflect the core part of epileptogenic area as similarly as ictal direct current shifts and ictal HFOs do. IIS + HFO could be called as the term "red slow," which may be useful to delineate at least a part of the epileptogenic zone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNP.0000000000000527DOI Listing
March 2019