Search

Background: The unsurpassed sensitivity of intracranial electroencephalography (icEEG) and the growing interest in understanding human brain networks and ongoing activities in health and disease have make the simultaneous icEEG and functional magnetic resonance imaging acquisition (icEEG-fMRI) an attractive investigation tool. However, safety remains a crucial consideration, particularly due to the impact of the specific characteristics of icEEG and MRI technologies that were safe when used separately but may risk health when combined. Using a clinical 3-T scanner with body transmit and head-receive coils, we assessed the safety and feasibility of our icEEG-fMRI protocol., Methods: Using platinum and platinum-iridium grid and depth electrodes implanted in a custom-made acrylic-gel phantom, we assessed safety by focusing on three factors. First, we measured radio frequency (RF)-induced heating of the electrodes during fast spin echo (FSE, as a control) and the three sequences in our icEEG-fMRI protocol. Heating was evaluated with electrodes placed orthogonal or parallel to the static magnetic field. Using the configuration with the greatest heating observed, we then measured the total heating induced in our protocol, which is a continuous 70-min icEEG-fMRI session comprising localizer, echo-planar imaging (EPI), and magnetization-prepared rapid gradient-echo sequences. Second, we measured the gradient switching-induced voltage using configurations mimicking electrode implantation in the frontal and temporal lobes. Third, we assessed the gradient switching-induced electrode movement by direct visual detection and image analyses., Results: On average, RF-induced local heating on the icEEG electrode contacts tested were greater in the orthogonal than parallel configuration, with a maximum increase of 0.2°C during EPI and 1.9°C during FSE. The total local heating was below the 1°C safety limit across all contacts tested during the 70-min icEEG-fMRI session. The induced voltage was within the 100-mV safety limit regardless of the configuration. No gradient switching-induced electrode displacement was observed., Conclusion: We provide evidence that the additional health risks associated with heating, neuronal stimulation, or device movement are low when acquiring fMRI at 3 T in the presence of clinical icEEG electrodes under the conditions reported in this study. High specific absorption ratio sequences such as FSE should be avoided to prevent potential inadvertent tissue heating., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fujita, Khoo, Hirayama, Kawahara, Koyama, Tarewaki, Arisawa, Yanagisawa, Tani, Oshino, Lemieux and Kishima.)

Objectives: The aim of the present study was to investigate the analgesic effects of repetitive transcranial magnetic stimulation over the primary motor cortex (M1-rTMS) using different stimulation parameters to explore the optimal stimulus condition for treating neuropathic pain., Materials and Methods: We conducted a randomized, blinded, crossover exploratory study. Four single sessions of M1-rTMS at different parameters were administered in random order. The tested stimulation conditions were as follows: 5-Hz with 500 pulses per session, 10-Hz with 500 pulses per session, 10-Hz with 2000 pulses per session, and sham stimulation. Analgesic effects were assessed by determining the visual analog scale (VAS) pain intensity score and Short-Form McGill Pain Questionnaire 2 (SF-MPQ2) score immediately before and immediately after intervention., Results: We enrolled 22 adults (age: 59.8 ± 12.1 years) with intractable neuropathic pain. Linear-effects models showed significant effects of the stimulation condition on changes in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.01). Tukey multiple comparison tests revealed that 10-Hz rTMS with 2000 pulses provided better pain relief than sham stimulation, with greater decreases in VAS pain intensity (p = 0.03) and SF-MPQ2 (p = 0.02)., Conclusions: The results of this study suggest that high-dose stimulation (specifically, 10-Hz rTMS at 2000 pulses) is more effective than lower-dose stimulation for treating neuropathic pain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To clarify variations in the relationship between high-frequency activities (HFAs) and low-frequency bands from the tonic to the clonic phase in focal to bilateral tonic-clonic seizures (FBTCS), using phase-amplitude coupling., Methods: This retrospective study enrolled six patients with drug-resistant focal epilepsy who underwent intracranial electrode placement at Osaka University Hospital (July 2018-July 2019). We recorded 11 FBTCS. The synchronization index (SI) and receiver-operating characteristic (ROC) analysis were used to analyze the coupling between HFA amplitude (80-250 Hz) and lower frequencies phase., Results: In the tonic phase, the θ (4-8 Hz)-HFA coupling peaked, and the HFA power occurred at baseline (0 μV) of θ oscillations. In contrast, in the clonic phase, the δ (2-4 Hz)-HFA coupling peaked, and the HFA power occurred at the trough of δ oscillations. ROC analysis indicated that the δ-HFA SI discriminated well the clonic from the tonic phase., Conclusions: The main low-frequency band modulating the HFA shifted from the θ band in the tonic phase to the δ band in the clonic phase., Significance: Neurophysiological key frequency bands were implied to be the θ band and δ band in tonic and clonic seizures, respectively, which improves our understanding of FBTCS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: It remains unclear why some patients with the same heart rate during an atrial fibrillation (AF) have subjective symptoms, whereas others do not. We assessed the hypothesis that different responses of arterial and left atrial blood pressures to rapid stimulation may be associated with the symptoms of AF., Methods: A total of 110 patients who underwent catheter ablation for paroxysmal AF were retrospectively studied. Asymptomatic AF was defined as a European Heart Rhythm Association score of Ⅰ for AF-related symptoms. The left atrial pressure (LAP) was measured during sinus rhythm (SR), in 10 pacing per minute (ppm) increments from 100 ppm to the Wenckebach block rate in high right atrial pacing., Results: Asymptomatic AF was observed in 19/110 patients (17%). Patients with symptomatic AF showed higher E/e' ratio and gradual LAP increase that was dependent on the pacing rate. Patients with asymptomatic AF had decreased LAP at 100 ppm compared that at SR, and thereafter, LAP gradually increased depending on the pacing rate. The rate of LAP change compared to that at SR was significantly lower in patients with asymptomatic AF than that in patients with symptomatic AF. The rate of LAP change was independently associated with AF symptoms., Conclusion: Patients with asymptomatic AF showed lower E/e' ratio and decreased LAP at 100 ppm to rapid stimulation, followed by a steady increase in LAP afterwards. Factors other than left ventricular diastolic dysfunction may be involved in AF symptoms., (© 2022 Wiley Periodicals LLC.)

Objective. Diagnosing epilepsy still requires visual interpretation of electroencephalography (EEG) and magnetoencephalography (MEG) by specialists, which prevents quantification and standardization of diagnosis. Previous studies proposed automated diagnosis by combining various features from EEG and MEG, such as relative power (Power) and functional connectivity (FC). However, the usefulness of interictal phase-amplitude coupling (PAC) in diagnosing epilepsy is still unknown. We hypothesized that resting-state PAC would be different for patients with epilepsy in the interictal state and for healthy participants such that it would improve discrimination between the groups. Approach. We obtained resting-state MEG and magnetic resonance imaging (MRI) in 90 patients with epilepsy during their preoperative evaluation and in 90 healthy participants. We used the cortical currents estimated from MEG and MRI to calculate Power in the δ (1-3 Hz), θ (4-7 Hz), α (8-13 Hz), β (13-30 Hz), low γ (35-55 Hz), and high γ (65-90 Hz) bands and FC in the θ band. PAC was evaluated using the synchronization index (SI) for eight frequency band pairs: the phases of δ, θ, α , and β and the amplitudes of low and high γ . First, we compared the mean SI values for the patients with epilepsy and the healthy participants. Then, using features such as PAC, Power, FC, and features extracted by deep learning (DL) individually or combined, we tested whether PAC improves discrimination accuracy for the two groups. Main results. The mean SI values were significantly different for the patients with epilepsy and the healthy participants. The SI value difference was highest for θ /low γ in the temporal lobe. Discrimination accuracy was the highest, at 90%, using the combination of PAC and DL. Significance. Abnormal PAC characterized the patients with epilepsy in the interictal state compared with the healthy participants, potentially improving the discrimination of epilepsy., (Creative Commons Attribution license.)

Background: The surgical treatment for retro-odontoid pseudotumor (ROP) remains controversial. Posterior C1 laminectomy without fixation occasionally leads to postoperative enlargement of ROP. Because its pathogenesis is associated with atlantoaxial instability, atlantoaxial fixation with C1 laminectomy is commonly performed. Atlantoaxial fixation usually includes transarticular fixation and screw-rod fixation. However, these methods have some issues. That is, in transarticular fixation with C1 laminectomy, the bone grafting area is challenging to obtain. In screw-rod fixation with C1 laminectomy, extensive bleeding occurs at times if the lateral atlantoaxial joint is exposed to the transplant bone grafts., Observations: Herein, the authors report a case of ROP treated with combined C1-2 transarticular screw fixation and C1 laminoplasty with interlaminar bone transplant, which can help achieve adequate spinal cord decompression and can simultaneously secure the bone grafting area between the laminae. In addition, the volume of intraoperative blood loss decreased. Postoperative magnetic resonance imaging showed sufficient decompression of the spinal cord at the C1 level, and computed tomography performed after 6 months revealed bone union between the C1 and C2 laminae., Lessons: Combined C1-2 transarticular screw fixation and C1 laminoplasty with interlaminar bone transplant is a useful method for ROP.

Neural representations of visual perception are affected by mental imagery and attention. Although attention is known to modulate neural representations, it is unknown how imagery changes neural representations when imagined and perceived images semantically conflict. We hypothesized that imagining an image would activate a neural representation during its perception even while watching a conflicting image. To test this hypothesis, we developed a closed-loop system to show images inferred from electrocorticograms using a visual semantic space. The successful control of the feedback images demonstrated that the semantic vector inferred from electrocorticograms became closer to the vector of the imagined category, even while watching images from different categories. Moreover, modulation of the inferred vectors by mental imagery depended asymmetrically on the perceived and imagined categories. Shared neural representation between mental imagery and perception was still activated by the imagery under semantically conflicting perceptions depending on the semantic category., (© 2022. The Author(s).)

Background: The cortical bone trajectory (CBT) screws follow a caudocephalad and lateral path from the pedicle to the vertebral body. The bone fusion rate of CBT fixation is equal to or lower than conventional pedicle screw fixation. It remains unclear whether or not CVT screws exert equally compressive forces across the vertebral column. In this study, we intraoperatively examined the insertional torque of CBT screws, and investigated the compression loading and pressure distribution in conventional and CBT fixation using pig bones., Methods: The insertional torque was measured for a total of 115 CBT screws. Detailed positions of these screws were retrospectively confirmed using CT scans. Screw loosening and interbody fusion were examined 1 year after surgery. In the experiment using pig bones, we inserted screws by conventional trajectory ( n  = 3) and CBT ( n  = 4)., Results: Multiple regression analysis showed that the total screw length, the distance from the screw to the medial border of the pedicle and the distance from the superior endplate of the vertebrae were significant independent factors affecting the insertional torque. There was no significant association between the insertional torque and the radiographic bone fusion rate 12 months after surgery. The average pressure and the compression loading in the anterior column were significantly lower in CBT group., Conclusion: These results suggested that the long CBT screws as close to the endplate had high insertional torque, but the anterior column in CBT fixation showed low compression force leading to the insufficient holding intervertebral cage. CBT screws may cause the micromotion of cages, which lowers the bone fusion rate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Pygopagus is a type of conjoined twin binding at the buttocks. Some cases of pygopagus involve the fusion of the gastrointestinal tract, urinary tract, and spinal cord. Few cases of male pygopagus have been reported; however, the prognosis after separation is unclear. Herein, we report a case of male pygopagus in which successful separation was performed with the reconstruction of the anal canal., Case Presentation: Twins with male pygopagus were born at 35 weeks by cesarean section. They shared a common anus, penis, and scrotum with four testes. The infants had normal defecation and urination after birth. The separation surgery was scheduled when they were 5 months. Two distinct anesthesia teams and four surgical teams (neurosurgery, pediatric urology, plastic surgery, and pediatric surgery) were involved in the multidisciplinary approach. After separating the spinal cord, we found that the anal canal and sphincter muscle complex were fused near the anal aperture, and we separated them. The fused penis and testis were separated and reconstructed using the same incisional line as the other separation, and the reconstructions of the anal canals with the sphincter muscle complex were completed. Both patients had an uneventful postoperative course. At 2 years of age, they could walk and defecate independently. In addition, they voided spontaneously without urinary incontinence at the time of 3 years and 11 months., Conclusions: Separation of the spinal cord with anal canal and urethral reconstruction is important for male pygopagus patients as it allows them to preserve their independent function., (© 2022. The Author(s).)

Background and Purpose: Environmental factors are important with respect to the rupture of cerebral aneurysms. However, the relationship between the gut microbiome, an environmental factor, and aneurysm rupture is unclear. Therefore, we compared the gut microbiome in patients with unruptured intracranial aneurysms (UIAs) and ruptured aneurysms (RAs) to identify the specific bacteria causing the rupture of cerebral aneurysms., Methods: A multicenter, prospective case-control study was conducted over one year from 2019 to 2020. The fecal samples of patients with stable UIAs and RAs immediately after onset were collected. Their gut microbiomes were analyzed using 16S rRNA sequencing. Subsequently, a phylogenetic tree was constructed, and polymerase chain reaction was performed to identify the specific species., Results: A total of 28 RAs and 33 UIAs were included in this study. There was no difference in patient characteristics between RAs and UIAs: age, sex, hypertension, dyslipidemia, diabetes status, body mass index, and smoking. No difference was observed in alpha diversity; however, beta diversity was significantly different in the unweighted UniFrac distances. At the phylum level, the relative abundance of Campylobacter in the RA group was larger than that in the UIA group. Furthermore, the gut microbiome in the RA and UIA groups exhibited significantly different taxonomies. However, Campylobacter was focused on because it is widely known as pathogenic among these bacteria. Then, a phylogenetic tree of operational taxonomic units related to Campylobacter was constructed and 4 species were identified. Polymerase chain reaction for these species identified that the abundance of the genus Campylobacter and Campylobacter ureolyticus was significantly higher in the RA group., Conclusions: The gut microbiome profile of patients with stable UIAs and RAs were significantly different. The genus Campylobacter and Campylobacter ureolyticus may be associated with the rupture of cerebral aneurysms.

Background: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism., Methods: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age., Results: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content ( p  < 0.001) and higher extent of NETosis ( p  = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p  = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p  = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion ( p  < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99)., Conclusion: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy., Competing Interests: Dr. Kitano reports lecture fees from Stryker. Dr. Nakamura reports lecture fees from Johnson & Johnson, Medtronic, and Stryker. Dr. Todo reports lecture fees from Medtronic. The other authors have no conflicts relevant to the contents of this article to disclose., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Cancer-specific cell surface antigens are ideal therapeutic targets for monoclonal antibody (mAb)-based therapy. Here, we report that multiple myeloma (MM), an incurable hematological malignancy, can be specifically targeted by an mAb that recognizes a ubiquitously present protein, CD98 heavy chain (hc) (also known as SLC3A2). We screened more than 10,000 mAb clones raised against MM cells and identified R8H283, an mAb that bound MM cells but not normal hematopoietic or nonhematopoietic cells. R8H283 specifically recognized CD98hc. R8H283 did not react with monomers of CD98hc; instead, it bound CD98hc in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on MM cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not react with them. The glycoforms of CD98hc present on normal leukocytes were distinct from those present on MM cells, which may explain the lack of R8H283 reactivity to normal leukocytes. R8H283 exerted anti-MM effects without damaging normal hematopoietic cells. These findings suggested that R8H283 is a candidate for mAb-based therapies for MM. In addition, our findings showed that a cancer-specific conformational epitope in a ubiquitous protein, which cannot be identified by transcriptome or proteome analyses, can be found by extensive screening of primary human tumor samples.

To characterize Parkinson's disease, abnormal phase-amplitude coupling is assessed in the cortico-basal circuit using invasive recordings. It is unknown whether the same phenomenon might be found in regions other than the cortico-basal ganglia circuit. We hypothesized that using magnetoencephalography to assess phase-amplitude coupling in the whole brain can characterize Parkinson's disease. We recorded resting-state magnetoencephalographic signals in patients with Parkinson's disease and in healthy age- and sex-matched participants. We compared whole-brain signals from the two groups, evaluating the power spectra of 3 frequency bands (alpha, 8-12 Hz; beta, 13-25 Hz; gamma, 50-100 Hz) and the coupling between gamma amplitude and alpha or beta phases. Patients with Parkinson's disease showed significant beta-gamma phase-amplitude coupling that was widely distributed in the sensorimotor, occipital, and temporal cortices; healthy participants showed such coupling only in parts of the somatosensory and temporal cortices. Moreover, beta- and gamma-band power differed significantly between participants in the two groups (P < 0.05). Finally, beta-gamma phase-amplitude coupling in the sensorimotor cortices correlated significantly with motor symptoms of Parkinson's disease (P < 0.05); beta- and gamma-band power did not. We thus demonstrated that beta-gamma phase-amplitude coupling in the resting state characterizes Parkinson's disease., (© 2022. The Author(s).)

Background: Symptomatic pituitary metastasis is rare; furthermore, it can result in diabetes insipidus and panhypopituitarism. Since diabetes insipidus is masked by concurrent panhypopituitarism, it can impede the diagnosis of pituitary dysfunction., Case Presentation: A 68-year-old Japanese female suffering from pituitary and thalamic metastases caused by untreated breast cancer, underwent a biopsy targeting the thalamus, not the pituitary. She lacked prebiopsy pituitary dysfunction symptoms; however, these symptoms unexpectedly occurred after biopsy. Diabetes insipidus was masked by corticosteroid insufficiency, and she showed normal urinary output and plasma sodium levels. Upon commencement of glucocorticoid replacement therapy, the symptoms of diabetes insipidus appeared., Conclusions: In this case, thalamic biopsy, as opposed to pituitary biopsy, was performed to preserve pituitary function. However, pituitary dysfunction could not be avoided. Caution is necessary for asymptomatic patients with pituitary metastases as invasive interventions, such as surgery, may induce pituitary dysfunction. Moreover, with respect to masked diabetes insipidus, there is a need to carefully consider pituitary dysfunction to avoid misdiagnosis and delayed treatment., (© 2021. The Author(s).)

One of the challenges in glioblastoma (GBM) imaging is to visualize non-enhancing tumor (NET) lesions. The ratio of T1- and T2-weighted images (rT1/T2) is reported as a helpful imaging surrogate of microstructures of the brain. This research study investigated the possibility of using rT1/T2 as a surrogate for the T1- and T2-relaxation time of GBM to visualize NET effectively. The data of thirty-four histologically confirmed GBM patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11 C-methionine positron emission tomography (Met-PET) were available were collected for analysis. Two of them also underwent MR relaxometry with rT1/T2 reconstructed for all cases. Met-PET was used as ground truth with T2-FLAIR hyperintense lesion, with >1.5 in tumor-to-normal tissue ratio being NET. rT1/T2 values were compared with MR relaxometry and Met-PET. rT1/T2 values significantly correlated with both T1- and T2-relaxation times in a logarithmic manner ( p < 0.05 for both cases). The distributions of rT1/T2 from Met-PET high and low T2-FLAIR hyperintense lesions were different and a novel metric named Likeliness of Methionine PET high (LMPH) deriving from rT1/T2 was statistically significant for detecting Met-PET high T2-FLAIR hyperintense lesions (mean AUC = 0.556 ± 0.117; p = 0.01). In conclusion, this research study supported the hypothesis that rT1/T2 could be a promising imaging marker for NET identification.

Background and Purpose: To report 9 new cases of non-cavernous sinus dural arteriovenous fistulas (NCS-DAVFs) that closed spontaneously and systematically review reports of other cases in the literature., Material and Methods: We performed a retrospective analysis of 9 cases from 2 institutions of NCS-DAVFs that closed spontaneously. Using PubMed and Scopus in accordance with the PRISMA guidelines, we systematically reviewed English language articles about NCS-DAVFs showing spontaneous closure., Results: Review of the cases from 2 institutions identified 9 cases of NCS-DAVFs showing spontaneous closure in follow-up magnetic resonance angiography (MRA), and the systematic review of the literature yielded an additional 38 cases, which had been diagnosed by repeated arteriography. Collectively, the patients included 23 men and 24 women with a mean age of 54 years. The shunts were located in the transverse-sigmoid sinus in 24 cases (51%), anterior condylar confluence in 11, and other locations in 12. Based on the venous drainage pattern on arteriography, 27 cases (57%) were classified as low-risk NCS-DAVF (without cortical venous reflux) and 17 were classified as high-risk NCS-DAVF (with cortical venous reflux). Shunt closure was observed within 3 months in 17 cases (36%). Extrinsic predisposing factors for shunt closure were detected in 14 cases (30%). These included angiography in 7 cases, sinus recanalization in 4, development of sinus occlusion in 2, and sinus compression by a newly developed hematoma in 1., Conclusion: Spontaneous closures of NCS-DAVFs can occur for both high- and low-risk types. One-third of these closures occur within 3 months., (Copyright © 2020. Published by Elsevier Masson SAS.)

We have previously revealed the overexpression of Wilms' tumor gene 1 (WT1) in malignant glioma and developed WT1 peptide vaccine cancer immunotherapy. A phase II clinical trial indicated the clinical efficacy of the WT1 peptide vaccine for recurrent malignant glioma. Here, we aimed to investigate the immunological microenvironment in glioma tissues before and after WT1 peptide vaccine treatment. Paired tissue samples were obtained from 20 malignant glioma patients who had received the WT1 peptide vaccine for > 3 months and experienced tumor progression, confirmed radiographically and/or clinically, during vaccination. We discovered that the expression of WT1 and HLA class I antigens in the tumor cells significantly decreased after vaccination. Maintenance of WT1 expression, which is the target molecule of immunotherapy, in tumor cells during the vaccination period was significantly associated with a longer progression-free and overall survival. A high expression of HLA class I antigens and low CD4 + /CD8 + tumor-infiltrating lymphocytes (TIL) ratio in pre-vaccination specimens, were also associated with a good prognosis. No statistically significant difference existed in the number of infiltrating CD3 + or CD8 + T cells between the pre- and post-vaccination specimens, whereas the number of infiltrating CD4 + T cells significantly decreased in the post-vaccination specimens. This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

Background: In preoperative embolization for intracranial meningioma, endovascular intratumoral embolization is considered to be more effective for the reduction of tumorous vascularity than proximal feeder occlusion. In this study, we aimed to reveal different efficacies for reducing tumor blood flow in meningiomas by comparing endovascular intratumoral embolization and proximal feeder occlusion using dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI)., Methods: 28 consecutive patients were included. DSC-PWI was performed before and after embolization for intracranial meningiomas. Normalized tumor blood volume (nTBV) of voxels of interest of whole tumors were measured from the DSC-PWI data before and after embolization. ΔnTBV% was compared between the cases that received intratumoral embolization and proximal feeder occlusion., Results: ΔnTBV% in the intratumoral embolization group (42.4±29.8%) was higher than that of the proximal feeder occlusion group (15.3±14.3%, p=0.0039). We used three types of embolic materials and ΔnTBV% did not differ between treatments with or without the use of each material: 42.8±42.4% vs 28.7±20.1% for microspheres (p=0.12), 36.1±20.6% vs 28.1±41.1% for n-butyl cyanoacrylate (p=0.33), and 32.3±37.3% vs 34.1±19.0% for bare platinum coils (p=0.77)., Conclusions: The flow reduction effect of intratumoral embolization was superior to that of proximal feeder occlusion in preoperative embolization for intracranial meningioma in an assessment using DSC-PWI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex for neuropathic pain has been shown to be effective, according to systematic reviews and therapeutic guidelines. However, our large, rigorous, investigator-initiated, registration-directed clinical trial failed to show a positive primary outcome, and its subgroup analysis suggested that the analgesic effect varied according to the site of pain. The aim of this study was to investigate the differences in analgesic effects of rTMS for neuropathic pain between different pain sites by reviewing our previous clinical trials. We included three clinical trials in this mini meta-analysis: a multicenter randomized controlled trial at seven hospitals ( N = 64), an investigator-initiated registration-directed clinical trial at three hospitals ( N = 142), and an exploratory clinical trial examining different stimulation parameters ( N = 22). The primary efficacy endpoint (change in pain scale) was extracted for each patient group with pain in the face, upper limb, or lower limb, and a meta-analysis of the efficacy of active rTMS against sham stimulation was performed. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated for pain change using a random-effects model. The analgesic effect of rTMS for upper limb pain was favorable (SMD = -0.45, 95% CI: -0.77 to -0.13). In contrast, rTMS did not produce significant pain relief on lower limb pain (SMD = 0.04, 95% CI: -0.33 to 0.41) or face (SMD = -0.24, 95% CI: -1.59 to 1.12). In conclusion, these findings suggest that rTMS provides analgesic effects in patients with neuropathic pain in the upper limb, but not in the lower limb or face, under the conditions of previous clinical trials. Owing to the main limitation of small number of studies included, many aspects should be clarified by further research and high-quality studies in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mori, Hosomi, Nishi, Dong, Yanagisawa, Khoo, Tani, Oshino, Saitoh and Kishima.)

Purpose: Meningiomas are the most common primary intracranial neoplasms and clinical symptom appearance depends on their volume and location. This study aimed to identify factors that influence clinical symptoms and to determine a specific threshold tumor volume for the prediction of symptomatic progression in patients with convexity, parasagittal, and falx meningiomas. Materials and Methods: We retrospectively studied patients with radiologically suspected convexity, parasagittal, or falx meningiomas at our institution. Results: The data of three hundred thirty-three patients were analyzed. We further divided patients into two groups based on clinical symptoms: an asymptomatic group (250 cases) and a symptomatic group (83 cases). Univariate analysis revealed significant differences between the groups in terms of sex ( p = 0.002), age at the time of volumetric analysis ( p < 0.001), hyperintense lesions on T2-weighted images ( p = 0.029), peritumoral edema ( p < 0.001), maximum tumor diameter ( p < 0.001), and tumor volume ( p < 0.001). Further multivariate analysis revealed significant differences between the groups in terms of age at the time of volumetric analysis ( p = 0.002), peritumoral edema ( p < 0.001), and tumor volume ( p < 0.001). The receiver operating characteristic curve revealed a threshold tumor volume of 21.1 ml for predicting whether a patient would develop symptoms (sensitivity 0.843, specificity 0.880, an area under the curve 0.919 [95% confidence interval: 0.887-0.951]). Conclusion: We identified factors predictive of clinical symptoms in patients with convexity, parasagittal, and falx meningiomas and determined the first-ever threshold tumor volume for predicting symptomatic progression in such patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yamada, Kijima, Nakagawa, Hirayama, Kinoshita, Kagawa and Kishima.)

Recently, many neurospinal surgeons are utilizing spinal fusion techniques for lumbar degenerative diseases. This paper aims to summarize the standard techniques of lumbar spinal fusion. Lumbar spinal fusion is categorized into posterolateral fusion(PLF)and interbody fusion(IF)based on the location of bone grafting. PLF needs wide dissection of paraspinal muscles beyond the synovial joints. It is often utilized for long fusion at the thoraco-lumbar junction with open posterior instrumentation. Techniques for IF include posterior lumbar interbody fusion(PLIF)or transforaminal lumbar interbody fusion(TLIF)via the posterior approach, and anterior lumbar interbody fusion(ALIF), lateral lumbar interbody fusion(LLIF), and oblique lumbar interbody fusion(OLIF TM )performed via the anterior approach. PLIF/TLIF procedures include laminectomy and/or facetectomy for direct neural decompression, and local bone grafting into the interbody space through the interlaminar space or the vertebral foramen. ALIF/LLIF/OLIF TM are usually performed via the retroperitoneal approach. ALIF has an advantage of obtaining lordosis with insertion of a large angled cage from the anterior aspect of the intervertebral space. LLIF/OLIF TM are less invasive methods, in which bone grafting is performed through or beside the psoas muscle. As a larger cage can be plated between the bilateral edge of the intervertebral space, LLIF/OLIF TM has an advantage in the correction of scoliosis.

To realize a brain-machine interface to assist swallowing, neural signal decoding is indispensable. Eight participants with temporal-lobe intracranial electrode implants for epilepsy were asked to swallow during electrocorticogram (ECoG) recording. Raw ECoG signals or certain frequency bands of the ECoG power were converted into images whose vertical axis was electrode number and whose horizontal axis was time in milliseconds, which were used as training data. These data were classified with four labels (Rest, Mouth open, Water injection, and Swallowing). Deep transfer learning was carried out using AlexNet, and power in the high-[Formula: see text] band (75-150[Formula: see text]Hz) was the training set. Accuracy reached 74.01%, sensitivity reached 82.51%, and specificity reached 95.38%. However, using the raw ECoG signals, the accuracy obtained was 76.95%, comparable to that of the high-[Formula: see text] power. We demonstrated that a version of AlexNet pre-trained with visually meaningful images can be used for transfer learning of visually meaningless images made up of ECoG signals. Moreover, we could achieve high decoding accuracy using the raw ECoG signals, allowing us to dispense with the conventional extraction of high-[Formula: see text] power. Thus, the images derived from the raw ECoG signals were equivalent to those derived from the high-[Formula: see text] band for transfer deep learning.

Introduction: Pain relief from repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) is particularly poor in patients with leg pain. The optimal parameters for relieving leg pain remain poorly understood. The purpose of this study was to explore the optimal stimulation parameters of M1-rTMS for patients with leg pain., Methods: Eleven patients with neuropathic pain in the leg randomly underwent 6 conditions of M1-rTMS with different stimulation intensities, sites, and coil directions, including sham stimulation. The 5 active conditions were as follows: 90% or 110% of the resting motor threshold (RMT) on the M1 hand with an anteroposterior coil direction, 90% or 110% RMT on the M1 foot in the anteroposterior direction, and 90% RMT on the M1 foot in the mediolateral direction. Each condition was administered for 3 days. Pain intensity was evaluated using the Visual Analogue Scale and Short-Form McGill Pain Questionnaire 2 at baseline and up to 7 days after each intervention., Results: Visual Analogue Scale scores were significantly reduced after the following active rTMS conditions: 90% RMT on the M1 hand, 90% RMT on the M1 foot with any coil direction, and 110% RMT on the M1 foot. The Short-Form McGill Pain Questionnaire 2 results were similar to those obtained using the Visual Analogue Scale. The analgesic effect of rTMS with stimulus intensity above the RMT was not superior to that below the RMT., Conclusion: We suggest that the optimal stimulation parameters of rTMS for patients with neuropathic pain in the leg may target the M1 foot or M1 hand with an intensity below the RMT., Competing Interests: N. Mori, N. Mori, D. Dong, and Y. Saitoh were members of the Department of Neuromodulation and Neurosurgery, Osaka University Graduate School of Medicine, which was a joint research department established with sponsorship from Teijin Pharma Limited. This department closed on March 31, 2021. The remaining authors have no conflicts of interest to declare. This study was partly supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP17hk0102029, JP19ek0610016, JP19dm0307007, and JP19dm0307008 and the Japan Society for the Promotion of Science KAKENHI under grant numbers JP17K10893, JP18K08993, and JP19K19867.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective . To identify a new electrophysiological feature characterising the epileptic seizures, which is commonly observed in different types of epilepsy. Methods . We recorded the intracranial electroencephalogram (iEEG) of 21 patients (12 women and 9 men) with multiple types of refractory epilepsy. The raw iEEG signals of the early phase of epileptic seizures and interictal states were classified by a convolutional neural network (Epi-Net). For comparison, the same signals were classified by a support vector machine (SVM) using the spectral power and phase-amplitude coupling. The features learned by Epi-Net were derived by a modified integrated gradients method. We considered the product of powers multiplied by the relative contribution of each frequency amplitude as a data-driven epileptogenicity index (d-EI). We compared the d-EI and other conventional features in terms of accuracy to detect the epileptic seizures. Finally, we compared the d-EI among the electrodes to evaluate its relationship with the resected area and the Engel classification. Results . Epi-Net successfully identified the epileptic seizures, with an area under the receiver operating characteristic curve of 0.944 ± 0.067, which was significantly larger than that of the SVM (0.808 ± 0.253, n = 21; p = 0.025). The learned iEEG signals were characterised by increased powers of 17-92 Hz and >180 Hz in addition to decreased powers of other frequencies. The proposed d-EI detected them with better accuracy than the other iEEG features. Moreover, the surgical resection of areas with a larger increase in d-EI was observed for all nine patients with Engel class ⩽1, but not for the 4 of 12 patients with Engel class >1, demonstrating the significant association with seizure outcomes. Significance. We derived an iEEG feature from the trained Epi-Net, which identified the epileptic seizures with improved accuracy and might contribute to identification of the epileptogenic zone., (Creative Commons Attribution license.)

Syrinx resolution has been associated with an increase in the size of the posterior subarachnoid space (pSAS) after foramen magnum decompression (FMD) for type I Chiari malformation (CM1). The present study investigated the influence of pSAS increase on syrinx resolution and symptom improvement after FMD. 32 patients with CM1 with syrinx were analyzed retrospectively. FMD was performed for the 24 patients with CM1 with syrinx. pSAS areas were measured on sagittal magnetic resonance images. Neurological symptoms were grouped into three clinical categories and scored. The rates of symptom improvement in the CM1 patients with syrinx after FMD was 19.7% ± 12.9%. The mean times to the improvement of neurological symptoms in CM1 patients with syrinx after FMD was 23.4 ± 50.2 months. There were no significant differences between the patients with and without improvement of syrinx after FMD with regard to the age, length of tonsillar herniation, BMI, and preoperative pSAS areas. The rate of increase in the pSAS areas was significantly higher in the group with syrinx improvement within 1 year (p < 0.0001). All patients with a > 50% rate of increase in the pSAS area showed syrinx improvement. Our results suggested that the increasing postoperative pSAS area accelerated the timing of syrinx resolution., (© 2021. The Author(s).)

A novel radiological research field pursuing comprehensive quantitative image, namely "Radiomics," gained traction along with the advancement of computational technology and artificial intelligence. This novel concept for analyzing medical images brought extensive interest to the neuro-oncology and neuroradiology research community to build a diagnostic workflow to detect clinically relevant genetic alteration of gliomas noninvasively. Although quite a few promising results were published regarding MRI-based diagnosis of isocitrate dehydrogenase (IDH) mutation in gliomas, it has become clear that an ample amount of effort is still needed to render this technology clinically applicable. At the same time, many significant insights were discovered through this research project, some of which could be "reverse engineered" to improve conventional non-radiomic MR image acquisition. In this review article, the authors aim to discuss the recent advancements and encountering issues of radiomics, how we can apply the knowledge provided by radiomics to standard clinical images, and further expected technological advances in the realm of radiomics and glioma.

The purpose of the current study was to investigate the hypothesis that the spatial distribution of brain metastases could be affected by the biological subtypes of breast cancer. CT (n=1) or MRI (n=66) images of 67 patients with a total of 437 treatment-naive brain metastases from breast cancer were retrospectively reviewed. Patients were grouped according to the biological subtype of the tumor [luminal A, 28; luminal B, 9; human epidermal growth factor receptor 2 (HER2) positive, 14; triple-negative breast cancer (TNBC), 16]. All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. The distribution pattern of brain metastases after image standardization was analyzed. The cerebellum and the frontal lobe were more commonly affected by breast cancer brain metastases. Brain metastases from luminal A and B types of breast cancer arose more often in the cerebellum. Brain metastases from HER2-positive type breast cancer occurred more often in the putamen and the thalamus and less frequently in the cerebellum than other types (P=0.0057). The subtypes of breast cancer are related to differences in the spatial distributions of their brain metastases. These differences may be utilized to plan different cranial irradiation strategies according to the breast cancer subtypes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Izutsu et al.)

Objective: Secondary adrenal insufficiency (sAI) is a severe endocrinologic complication associated with nonfunctioning pituitary adenoma (NFPA). However, its prevalence is not simply related to tumor size. In this study, we aimed to detect the clinical characteristics of NFPAs that cause sAI., Methods: We retrospectively investigated the clinical data of 218 patients with newly diagnosed macro NFPA between April 2011 and March 2020. The patients for whom endocrinologists had prescribed hydrocortisone after comprehensive endocrinologic evaluation were defined as having sAI. The 7 clinical factors analyzed for association with sAI were age, sex, presence of neurologic symptoms, hospitalization for emergency management of pituitary apoplexy, degree of optic chiasm compression, and Knosp grades on both sides., Results: Seventy-three patients (33%) were classified into the sAI group. Multinomial logistic regression showed the strongest correlation between sAI and Knosp grade on the less extending side (P = 0.0001), followed by sex (male) (P = 0.0013) and pituitary apoplexy (P = 0.098). Tumors that extended bilaterally and had Knosp grades of 1-3 were frequently observed in sAI and were common in males., Conclusions: The NFPAs that occupy the sella space and compress the walls on both sides of the cavernous sinus, but do not penetrate them, have a higher risk of developing sAI. This type is more common in males and is seen even in patients without visual field disturbances. This clinical finding will be beneficial in management of patients with NFPA., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Infraslow activity (ISA) and high-frequency activity (HFA) are key biomarkers for studying epileptic seizures. We aimed to elucidate the relationship between ISA and HFA around seizure onset. We enrolled seven patients with drug-resistant focal epilepsy who underwent intracranial electrode placement. We comparatively analyzed the ISA, HFA, and ISA-HFA phase-amplitude coupling (PAC) in the seizure onset zone (SOZ) or non-SOZ (nSOZ) in the interictal, preictal, and ictal states. We recorded 15 seizures. HFA and ISA were larger in the ictal states than in the interictal or preictal state. During seizures, the HFA and ISA of the SOZ were larger and occurred earlier than those of nSOZ. In the preictal state, the ISA-HFA PAC of the SOZ was larger than that of the interictal state, and it began increasing at approximately 87 s before the seizure onset. The receiver-operating characteristic curve revealed that the ISA-HFA PAC of the SOZ showed the highest discrimination performance in the preictal and interictal states, with an area under the curve of 0.926. This study demonstrated the novel insight that ISA-HFA PAC increases before the onset of seizures. Our findings indicate that ISA-HFA PAC could be a useful biomarker for discriminating between the preictal and interictal states., (© 2021. The Author(s).)

One of the most crucial yet challenging issues for glioma patient care is visualizing non-contrast-enhancing tumor regions. In this study, to test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11 C-methionine (MET) on positron emission tomography (PET). Moreover, we compared the T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. Regions that presented a T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated a high MET uptake. In addition, the stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850-3200 ms significantly indicated a higher TCD ( p = 0.04). However, ADC was unable to show a significant correlation with MET uptake or with TCD. Finally, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET.

Introduction: The neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it., Methods: Comprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks., Results: The Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened., Conclusion: Fear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Accurate histological diagnosis and molecular testing using a sufficient tumor sample of advanced lung cancer, especially non-small cell lung cancer (NSCLC), are crucial for precision medicine. The aim of this study was to assess the feasibility and safety of surgical biopsy for intrathoracic lesions, and, in addition, overall survival after surgical biopsy., Methods: One hundred-one patients who underwent surgical biopsy for intrathoracic lesions of lung cancer at our hospital between 2011 and 2019 were retrospectively reviewed. Their clinical and pathologic records were reviewed. In addition to evaluating the oncologic safety of the surgical biopsy, the overall survival based on the biopsy results was estimated., Results: The total number of surgical sites of the 101 patients was 131, and common biopsy sites were the lungs (82, 62.6%) followed by hilar/mediastinal lymph nodes (27, 20.6%). There were 13 postoperative complications (12.9%) without surgery-related deaths. The median time from surgical biopsy to the initiation of treatment was 27 days. Appropriate amounts of specimens for diagnosis and molecular testing were obtained from all patients (100%). When limited to treatment-naïve patients with stage IV adenocarcinoma, patients treated with tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) based on molecular testing had a better prognosis., Conclusions: Surgical biopsy for intrathoracic lesions of lung cancer may be a safe and effective method to make a definitive diagnosis, including companion diagnostics for advancing precision therapy in selected patients with inoperable advanced NSCLC., (© 2021. The Japanese Association for Thoracic Surgery.)

Very few studies have described the blood flow pattern in the ipsilateral ophthalmic artery (OphA) during internal carotid artery (ICA) balloon test occlusion performed to estimate the risk of cerebral ischemia associated with therapeutic ICA sacrifice. This study aimed to investigate the relationship between ipsilateral OphA flow patterns just after ICA temporary occlusion and balloon test occlusion findings. We retrospectively reviewed 32 balloon test occlusion procedures performed at our institution between 2010 and 2019, and analyzed the OphA flow patterns and the conventional balloon test occlusion assessment items: neurological symptoms, stump pressure, stump-pressure ratio, collateral circulations, and venous phase delay. The flow patterns were categorized as type I (retrograde flow reaching the middle cerebral artery [MCA]), type II (retrograde flow to the ICA not reaching the MCA), or type III (no retrograde flow). Tolerance to balloon test occlusion was observed in 4/21 patients (19.0%), 4/6 patients (66.7%), and all five patients with types I, II, and III flows, respectively. The mean pressure ratios during balloon test occlusion in flow types I, II, and III were 35.6% ± 3.5%, 56.4% ± 6.5%, and 69.4% ± 7.1%, respectively (P <0.001). The mean stump pressures in flow types I, II, and III were 36.2 ± 3.6 mmHg, 46.6 ± 6.7 mmHg, and 66.6 ± 7.3 mmHg, respectively (P = 0.003). The mean venous phase delay in flow types I, II, and III were 0.99 ± 0.14 s, 0.25 ± 0.25 s, and 0.0 ± 0.28 s, respectively (P = 0.004). All the above variables showed significant flow-related differences. These results suggest that the OphA flow patterns may provide an additional diagnostic criterion for balloon test occlusion.

Background: Midline brain lesions, such as falx meningioma, arteriovenous malformations, and cavernous malformations, are usually approached from the ipsilateral interhemispheric fissure. To this end, patients are positioned laterally with the ipsilateral side up. However, some studies have reported the usefulness of gravity-assisted brain retraction surgery, in which patients are placed laterally with the ipsilateral side down or up, enabling surgeons to approach the lesions through the ipsilateral side or through a contralateral interhemispheric fissure, respectively. This surgery requires less brain retraction. However, when using an operative microscope, performing this surgery requires the surgeon to operate in an awkward position. A recently developed high-definition (4K-HD) 3-D exoscope system, ORBEYE, can improve the surgeon's posture while performing gravity-assisted brain retraction surgery., Methods: We report five cases with midline brain tumors managed by resectioning with gravity-assisted brain retraction surgery using ORBEYE. We also performed an ergonomic analysis of gravity-assisted brain retraction surgery with a craniotomy model and a neuronavigation system., Results: Gravity-assisted brain retraction surgery to the midline brain tumors was successfully performed for all five patients, using ORBEYE, without any postoperative neurological deficit., Conclusion: Gravity-assisted brain retraction surgery to the midline brain lesions using ORBEYE is feasible, and ORBEYE is ergonomically more favorable than a microscope. ORBEYE has the potential to generalize neurosurgical approaches considered difficult due to the surgeon's awkward position, such as gravity-assisted brain retraction surgery., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Objective: Spinal cord stimulation (SCS) has been considered an ineffective procedure for patients with central poststroke pain (CPSP). However, recent case series that included small numbers of patients reported the possible efficacy of SCS as a treatment of CPSP. This multicenter retrospective study aimed to examine the outcomes of using SCS to treat patients with CPSP and to explore factors related to outcomes., Methods: The authors reviewed the medical records of patients with CPSP who underwent SCS to collect data regarding their background, surgical information, and outcomes of SCS at trial stimulation and last follow-up after long-term implantation in six study centers. Outcomes were evaluated with a pain score for intensity (range 0-10) and the Patient Global Impression of Changes (PGIC) scale. Factors associated with outcomes were explored with univariable and multivariable analyses., Results: The authors collected data from a total of 166 patients (mean age 63.4 years; mean pain score at baseline 8.2). Of these patients, 163 underwent trial stimulation. The mean pain score decreased by 42.0%, 104 (64%) patients had ≥ 30% decrease in pain score, and 96 (59%) reported much or very much improved condition on the PGIC scale at trial stimulation. Moreover, 106 (64%) patients underwent long-term implantation of SCS devices. The mean decrease in pain score was 41.4%, 63 (59%) patients continued to show ≥ 30% decrease in pain score at last follow-up, and 60 (56%) reported much or very much improved condition on the PGIC scale at last follow-up (median [range] follow-up period 24 [24-63] months). Eleven device-related complications and 10 permanent explantations were observed. Univariable and multivariable analyses suggested that young age, less sensory disturbance, implantation of cervical leads, treatment of upper-limb pain, and extensive treated regions were associated with satisfactory outcomes at last follow-up after long-term implantation., Conclusions: These findings indicate that SCS may modestly benefit patients with CPSP. SCS has therapeutic potential for patients with intractable CPSP owing to the lower invasiveness of the SCS procedure and refractory nature of CPSP. Nevertheless, trial stimulation is necessary because of the high initial failure rate.

Objective: Meningiomas are the most frequent primary brain tumors. The long-term natural history of asymptomatic meningiomas remains unclear and difficult to predict accurately, however. The purpose of this study was to determine the subsequent course of asymptomatic meningiomas preceded by 5 years of no treatment., Methods: We retrospectively studied patients with radiologically suspected intracranial asymptomatic meningiomas preceded by 5 years of no treatment. We volumetrically measured the lesions' chronological changes during the initial 5 years to obtain the 5-year tumor doubling time (5y-TdT)., Results: A total of 201 cases met the inclusion criteria. They were further divided into 3 subgroups: those who remained asymptomatic (group A; 174 cases), those who developed neurological symptoms and underwent treatment (group B; 8 cases), and those who received intentional intervention for a preventative reason (group C; 19 cases). 5y-TdT of group B (median: 46.5 months) was significantly shorter than that of group A (median: 216.3 months) (P < 0.001). Progression-free survival (PFS) was significantly different between tumors that exhibited 5y-TdT ≥ 98.8 months and <98.8 months (P < 0.001). When we combined groups B and C and set the PFS endpoint as either disease progression or treatment, we found that more than 20% of patients would require treatment within 15 years., Conclusions: The present study revealed the subsequent course of asymptomatic meningiomas after 5 years of no treatment and demonstrated that 5y-TdT is useful to detect patients who may require treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although tremor is one of the most common movement disorders, there are many different types, and proper diagnosis is important for appropriate treatment. Action tremor has a significant impact on daily life, but the effectiveness of medical treatment is insufficient, and surgery is often the treatment of choice. Surgical treatment is effective in suppressing tremor, and a large percentage of tremors can be adequately controlled. Currently available surgical treatments for tremor include the ventral intermediate nucleus of thalamus-deep brain stimulation(DBS), radiofrequency(RF)-thalamotomy, focused ultrasound(FUS)-thalamotomy, and gamma knife thalamotomy. DBS is often considered the first choice for surgical treatment due to the number of past cases in which DBS has been applied, reported evidence, long-term efficacy, safety, adjustability, and the possibility of bilateral treatment, but RF-thalamotomy is also expected to improve efficacy and safety because of recent advancements in coagulation technology and the accumulation of anatomical knowledge regarding the target nucleus. In addition, the number of cases in which FUS-thalamotomy has been applied has been increasing in the past few years due to its minimally invasive nature, which does not require puncture of the brain. As neurosurgeons, we have the responsibility to select and perform appropriate surgical treatment based on sufficient knowledge of tremor to yield beneficial results in patients.

Background: Wilms' tumor gene 1 (WT1) peptide vaccine and anti-programmed cell death-1 (anti-PD-1) antibody are expected as immunotherapies to improve the clinical outcome of glioblastoma. The aims of this study were to clarify how each immunotherapy affects tumor-infiltrating immune cells (TIIs) and to determine whether the combination of these two therapies could synergistically work., Methods: Mice were transplanted with WT1 and programmed cell death-ligand 1 doubly expressing glioblastoma cells into brain followed by treatment with WT1 peptide vaccine, anti-PD-1 antibody, or the combination of the two, and survival of each therapy was compared. CD45 + cells were positively selected as TIIs from the brains with tumors, and TIIs were compared between WT1 peptide vaccine and anti-PD-1 antibody therapies., Results: Most mice seemed to be cured by the combination therapy with WT1 peptide vaccine and anti-PD-1 antibody, which was much better survival than each monotherapy. A large number of CD4 + T cells, CD8 + T cells, and NK cells including WT1-specific CD8 + and CD4 + T cells infiltrated into the glioblastoma in WT1 peptide vaccine-treated mice. On the other hand, the number of TIIs did not increase, but instead PD-1 molecule expression was decreased on the majority of the tumor-infiltrating CD8 + T cells in the anti-PD-1 antibody-treated mice., Conclusion: Our results clearly demonstrated that WT1 peptide vaccine and anti-PD-1 antibody therapies worked in the different steps of cancer-immunity cycle and that the combination of the two therapies could work synergistically against glioblastoma., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Swallowing is attributed to the orchestration of motor output and sensory input. We hypothesized that swallowing can illustrate differences between motor and sensory neural processing. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus. Mouth opening and swallowing were treated as motor tasks, whereas water injection was treated as a sensory task. Phase-amplitude coupling between lower-frequency and high γ (HG) bands (75-150 Hz) was investigated. An α (10-16 Hz)-HG coupling appeared before motor-related HG power increases (burst), and a θ (5-9 Hz)-HG coupling appeared during sensory-related HG bursts. The peaks of motor-related coupling were 0.6-0.7 s earlier than that of HG power. The motor-related HG was modulated at the trough of the α oscillation, and the sensory-related HG amplitude was modulated at the peak of the θ oscillation. These contrasting results can help to elucidate the brain's sensory motor functions., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time-outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (< 70, 70 to < 80, and ≥ 80 years), the mRS scores at 90 days were analyzed according to 4 categories of onset-to-reperfusion time (< 180, 180 to < 240, 240 to < 300, and ≥ 300 min). In each age subgroup, the distributions of mRS scores were better with shorter onset-to-reperfusion times. The adjusted common odds ratios for better outcomes per 1-category delay in onset-to-reperfusion time were 0.66 (95% CI 0.55-0.80) in ages < 70 years, 0.66 (95% CI 0.56-0.79) in ages 70 to < 80 years, and 0.83 (95% CI 0.70-0.98) in ages ≥ 80 years. Early reperfusion was associated with better outcomes across all age subgroups. Achieving early successful reperfusion is important even in elderly patients.

Choline acetyltransferase (ChAT), responsible for the synthesis of acetylcholine, plays an important role in neurotransmission. However, no method to visualize the ChAT activity in tissues has been reported to date. In this study, mass spectrometry imaging (MSI) was used to visualize ChAT activity in situ , which is difficult with conventional enzyme histochemistry. By using choline chloride-trimethyl-d9 (choline-d9) as a substrate and simultaneously supplying an inhibitor of cholinesterase to tissues, we succeeded in directly visualizing the ChAT activity in the rodent brain and spinal cord. The findings revealed heterogeneous ChAT activity in the striatum of the mouse brain and in the spinal lower motor neurons that connect the anterior horn to the ventral root. Furthermore, extending the developed method to spinal cord injury (SCI) model mice revealed the site-specific effect of primary and secondary injury on ChAT activity. This study shows that the MSI-based enzyme histochemistry of ChAT could be a useful tool for studying cholinergic neurons.