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DNA polymeraseß(Polß) has been implicated in base excision repair. Polßknockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth. Also, mice deficient in nonhomologous end-joining (NHEJ), a major pathway for DNA double-strand break repair, cause massive neuronal apoptosis. Severe combined immunodeficiency (SCID) mice have a mutation in the gene encoding DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the component of NHEJ, and exhibit defective lymphogenesis. To study the interaction between Polßand DNA-PKcs, we generated mice doubly deficient in Polßand DNA-PKcs. Polß-/-DNA-PKcsscid/scid embryos displayed greater developmental delay, more extensive neuronal apoptosis, and earlier lethality than Polß-/- and DNA-PKcsscid/scid embryos. Furthermore, to study the involvement of p53 in the phenotype, we generated Polß-/-DNA-PKcsscid/scidp53-/- triple-mutant mice. The mutants did not exhibit apoptosis but were lethal with defective neurulation at midgestation. These results suggest a genetic interaction between Polßand DNA-PKcs in embryogenesis and neurogenesis.Cell Death and Differentiation (2005) 12, 184-191. doi:10.1038/sj.cdd.4401543 [ABSTRACT FROM AUTHOR]

Mechanical thrombectomy (MT) is an established treatment for large vessel occlusion in the acute phase of stroke. However, its efficacy and safety in patients with cancer remain unclear. This study aimed to evaluate the therapeutic effect of MT against large vessel occlusion between patients with and without cancer. A total of 71 patients who underwent MT from August 2014 to November 2021 were included in this study. Patients with cancer and/or a history of cancer (n = 16) were included in the with cancer group and the remaining patients in the without cancer group (n = 55). The frequency of preoperative tissue plasminogen activator administration was significantly lower in the with cancer group (n = 2 [12.5%]) than in the without cancer group (n = 24 [43.6%]). However, there were no significant differences between the two groups in terms of treatment time, pass frequency, thrombolysis in cerebral infarction grade, modified Rankin scale score at 1 week after treatment [mRS (1w) ], modified Rankin scale score at discharge [mRS (ENT) ], modified Rankin scale score at 90 days after treatment [mRS (90 days) ], and length of hospital stay (days). In the multivariate analysis, if the objective variables were mRS (1w) and mRS (90 days), the National Institutes of Health Stroke Scale (NIHSS) and preonset mRS scores were considered significant variables. The presence or absence of cancer was not considered an independent factor of mRS (1w), mRS (ENT), or mRS (90 days). Aggressive treatment may be recommended to patients with cancer and/or a history of cancer who present with a systemic condition that can be managed with MT.

Single-molecule imaging (SMI) is a powerful approach to quantify the spatiotemporal dynamics of transcription in living cells. Here, we describe a protocol of SMI for transcription and epigenetic factors in human cortical neurons derived from embryonic stem cells or induced pluripotent stem cells. Specifically, we detail the procedures for neural stem cell culture, gene transfer, microscopy, and data analysis. This protocol can be applied to the study of transcription dynamics in response to various cellular stimuli. For complete details on the use and execution of this protocol, please refer to Atsumi et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether diffusion tensor image (DTI) parameters and regional cerebral blood flow (rCBF) serve to preoperatively predict postoperative motor outcomes in patients with brain tumors., Methods: We included 81 patients with brain tumors who underwent surgical treatment. Motor function was assessed using the manual muscle test in the upper and lower limbs at admission and discharge. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and their ratios (rFA, rMD, rAD, and rRD) were measured at the corona radiata, internal capsule, and cerebral peduncle of the corticospinal tract (CST). In addition, DTI and single photon emission computed tomography (SPECT) were synthesized to measure rCBF at the CST., Result: Both DTI parameters and rCBF at the CST in the preoperative motor weakness group significantly differed from those of the preoperative normal function group. rFA at the cerebral peduncle and the internal capsule was considerably higher in those showing postoperative motor recovery than in those postoperative unchanged or with deteriorated motor function (P < 0.05). Moreover, there was significantly lower rMD and rRD at the internal capsule in the motor recovery group (P < 0.05, P < 0.01). Furthermore, rCBF was higher at all the cerebral peduncle, internal capsule, and corona radiate in the motor recovery group than in the unchanged and deteriorated motor function group (P < 0.05, P < 0.01, P < 0.01)., Conclusion: The analysis of DTI parameters and rCBF is useful in predicting postoperative motor outcomes in patients with brain tumors., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Toho University Omori Hospital issued approval No. M22111. 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: 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, Matsuura et al.)

Objective: To determine the usefulness of cerebrospinal fluid (CSF) presepsin in the diagnosis of neurosurgical postoperative meningitis (POM)., Methods: The study included patients admitted to the Department of Neurosurgery, Toho University Medical Center Omori Hospital from May 1, 2020 to March 31, 2022 with suspected meningitis after neurosurgery who clinically required CSF sampling and patients who underwent CSF sampling for examination of idiopathic normal pressure hydrocephalus (iNPH). Participants were divided into a POM and a postoperative non meningitis (PONM) group based on the POM diagnostic criteria established for this study. The control group included patients from whom a CSF sample for iNPH was collected by tap test., Results: A total of 238 CSF samples were collected from 90 patients. There were 39 samples in the POM, 180 samples in the PONM, and 19 samples in the control group. CSF presepsin levels in the POM were significantly higher than in the PONM group (1764.5 and 440.9 pg./mL, respectively; p  < 0.0001). The control group had CSF presepsin levels of 95.5 pg./mL. A cutoff value of 669 pg./mL for CSF presepsin in POM and PONM groups had 76.9% sensitivity and 78.3% specificity for the diagnosis of POM. In analyzes including only subarachnoid hemorrhage (SAH) cases (123 samples), CSF presepsin (1251.2 pg./mL) in the POM was significantly higher than in the PONM subgroup (453.9 pg./mL; p  < 0.0001). The cutoff value for presepsin in CSF among patients with SAH (669 pg./mL) had 87.5% sensitivity and 76.6% specificity, similar to that of all patients., Conclusion: CSF presepsin is a useful marker in the diagnosis of neurosurgical POM even in patients with blood components, such as SAH. When POM is suspected, measurement of CSF presepsin may be recommended in addition to a general CSF examination., 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 © 2024 Fuchinoue, Kondo, Sakaeyama, Nakada, Terazono, Kubota, Mikai, Abe, Ujiie, Morita and Sugo.)

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature., Competing Interests: HH, HS, SH, GS, YT, MT, MI, MS, IH, KH, MH, AN, YM, SO, MM, AU, YK, AM, KN, SK, TS, TI, HN, YG, MR, TT, KY, NT, HK, JI, IN, TK, TT, MD, HN, KT, KS, KN, TT, HF, YS, KY, LR, NH, HM, TY, SW, TA, KT, TN, HK, FH, AH, HH, KT, TT, TK, TK, IG, GC, NA, HH, SK, TK, MH, YH, RM, KO, AH, LB, IY, YH, HK, YM, KI, HK, BK, HO, YY, AT, NK, SG, MI, MN, KM, EO, IO, TS, KY, HA, KT, KI, TS, AK, MF, NU, TK, TT, YY, MI, TH, KI, KN, SH, KE, KH, YT, SN, NS, TY, NU, TY, YK, RO, NS, KS, SH, KO, HM, TF, MT, HS, DS, YI, TI, YK, TY, KS, TM No competing interests declared, SY, NN Employee of Takeda Pharmaceutical Company, Ltd

3D printers have been applied in bone-based surgeries, including craniofacial, plastic, oral, and orthopedic surgeries. The improved capabilities of diagnostic imaging equipment and 3D printers have enabled the development of more precise models, and research on surgical simulations and training in the field of neurosurgery is increasing. This review outlines the use of 3D printers in neurosurgery at our institution in terms of modeling methods and surgical simulations. Modeling with the powder-sticking lamination method using plaster as the material allows drilling, which is a surgical procedure. Therefore, it is useful for simulating skull base tumors, such as petrosectomy in a combined transpetrosal approach or anterior clinoidectomy in an orbitozygomatic approach. The color coding of each part of the model facilitates anatomical understanding, and meshed tumor modeling allows deep translucency. As shown above, the 3D printer's modeling ingenuity allows for useful surgical simulations for each case.

Background: There have been many reports of tumor-to-tumor metastasis, in which cancer metastasizes directly into meningiomas. However, metastasis infiltrating tumors in which cancer metastasizes around meningiomas are rare. Therefore, we report a case of metastasis originating from lung cancer that infiltrated meningioma., Case Presentation: A 79-year-old Japanese woman underwent head magnetic resonance imaging for brain metastasis screening before lung cancer surgery. At that time, asymptomatic meningioma of the left frontal region was accidentally found. Magnetic resonance imaging 6 months later revealed a lesion suspected to be a metastatic brain tumor close to the meningioma. Brain tumor resection was performed, and histopathological diagnosis was meningioma and metastatic brain tumor. Metastatic cancer had invaded the meningioma at the boundary between the brain tumor and metastasis., Conclusions: A sudden change in imaging findings on routine examination of meningiomas in patients with lung carcinoma may indicate a metastatic brain tumor. The form of cancer metastasis to meningioma is not limited to tumor-to-tumor metastasis, but also includes metastasis infiltrating tumors near the meningioma., (© 2024. The Author(s).)

Purpose: Plaque stiffness in carotid artery stenosis is a clinically important factor involved in the development of stroke and surgical complications. The purpose of this study was to clarify which local and systemic factors are associated with the quantitatively measured stiffness of plaque., Methods: The subjects were 104 consecutive patients who underwent carotid endarterectomy at our institution. To measure quantitative stiffness of plaque, we used an industrial hard meter in the operating room within 1 h after removal of plaque. Local factors related to carotid plaque hardness were evaluated, including maximum intima-media thickness (max IMT), degree of stenosis using the European Carotid Surgery Trial (ECST), presence of ulceration or calcification, and echo brightness on preoperative carotid ultrasound. The degree of stenosis was also evaluated using the North American Symptomatic Carotid Endarterectomy Trial method in digital subtraction angiography. Age, sex, and presence or absence of hypertension, diabetes, and dyslipidemia (low-density lipoprotein cholesterol and triglyceride [TG] levels) served as systemic factors and were compared with the quantitative stiffness of carotid plaque., Results: In multivariate analysis, ECST stenosis degree, calcification, and IMT max as local factors affected plaque stiffness. As a systemic factor, plaque stiffness was statistically significantly negatively correlated with TG values in multivariate analysis (p < 0.05)., Conclusion: The quantitative stiffness of the plaque was negatively correlated with TG levels as a systemic factor in addition to local factors. This might suggest that reducing high TG levels is associated with plaque stabilization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Neuronal activity-dependent transcription plays a key role in plasticity and pathology in the brain. An intriguing question is how neuronal activity controls gene expression via interactions of transcription factors with DNA and chromatin modifiers in the nucleus. By utilizing single-molecule imaging in human embryonic stem cell (ESC)-derived cortical neurons, we demonstrate that neuronal activity increases repetitive emergence of cAMP response element-binding protein (CREB) at histone acetylation sites in the nucleus, where RNA polymerase II (RNAPII) accumulation and FOS expression occur rapidly. Neuronal activity also enhances co-localization of CREB and CREB-binding protein (CBP). Increased binding of a constitutively active CREB to CBP efficiently induces CREB repetitive emergence. On the other hand, the formation of histone acetylation sites is dependent on CBP histone modification via acetyltransferase (HAT) activity but is not affected by neuronal activity. Taken together, our results suggest that neuronal activity promotes repetitive CREB-CRE and CREB-CBP interactions at predetermined histone acetylation sites, leading to rapid gene expression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aims to determine the cutoff values for the compound muscle action potential (CMAP) stimulus in anatomically identified anterior (motor nerve) and posterior roots (sensory nerve) during cervical intradural extramedullary tumor surgery. The connection between CMAP data from nerve roots and postoperative neurological symptoms in thoracolumbar tumors was compared with data from cervical lesions. The participants of the study included 22 patients with intradural extramedullary spinal tumors (116 nerve roots). The lowest stimulation intensity to the nerve root at which muscle contraction occurs was defined as the minimal activation intensity (MAI) in the CMAP. In cervical tumors, the MAI was measured after differentiating between the anterior and posterior roots based on the anatomical placement of the dentate ligament and nerve roots. The MAIs for 20 anterior roots in eight cervical tumors were between 0.1 and 0.3 mA, whereas those for 19 posterior roots were between 0.4 and 2.0 mA. The cutoff was <0.4 mA for both the anterior and posterior roots, and sensitivity and specificity were both 100%. In thoracolumbar tumors, the nerve root was severed in 12 of 14 cases. All MAIs were determined to be at the dorsal roots as their scores were higher than the cutoff and did not indicate motor deficits. The MAIs of the anatomically identified anterior and posterior root CMAPs were found to have a cutoff value of <0.4 mA in the cervical lesions. Similar MAI cutoffs were also applicable to thoracolumbar lesions. Thus, CMAP may be useful in detecting anterior and posterior roots in spinal tumor surgery.

This study aims to evaluate the academic activities of female neurosurgeons at all branch meetings of the Japan Neurosurgical Society and identify related issues they encountered. The programs of all seven branch meetings of the Japan Neurosurgical Society (Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku/Shikoku, and Kyushu) were used to determine the number of presentations and chairpersons by sex. The covered period was from January 2008 to December 2020, which was available for viewing during the survey. Of note, only the Kinki branch used data from January 2008 to December 2019. The Neurologia Medico-chirurgica (NMC), the journal of the Japan Neurosurgical Society, was also reviewed to identify publication achievements during the same period. In all seven branches, the percentage of presentations given by female physicians increased from 7.9% in 2008 to 9.6% in 2020 (p < 0.05).Conversely, the percentage of female chairpersons in all branch meetings did not change over time and it was significantly lower (1.1%) than that of female presenters (7.9%) for all branch meetings combined in over 13 years (p < 0.01). In the NMC, the number of articles with female physicians as first authors did not increase or decrease over the years. We conclude that efforts to smoothly promote female neurosurgeons as chairpersons and increase the number of female first authors are necessary to facilitate their academic activities.

Background: The consistency of intracranial meningiomas is an important clinical factor because it affects the success of surgical resection. This study aimed at identifying and quantitatively measuring pathological factors that contribute to the consistency of meningiomas. Furthermore, we investigated the relationship between these factors and preoperative neuroradiological imaging., Methods: We analyzed 42 intracranial meningioma specimens, which had been removed at our institution between October 2012 and March 2018. Consistency was measured quantitatively after resection using an industrial stiffness meter. For pathological evaluation, we quantitatively measured the collagen-fiber content through binarization of images of Azan-Mallory-stained section. We assessed calcification and necrosis semi-quantitatively using images acquired of Hematoxylin and Eosin stained samples. The relationship between collagen-fiber content rate and imaging findings was examined., Results: The content of collagen fibers significantly positively correlated with meningioma consistency (p < 0.0001). Collagen-fiber content was significantly higher in low- and iso-intensity regions compared with high-intensity regions on the magnetic resonance T2-weighted images (p = 0.0148 and p = 0.0394, respectively). Calcification and necrosis showed no correlation with tumor consistency., Conclusions: The quantitative hardness of intracranial meningiomas positively correlated with collagen-fiber content; thus, the amount of collagen fibers may be a factor that determines the hardness of intracranial meningiomas. Our results demonstrate that T2-weighted images reflect the collagen-fiber content and are useful for estimating tumor consistency preoperatively and non-invasively., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Plaque hardness in carotid artery stenosis correlates with cerebral infarction. This study aimed to quantitatively compare plaque hardness with histopathological findings and identify the pathological factors involved in plaque hardness., Methods: This study included 84 patients (89 lesions) undergoing carotid endarterectomy (CEA) at our institution. Plaque hardness was quantitatively measured immediately after excision using a hardness meter. Collagen and calcification were evaluated as the pathological factors. Collagen was stained with Elastica van Gieson stain, converted to a gray-scale image, and displayed in a 256-step histogram. The median gray-scale median (GSM) was used as the collagen content. The degree of calcification was defined by the hematoxylin-eosin stain as follows: "0:" no calcification, "1:" scattered microcalcification, or "2:" calcification greater than 1 mm or more than 2% of the total calcification. Carotid echocardiographic findings, specifically echoluminance or the brightness of the narrowest lesion of the plaque, classified as hypo-, iso-, or hyper-echoic by comparison with the intima-media complex surrounding the plaque, and clinical data were reviewed., Results: Plaque hardness was significantly negatively correlated with GSM [Spearman's correlation coefficient: -0.7137 (p < 0.0001)]: the harder the plaque, the higher the collagen content. There were significant differences between plaque hardness and degree of calcification between "0" and "2" (p = 0.0206). For plaque hardness and echoluminance (hypo-iso-hyper), significant differences were found between hypo-iso (p = 0.0220), hypo-hyper (p = 0.0006), and iso-hyper (p = 0.0015): the harder the plaque, the higher the luminance. In single regression analysis, GSM, sex, and diabetes mellitus were significant variables, and in multiple regression analysis, only GSM was extracted as a significant variable., Conclusions: Plaque hardness was associated with a higher amount of collagen, which is the main component of the fibrous cap. Greater plaque hardness was associated with increased plaque stability. The degree of calcification may also be associated with plaque hardness., (© 2022. The Author(s).)

Background: N-isopropyl- ( 123 I) p-iodoamphetamine ( 123 I-IMP) is specifically accumulated in primary central nervous system lymphoma (PCNSL) during single-photon emission tomography (SPECT) and contributes to its diagnostic imaging. However, whether 123 I-IMP is accumulated in ocular adnexal lymphoma (OAL), one of the malignant intraorbital tumors, remains unclear. This study aimed to evaluate the diagnostic value of 123 I-IMP SPECT in OAL., Methods: Between August 2005 and June 2020, 26 patients with intraorbital tumors underwent neurosurgery at the tertiary care center. Of these, 15 patients who underwent 123 I-IMPSPECT before surgery were retrospectively examined. The region of interest was set in the cerebellum ipsilateral to the intraorbital tumor on 123 I-IMP SPECT, and the tumor-to-cerebellum ratio (T/C ratio) was calculated using the following formula: T/C ratio = [accumulation of tumor (count/pixel)]/[accumulation of ipsilateral normal cerebellar hemisphere (count/pixel)]., Results: Six patients were included in the OAL group, who were pathologically diagnosed with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), diffuse large B-cell lymphoma (DLBCL), and plasmacytoma. The T/C ratio in the OAL group was statistically higher than that in the non-OAL group (p < 0.01). The optimal cutoff values for both groups were between 0.76 and < 0.93. The sensitivity and specificity were 1.00, respectively., Conclusions: 123 I-IMP SPECT is useful as one of the examinations in the differential diagnoses of OAL, because it showed a significantly higher accumulation in OAL group than in non-OAL group., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Aim: Stroke is well known to lead to hypertension; nevertheless, the role of vascular function in hypertension remains unclear. In this study, we aimed to clarify the mechanism underlying increased arterial stiffness following stroke., Methods: The cardio-ankle vascular index (CAVI) was measured in five New Zealand White rabbits. Under general anesthesia, intracranial pressure (ICP) was increased by injecting saline (15 mL) into the cisterna magna. ICP was monitored using a catheter inserted into the subarachnoid space via right frontal bone craniotomy. Blood pressure (BP), CAVI, and common carotid flow (CCF) were evaluated, and the responses of these parameters to increased ICP were analyzed., Results: Saline injection into the cisterna magna increased the ICP by over 20 mmHg. Both BP and CAVI increased from 63.2±4.84 to 128.8±14.68 mmHg and from 4.02±0.28 to 4.9±0.53, respectively. Similarly, BP and CCF increased. When hexamethonium was administered before the increase in ICP, the increase in BP (132.2±9.41 mmHg with 10 mg/kg hexamethonium vs. 105.6±11.01 mmHg with 100 mg/kg hexamethonium) and CAVI (5.02±0.64 with 10 mg/kg hexamethonium vs. 4.82±0.42 with 100 mg/kg hexamethonium) were suppressed in a dose-dependent manner., Conclusion: Increased ICP causes an increase in BP and CAVI, suggesting that enhanced stiffness of the muscular arteries contributes to high BP. Blocking the autonomic nervous system with hexamethonium suppresses the increase in BP and CAVI, indicating that these increases are mediated by activation of the autonomic nervous system.

The current study aimed to evaluate the relationship between preoperative neuroradiological findings and intraoperative bulbocavernosus reflex (BCR) amplitude in patients with intradural extramedullary tumors. A total of 24 patients with lesions below the 12th thoracic vertebra were included in the analysis. Objective and subjective urinary symptoms were investigated using data obtained from medical records and the core lower urethral symptom score (CLSS) questionnaire. The lesion compression rate was evaluated with MRI. In the epiconus-to-conus medullaris (Epi-CM) group, BCR amplitude changes were found to be correlated with the compression rate (p <0.05). The preoperative CLSS of the group with a BCR amplitude of <50% was worse than that of the group with ≥50% (p <0.01). The group did not experience symptom improvement 6 months postoperatively based on the CLSS. The preoperative CLSS of the group with compression rate of ≥80% on imaging was worse than that of the group with <80% (p <0.05). In the group with preoperative compression rate of ≥80%, CLSS at 1 month and 6 months postoperatively was improved as compared to preoperative CLSS (p <0.01, p <0.05). Hence, BCR amplitude changes are associated with the degree of lesion compression on preoperative images and pre- and postoperative urinary symptoms. Patients with intradural extramedullary Epi-CM lesions with strong compression are likely to present with low BCR amplitude and worsened postoperative symptoms. It is considered that the risk of postoperative urinary symptoms increases even with careful surgical manipulation under these conditions.

Background: Atopic dermatitis is a chronic inflammatory skin disease associated with pruritus. Skin affected by atopic dermatitis not only shows a high percentage of Staphylococcus aureus colonization, but corneal barrier dysfunction is also known to occur. It is considered a risk factor for bacterial infections in various areas of the body. However, the relationship between atopic dermatitis and bacterial infection following neurological surgery has not yet been reported. Here, we present a case of atopic dermatitis in which the surgical site became infected twice and finally resolved only after the atopic dermatitis was treated., Case Presentation: A 50-year-old Japanese woman with atopic dermatitis underwent cerebral aneurysm clipping to prevent impending rupture. Postoperatively, she developed repeated epidural empyema following titanium cranioplasty. As a result of atopic dermatitis treatment with oral antiallergy medicines and external heparinoids, postoperative infection was suppressed by using an absorbable plastic plate for cranioplasty. The patient's postoperative course was uneventful for 16 months., Conclusions: Atopic dermatitis is likely to cause surgical-site infection in neurosurgical procedures, and the use of a metal implant could promote the development of surgical-site infection in patients with dermatitis., (© 2021. The Author(s).)

Genome stability is essential for brain development and function, as de novo mutations during neuronal development cause psychiatric disorders. However, the contribution of DNA repair to genome stability in neurons remains elusive. Here, we demonstrate that the base excision repair protein DNA polymerase β (Polβ) is involved in hippocampal pyramidal neuron differentiation via a TET-mediated active DNA demethylation during early postnatal stages using Nex-Cre/Pol β fl/fl mice of either sex, in which forebrain postmitotic excitatory neurons lack Polβ expression. Polβ deficiency induced extensive DNA double-strand breaks (DSBs) in hippocampal pyramidal neurons, but not dentate gyrus granule cells, and to a lesser extent in neocortical neurons, during a period in which decreased levels of 5-methylcytosine and 5-hydroxymethylcytosine were observed in genomic DNA. Inhibition of the hydroxylation of 5-methylcytosine by expression of microRNAs miR-29a/b-1 diminished DSB formation. Conversely, its induction by TET1 catalytic domain overexpression increased DSBs in neocortical neurons. Furthermore, the damaged hippocampal neurons exhibited aberrant neuronal gene expression profiles and dendrite formation, but not apoptosis. Comprehensive behavioral analyses revealed impaired spatial reference memory and contextual fear memory in adulthood. Thus, Polβ maintains genome stability in the active DNA demethylation that occurs during early postnatal neuronal development, thereby contributing to differentiation and subsequent learning and memory. SIGNIFICANCE STATEMENT Increasing evidence suggests that de novo mutations during neuronal development cause psychiatric disorders. However, strikingly little is known about how DNA repair is involved in neuronal differentiation. We found that Polβ, a component of base excision repair, is required for differentiation of hippocampal pyramidal neurons in mice. Polβ deficiency transiently led to increased DNA double-strand breaks, but not apoptosis, in early postnatal hippocampal pyramidal neurons. This aberrant double-strand break formation was attributed to active DNA demethylation as an epigenetic regulation. Furthermore, the damaged neurons exhibited aberrant gene expression profiles and dendrite formation, resulting in impaired learning and memory in adulthood. Thus, these findings provide new insight into the contribution of DNA repair to the neuronal genome in early brain development., (Copyright © 2020 the authors.)

Intracranial teratoma is a rare disease that frequently occurs in children and young adults. It comprises of approximately 0.1% of the brain tumors. We report a case of a large mature teratoma in the third ventricle with Holmes tremor. A 5-year-old boy presented with tremors 2 years ago. CT showed a 56×48 mm tumor in the third ventricle and hydrocephalus. The tumor was well demarcated from the surrounding brain tissue and contained calcification. MRI indicated a partially high-intensity signal on T1-weighted and T2-weighted images. The preoperative diagnosis was teratoma. Initially, the tumor was biopsied using neuroendoscopy and the Ommaya reservoir was set. The pathological results showed fat-like tissues and fibroblasts. Subsequently, the tumor was completely removed using the interhemispheric transcallosal transchoroidal approach. The tumor included fat and hair tissues. It also included calcification similar to that observed in a tooth. It was strongly adhered near the pineal gland. Pathologically, the diagnosis was a mature teratoma. Postoperatively, the tremor disappeared and the patient was discharged from the hospital without neurological deficits. We believe that compression of the Guillain-Mollaret triangle was relieved by removal of the tumor. Hence, the tremor disappeared after the operation.

We herein report a patient who was diagnosed as having olfactory groove schwannoma (OGS) which was negative for CD57 (Leu7) but positive for Schwann/2E and Sox10. A 13-year-old female with a chief complaint of headache was referred to our department due to a tumor lesion in the anterior skull base identified by magnetic resonance imaging (MRI). At the first visit, she did not exhibit altered consciousness, motor palsy, anosmia, seizures, or café au lait spots. On contrast-enhanced computed tomography (CT), a heterogeneously enhanced tumor, 50 × 45 × 50 mm in size, was observed at the anterior skull base. The left cribriform plate was thinner on bone window CT. The tumor exhibited strong, heterogeneous gadolinium enhancement on MRI as well. Slight tumor staining was observed by angiography of the left internal carotid artery but not the left external carotid artery. The patient was preoperatively diagnosed as having meningioma and underwent gross tumor resection via the basal interhemispheric approach. The tumor was strongly positive for S-100 protein and negative for epithelial membrane antigen and CD57 by immunostaining. The tumor was positive for both Schwann/2E and Sox10, which aided in the differential diagnosis between OGSs and olfactory ensheathing cell (OEC) tumors, and the definitive diagnosis was OGS. The assessment of immunoreactivities for Schwann/2E and Sox10 might be necessary to differentiate CD57-negative Schwannomas from OEC tumors., (© 2020 Japanese Society of Neuropathology.)

Objective: To analyze why women quit full-time employment as neurosurgeons and to discuss the conditions required for their reinstatement., Methods: We asked 94 core hospitals providing training programs in the board certification system adopted by the Japan Neurosurgical Society to indicate the total number and present status of women in their department and to send our anonymous questionnaire to women who had formerly worked as full-time neurosurgeons. The questionnaire consisted of closed and open questions on their reasons for quitting as full-time neurosurgeons., Results: Among 427 women evaluated, 72 (17%) had quit full-time employment as neurosurgeons. Twenty-one women who had quit 3-21 years after starting their neurosurgery careers responded to the questionnaire, including 17 board-certified neurosurgeons, 11 individuals with master's degrees, and 16 mothers. Their main reasons for quitting full-time work were difficulty in balancing their neurosurgical career and motherhood (52%) and the physical burden (38%). At the time of quitting, only 2 units (5%) had a career counseling system for women. Two thirds of participants might resume full-time work as neurosurgeons in the future. Their support system during pregnancy and the child-raising period, and understanding of male bosses and colleagues were identified as the key themes., Conclusions: The Japan Neurosurgical Society could facilitate supportive environments for women in neurosurgery by enhancing adequate childcare services, changing the work style of full-time neurosurgeons to incorporate diverse working styles, shorter working hours, understanding of their bosses and colleagues, and a career counseling system., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Central nervous system (CNS) tumour consistency is one of the factors determining the difficulty of surgery for such lesions. We measured the consistency of surgically excised CNS tumour specimens using a hardness meter. The purpose of this study was to identify imaging parameters that reflect tumour consistency by comparing preoperative imaging findings with CNS tumour consistency measurements. Material and methods: Of 175 consecutive patients with CNS tumours who underwent surgery at our hospital between October 2012 and October 2018, 127 were included in this study (those whose specimens were difficult to measure were excluded). CNS tumour consistency was measured immediately after surgical excision using a hardness meter and compared with preoperative T1-weighted, T2-weighted (T2WI), fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging, gadolinium-enhanced magnetic resonance imaging, plain computed tomography (CT), and contrast-enhanced CT findings. Tumour consistency was also subjectively classified by the surgeon into soft, hard, or very hard. Results: The intracranial meningiomas were harder than the metastatic tumours and gliomas ( p = 0.03 and p = 0.03, respectively). Among the intracranial meningiomas, the tumours that exhibited high intensity on T2WI were softer than those that displayed isointensity or low intensity ( p < 0.001 and p < 0.001, respectively), and the isointense tumours were softer than the low intensity tumours ( p = 0.02). Among the metastatic tumours, the tumours that exhibited high intensity on T2WI were softer than those that displayed isointensity or low intensity ( p < 0.001 and p < 0.001, respectively). Among the intracranial meningiomas and metastatic tumours, significant correlations were detected between the T2WI findings and subjective tumour consistency according to the surgeon or quantitative tumour consistency ( p = 0.01 and p = 0.03, respectively). Conclusions: The preoperative T2WI findings of intracranial meningiomas and metastatic tumours were significantly correlated with quantitatively measured tumour consistency and subjectively evaluated tumour consistency. Therefore, we concluded that T2WI findings are useful for preoperatively predicting the consistency of such tumours.

Background: The combined transpetrosal approach is a complicated skull base surgery with a high degree of difficulty. Herein, we made a 3-dimensional (3D) printed petrous bone with color-coded anatomic sites and evaluated its usefulness as a model to practice drilling associated with combined transpetrosal surgery., Methods: To design a 3D model of the petrous bone, we chose a representative epidermoid petroclival tumor case who underwent combined transpetrosal surgery at our hospital. A 3D image of the petrous bone embedded with color-coded anatomic sites, including cranial nerves, brainstem, and internal carotid and vertebrobasilar arteries, was created based on preoperative computed tomography scan, magnetic resonance, and digital subtraction angiography images and was then 3D printed. Thirteen neurosurgeons from our department evaluated the anatomic reproducibility and estimated distance between each anatomic site of the 3D image and model and the usefulness of the model for drilling practice., Results: The anatomic reproducibility of both the 3D image and model was high, and the 3D model was considered good for drilling practice (P < 0.05). The error in the estimated distance between anatomic sites in the 3D model was significantly smaller than that of the 3D image (P < 0.0001)., Conclusions: These results indicate that our 3D printed model is very useful for practice with craniotomy and petrosectomy drilling, necessary in the combined transpetrosal approach., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The levels of plasma sLR11, released from intimal SMCs, are positively associated with intima-media thickness (IMT) in asymptomatic subjects. We have evaluated the yet unknown pathological significance of sLR11 for plaque conditions in patients with carotid artery stenosis., Methods: The presence of LR11 in carotid plaques was investigated using autopsy specimens. A clinical ultrasonography study for elucidating relationships between sLR11 and plaque condition was performed in 46 patients., Results: Immunohistochemistry showed high levels of LR11 in SMCs within thickened intima and at the media-intima border of atherosclerotic carotid plaques. The levels of sLR11 in patients were clearly elevated compared to healthy controls. Univariate analysis of sLR11 revealed significant positive correlation with plaque score and a tendency to correlate with the stenotic fraction. Univariate and multiple regression analyses of plaque scores showed that sLR11, maximum IMT, and HDL-cholesterol independently determined plaque score. Finally, univariate analysis of initial sLR11 levels for changes in imaging markers after one-year follow-up showed that initial sLR11 levels significantly correlated with stenotic fraction progression., Conclusions: The levels of sLR11, abundantly expressed in carotid atherosclerotic plaques, are highly associated with increased plaque score. sLR11 levels may be predictive of plaque conditions in patients with advanced carotid atherosclerosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hemorrhagic low-grade glioma(LGG)without malignant transformation is rare, accounting for less than 1% of cases. To the best of our knowledge, hemorrhagic LGG with an arteriovenous(AV)shunt has not been reported. We report the case of 17-year-old man with LGG with an AV shunt. He presented to our hospital with seizure. Computed tomography(CT)demonstrated a hypodense lesion with mass effect in the right frontal lobe. T1-weighted images(WI)and T2WI on magnetic resonance imaging(MRI)revealed acute-onset hemorrhage in the right frontal lobe. Furthermore, a ring-enhancing lesion was noted on gadolinium(Gd)-DTPA T1WI, and an AV shunt was found in the same region on angiography. Gross total tumor resection was performed. The pathological diagnosis was diffuse astrocytoma with pilomyxoid features(WHO grade II). Without adjuvant therapy, no residual tumor was found on MRI at the 6-year follow-up examination. We treated a case of hemorrhagic LGG with an AV shunt. Intratumoral hemorrhage in LGG may occur and should be considered for the differential diagnosis.

Introduction: We report a rare case in which a pituitary tumor co-occurred with a giant mucocele. The mucocele's computed tomography(CT)values fell markedly when it collapsed, and we report the associated considerations., Case: This case involved a 42-year-old male patient. For 20 years, his visual acuity had progressively declined, and it suddenly rapidly worsened over a month. Cranial CT revealed a massive tumor in the sphenoid sinus and a pituitary tumor. A region of high absorption extended from the paranasal sinus to the skull base. Two days after the patient's initial presentation, he experienced a sudden loss of vision. Therefore, we performed an urgent re-examination. The CT value of the paranasal lesion was found to have sharply declined. The sinus lesion was diagnosed as a mucocele. Emergent endoscopic surgery was performed. Actinomyces meyeri was detected in the samples cultures., Discussion: The causes of mucocele exhibiting abnormally high signal intensity on CT include the accumulation of hemosiderin due to repeated bleeding in the cyst. Furthermore, we inferred that the Actinomyces meyeri had been taking up metallic elements in vivo for a long time. The marked reduction in the lesion's CT value was considered to have been due to the destruction of the mucocele. The contents of the mucocele flowed out and were replaced with newly produced mucus, which exhibits low absorption values., Conclusion: We treated a patient with a giant mucocele involving distraction of the frontal base and a pituitary adenoma. In such cases, surgery should be performed when visual acuity deteriorates suddenly.

Male breast cancer accounts for less than 1.0% of all breast cancer cases, and its brain metastasis is very rare. We encountered a male patient in whom brain metastasis occurred more than 20 years after the development of breast cancer. The patient was a 78-year-old male who underwent surgery for right breast cancer 24 years ago. Nausea and anorexia had appeared 2 months earlier, and the patient was referred to our department because a brain tumor was suspected on MRI. A 4×4-cm tumorous lesion was observed in the right temporal lobe, and it was heterogeneously enhanced with gadolinium. Suspecting a metastatic brain tumor, tumor resection with craniotomy was performed. Through pathological examination, the patient was diagnosed with brain metastasis of the breast cancer. Whole-brain irradiation was additionally performed. The patient recovered smoothly without neurological deficit and was discharged. No intracranial recurrence was noted on follow-up imaging, but the general condition aggravated, and the patient died after 13 months. Breast cancer in males may metastasize to the brain after a prolonged period in rare cases, for which follow-up examinations by imaging may be necessary.

Background: The incidence of acute epidural hematoma not accompanied by fracture is low, and it mostly occurs right below the impact point in children. Acute epidural hematoma on the contralateral side of the impact point without fracture is very rare., Case Presentation: Case 1: a 52-year-old Japanese woman fell and was bruised in the left occipital region, and acute epidural hematoma developed in the right frontal region. No fracture line was observed in the right frontal region on head computed tomography or during surgery, and the source of bleeding was the middle meningeal artery. Case 2: a 56-year-old Japanese man fell down the stairs and was bruised in the right occipital region, and acute epidural hematoma developed in the right occipital supra- and infratentorial regions and left frontal region. Separation of the lambdoid suture was noted in the right occipital region, but no fracture line was present in the left frontal region on either head computed tomography or during surgery, and the source of bleeding was the middle meningeal artery., Conclusions: Two rare cases of frontal contrecoup acute epidural hematoma without facture near the hematoma were reported. It is possible that the dura mater detaches from the inner surface of the skull due to cavitation theory-related negative pressure and blood vessels in the dura mater are damaged, causing contrecoup acute epidural hematoma even though no fracture occurs, for which careful course observation is necessary.

Background: Subarachnoid hemorrhage (SAH) with an intracerebral hematoma (ICH) shows an unfavorable prognosis. In the present study, we examined the characteristics of SAH with ICH and its prognosis., Methods: Subjects comprised 218 patients with SAH who underwent surgery between January 2007 and December 2015. We compared age, sex, the location of the aneurysm, treatment procedures, medical history (hypertension, diabetes, and heart disease), the Glasgow Coma Scale (GCS) score on admission, rerupture rate, hydrocephalus, the diameter of the aneurysm, cerebral vasospasm, perioperative cardiopulmonary complications, and the Glasgow Outcome Scale (GOS) score after 2 months between patients with SAH with and without ICH. The interval from the onset of SAH until surgery, the location of ICH, and hematoma volume were investigated as prognostic factors for SAH with ICH., Results: Among all subjects, 82 had SAH with ICH. GCS scores on admission were poorer in patients with SAH with ICH than in those without ICH (P < .001), and middle cerebral artery aneurysms were more likely to form hematomas (P < .001). GOS scores after 2 months were also poorer in patients with SAH with ICH (P < .01). The size of aneurysms was larger in the 82 patients with SAH with ICH than in those without ICH (P < .001), and the rerupture rate was higher (P < .001). The unfavorable prognosis of patients with SAH with ICH was associated with age and GCS score on admission., Conclusions: A young age and a favorable GCS score on admission may be associated with a favorable prognosis for patients with SAH with ICH, and SAH with ICH may easily rerupture., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: As the anatomical three-dimensional (3D) positional relationship around the anterior clinoid process (ACP) is complex, experience of many surgeries is necessary to understand anterior clinoidectomy (AC). We prepared a 3D synthetic image from computed tomographic angiography (CTA) and magnetic resonance imaging (MRI) data and a rapid prototyping (RP) model from the imaging data using a 3D printer. The objective of this study was to evaluate anatomical reproduction of the 3D synthetic image and intraosseous region after AC in the RP model. In addition, the usefulness of the RP model for operative simulation was investigated., Methods: The subjects were 51 patients who were examined by CTA and MRI before surgery. The size of the ACP, thickness and length of the optic nerve and artery, and intraosseous length after AC were measured in the 3D synthetic image and RP model, and reproducibility in the RP model was evaluated. In addition, 10 neurosurgeons performed AC in the completed RP models to investigate their usefulness for operative simulation., Results: The RP model reproduced the region in the vicinity of the ACP in the 3D synthetic image, including the intraosseous region, at a high accuracy. In addition, drilling of the RP model was a useful operative simulation method of AC., Conclusions: The RP model of the vicinity of ACP, prepared using a 3D printer, showed favorable anatomical reproducibility, including reproduction of the intraosseous region. In addition, it was concluded that this RP model is useful as a surgical education tool for drilling.

DNA repair is crucial for genome stability in the developing cortex, as somatic de novo mutations cause neurological disorders. However, how DNA repair contributes to neuronal development is largely unknown. To address this issue, we studied the spatiotemporal roles of DNA polymerase β (Polβ), a key enzyme in DNA base excision repair pathway, in the developing cortex using distinct forebrain-specific conditional knock-out mice, Emx1-Cre/Pol β fl/fl and Nex-Cre/Pol β fl/fl mice. Polβ expression was absent in both neural progenitors and postmitotic neurons in Emx1-Cre/Pol β fl/fl mice, whereas only postmitotic neurons lacked Polβ expression in Nex-Cre/Pol β fl/fl mice. We found that DNA double-strand breaks (DSBs) were frequently detected during replication in cortical progenitors of Emx1-Cre/Pol β fl/fl mice. Increased DSBs remained in postmitotic cells, which resulted in p53-mediated neuronal apoptosis. This neuronal apoptosis caused thinning of the cortical plate, although laminar structure was normal. In addition, accumulated DSBs also affected growth of corticofugal axons but not commissural axons. These phenotypes were not observed in Nex-Cre/Pol β fl/fl mice. Moreover, cultured Polβ-deficient neural progenitors exhibited higher sensitivity to the base-damaging agent methylmethanesulfonate, resulting in enhanced DSB formation. Similar damage was found by vitamin C treatment, which induces TET1-mediated DNA demethylation via 5-hydroxymethylcytosine. Together, genome stability mediated by Polβ-dependent base excision repair is crucial for the competence of neural progenitors, thereby contributing to neuronal differentiation in cortical development. SIGNIFICANCE STATEMENT DNA repair is crucial for development of the nervous system. However, how DNA polymerase β (Polβ)-dependent DNA base excision repair pathway contributes to the process is still unknown. We found that loss of Polβ in cortical progenitors rather than postmitotic neurons led to catastrophic DNA double-strand breaks (DSBs) during replication and p53-mediated neuronal apoptosis, which resulted in thinning of the cortical plate. The DSBs also affected corticofugal axon growth in surviving neurons. Moreover, induction of base damage and DNA demethylation intermediates in the genome increased DSBs in cultured Polβ-deficient neural progenitors. Thus, genome stability by Polβ-dependent base excision repair in neural progenitors is required for the viability and differentiation of daughter neurons in the developing nervous system., (Copyright © 2017 the authors 0270-6474/17/378444-15$15.00/0.)

Background: CRISPR/Cas9 system is a powerful method to investigate the role of genes by introducing a mutation selectively and efficiently to specific genome positions in cell and animal lines. However, in primary neuron cultures, this method is affected by the issue that the effectiveness of CRISPR/Cas9 is different in each neuron. Here, we report an easy, quick and reliable method to identify mutants induced by the CRISPR/Cas9 system at a single neuron level, using immunocytochemistry (ICC) and fluorescence imaging., Results: Dissociated cortical cells were transfected with CRISPR/Cas9 plasmids targeting the transcription factor cAMP-response element binding protein (CREB). Fluorescence ICC with CREB antibody and quantitative analysis of fluorescence intensity demonstrated that CREB expression disappeared in a fraction of the transfected neurons. The downstream FOS expression was also decreased in accordance with suppressed CREB expression. Moreover, dendritic arborization was decreased in the transfected neurons which lacked CREB immunoreactivity., Conclusions: Detection of protein expression is efficient to identify individual postmitotic neurons with CRISPR/Cas9-mediated gene disruption in primary cortical cultures. The present method composed of CRISPR/Cas9 system, ICC and fluorescence imaging is applicable to study the function of various genes at a single-neuron level.

During development, thalamocortical (TC) axons form branches in an activity-dependent fashion. Here we investigated how neuronal activity is converted to molecular signals, focusing on an epigenetic mechanism involving histone deacetylases (HDACs). Immunohistochemistry demonstrated that HDAC9 was translocated from the nucleus to the cytoplasm of thalamic cells during the first postnatal week in rats. In organotypic co-cultures of the thalamus and cortex, fluorescent protein-tagged HDAC9 also exhibited nuclueocytoplasmic translocation in thalamic cells during culturing, which was reversed by tetrodotoxin treatment. Transfection with a mutant HDAC9 that interferes with the translocation markedly decreased TC axon branching in the culture. Similarly, TC axon branching was significantly decreased by the mutant HDAC9 gene transfer in vivo. However, axonal branching was restored by disrupting the interaction between HDAC9 and myocyte-specific enhancer factor 2 (MEF2). Taken together, the present results demonstrate that the nucleocytoplasmic translocation of HDAC9 plays a critical role in activity-dependent TC axon branching by affecting transcriptional regulation and downstream signaling pathways.

Transcriptional regulation is crucial for neuronal activity-dependent processes that govern neuronal circuit formation and synaptic plasticity. An intriguing question is how neuronal activity influences the spatiotemporal interactions between transcription factors and their target sites. Here, using a single-molecule imaging technique, we investigated the activity dependence of DNA binding and dissociation events of cAMP-response element binding protein (CREB), a principal factor in activity-dependent transcription, in mouse cortical neurons. To visualize CREB at the single-molecule level, fluorescent-tagged CREB in living dissociated cortical neurons was observed by highly inclined and laminated optical sheet microscopy. We found that a significant fraction of CREB spots resided in the restricted locations in the nucleus for several seconds (dissociation rate constant: 0.42 s -1 ). In contrast, two mutant CREBs, which cannot bind to the cAMP-response element, scarcely exhibited long-term residence. To test the possibility that CREB dynamics depends on neuronal activity, pharmacological treatments and an optogenetic method involving channelrhodopsin-2 were applied to cultured cortical neurons. Increased neuronal activity did not appear to influence the residence time of CREB spots, but markedly increased the number of restricted locations (hot spots) where CREB spots frequently resided with long residence times (>1 s). These results suggest that neuronal activity promotes CREB-dependent transcription by increasing the frequency of CREB binding to highly localized genome locations., Significance Statement: The transcription factor, cAMP response element-binding protein (CREB) is known to regulate gene expression in neuronal activity-dependent processes. However, its spatiotemporal interactions with the genome remain unknown. Single-molecule imaging in cortical neurons revealed that fluorescent-tagged CREB spots frequently reside at fixed nuclear locations in the time range of several seconds. Neuronal activity had little effect on the CREB residence time, but increased the rapid and frequent reappearance of long-residence CREB spots at the same nuclear locations. Thus, activity-dependent transcription is attributable to frequent binding of CREB to specific genome loci., (Copyright © 2017 the authors 0270-6474/17/370001-10$15.00/0.)

Using a stiffness meter, we quantitatively measured the stiffness of fresh plaques that had been excised by carotid endarterectomy. The objective of this study was to clarify the correlation between plaque stiffness and pre-operative carotid ultrasonographic findings, and predict the stiffness of plaques before surgery by comparison with the stiffness of common items. The study population comprised 44 patients (44 lesions) who had undergone carotid endarterectomy at our institution between December 2009 and October 2014. The stiffness of excised fresh plaques was measured using a stiffness meter and compared with the pre-operative echographic findings for the plaques and the stiffness of selected foods and common items. The mean stiffness value for all plaques was 4.52 ± 3.30 MPa (mean ± standard deviation). The plaques exhibiting calcification were significantly harder (p = 0.001). On classification of lesions on the basis of echographic findings, plaque hardness was in the order low-echoic (15 lesions) < iso-echoic (20 lesions) < high-echoic (9 lesions) (p = 0.02). The stiffness of the low-echoic group was equivalent to that of tofu or sliced cheese, whereas the plaques in the iso- and high-echoic groups exhibited stiffness similar to that of ham and a plastic eraser, respectively. A significant correlation was observed between the quantitative stiffness values of carotid plaques and their brightness on carotid ultrasonography. Using these data, operators might be able to predict plaque stiffness from pre-operative echographic findings. In addition, it might be useful for operators to compare such quantitative stiffness measurements with stiffness data for foods and common items to gain an understanding of the state of the target plaque before treatment., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

We encountered a rare case of metastatic brain tumors in the bilateral cerebellopontine angles. The patient was a 61-year-old man, who visited an otorhinolaryngology clinic with complaints of rapidly progressing bilateral hearing impairment and facial palsy. The patient was referred to our hospital because tumorous lesions were suspected in the bilateral cerebellopontine angles on brain magnetic resonance imaging. Regarding tumor markers, the patient's cancer antigen 19-9 and carcinoembryonic antigen levels were high, which suggested metastasis. However, no abnormal findings other than abdominal lymph node enlargement were detected on whole-body examination, and no primary lesion was identified. The tumor in the right cerebellopontine angle was excised using the lateral suboccipital approach and subjected to pathological examination. It was diagnosed as an adenocarcinoma; thus, both lesions were considered brain metastases from a malignant abdominal tumor, and radiochemotherapy was administered to the patient. Unfortunately, the patient died after 89 days of treatment, and a pathological autopsy revealed that the primary lesion was a common bile duct tumor. No dural metastasis was noted in the brain or spinal cord; however, tumors were detected in the epiarachnoid space during surgery. Metastasis to the bilateral cerebellopontine angles occurred in the same period, which was indicative of ascending metastasis through the vertebrobasilar artery. Hence, we suggest that progressive bilateral hearing impairment and facial palsy were a consequence of brain tumors that had metastasized bilaterally to the cerebellopontine angles.

Background: Deep regions are not visible in three-dimensional (3D) printed rapid prototyping (RP) models prepared from opaque materials, which is not the case with translucent images. The objectives of this study were to develop an RP model in which a skull base tumor was simulated using mesh, and to investigate its usefulness for surgical simulations by evaluating the visibility of its deep regions., Methods: A 3D printer that employs binder jetting and is mainly used to prepare plaster models was used. RP models containing a solid tumor, no tumor, and a mesh tumor were prepared based on computed tomography, magnetic resonance imaging, and angiographic data for four cases of petroclival tumor. Twelve neurosurgeons graded the three types of RP model into the following four categories: 'clearly visible,' 'visible,' 'difficult to see,' and 'invisible,' based on the visibility of the internal carotid artery, basilar artery, and brain stem through a craniotomy performed via the combined transpetrosal approach. In addition, the 3D positional relationships between these structures and the tumor were assessed., Results: The internal carotid artery, basilar artery, and brain stem and the positional relationships of these structures with the tumor were significantly more visible in the RP models with mesh tumors than in the RP models with solid or no tumors., Conclusions: The deep regions of PR models containing mesh skull base tumors were easy to visualize. This 3D printing-based method might be applicable to various surgical simulations.