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Secreted protein Reelin is implicated in neuropsychiatric disorders and its supplementation ameliorates neurological symptoms in mouse disease models. Recombinant human Reelin protein may be useful for the treatment of human diseases, but its properties remain uncharacterized. Here, we report that full-length human Reelin was well secreted from transfected cells and was able to induce Dab1 phosphorylation. Unexpectedly, the central fragment of human Reelin was much less secreted than that of mouse Reelin. Three residues in the sixth Reelin repeat contributed to the secretion inefficiency, and their substitutions with mouse residues increased the secretion without affecting its biological activity. Our findings help efficient production of human Reelin protein for the supplementation therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motor-evoked potential (MEP) monitoring by transcranial electrical stimulation (TES) is important for intraoperative motor function assessment in neurosurgery; however, false-negative results sometimes occur, and these findings should be interpreted with caution. Herein, we report an interesting MEP change resulting from a pons transection. The patient was a boy aged 5 years and 2 months. He underwent multiple craniotomies for cerebellar anaplastic ependymoma and was already paralyzed in the right upper and lower limbs. Therefore, we decided to remove the recurrent lesion from the left anterior pons. MEPs were recorded on both the right and left sides after the start of surgery but disappeared 1 h 30 min after the start of surgery in the TES on the operative side, even when the stimulation intensity was increased. The contralateral TES consistently recorded stable MEPs throughout the surgery. The tumor was completely resected on imaging. Immediately postoperatively, the patient experienced flaccid paralysis on the right side of the body, which recovered to preoperative levels over time. A transcranial MEP cannot be derived if the corticospinal tract is transected at the pons. Transcranial MEP findings may accurately reflect the corticospinal tract function if the injury is caudal to the pons., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration., Methods: Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (-) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO(3-4 Hz) were evaluated., Results: During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO(3-4 Hz) in the Ictal (+) group ( P < 0.01). By contrast, the Ictal (-) group exhibited a paradoxical increase in the rate of ripples and fast ripple ( P < 0.05)., Conclusions: Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4) ) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Background: Dural arteriovenous fistula (DAVF) in the anterior cranial fossa (ACF) is known to show a high risk of intracranial hemorrhage. Recently, multi-modal fusion imaging with computed tomography angiography, computed tomography venography, and three-dimensional (3D) rotation angiography have been used preoperatively to ensure anatomical safety. We report on endovascular treatment as a first-line approach for ACFDAVF based on the understanding of vascular anatomy obtained from multi-modal fusion imaging., Methods: All patients with ACF-DAVF treated endovascularly as a first-line approach were included in this study. Analyses took into account complications (particularly visual function), immediate angiographic outcomes, and follow-up findings in consecutive patients with ACF-DAVF treated with interventional treatment based on multi-modal fusion imaging., Results: Five patients with ACF-DAVF underwent six sessions of transarterial embolization (TAE) in our institution. The five male patients (mean age, 74.5 years; range, 60-84 years) were treated with liquid embolic agents (Onyx, four procedures; n-butyl 2-cyanoacrylate, two procedures). No difference was seen between preoperative image evaluation and image evaluation during the endovascular procedure, and in all cases, a microcatheter was navigated into a target artery assumed from preoperative multi-modal imaging, allowing treatment completion in a single procedure. In all cases, the shunt disappeared completely and visual function after procedure was maintained. At the last follow-up, all patients showed a modified Rankin scale score of 0 or 1 with no recurrences., Conclusion: Multi-modal fusion imaging facilitates a 3D understanding of the vascular anatomy, allowing TAE as the first-line treatment for ACF-DAVF., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Introduction: This study aimed to compare the outcomes and safety in patients aged ≥75 years and those aged <75 years who underwent stent-assisted endovascular treatment for unruptured cerebral aneurysms, specifically focusing on perioperative antiplatelet therapy (APT)., Methods: This multicenter retrospective study comprised patients who underwent stent-assisted coiling (SAC) or flow diverter stent (FDS) placement for unruptured cerebral aneurysms. The primary outcome was defined as the composite outcomes of perioperative thromboembolic events, bleeding events, or death., Results: Among 632 patients, 533 (84.3%) were aged <75 years and 99 (15.6%) were aged ≥75 years. No significant differences were observed in the dual APT duration. The primary outcome occurred in 14.3% of patients aged <75 years and in 14.1% of those aged ≥75 years, with no significant difference (p = 1.0). The composites of the primary outcome, including thromboembolic events, bleeding events, and death differed insignificantly. Similar findings were observed when the primary outcomes for SAC (12.7% vs. 11.5%, p = 0.95) and FDS (17.5% vs. 18.4%, p = 1.0) were analyzed. The 30-day, 1-year, and 2-year cumulative event-free survival rates for the primary outcome were 89.5, 87.2%, and 85.2%, respectively, in patients aged <75 years, and 90.9%, 88.7%, and 87.0%, respectively, in those aged ≥75 years. These trends were similar (log-rank test, p = 0.92)., Conclusion: No significant differences were observed in the rates of the primary outcomes between patients aged <75 years and those aged ≥75 years. Therefore, refraining from stent-assisted treatment for unruptured aneurysms based solely on age might be inappropriate., (© 2024 S. Karger AG, Basel.)

Background: Post-stroke epilepsy can reduce patients' abilities to carry out various activities of daily living. Despite their importance in preventing the onset of post-stroke epilepsy, the prophylactic administration of antiepileptic drugs is controversial due to a lack of high-level clinical research. In this study, we initiated a prospective interventional study of prophylactic antiepileptic drug administration in patients with a subcortical hemorrhage, who are at the highest risk of developing epilepsy after experiencing a stroke., Methods: The study was conducted in a single-center setting and was a single-arm study with no control group; the case entry period started in November 2023 and is due to end in March 2025. Only cases with a subcortical hemorrhage will be included. The treatment regimen used in this study is 2 mg of perampanel per day. Perampanel will be administered for one year, followed by two years of follow-up, for a total study period of three years. The primary endpoint will be the development of epilepsy., Results: Perampanel administration is expected to reduce the incidence of post-stroke epilepsy in comparison to the results of previous reports on the use of alternative treatments., Conclusions: The results of this study will provide new insights into the prevention of post-stroke epilepsy. The relatively small size of this study makes it difficult to provide strong evidence of the efficacy of perampanel, but it may serve as a basis for larger clinical trials.

Pathogenic bacteria must secure the uptake of nutritional metals such as iron for their growth, making their import systems attractive targets for the development of new antimicrobial modalities. In the pathogenic bacterium Streptococcus pyogenes, the iron uptake system FtsABCD transports iron encapsulated by siderophores of the hydroxamate class. However, the inability of S. pyogenes to produce these metabolites makes the biological and clinical relevance of this route unresolved. Herein, we demonstrated that the periplasmic binding protein FtsB recognizes not only the hydroxamate siderophore ferrichrome, as previously documented, but also ferrioxamine E (FOE), ferrioxamine B (FOB), and bisucaberin (BIS), each of them with high affinity (nM level). Up to seven aromatic residues in the binding pocket accommodate the variable backbones of the different siderophores through CH-π interactions, explaining ligand promiscuity. Collectively, our observations revealed how S. pyogenes exploits the diverse xenosiderophores produced by other microorganisms as iron sources to secure this precious nutrient., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Closure of the ventral dura mater of the thoracic spinal cord is challenging because it requires both avoiding spinal cord damage and obtaining sufficient working space in an anatomically narrow area. We report a case of superficial siderosis (SS) due to chronic bleeding from a thoracic ventral dural defect in which we preformed dural repair using as a simple sutureless method and obtained good results., Case Description: A 75-year-old man complained of slowly progressive gait, speech, and hearing disturbances over 5 years. Magnetic resonance imaging (MRI) showed SS in the brain and the spinal cord and a dural defect ventral to the spinal cord at the T2 level. Neurological examination revealed bilateral cerebellar ataxia and mild motor weakness in left iliopsoas muscle. T2 and T3 hemi-laminectomy was performed in the prone position. Transdurally, a dural defect on the ventral side of the spinal cord and a fluid-filled space beyond it could be observed. With endoscopic assistance, a blood clot in the space was confirmed. For dural closure, we performed a simple manipulation using a collagen-based dural graft. The graft was cut into pieces, softened with saline, and simply packed into the space with minimal strain on the spinal cord despite the narrow space. The postoperative clinical course was uneventful. Postoperative MRI at 1 year showed the space had disappeared., Conclusion: In patients with SS, sutureless dural closure using a collagen-based dural graft allows for effective, minimally invasive dural closure, even for thoracic ventral lesions.

Background: Transarterial embolization (TAE) is generally the endovascular treatment of choice for tentorial dural arteriovenous fistula (dAVF). Although flow control of the feeder vessel has been reported to achieve complete shunt blockade, flow control in the absence of ischemia tolerance of internal carotid artery as a feeder has not been reported. We present a case in which treatment by Onyx TAE with intermittent flow control of the meningohypophyseal trunk as the feeder was successful for a tentorial dAVF presenting with myelopathy without tolerance of ischemia., Methods: The intermittent flow control is presented for a tentorial dAVF presenting with myelopathy without tolerance for ischemia. An inflation of the balloon in the internal carotid artery was set for 5 minutes, and the Onyx injection was repeated at intervals of at least 2 minutes. Injections and pauses were repeated to allow Onyx to reach the shunt pouch., Results: The patient underwent successful TAE with intermittent flow control for a tentorial dAVF presenting with myelopathy. The disappearance of the shunt was confirmed with gait disturbance resolution postoperatively., Conclusions: Intermittent flow control of the meningohypophyseal trunk using a balloon may be safe and effective for cases showing no tolerance for ischemia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Glioblastoma (GBM) is the most frequent invasive brain tumor and a rapidly progressive disease with a poor prognosis that predominantly affects middle-aged and older adults. The relationship between daily functioning and prognosis in patients with GBM will become more important as advances in multimodality treatment are expected to increase the number of long-term survivors. Methods Sixty-seven patients were initially diagnosed with GBM at our hospital between December 2013 and December 2022. All patients were divided into two groups: those who survived for one year or longer from the date of discharge (Group A) and those who died within one year from the date of discharge (Group B). Muscle strength, nutritional status, and Karnofsky Performance Status (KPS) were examined upon admission (p1), post-surgery (p2), and discharge (p3), and their relationships with prognosis were investigated. Results Group A was significantly younger than Group B, with a significant difference in the total radiation dose. There were no significant differences in the anatomical tumor location, whether the tumor occurred on the left or right side, or tumor size. KPS at discharge (p3) and the degree of improvement in the KPS between p1 and p3 were associated with a good prognosis. Conclusions The KPS varies throughout the treatment. When considering the KPS as a prognostic indicator, the KPS at discharge is the most important, given the structure of the disability and the course of treatment for GBM., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Ethics Committee of Nara Medical University Hospital issued approval 3404. This study was approved by the Ethics Committee of Nara Medical University Hospital, and information was collected from medical records in accordance with the Declaration of Helsinki while maintaining patient anonymity and confidentiality. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: A.K. was funded by by JSPS KAKENHI (grant numbers JP 18K10753 and JP23K10510). . Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sasaki et al.)

Background: Ventriculoperitoneal (VP) shunt tube migration is recognized as an occasional complication; however, migration into the cardiac system is rare. The authors report a case of VP shunt tube migration into the heart and pulmonary artery and the safe removal of the tube., Observations: The patient had a VP shunt implanted for hydrocephalus after a subarachnoid hemorrhage. The screening chest radiograph taken a few months later showed the migration of the abdominal tube into the heart. Examinations revealed that the abdominal tube had migrated from the left subclavian vein, passed through the superior vena cava, right atrium and ventricle, and looped into the pulmonary artery. The patient had no symptoms; however, there were some risks, such as damage to the valves or fatal arrhythmia. The authors therefore decided to remove the tube. To avoid various intraoperative risks, in particular tube knot formation, the tube was removed under fluoroscopy with a guidewire inserted, which was 0.035 inches for the angiography catheter. The tube was successfully removed without any complications., Lessons: Knot formation can be one of the fatal complications of shunt tube removal. The authors' technique is an effective method for safe removal. https://thejns.org/doi/10.3171/CASE24127.

Purpose: To evaluate the motor function of the lower extremity (LE), we used direct cortical stimulation motor-evoked potential (D-MEP) monitoring with a single six-contact subdural strip electrode placed in the interhemispheric fissure., Methods: Intraoperative neuromonitoring using D-MEPs in the LE was performed in 18 cases (16 patients) for brain tumor surgery from December 2018 to April 2023 with a follow-up period of at least 3 months. After dural opening, a single six-contact subdural strip electrode was placed inside the interhemispheric fissure. To identify the central sulcus, phase reversal was recorded using somatosensory evoked potentials. Next, direct cortical stimulation was applied to the primary motor cortex. The baseline waveform was defined as a reproducible waveform of 30 µV or higher, and a significant decrease of ≥50% in the amplitude resulted in a warning during surgery., Results: The success rate of central sulcus identification in the LE was 66.7% (12/18 cases). Direct cortical stimulation motor-evoked potential monitoring could record stable contralateral motor-evoked potentials of the tibialis anterior, gastrocnemius, and abductor hallucis in 16 of 18 cases (88.9%). The mean intensity of stimulation for D-MEPs was 20.5 ± 9.9 mA, and the 16 cases showed no significant reduction in amplitude. Seventeen cases showed no deterioration of motor function of the LE at 1 and 3 months postoperatively. In the remaining case with unsuccessful D-MEP, paralysis of the LE worsened at 1 and 3 months postoperatively., Conclusions: The placement of electrodes in the interhemispheric fissure on the primary motor cortex of the LE enabled motor-function monitoring in the LE with D-MEPs, suggesting that D-MEP-based monitoring may be a reliable approach., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

The composition of human skin microbiome profoundly impacts host skin health and disease. However, the relationship between skin homeostasis or the development of skin diseases and daily changes in skin microbial composition is poorly understood. Longitudinal samplings at more frequent intervals would address this issue, while conventional sampling methods have technical difficulties, leading to limitations in sampling opportunities. Here, we developed a simple and stable tape-stripping method regardless of the operator's skill. Our method enables skin microbial sampling within 30 seconds and taking multiple skin microbial samples from the same body site. The amount of microbial DNA among multiple sampling sites could be measured within 13.5%. The sequencing results of multiple sampling showed high consistency, Pearson's correlation coefficient between multiple samples of 0.98. Furthermore, these results were comparable to those collected by the conventional swabbing method. These results demonstrate that our tape-stripping method enables simple microbiome collection and highly reliable quantitative skin microbiome analysis. These features of our method would lead to a further understanding of skin disease development or diagnosis of skin conditions in clinical research by increasing the opportunities for microbial sampling., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: As a treatment for tubal infertility, falloposcopic tuboplasty (FT) is one of the options for patients who wish to conceive naturally. Based on the results of FT, we propose an appropriate time of transitioning to assisted reproductive technology (ART) for tubal infertility., Objects and Methods: We examined the outcomes of cases of tubal infertility during the period from June 1999 through March 2021 who were performed tuboplasty at our hospital using the FT catheter system under laparoscopy., Results: The number of treated cases was 828. There were 243 cases of endometriosis and 119 cases of genital chlamydial infection. By FT, 712 cases (86.0%) were successfully recanalized. Of the 712 cases, 189 conceived naturally (26.5%) and miscarriages were 23 cases (12.2%), ectopic pregnancies were 8 cases (4.2%). The mean duration from FT to pregnancy was 6.5 months in natural pregnancy group, 90% of them were pregnant within 14 months. In endometriosis cases, the pregnancy rate after FT did not change significantly among clinical stage., Conclusions: Even when the fallopian tube was recanalized by FT, if the couple is unable to conceive naturally, they had better to consider switching to ART at about 14 months. When the couples with endometriosis consider switching to ART, we suggest deciding without considering the rASRM stage., (© 2024 Japan Society of Obstetrics and Gynecology.)

Objective: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation., Methods: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns-classified as local, diffuse, distant, or multifocal-and time to recurrence were compared between patients with and without VO., Results: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7-38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35)., Conclusion: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.

Objective: Puncture-site complications in interventional radiology sometimes cause severe conditions. Vascular closure devices play an important role in preventing puncture-site complications. Vascular closure devices are divided into 2 types, the directly suturing or clipping type (active approximators) and adherent sealant types (passive approximators). However, which types of vascular closure device are the safest and most effective for achieving hemostasis remains unclear. We analyzed the efficacy of each type of vascular closure device and risk factors for puncture-site complications., Methods: This study investigated 327 consecutive cases of neuroendovascular surgery using a transfemoral procedure during a 2-year study period. Passive approximators (Angioseal [St Jude Medical, Saint Paul, MN] and Exoseal [Cordis Corporation, Miami, FL]) were mainly used in the first half and active approximators (Perclose [Abbot Vascular, Santa Clara, CA]) in the second. We compared groups and estimated risk factors for puncture-site complications., Results: All procedures were successful. Comparing groups with and without puncture-site complications, use of passive approximators and ≥3 antithrombotic medications tended to be more frequent and distance from skin to femoral artery and body mass index tended to be lower in the group with complications without significance. The cutoff for femoral artery depth calculated from a receiver operating characteristic curve was 16.43 mm. Multivariate analysis revealed ≥3 antithrombotic medications (P = 0.002, OR 15.29, 95% CI 2.76-85.76) and passive approximator use in patients with femoral artery depth <16.43 mm (P < 0.001, OR 17.08, 95% CI 2.95-57.80) were significantly higher in the group with puncture-site complications., Conclusions: Passive approximator use in patients with shallow femoral artery depth increases puncture-site complications in neuroendovascular treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Staphylococcus epidermidis is a member of the human skin microbiota as a commensal organism but could be an important opportunistic pathogen for immunocompromised individuals. Here, we report the complete genome sequence of three S . epidermidis strains isolated from patients with skin diseases., Competing Interests: The authors declare no conflict of interest.

Traumatic brain injuries lead to post-traumatic seizures (PTS), with acute subdural hematomas (ASDH) posing a particularly elevated risk. The development of refractory nonconvulsive status epilepticus (NCSE) in such cases, especially in older patients, requires immediate and effective management. This case report highlights the improvement of refractory NCSE in an elderly patient with ASDH through endoscope-assisted evacuation. An 88-year-old woman was hospitalized for dysarthria and right hemiparesis 3 days after a fall. Computed tomography (CT) revealed a left hemispheric ASDH, 9 mm thick, along with minor traumatic subarachnoid bleeding in the interpeduncular cistern. The initial treatment was conservative, including the administration of lacosamide at 100 mg/day. However, her consciousness deteriorated 4 days after admission, and she experienced convulsions in the right face and arm on day 5. Although the convulsions stopped after the administration of diazepam 10 mg IV and her consciousness temporarily improved, it worsened again on day 6, leading to a diagnosis of NCSE on an electroencephalogram (EEG). Despite aggressive pharmacological interventions with fosphenytoin (750 mg initially followed by 262 mg/day) and phenobarbital (625 mg/day), the patient's cognitive state and EEG findings did not improve. Consequently, on the 13th day, she underwent an endoscopic procedure to remove the SDH, which alleviated her symptoms and ended the seizures. This case demonstrates that even the absence of a significant mass effect from ASDH can trigger NCSE, underscoring the necessity for swift diagnosis and consideration of surgical options when conventional treatment fails. Endoscope-assisted evacuation is a safe and effective treatment option, particularly in older patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Arai et al.)

Augmented reality (AR) is expected to serve as an assistive intraoperative technology in neurosurgery.1 Awake craniotomy (AC) for gliomas benefits the extent of resection, survival, and postoperative neurofunctional outcomes.2 In AC, it is critical to understand the cortical and subcortical anatomy.3 We describe the use of AR superimposing tumor and deep white matter tracts in AC. A 29-year-old right-handed woman presented to a local hospital after an episode of generalized convulsions. MRI of the head revealed a widely spreading tumor in the left middle frontal gyrus. After a left frontal craniotomy while the patient was asleep, AR was used to indicate the tumor boundary with subcortical fibers including the corticospinal tract, inferior fronto-occipital fasciculus, and cingulate fasciculus. We performed AR-assisted removal of the tumor on the surface of the middle frontal gyrus. On subcortical stimulation (SCS) of the frontal aslant tract and inferior fronto-occipital fasciculus, the patient stopped naming objects in the picture-naming test, while SCS of the left cingulate gyrus caused the patient to mistake colors in the Stroop test. The subcortical fibers identified by AR coincided with the sites of symptom elicitation by SCS. We eventually removed a large part of the tumor. Postoperative MRI confirmed 96.2% resection. The patient was discharged without any new neurological deficits. AC with AR is useful for resection of gliomas in the dominant hemisphere. The patient consented to the procedure and to the publication of her image. The ethics committee of our hospital does not require approval for case reports., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) are based on neutrophil, monocyte, platelet, and lymphocyte counts. The SIRI and SII are used to predict the survival of patients with malignant tumors. It is well known that the inflammatory immune response is closely related to cancer occurrence and progression. In the present study, we evaluated the potential prognostic significance of SIRI and SII in patients with primary central nervous system lymphoma (PCNSL)., Methods: Fifty-eight consecutive patients were enrolled in this study between November 2006 and May 2022. Among the 58 patients, 47 patients with sufficient blood test data and follow-up were analyzed. The patients with steroid intake at the time point of the blood test and higher C-reactive protein were excluded., Results: The median follow-up and survival times were 31 and 36 months, respectively. The optimal cutoff SIRI value was based on the receiver operating characteristic curve (ROC) for overall survival (OS) and stratified patients into low (< 1.43 × 10 9 /L, n = 22) and high (≥ 1.43 × 10 9 /L, n = 25) SIRI groups. The optimal cutoff SII value based on the ROC for OS stratified patients into low (< 694.9, n = 28) and high (≥ 694.9, n = 19) SII groups. A low SIRI value was associated with longer OS (p = 0.006). Furthermore, a low SII value was associated with longer OS (p = 0.044). The prognostic factors associated with prolonged survival in univariate analysis using the Cox proportional hazard model were age < 65 years, low SIRI, and low SII. The multivariate analysis demonstrated that age < 65 years and low SIRI independently predicted longer OS., Conclusion: Simple, less expensive, and routinely ordered preoperative blood count assessments such as SIRI and SII predict the OS of patients with PCNSL. This study demonstrated that PCNSL is associated with pre-treatment systemic immune-inflammation states., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We report a rare case involving improved hearing after surgery for a jugular foramen schwannoma despite the lack of response during the preoperative auditory brainstem response (ABR) test. A left jugular foramen tumor was diagnosed in a 79-year-old man with hearing loss. No response was observed during the preoperative ABR test. However, his hearing improved after surgery using the lateral suboccipital approach. Following Gamma Knife radiation to the residual tumor post-surgery, the ABR test detected V waves. The hearing of patients with cerebellopontine angle tumors can improve even when there is no response during the preoperative ABR test., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Morisaki et al.)

Biparatopic antibodies (bpAbs) are engineered antibodies that bind to multiple different epitopes within the same antigens. bpAbs comprise diverse formats, including fragment-based formats, and choosing the appropriate molecular format for a desired function against a target molecule is a challenging task. Moreover, optimizing the design of constructs requires selecting appropriate antibody modalities and adjusting linker length for individual bpAbs. Therefore, it is crucial to understand the characteristics of bpAbs at the molecular level. In this study, we first obtained single-chain variable fragments and camelid heavy-chain variable domains targeting distinct epitopes of the metal binding protein MtsA and then developed a novel format single-chain bpAb connecting these fragment antibodies with various linkers. The physicochemical properties, binding activities, complex formation states with antigen, and functions of the bpAb were analyzed using multiple approaches. Notably, we found that the assembly state of the complexes was controlled by a linker and that longer linkers tended to form more compact complexes. These observations provide detailed molecular information that should be considered in the design of bpAbs., (© 2024 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Objective: The prognosis for patients with cancer with brain metastasis (BM) requiring surgical removal is quite limited. Preoperative prognostic factors can provide meaningful information to surgeons, oncologists, and patients. This study evaluated the preoperative blood counts in patients with BM who were treated with surgical removal., Methods: Between January 2011 and November 2021, 221 consecutive surgeries were conducted on 198 patients with BM. Among the 198 patients, 188 patients with sufficient blood test data and follow-up were analyzed in this study. The tumors originated from the lungs (n = 102, 54.3%), colon (n = 26, 13.3%), breast (n = 13, 6.9%), kidney (n = 8, 4.3%), stomach (n = 6, 3.2%), and others (n = 33, 17.6%). The blood test data included neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count, hemoglobin, and albumin., Results: The median follow-up and median survival times were both 11 months (range: 0-139 months). Higher neutrophil-lymphocyte ratio ≥ 3.17, platelet-lymphocyte ratio ≥112.7, systemic immune-inflammation index ≥594.4, systemic inflammation response index ≥1.25 were unfavorable predictors of prognosis for the patients treated with surgical removal for BM (P < 0.001). Furthermore, lower lymphocyte-monocyte ratio < 2.33 and prognostic nutritional index < 48.5 were unfavorable predictors., Conclusions: Simple, less expensive, routinely ordered preoperative blood count assessments, such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and prognostic nutritional index, can predict the overall survival of patients treated with surgical removal for BM., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA-Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR-Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM.

Understanding the risks of contrast-induced encephalopathy (CIE), a serious complication of contrast agents, is crucial in endovascular treatment. We present the case of a 73-year-old woman who developed CIE in the medulla and cervical cord during coil embolization for unruptured left basilar-superior cerebellar artery and basilar artery tip aneurysms. The CIE was identified via neuromonitoring. In this case, spinal cord ischemia might have occurred due to reduced perfusion pressure after inserting the distal access catheter (DAC) in the vertebral artery. Multiple injections of contrast medium via the DAC during coil embolization likely contributed to an unusual form of CIE. Extreme caution is warranted during endovascular treatments involving the posterior circulation, due to the relatively high incidence of contrast-mediated encephalopathy, which can lead to severe consequences such as perforator infarction. Neuromonitoring is very useful for the early detection of neurological changes, particularly because intraoperative angiography may not reveal all irregularities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Dual antiplatelet therapy (DAPT) is necessary to prevent thromboembolic complications after stent-assisted coiling (SAC) or flow-diversion (FD) for cerebral aneurysms, but the optimal antiplatelet regimen remains unclear., Objective: To determine the optimal DAPT duration in patients with SAC/FD., Methods: This multicenter cohort study enrolled patients who received SAC/FD for cerebral aneurysms at seven Japanese institutions between January 2010 and December 2020. The primary outcome was the time from procedure to the occurrence of a composite of target vessel-related thromboembolic events, procedure-unrelated major bleeding events, or death. The cumulative event-free survival rates were analyzed using a Kaplan-Meier curve, and the differences in each outcome between the groups dichotomized by the duration of DAPT were analyzed using the log-rank test., Results: Of 632 patients (median observational period, 646 days), primary outcome occurred in 63 patients (10.0%), most frequently within 30 days after the procedure. The cumulative event-free survival rates at 30 days, 1 year, and 2 years after the procedure were 93.3% (91.4 to 95.3%), 91.5% (89.3 to 93.7%), and 89.5% (87.0 to 92.0%), respectively. The cumulative event-free survival rates after switching to monotherapy were similar for the >91 and <90 days DAPT groups in the population limited to patients who were switched from DAPT to monotherapy without major clinical events., Conclusions: Thromboembolic events rarely occurred beyond 30 days after SAC/FD. The duration of DAPT may be shortened if patients have a periprocedural period without events. Further prospective studies are warranted to determine the optimal duration of antiplatelet therapy., Trial Registration Number: UMIN000044122 :https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000050384., Competing Interests: Competing interests: YEn received a research grant from Sysmex; a lecture fee from Stryker, Medtronic, Johnson and Johnson, Daiichi-Sankyo and Otsuka Pharmaceutical. AI received a lecture fee feom Medtronic, Stryker, Terumo, Johnson and Johnson, Medico's Hirata, Kaneka, Daiichi-Sankyo and Otsuka Pharmaceutical; a research glant from Fuji film. MS received a lecture fee from Medtronic. KSu received a lecture fee from Stryker and Daiichi-Sankyo. IN received a lecture fee from Terumo, Kaneka and Daiichi-Sankyo. TH received a lecture fee from Stryker, Medtronic, Johnson and Johnson, Daiichi-Sankyo and Abbott; a research grant from Stryker, Medtronic, Asahi Intec, Kaneka, Medico's Hirata, Boehringer Ingelheim and Eisai. SY recieved a research grant from Asahi Intec, Biomedical Solution, Medico's Hirata, Medtronic, Otsuka Pharmaceutical, Stryker and Terumo; a lecture fee from Stryker, Medtronic, Johnson and Johnson, Kaneka, Daiichi-Sankyo, Bayer and Bristol-Meyers Squibb., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Invasive bacterial pathogens are internalized by host cells through endocytosis, which is regulated by a cascade of actin rearrangement signals triggered by host cell receptors or bacterial proteins delivered into host cells. However, the molecular mechanisms that mediate actin rearrangement to promote bacterial invasion are not fully understood. Here, we show that the autophagy-related (ATG) protein ATG9B regulates the internalization of various bacteria by controlling actin rearrangement. ATG knockout screening and knockdown experiments in HeLa cells identified ATG9B as a critical factor for bacterial internalization. In particular, cells with ATG9B knockdown exhibited an accumulation of actin filaments and phosphorylated LIM kinase and cofilin, suggesting that ATG9B is involved in actin depolymerization. Furthermore, the kinase activity of Unc-51-like autophagy-activating kinase 1 was found to regulate ATG9B localization and actin remodeling. These findings revealed a newly discovered function of ATG proteins in bacterial infection rather than autophagy-mediated immunity., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background Treatment of patients with a giant pituitary neuroendocrine tumor (GPitNET) is challenging. Here, we present the methods used for the clinical management of patients who underwent GPitNET resection mainly via endoscopic endonasal surgery along with multimodal support to avoid surgical complications, which can affect the outcomes. Methodology The medical records of 25 patients with a GPitNET who underwent endonasal endoscopic surgery were retrospectively reviewed. Complications were analyzed and factors affecting the extent of resection were evaluated. Results Gross total resection was achieved in six (24%), near-total resection (>90%) in nine (36%), and partial resection in 10 (40%) patients. Multivariate analyses revealed that tumors invading the middle fossa had negative effects on the extent of resection (odds ratio = 0.092, p = 0.047). Postoperative vision improved or normalized in 16 (64%), remained stable in eight (32%), and worsened in one (4%), while a new hormonal deficit was noted in seven (28%) patients. Complications included permanent oculomotor nerve palsy in one (4%) and transient oculomotor palsy in one (4%), apoplexy of the residual tumor resulting in ischemic stroke in one (4%), postoperative cerebrospinal fluid leakage in one (4%), and permanent diabetes insipidus in six (24%) patients. Conclusions For GPitNETs that extend into the middle fossa, our study underscored the difficulties in surgical extraction and the necessity for tailored treatment approaches. To ensure the safest and most complete removal possible, the surgical strategy must be specifically adapted to each case. Additionally, employing a comprehensive support approach is essential to reduce the chance of complications in patients impacted by this condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nakase et al.)

The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-K ATP ) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through low-conductance opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca 2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory post-synaptic currents (sEPSCs), intracellular Ca 2+ concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca 2+ concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca 2+ concentrations against I/R injury., (© 2024. The Author(s).)

In Gram-positive bacteria, sophisticated machineries to acquire the heme group of hemoglobin (Hb) have evolved to extract the precious iron atom contained in it. In the human pathogen Streptococcus pyogenes, the Shr protein is a key component of this machinery. Herein we present the crystal structure of hemoglobin-interacting domain 2 (HID2) of Shr bound to Hb. HID2 interacts with both, the protein and heme portions of Hb, explaining the specificity of HID2 for the heme-bound form of Hb, but not its heme-depleted form. Further mutational analysis shows little tolerance of HID2 to interfacial mutations, suggesting that its interaction surface with Hb could be a suitable candidate to develop efficient inhibitors abrogating the binding of Shr to Hb., (© 2024. The Author(s).)

Objective: This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator., Methods: Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years., Results: The tumors originated from the lungs (n = 90; 89.1%), colon (n = 2; 2.0%), and others (n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median follow-up time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status., Conclusions: The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Accurately evaluating plaque characteristics is essential because lesions with lipid-rich plaque put patients at risk of thromboembolic complications from carotid artery stenting. Near-infrared spectroscopy (NIRS) is a diagnostic imaging modality that identifies lipid components from the near-infrared absorption pattern but does not reveal the distribution of calcification. The purpose of this study was to investigate the calcification characteristics of unstable carotid plaques, focusing on relationships between the calcification characteristics revealed by computed tomography angiography and the lipid core distribution derived from NIRS., Methods: Participants in this retrospective analysis comprised 35 patients (29 men, 6 women; mean age, 76.0 years; range, 52-89 years) who underwent carotid artery stenting in our institute between January 2021 and December 2022. We evaluated the thickness and length of carotid calcifications at the minimal lumen level from preoperative computed tomography angiography and analyzed the relationship with maximum lipid core burden index (max-LCBI) from NIRS., Results: Strong negative linear correlations were observed between the thickness of calcification and max-LCBI at Area (any segment in a target lesion) (r = -0.795, P < 0.001), max-LCBI at minimal lumen area (r = -0.795, P < 0.001) and lipid core burden index (LCBI) at lesion (rate of LCBI in entire plaque lesion) (r = -0.788, P < 0.001), respectively. Significant negative linear correlations were observed between distribution of calcification length and max-LCBI at area (r = -0.429, P = 0.01), max-LCBI at minimal lumen area (r = -0.373, P = 0.027), and LCBI at lesion (r = -0.443, P = 0.008)., Conclusions: Thin and ubiquitous carotid calcification was associated with LCBI values derived from NIRS indicative of carotid lipid plaque distribution, implying the possibility of predicting lesion instability., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE., Methods and results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer., Conclusions: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Introduction: Innate immune cells are important in tumor immunotherapy. Natural killer cells (NKCs) are also categorized as innate immune cells and can control tumor growth and metastatic spread. Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. NKC-based immunotherapy is a promising treatment strategy against GBM. We previously reported a feeder-free expansion system that yielded large-scale highly purified and cytotoxic NKCs derived from human cord blood (CB). In the present study, we performed comprehensive genomic analyses of NKCs generated from human CB (CBNKCs) as compared those from human peripheral blood (PB) (PBNKCs)., Methods: Frozen T cell-free CB mononuclear cells were cultured with recombinant human interleukin (rhIL)-18 and rhIL-2 in anti-NKp46 and anti-CD16 antibody immobilization settings. After 14-day expansion, the total RNA of the CBNKCs or PBNKCs was extracted and transcriptomic analyses was performed to determine their similarities and differences. We also examined CBNKC and PBNKC activity against a GBM cell line., Results: Differential expression gene analysis revealed that some NK activating and inhibitory receptors were significantly downregulated in the CBNKCs compared to PBNKCs. Furthermore, genes related to anti-apoptosis and proliferation were upregulated in the CBNKCs. Enrichment analysis determined that the gene sets related to immune response and cytokines were enriched in the CBNKCs. Gene set enrichment analysis demonstrated that the immune response pathway was upregulated in the CBNKCs. Cytotoxic assays using impedance-based cell analyzer revealed that the CBNKCs enhanced NKC-mediated cytotoxicity on GBM cells as compared to the PBNKCs., Conclusions: We demonstrated the characteristics of human CBNKCs. Cell-based therapy using the CBNKCs is promising for treating GBM., Competing Interests: TM is registered with Nara Medical University as a postdoctoral fellow member paying registration fees., (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors' ligands, inhibitory receptors' ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM.

Although patients with symptomatic Rathke's cleft cysts (RCCs) receive surgical treatment, recurrence sometimes occurs after surgery. However, the mechanism underlying recurrence remains unclear. We evaluated the outcomes of RCC decompression over a long-term follow-up period. We retrospectively reviewed the medical records of 35 patients with symptomatic RCC who underwent endonasal endoscopic surgery (EES) at our institution between 2008 and 2023. Patients' characteristics, intraoperative findings, and postoperative follow-up outcomes were evaluated. A univariate regression model was used to identify the predictors of recurrence. The median patient age was 48.0 years, and 74.2% of the patients were female. The mean follow-up duration was 94.7 ± 47.6 months. Cyst content recurrence was observed in 15 patients (42.8%). Five patients (14.2%) with symptomatic recurrence underwent reoperation. Postoperative vision improved in all 23 patients (100%); headaches improved in 20 patients (90.9%). A new hormonal deficit occurred in two patients (5.7%). Complications included intraoperative cerebrospinal fluid (CSF) leak in 10 patients (28.5%), postoperative CSF leak in two patients (5.7%), permanent diabetes insipidus in two patients (5.7%), and postoperative infection in three patients (8.5%). Univariate analyses revealed that the position of the anterior pituitary lobe (p = 0.019) and preoperative visual disturbances (p = 0.008) significantly affected recurrence after surgery. Although EES was efficient, the recurrence rate was relatively high over a long-term period. The anterior pituitary lobe position and preoperative visual disturbances were significantly associated with recurrence. The anterior-inferior position can predict a high risk of recurrence before surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Streptococcus suis is a gram-positive bacterium that causes meningitis, septicemia, endocarditis, and other disorders in pigs and humans. We obtained 42 and 50 S. suis isolates from lesions of porcine endocarditis and palatine tonsils, respectively, of clinically healthy pigs in Japan; we then determined their sequence types (STs) by multilocus sequence typing (MLST), cps genotypes, serotypes, and presence of classical major virulence-associated marker genes (mrp, epf, and sly). The 42 isolates from endocarditis lesions were assigned to a limited number of STs and clonal complexes (CCs). On the other hand, the 50 isolates from tonsils were diverse in these traits and seemingly in the degree of virulence, suggesting that tonsils can accommodate a variety of S. suis isolates. The goeBURST full algorithm using tonsil isolates obtained in this study and those retrieved from the database showed that major CCs as well as many other clusters were composed of isolates originating from different countries, and some of the STs were very similar to each other despite the difference in country of origin. These findings indicate that S. suis with not only different but also similar mutations in the genome have survived in tonsils independently across different geographical locations. Therefore, unlike the lesions of endocarditis, the tonsils of pigs seemingly accommodate various S. suis lineages. The present study suggests that S. suis acquired its diversity by natural mutations during colonization and persistence in the tonsils of pigs., (© 2024. The Author(s).)

Background: Careful examination of motor-evoked potential (MEP) findings is critical to the safety of intraoperative neuromonitoring during neurosurgery. We reviewed the intraoperative MEP findings in a pediatric patient who had undergone hemispherotomy for refractory epilepsy., Case Description: The patient was a 4-year-and-2-month-old boy with extensive right cerebral hemisphere, drug-resistant epilepsy, left upper and lower extremity paralysis, and cognitive impairment. We examined intraoperative MEP results both before and after hemispherotomy. Post-hemispherotomy and MEPs were successfully elicited through transcranial electrical stimulation (TES) but not via direct cortical stimulation on the right side. Furthermore, TES on the right side, following hemispherotomy, led to a reduction in the MEP amplification effect resulting from tetanic stimulation of the left unilateral median and tibial nerves. Conversely, we observed the effects of MEP amplification during TES on the left side after tetanic stimulation of these nerves. Postoperatively, the patient underwent magnetic resonance imaging and electroencephalogram examinations, confirming the anatomical and electrophysiological completeness of the dissection. Notably, the seizures disappeared, and no apparent complications were observed., Conclusion: Collectively, our findings suggest that TES can still activate deep structures and elicit MEPs, even in cases where the corticospinal connections to the posterior limb of the internal capsule are entirely severed. Thalamo-cortical interactions may affect the MEP amplification, observed during tetanic stimulation. Injury to the corticospinal tracts of the white matter may be obscured on conventional MEP findings; however, it may be identified by MEP changes in tetanic stimulation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Intracranial chondroma is an extremely rare type of tumor composed of mature hyaline cartilaginous tissues. No previous cases of skull base periosteal chondroma have been presented., Observations: A 31-year-old male had progressive memory loss and diminished motivation for the previous 1.5 years. Magnetic resonance imaging revealed a giant tumor with partial calcification arising from the upper clivus and extending to the prepontine cistern. Compression of the brainstem and hypothalamus was significant. Surgery was performed and intentionally limited to an intracapsular resection with endoscopic endonasal surgery (EES), and the brainstem and hypothalamus were successfully decompressed. Pathological examination findings showed a composition of hyaline cartilage with chondrocyte clusters. Genetic testing with next-generation sequencing indicated alternations in IDH1 R132C, KDR Q472H, IDH2 I142L, and TP53 P72R. On the basis of these findings, a diagnosis of periosteal chondroma was made. Postoperatively, complete relief from all symptoms was noted, and MRI one year later showed no evidence of tumor regrowth., Lessons: This is the first known report of skull base periosteal chondroma. Genetic testing was useful for confirming the diagnosis, and EES was effective for treatment. Should such a tumor show adhesion to an important structure, an intracapsular excision can be beneficial for avoiding complications.

Background: Periprocedural lipid core plaque (LCP) has been detected in carotid arteries assessed by catheter-based near-infrared spectroscopy (NIRS). High LCP is associated with cerebral embolism after carotid artery stenting (CAS) using a first-generation stent. We aimed to evaluate whether dual-layered stents reduce embolic infarcts in patients with high LCP and change of lipid signal as assessed by NIRS during CAS., Methods: Participants comprised 210 consecutive patients undergoing CAS. The study was divided into two distinct periods, with first-generation closed-cell stents used in the earlier period and dual-layered stents used in the later period. NIRS was performed at baseline, after stent implantation, and after balloon post-dilatation to analyze maximal lipid core burden index at minimal luminal area (max-LCBI MLA )., Results: The ipsilateral cerebral embolism rate was significantly lower with dual-layered stents (9%) than with first-generation stents (33%, p<0.001), particularly with highly lipidic lesions (12% vs 60%, p<0.001). On multivariate logistic regression analysis, high LCP and first-generation stent usage were factors related to ipsilateral cerebral embolism (both p<0.001; OR 8.28 (95% CI 3.49 to 19.64) and OR 8.07 (95% CI 2.33 to 27.93), respectively). Max-LCBI MLA decreased significantly after stenting in both groups (both p<0.01) and max-LCBI MLA after balloon post-dilatation was significantly lower with dual-layered stents (22.4±65.6) than with first-generation stents (124.2±208.2; p=0.006)., Conclusions: Dual-layered stents reduce embolic infarcts in patients with highly lipidic plaque lesions as assessed by NIRS who undergo CAS. Dual-layered stents significantly reduced NIRS-derived lipid signals after stenting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A 45-year-old man suffered multiple cerebral infarctions in the vertebrobasilar artery territory, followed by second stroke against conservative treatment. Radiological examinations revealed intra-arterial defect in left persistent 1st intersegmental artery (PFIA) at C1 level, suggesting mural thrombus, and mechanical compression of left PFIA at the level with head rotation to the right clearly revealed by reconstructed 3-dimensional radiological images, but no findings of atlantoaxial instability. One month after the second stroke, posterior fixation was performed. Postoperative course was uneventful without subsequent stroke for 24 months. This unique case demonstrated that PFIA might associate with cerebral stroke as a clinical condition of bow hunter's stroke even in middle age. Reconstructed 3-dimensional radiological images might be useful for clear demonstration of the pathophysiology in this complex clinical entity.

Summary: Temporal pole encephalocele (TE) is an increasingly recognized surgically treatable subtype of refractory temporal lobe epilepsy that rarely shows hippocampal involvement. A 27-year-old patient presented with medically intractable epilepsy because of a left temporal pole encephalocele with a normal hippocampus on MRI. Extraoperative electrocorticography showed independent seizure onset with distinct morphology of seizure onset pattern from the temporal pole encephalocele and hippocampus. Additional analysis of ictal and interictal fast ripples revealed different electrophysiological fast ripple profiles in the two seizure onset zones. The patient underwent temporopolar disconnection, eliminating the need for large dural repair and multiple hippocampal transections that helped preserve the intrahippocampal and extrahippocampal memory pathways. Herein, the authors report that independent hippocampal seizures can be observed in patients with temporal pole encephalocele. Features of the ictal and interictal fast ripples can differ depending on the morphology of the seizure onset pattern. The authors suggest that, the interpretation of fast ripples in clinical practice should take seizure onset patterns into consideration., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Cation diffusion facilitators (CDFs) are a large family of divalent metal transporters with broad specificities that contribute to intracellular metal homeostasis and toxicity in bacterial pathogens. Streptococcus pyogenes (Group A Streptococcus [GAS]) expresses two homologous CDF efflux transporters, MntE and CzcD, which selectively transport Mn and Zn, respectively. We discovered that the MntE- and CzcD-deficient strains exhibited a marked decrease in the viability of macrophage-differentiated THP-1 cells and neutrophils. In addition, the viability of mice infected with both deficient strains markedly increased. Consistent with a previous study, our results suggest that MntE regulates the PerR-dependent oxidative stress response by maintaining intracellular Mn levels and contributing to the growth of GAS. The maturation and proteolytic activity of streptococcal cysteine protease (SpeB), an important virulence factor in GAS, has been reported to be abrogated by zinc and copper. Zn inhibited the maturation and proteolytic activity of SpeB in the culture supernatant of the CzcD-deficient strain. Furthermore, Mn inhibited SpeB maturation and proteolytic activity in a MntE-deficient strain. Since the host pathogenicity of the SpeB-deficient strain was significantly reduced, maintenance of intracellular manganese and zinc levels in the GAS via MntE and CzcD may not only confer metal resistance to the bacterium, but may also play an essential role in its virulence. These findings provide new insights into the molecular mechanisms of pathogenicity, which allow pathogens to survive under stressful conditions associated with elevated metal ion concentrations during host infection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)