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AIMS/INTRODUCTION: Fatty acid-binding protein (FABP) 4, which acts as an adipokine secreted by adipocytes, macrophages, and capillary endothelial cells, is expressed in injured glomerular cells. It has been reported that urinary (U-) FABP4 is associated with renal dysfunction and proteinuria in several glomerular kidney diseases. However, the clinical significance of U-FABP4 in diabetic kidney disease (DKD) remains undetermined. MATERIALS AND METHODS: Immunohistological analyses of FABP4 and FABP1 (liver-type FABP), an established biomarker for impaired proximal tubules, were performed in the kidneys of patients with DKD and nonobese diabetic mice (KK-Ta/Akita mice). The associations between U-FABP4 and U-FABP1 with kidney function and metabolic indices were also investigated in patients with type 1 diabetes (n = 57, mean age: 61 years) and patients with type 2 diabetes (n = 608, mean age: 65 years). RESULTS: In both patients with diabetes and diabetic mice, FABP4 was expressed in injured glomeruli with increased markers of endoplasmic reticulum stress in addition to peritubular capillaries, whereas FABP1 was mainly expressed in proximal tubules. Levels of U-FABP4 and U-FABP1 were independently associated with each other, and both levels were independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) after adjustment of age, sex, type of diabetes, duration of diabetes, and systolic blood pressure in patients with diabetes. CONCLUSIONS: Urinary level of FABP4 derived from injured glomeruli with increased endoplasmic reticulum stress is independently associated with eGFR and UACR, suggesting a promising biomarker for glomerular damage in patients with diabetes.

DOI： 10.1111/jdi.14388

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Extraventricular neurocytoma (EVN) is a rare neuronal tumor with a marked tendency towards ganglionic or glial differentiation. Although EVN commonly occurs in young adults, congenital cases are extremely rare, and standardized therapeutic strategies remain undetermined. The presence of atypical features such as increased mitotic activity on histological analysis is correlated with a higher rate of recurrence and poor prognosis. A 3-d-old infant with no abnormalities at birth presented with recurrent apnea and paroxysmal eye deviation on the upper right side. Magnetic resonance imaging revealed a large intracranial tumor located anterior to the brainstem. The patient underwent biopsy via craniotomy, leading to a histological diagnosis of EVN with atypical features. Despite the absence of adjuvant radiation therapy or chemotherapy, the lesion remained stable over 18 months, and the patient's growth was within normal limits. EVN is an important differential diagnosis of congenital brain tumors. Therapeutic strategies for congenital cases should be distinguished from those used for older children, and treatment decisions should be based on individual patient risks.

DOI： 10.1007/s00381-024-06725-w

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BACKGROUND AND PURPOSE: Elevated intracranial pressure (ICP) resulting from severe head injury or stroke poses a risk of secondary brain injury that requires neurosurgical intervention. However, currently available noninvasive monitoring techniques for predicting ICP are not sufficiently advanced. We aimed to develop a minimally invasive ICP prediction model using simple CT images to prevent secondary brain injury caused by elevated ICP. METHODS: We used the following three methods to determine the presence or absence of elevated ICP using midbrain-level CT images: (1) a deep learning model created using the Python (PY) programming language; (2) a model based on cistern narrowing and scaling of brainstem deformities and presence of hydrocephalus, analyzed using the statistical tool Prediction One (PO); and (3) identification of ICP by senior residents (SRs). We compared the accuracy of the validation and test data using fivefold cross-validation and visualized or quantified the areas of interest in the models. RESULTS: The accuracy of the validation data for the PY, PO, and SR methods was 83.68% (83.42%-85.13%), 85.71% (73.81%-88.10%), and 66.67% (55.96%-72.62%), respectively. Significant differences in accuracy were observed between the PY and SR methods. Test data accuracy was 77.27% (70.45%-77.2%), 84.09% (75.00%-85.23%), and 61.36% (56.82%-68.18%), respectively. CONCLUSIONS: Overall, the outcomes suggest that these newly developed models may be valuable tools for the rapid and accurate detection of elevated ICP in clinical practice. These models can easily be applied to other sites, as a single CT image at the midbrain level can provide a highly accurate diagnosis.

DOI： 10.1111/jon.13241

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BACKGROUND: Systemic hypertension (HT) is associated with the development of increased intraocular pressure (IOP), a risk factor for glaucoma. However, it remains unclear whether high IOP is a risk factor for HT. METHODS AND RESULTS: We investigated 7,487 Japanese individuals (4,714 men, 2,773 women; mean [±SD] age 49±9 years) who underwent annual health checkups in 2006. Over the 10-year follow-up period, 1,232 (24.3%) men and 370 (11.5%) women developed new-onset HT, defined as initiation of antihypertensive drug treatment or blood pressure ≥140/90 mmHg. After dividing IOP into tertiles (T1-T3), Cox proportional hazards analysis (adjusted for age, sex, systolic blood pressure, obesity, current smoking, alcohol consumption, family history of HT, estimated glomerular filtration rate, and diabetes and dyslipidemia diagnoses at baseline) revealed a significantly higher risk of newly developed HT in T3 (IOP ≥14 mmHg; hazard ratio 1.14; 95% confidence interval 1.01-1.29; P=0.038) using T1 (IOP ≤11 mmHg) as the reference group. There was no significant interaction between sex and IOP tertile (P=0.153). A restricted cubic spline model showed a gradual but robust increase in the hazard ratio for new-onset HT with increasing IOP. CONCLUSIONS: High IOP is an independent risk factor for the development of HT over a 10-year period.

DOI： 10.1253/circj.CJ-24-0241

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AIMS: The new nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD). METHODS: We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or positive for urinary protein, during a 10-year period in 12 138 Japanese subjects (men / women, 7984/4154; mean age, 48 years) who received annual health examinations including abdominal ultrasonography. RESULTS: The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men / women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p = 0.001) and those with ALD (1.41 [1.05-1.88], p = 0.022), but not those with MetALD (1.11 [0.90-1.36], p = 0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p = 0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity. CONCLUSIONS: MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.

DOI： 10.1111/hepr.14097

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AIMS: To investigate effects of tirzepatide, a dual receptor agonist for glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), on eating behaviors. METHODS: Eating behaviors were evaluated by using a validated questionnaire survey in 33 Japanese patients with type 2 diabetes mellitus (T2DM) (mean age: 51.8 years) who were treated with tirzepatide (2.5 mg/week for 4 weeks and then 5.0 mg/week) for 6 months (M). RESULTS: Treatment with tirzepatide significantly decreased median hemoglobin A1c (HbA1c) (baseline/3 M/6 M: 7.3 %/6.0 %/5.8 %), mean body weight (BW) (baseline/3 M/6 M: 87.7 kg/82.0 kg/79.6 kg) and mean relative score of eating behaviors (baseline/3 M/6 M: 57.0/50.7/45.9). In the GLP-1 receptor agonist (GLP-1RA) naïve group (n = 20, men/women: 13/7), HbA1c and BW were continuously decreased up to 6 M. Changes in eating behaviors were mainly observed in the first 3 M. In the GLP-1RA non-naïve group (n = 13, men/women: 8/5), reductions in HbA1c and BW were predominant in the first 3 M, and changes in eating behaviors were observed up to 6 M. There were no significant correlations of changes in scores of eating behaviors with changes in glycemic control or those in BW. CONCLUSIONS: Tirzepatide ameliorates eating behaviors as well as glycemic management and obesity in Japanese patients with T2DM, and the patterns of improvement are partially dependent on prior exposure to GLP-1RAs.

DOI： 10.1016/j.jdiacomp.2024.108779

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BACKGROUND AND AIM: New nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: Japanese individuals who received annual health checkups including abdominal ultrasonography (n = 15 788, men/women: 10 250/5538, mean age: 49 years) were recruited. RESULTS: The numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t-distributed stochastic neighbor embedding and K-means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low-grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning-based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides, was selected as a useful feature for SLDs. CONCLUSIONS: The new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs.

DOI： 10.1111/jgh.16552

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AIM: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. A method for estimating sdLDL-C by using Sampson's equation that includes levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglycerides (TG) has recently been proposed. We investigated the validation and exploration of estimated sdLDL-C level. METHODS: The associations between measured and estimated sdLDL-C levels were investigated in 605 Japanese subjects (men/women: 280/325; mean age: 65±15 years) who received annual health check-ups in the Tanno-Sobetsu Study, a population-based cohort. RESULTS: Estimated sdLDL-C level was highly correlated with measured sdLDL-C level in all subjects (R2=0.701), nondiabetic subjects without any medication (n=254, R2=0.686) and subjects with diabetes mellitus (n=128, R2=0.721). Multivariable regression analysis showed that levels of non-HDL-C, TG and γ-glutamyl transpeptidase (γGTP) were independent predictors of measured sdLDL-C level. In a stratification of the LDL window, all of the subjects with a combination of high non-HDL-C (≥ 170 mg/dL) and high TG (≥ 150 mg/dL) had high levels of measured and estimated sdLDL-C (≥ 35 mg/dL). Furthermore, machine learning-based estimation of sdLDL-C level by artificial intelligence software, Prediction One, was substantially improved by using components of Sampson's equation (R2=0.803) and by using those components with the addition of γGTP and deletion of TC (R2=0.929). CONCLUSIONS: sdLDL-C level estimated by Sampson's equation can be used instead of measured sdLDL-C level in general practice. By building multiple machine learning models of artificial intelligence, a more accurate and practical estimation of sdLDL-C level might be possible.

DOI： 10.5551/jat.64578

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The pterygopalatine fossa and infratemporal fossa are often approached through an external incision because of their deep facial location, but this can present problems such as facial scarring and deformity. In schwannoma surgery, intraneural dissection is a useful surgical technique for achieving gross total resection while preserving the capsule, including the nerves. For appropriate enucleation and preservation of the functional nerve, it is indispensable to distinguish between the pseudocapsule and the tumor capsule. This case report presents a case of endonasal surgical intervention for an extracranial trigeminal schwannoma employing the tri-port approach and narrow-band imaging.

DOI： 10.7759/cureus.58200

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AIM: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for ischemic heart disease (IHD). However, it remains unclear whether estimated sdLDL-C level is a predictor for IHD. We investigated the associations of new onset of IHD with levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), LDL-C and calculated sdLDL-C by Sampson's equation. METHODS: After exclusion of subjects with IHD or those with TG ≥ 800 mg/dL, a total of 18,176 subjects (men/women: 11,712/6,464, mean age: 46 years) were recruited among 28,990 Japanese individuals who received annual health checkups. RESULTS: During the 10-year follow-up period, 456 men (3.9%) and 121 women (1.9%) newly developed IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) (1.38 [95% confidence interval: 1.03-1.85]) for new onset of IHD in subjects with the 4th quartile (Q4) of sdLDL-C (≥ 42 mg/dL) was significantly higher than that in subjects with the 1st quartile (Q1) (≤ 24 mg/dL) as the reference, though the adjusted HRs in subjects with Q2-Q4 of TC, HDL-C, non-HDL-C, LDL-C and TG were comparable with those in subjects with Q1 of the respective lipid fractions. The adjusted HR with a restricted cubic spline increased with a higher level of calculated sdLDL-C as a continuous value at baseline. CONCLUSIONS: sdLDL-C level calculated by Sampson's equation is a predominant predictor for the development of IHD in a general Japanese population.

DOI： 10.5551/jat.64369

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Hypothyroidism has been reported to be associated with chronic kidney disease (CKD). However, the impact of thyroid-stimulating hormone (TSH) on new onset of CKD and its gender dependence remain undetermined. We investigated the association of serum TSH level and the development of CKD defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or positive for urine protein in 28,990 Japanese subjects who received annual health examinations. After excluding subjects with no data for serum TSH, urinalysis and eGFR and those with CKD at baseline, a total of 10,392 subjects (men/women: 6802/3590, mean age: 48 years) were recruited. During a 10-year follow-up, 1185 men (6.7%) and 578 women (2.9%) newly developed CKD. Multivariable Cox proportional hazard models after adjustment of age, body mass index, smoking habit, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease and eGFR (≥ 90 mL/min/1.73 m2) showed that the hazard ratio (HR) for the development of CKD in the high TSH (> 4.2 mU/L) group was significantly higher than that in the low TSH (≤ 4.2 mU/L) group in men (HR [95% confidence interval]: 1.41 [1.09-1.83]) but not in women (1.08 [0.77-1.51]). There was a significant interaction between sex and the category of TSH level for the development of CKD (p = 0.02). The adjusted HR with a restricted cubic spline increased with a higher level of TSH in men but not in women. In conclusion, a high level of TSH is associated with an increased risk for the development of CKD in men but not in women.

DOI： 10.1038/s41440-023-01453-1

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BACKGROUND: The EF-14 clinical trial demonstrated the safety and efficacy of tumor-treating fields (TTFields) for newly diagnosed glioblastoma. This study aimed to clarify the current status, safety, and efficacy of TTFields in Japanese patients who meet the EF-14 inclusion criteria. METHODS: This was a multicenter retrospective cohort study. Background, treatment, and outcome data of patients who satisfied the inclusion criteria of the EF-14 trial were collected from 45 institutions across Japan. The rate, determinants, and current status of TTField use, including its safety and efficacy in terms of progression and survival, were retrospectively investigated. This study was conducted in accordance with the STROBE checklist. RESULTS: Among the 607 patients enrolled, 70 were excluded due to progressive disease during radiation and temozolomide therapy, age > 80 years old, and Karnofsky Performance Status score of <70. Among the remaining 537 patients, 210 (39%) underwent TTField treatment. Multivariate analysis revealed younger age and spouse as a caregiver as significant factors for TTField use. The compliance rate of TTField use exceeded 75% in 60% of patients, with a median TTField usage duration of 11 months. Skin disorders requiring medical treatment occurred in 56% of patients. Multivariate Cox proportional hazards analysis in the whole series and propensity score-matched analysis revealed that TTField use was not a prognostic factor for progression-free survival (PFS) or overall survival (OS). CONCLUSIONS: TTField use did not have a substantial effect on either PFS or OS in Japanese patients with glioblastoma, despite compliance rates comparable to those observed in the EF-14.

DOI： 10.1093/noajnl/vdae176

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Neurosarcoidosis is a condition that is characterized by the occurrence of noncaseating epithelioid granulomas in various organs throughout the body, including the lungs, heart, and central nervous system. It is particularly prevalent in cases of noncommunicating hydrocephalus. While its clinical presentations may vary, neurological deficits such as hemiparesis are extremely uncommon. We herein present a case of unilateral hydrocephalus resulting from neurosarcoidosis presenting with hemiparesis. A 58-year-old woman exhibited right hemiparesis, altered mental status, and aphasia persisting for 1 month. Magnetic resonance imaging showed unilateral hydrocephalus of uncertain etiology. The patient underwent external ventricular drainage, endoscopic fenestration of the septum pellucidum (septostomy), and lesion biopsy, which led to a histopathological diagnosis. Hemiparesis can accompany unilateral hydrocephalus caused by neurosarcoidosis. Endoscopic procedures provide an effective option for the diagnosis and treatment of noncommunicating hydrocephalus caused by neurosarcoidosis.

DOI： 10.2176/jns-nmc.2023-0298

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A disorder of lipid metabolism is involved in cardiovascular diseases including hypertension. A high level of small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. However, the association between sdLDL-C and hypertension has not been fully investigated. We investigated the associations between the development of hypertension during a 10-year period and levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), and LDL-C and sdLDL-C calculated by using the Sampson equations in 28,990 Japanese subjects who received annual health examinations. After exclusion of subjects with missing data, those with hypertension, and those with TG ≥ 800 mg/dL at baseline, a total of 15,177 subjects (men/women: 9374/5803, mean age: 46 years) were recruited. During the 10-year period, 2379 men (25.4%) and 724 women (12.5%) had new onset of hypertension. Multivariable Cox proportional hazard model analyses showed that levels of HDL-C, non-HDL-C, TG and sdLDL-C, but not levels of TC and LDL-C, were independent risk factors for the development of hypertension after adjustment of age, sex, family history of hypertension, systolic blood pressure, obesity, current smoking habit, alcohol drinking habit, estimated glomerular filtration rate, diagnosis of diabetes mellitus and use of lipid-lowering drugs and that the adjusted risk of sdLDL-C (per 1-standard deviation) was highest (hazard ratio [95% confidence interval: 1.09 [1.05-1.13]). The addition of sdLDL-C to traditional risk factors for hypertension significantly improved the discriminatory capability, which was better than that of other lipid fractions. In conclusion, a high level of calculated sdLDL-C predicts the development of hypertension.

DOI： 10.1038/s41440-023-01392-x

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.deman.2023.100191

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It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion.

DOI： 10.1007/s10143-023-02180-4

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The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

DOI： 10.2176/jns-nmc.2023-0005

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Impaired reperfusion in ischemic brain disease is a condition that we are increasingly confronted with owing to recent advances in reperfusion therapy. In the present study, rat models of reperfusion were investigated to determine the causes of acute seizures using magnetic resonance imaging (MRI) and histopathological specimens. Rat models of bilateral common carotid artery ligation followed by reperfusion and complete occlusion were created. We compared the incidence of seizures, mortality within 24 h, MRI, and magnetic resonance spectroscopy (MRS) to evaluate ischemic or hemorrhagic changes and metabolites in the brain parenchyma. In addition, the histopathological specimens were compared with those observed on MRI. In multivariate analysis, the predictive factors of mortality were seizure (odds ratios (OR), 106.572), reperfusion or occlusion (OR, 0.056), and the apparent diffusion coefficient value of the striatum (OR, 0.396). The predictive factors of a convulsive seizure were reperfusion or occlusion (OR, 0.007) and the number of round-shaped hyposignals (RHS) on susceptibility-weighted imaging (SWI) (OR, 2.072). The incidence of convulsive seizures was significantly correlated with the number of RHS in the reperfusion model. RHS on SWI was confirmed pathologically as microbleeds in the extravasation of the brain parenchyma and was distributed around the hippocampus and cingulum bundle. MRS analysis showed that the N-acetyl aspartate level was significantly lower in the reperfusion group than in the occlusion group. In the reperfusion model, RHS on SWI was a risk factor for convulsive seizures. The location of the RHS also influenced the incidence of convulsive seizures.

DOI： 10.2176/jns-nmc.2022-0372

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OBJECTIVE: Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses. METHODS: The stimulation of C1(+)-C4(-) or C2(+)-C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed. RESULTS: The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 μV, respectively. CONCLUSIONS: The C1(+)-C4/C2(+)-C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses. SIGNIFICANCE: Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery.

DOI： 10.1016/j.clinph.2023.03.017

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DOI： 10.1007/s00540-022-03146-4

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Remimazolam is a short-acting benzodiazepine that was approved for clinical use in 2020. We report three patients who underwent surgery for cerebral and spinal cord tumors, in whom transcranial electrical stimulation-motor-evoked potential (TES-MEP) was successfully monitored under general anesthesia with remimazolam. During total intravenous anesthesia with propofol at a target concentration of 2.7 - 3.5 µg/mL and 0.1 - 0.35 µg/kg/min of remifentanil, delayed awakening, bradycardia, and hypotension during propofol anesthesia were expected in all three cases. With patient safety as the top priority, we considered changing the anesthetic agent. Propofol was replaced with remimazolam at a loading dose of 12 mg/kg/h for a few seconds (case 3), followed by 1 mg/kg/h for maintenance (cases 1-3). TES-MEP was recorded during propofol and remimazolam administration in all three patients. Amplitudes of TES-MEP during anesthesia with propofol and remimazolam were 461.5 ± 150 µV and 590.5 ± 100.9 µV, 1542 ± 127 µV and 1698 ± 211 µV, and 581.5 ± 91.3 µV and 634 ± 82.7 µV sequentially from Case 1. Our findings suggest that intraoperative TES-MEP could be measured when anesthesia was managed with remimazolam at 1 mg/kg/h.

DOI： 10.1007/s00540-022-03112-0

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There are very few reports on the effects of benzodiazepines such as midazolam and diazepam on intraoperative visual-evoked potential (VEP), and there is no report on the effect of remimazolam at all. Five patients underwent neurosurgery using VEP monitoring for avoiding surgical injury to the optic nerve. In all cases, drug administration was based on actual body weight. General anesthesia was induced with propofol and remifentanil, and then maintained with propofol at target concentrations of 2.7-3.5 µg/ml for maintaining bispectral index (BIS) between 40 and 60. After resection of the tumor under stable VEP, we discontinued propofol immediately followed by infusion of remimazolam at 12 mg/kg/h for a few seconds, then reduced to 1 mg/kg/h. After a time, when blood levels of remimazolam appeared to be stable, VEP was monitored again and compared to controls. In all cases, we were able to confirm that there was reproducibility. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for VEP in neurosurgery.

DOI： 10.1007/s00540-022-03159-z

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DOI： 10.1111/ped.15653

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OBJECTIVE: This study aimed to enable the automatic detection of the hippocampus and diagnose mesial temporal lobe epilepsy (MTLE) with the hippocampus as the epileptogenic area using artificial intelligence (AI). We compared the diagnostic accuracies of AI and neurosurgical physicians for MTLE with the hippocampus as the epileptogenic area. METHOD: In this study, we used an AI program to diagnose MTLE. The image sets were processed using a code written in Python 3.7.4. and analyzed using Open Computer Vision 4.5.1. The deep learning model, which was a fine-tuned VGG16 model, consisted of several layers. The diagnostic accuracies of AI and board-certified neurosurgeons were compared. RESULTS: AI detected the hippocampi automatically and diagnosed MTLE with the hippocampus as the epileptogenic area on both T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) images. The diagnostic accuracies of AI based on T2WI and FLAIR data were 99% and 89%, respectively, and those of neurosurgeons based on T2WI and FLAIR data were 94% and 95%, respectively. The diagnostic accuracy of AI was statistically higher than that of board-certified neurosurgeons based on T2WI data (p = 0.00129). CONCLUSION: The deep learning-based AI program is highly accurate and can diagnose MTLE better than some board-certified neurosurgeons. AI can maintain a certain level of output accuracy and can be a reliable assistant to doctors.

DOI： 10.1371/journal.pone.0282082

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This study aimed to assess the risk factors for the recurrence of WHO grade I intracranial meningiomas using the Brain Tumor Registry of Japan (BTRJ) database. We extracted the data of 4641 patients with intracranial WHO grade I meningiomas treated only by surgical resection between 2001 and 2008. We conducted complete data analysis (n = 3690) and multiple imputation analysis (n = 4641) to adjust for missing data on tumor size. The influence of factors including age, sex, size, extent of resection, location, and preoperative symptoms on PFS was assessed. Univariate analyses of the complete data set showed that age did not affect PFS; however, male sex (p < 0.001), tumor size ≥ 30 mm (p < 0.001), low extent of resection, tumor location at the skull base (p < 0.001), and the presence of preoperative symptoms (p < 0.001) were risk factors for a significantly shorter PFS. Multivariate analysis demonstrated that male sex (p < 0.001) and presence of preoperative symptoms (p = 0.027) were independent risk factors for shorter PFS alongside large tumor size (p < 0.001) and non-gross total resection (p < 0.001). These results were confirmed for the imputed dataset. While most previous large nationwide studies of meningiomas have evaluated overall survival, progression-free survival has yet to be thoroughly examined. This study suggests that even histologically benign meningiomas may have a sex difference in postoperative behavior. This observation may provide clues to understanding the mechanism of meningioma cell proliferation.

DOI： 10.1007/s10143-022-01907-z

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OBJECTIVES: Cerebrovascular event after open-heart surgery is a critical complication and contributes to poor prognosis, including increased mortality. The purpose of this study is to investigate the appropriate preoperative risk assessment and monitoring for reducing the risk of ischemic stroke after open-heart surgery. MATERIALS AND METHODS: 184 patients who underwent surgery for valvular heart disease were included in this study. Near-infrared oxygen saturation monitoring (INVOS system) was performed during open-heart surgery. For the purpose of perioperative stroke risk assessment, we evaluated the clinical and radiological factors of the group that underwent preoperative consultation and the group that did not, and of the patients with and without postoperative ischemic stroke. RESULTS: Preoperative consultation was performed in 60 cases. Large vessel steno-occlusive disease was found in nine cases, of which three had undergone revascularization surgery. Cerebral infarction developed in four cases, all of which had no large vessel steno-occlusive disease. There was no significant association between the development of postoperative ischemic stroke and presence of large vessel steno-occlusive disease. Preoperative baseline INVOS value was significantly low in the ischemic stroke group (49.5 ± 12.5) compared to the non-ischemic stroke group (66.8 ± 10.0), (P = 0.012). CONCLUSIONS: In open-heart surgery for valvular heart disease, low preoperative baseline INVOS values were associated with cerebral ischemic stroke after surgery. The combination of appropriate preoperative screening for large vessel steno-occlusive disease and measurement of INVOS could be used as a simple and useful method in screening for the risk of ischemic stroke after open-heart surgery.

DOI： 10.1016/j.jstrokecerebrovasdis.2022.106584

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BACKGROUND: Predicting the prognosis of patients with solitary fibrous tumor (SFT) is often difficult. The prognostic risk models developed by Demicco et al. are now the standard for evaluating the risk of SFT metastasis in the current World Health Organization classification of soft tissue and bone tumors. METHODS: In this study, we examined the prognostic usefulness of a modified version of the Demicco risk models that replaces the mitotic count with the Ki-67 labeling index. We compared the three-variable and four-variable Demicco risk models with our modified risk models using Kaplan-Meier curves based on data for 43 patients with SFT. RESULTS: We found a significant difference in metastasis-free survival when patients were classified into low-risk and intermediate/high-risk groups using the three-variable (P = 0.022) and four-variable (P = 0.046) Demicco models. There was also a significant difference in metastasis-free survival between the low-risk and intermediate/high-risk groups when the modified three-variable (P = 0.006) and four-variable (P = 0.022) models were used. CONCLUSION: Modified risk models that include the Ki-67 labeling index are effective for prediction of the prognosis in patients with SFT.

DOI： 10.1186/s12957-022-02497-2

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INTRODUCTION: Moyamoya disease is characterized by progressive stenotic changes in the terminal segment of the internal carotid artery and the development of abnormal vascular networks called moyamoya vessels. The objective of this review was to provide a holistic view of the epidemiology, etiology, clinical findings, treatment, and pathogenesis of moyamoya disease. A literature search was performed in PubMed using the term "moyamoya disease," for articles published until 2021. RESULTS: Artificial intelligence (AI) clustering was used to classify the articles into 5 clusters: (1) pathophysiology (23.5%); (2) clinical background (37.3%); (3) imaging (13.2%); (4) treatment (17.3%); and (5) genetics (8.7%). Many articles in the "clinical background" cluster were published from the 1970s. However, in the "treatment" and "genetics" clusters, the articles were published from the 2010s through 2021. In 2011, it was confirmed that a gene called Ringin protein 213 (RNF213) is a susceptibility gene for moyamoya disease. Since then, tremendous progress in genomic, transcriptomic, and epigenetic profiling (e.g., methylation profiling) has resulted in new concepts for classifying moyamoya disease. Our literature survey revealed that the pathogenesis involves aberrations of multiple signaling pathways through genetic mutations and altered gene expression. CONCLUSION: We analyzed the content vectors in abstracts using AI, and reviewed the pathophysiology, clinical background, radiological features, treatments, and genetic peculiarity of moyamoya disease.

DOI： 10.1159/000520099

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OBJECTIVE: The present study investigated the effects of the stimulus polarity and location of motor evoked potential (MEP) to establish a stimulation protocol. METHODS: Nineteen patients who intraoperatively underwent MEP in bipolar direct cortical stimulation were enrolled in the present study. Somatosensory evoked potentials (SEP) of the contralateral median nerve stimulation were recorded to determine stimulation sites. MEP was performed under two settings in all patients: 1. Anodal bipolar stimulation: an anode on the precentral gyrus and a cathode on the postcentral gyrus, 2. Cathodal bipolar stimulation: a cathode on the precentral gyrus and an anode on the postcentral gyrus. MEP amplitudes and the coefficient of variation (CV) at a stimulation intensity of 25 mA and the thresholds of induced MEP were compared between the two settings. RESULTS: An electrical stimulation at 25 mA induced a significantly higher amplitude in cathodal bipolar stimulation than in anodal bipolar stimulation. Cathodal bipolar stimulation also showed significantly lower thresholds than anodal stimulation. CV did not significantly differ between the two groups. CONCLUSIONS: These results indicate that cathodal bipolar stimulation is superior to anodal bipolar stimulation for intraoperative MEP monitoring. SIGNIFICANCE: MEP in cathodal bipolar cortical stimulation may be used in a safe and useful evaluation method of motor fiber damage that combines sensitivity and specificity.

DOI： 10.1016/j.clinph.2021.06.032

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OBJECTIVES: Improvement of patient visual outcome is very important in the treatment of clinoidal meningioma (CLM). The purpose of this study is to determine the association between arachnoid preservation and visual outcome. PATIENTS: Fifteen patients with CLMs that caused visual impairment underwent surgery in our hospital. The patients included 4 men and 11 women, and the mean age was 53.3 years. METHODS: The clinical findings of these patients were retrospectively reviewed. We divided the patients into two groups based on the presence or absence of the arachnoid membrane. Group 1 comprised cases in which arachnoid preservation was intraoperatively confirmed. Group 2 comprised cases in which the arachnoid membrane was not preserved. The Landolt C chart was used to evaluate visual acuity, and dynamic visual field tests using Goldmann perimetry were used to evaluate the visual field. Results were compared before and after surgery. RESULTS: The visual acuity of the ipsilateral eye was significantly improved in Group 1 (p = 0.038). There were no other significant differences between the two groups in terms of tumor volume, patient age, and symptom duration. CONCLUSIONS: Patients in which arachnoid preservation could be intraoperatively confirmed had good improvement in visual acuity. Further research with an increased number of cases is needed to confirm these findings.

DOI： 10.1016/j.clineuro.2021.106874

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In specific cases of moyamoya disease (MMD), posterior cerebral artery (PCA) stenosis can develop after treatment of the anterior circulation and require additional revascularization. Here, we report two cases that underwent additional posterior indirect revascularization with multiple burr holes for PCA involvement after bilateral revascularization treatment of the anterior circulation. They presented with transient ischemic attack even after bilateral superficial temporal artery-middle cerebral artery bypass, and magnetic resonance angiography (MRA) showed that PCA stenosis had worsened. Indirect revascularization with multiple burr holes using Benz-marked skin incisions was performed. After surgery, the symptoms improved without perioperative complications, and cerebral angiography showed collateral circulation via the burr hole. Indirect revascularization for MMD is often combined with direct revascularization, and there are only a few reports on the use of multiple burr hole surgery alone. In addition, there are few reports of posterior circulation, despite the emphasis on the importance of PCA involvement in MMD. Indirect revascularization with multiple burr holes alone can be performed in multiple areas and applied to patients who cannot undergo direct revascularization using the occipital artery. The procedure is simple and less invasive than traditional direct revascularization procedures. Therefore, it can be effective, especially in pediatric cases of MMD with PCA involvement.

DOI： 10.1016/j.jstrokecerebrovasdis.2021.105852

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PURPOSE: This study aimed to improve the understanding of the role of adjuvant radiotherapy (AR) after subtotal resection (STR) of World Health Organization (WHO) grade I meningiomas. METHODS: We retrospectively reviewed the Brain Tumor Registry of Japan database. Among 7341 patients diagnosed with intracranial meningioma during 2001-2008, we identified 406 patients with WHO grade I meningioma treated with STR as initial treatment. Data on progression-free survival (PFS) were assessed for their relevance to clinical factors including age, sex, tumor location and size, presence of preoperative symptoms, and AR. RESULTS: AR was administered for 73 patients (18.0%). Regrowth occurred in 90 cases (22.2%) during the median follow-up period of 6.0 years (interquartile range, 2.7-7.7 years). Multivariate Cox regression analysis of the entire cohort showed that no AR was associated with significantly shorter PFS (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.33-5.42, p = 0.004). The therapeutic effect of AR was confirmed for skull base, but not non-skull base, meningiomas (p = 0.003 and 0.69, respectively). Propensity score matching analysis balanced the influence of confounding factors to generate AR+ and AR- cohorts of 73 patients each. PFS was significantly longer in the AR+ cohort than in the AR- cohort (HR 3.46, 95% CI 1.53-8.59, p = 0.003). Subgroup analysis demonstrated the favorable effect of AR only for skull base meningiomas. CONCLUSIONS: Our study revealed that AR improves tumor control after STR in WHO grade I meningiomas. However, this beneficial effect might be limited to skull base meningiomas.

DOI： 10.1007/s11060-021-03775-x

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While the bilateral common carotid artery (CCA) ligation model is widely used in cerebrovascular disease and dementia studies, it can frequently cause seizures. We examined the validity of seizure as an experimental model of ischemia. Eight-week-old male Wistar and Sprague-Dawley (SD) rats were implanted with electrocorticography (ECoG) electrodes and bilateral CCA ligation was performed and compared to the sham groups. ECoG monitoring was used to confirm the seizure discharge and count the number of spikes in the interictal phase 2 h after ligation, followed by power spectral analysis. Magnetic resonance imaging (MRI) was performed 6 h after bilateral CCA ligation to assess fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) values. Magnetic resonance spectroscopy (MRS) was also performed and the ischemic parameters and electrophysiological changes were compared. The Wistar rat group had significantly higher mortality, frequency of seizures, incidence of non-convulsive seizures, and number of spikes in the interictal period compared to those in the SD rat group. Power spectral analysis showed increased power in the delta band in both Wistar and SD rat groups. MRI, after CCA ligation, showed significantly lower ADC values, lower glutamine and glutamate levels, and higher lactate values in Wistar rats, although there was no difference in FA values. Metabolic and electrophysiological changes after CCA ligation differed according to the rat strain. Wistar rats were prone to increased lactate and decreased glutamine and glutamate levels and the development of status epilepticus. Seizures can affect the results of ischemic experiments.

DOI： 10.2176/nmc.oa.2020-0365

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BACKGROUND: The physiological and pathological significance of the arachnoid membrane (AM) is still unknown. In this study, we investigated various characteristics of the AM, focusing on the influence of inflammation and fibrosis. METHODS: Small pieces of AM sample were obtained during neurosurgical procedures from 74 cases. The clinical and pathological characteristics of the hyperplastic AM group (≥ 50 μm) and the non-hyperplastic AM group (< 50 μm) were compared. Then, potential correlations between AM thickness and clinical characteristics were analyzed. Moreover, VEGFα, TGFβ, and TGFα levels were quantitated by real time PCR. Then, the potential correlations between AM thickness and these inflammatory or anti-inflammatory markers, and the influence of the original disease were calculated. RESULTS: The median age of the patients in hyperplastic AM group was significantly older than that of the non-hyperplastic AM group. Moreover, the number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells in the hyperplastic AM group was significantly higher than that in the non-hyperplastic AM group. The AM thickness was significantly correlated to age and number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells. The thickness of the AM was significantly correlated to the messenger RNA expression levels of VEGFα (ρ = 0.337), and the VEGFα expression levels were significantly correlated with TGFβ and TNFα. CONCLUSIONS: The AM hyperplasia was influenced by aging and could be a result of inflammation and fibrosis through cytokine secretion from the inflammatory cells and fibroblasts in the AM.

DOI： 10.1186/s12883-021-02202-y

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The clearance system in the brain is not completely understood. The aim of this study was to prove the presence of the "glymphatic system" in the human brain using magnetic resonance spectroscopy (MRS).Spectral data of the brain white matter were obtained from healthy volunteers and patients with hydrocephalic dementia and used to measure intracerebral metabolites, including macromolecules (MMs) and lipids. Data were transferred from the MRS scanners to a workstation, and metabolites were quantified with the spectrogram-based eddy current method and water scaling.MM levels were significantly higher in patients with a slow gait and executive dysfunction due to normal pressure hydrocephalus (NPH) than in asymptomatic volunteers (p <0.01). In contrast, the N-acetyl aspartate (NAA) level was significantly lower in patients with executive dysfunction than in asymptomatic volunteers (p <0.01). There were no statistically significant differences in metabolites, including alanine, aspartate, creatine, γ-amino butyric acid, D-glucose, glutamine, glutamate, glycerophosphorylcholine, phosphorylcholine, lactate, myoinositol, N-acetyl-aspartyl-glutamate, scyllo-inositol, taurine, creatine methylene, and guanine, in the centrum semiovale between patients with NPH and asymptomatic volunteers.We quantitatively evaluated cerebral metabolites, particularly in the centrum semiovale, with MRS. In the brain of patients with a slow gait and executive dysfunction due to NPH, MRS revealed significantly higher MM levels and lower NAA levels compared to healthy volunteers. Therefore, it may be concluded that the patients have a dysfunctional glymphatic system in the brain.

DOI： 10.2176/nmc.oa.2020-0274

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BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

DOI： 10.1093/neuonc/noaa199

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Although surgical resection is the most preferred treatment for intracranial meningiomas, a detailed analysis of the surgery-related risks based on large population data has not been conducted to date. In this study, we analyzed the nation-wide brain tumor registry to assess the surgical risk factors for intracranial meningiomas to provide information for an optimal treatment strategy. Data of 4081 meningioma patients who underwent initial resection between 2001 and 2008 were extracted from the Brain Tumor Registry of Japan (BTRJ) database and reviewed for postoperative mortality, aggravation of Karnofsky Performance Score (KPS), and complications. The total in-hospital mortality rate was 0.59%. Male sex and tumor size ≥30 mm were independent risk factors for mortality. Among 4081 cases, 4.4% of patients had KPS that were lowered by 20 or more points at the time of discharge after surgery. Age ≥65 years, higher WHO grading, tumor location at the skull base, tumor size ≥30 mm, and non-gross total resections were associated with lowering of KPS scores by 20 or more points. The overall incidence of surgical complications was 19.3%. The rate of occurrence of new postoperative seizure in patients with supratentorial meningioma was 10.9%. All complications except for vascular complications occurred with significantly lower frequencies in asymptomatic patients than in symptomatic patients. Our results provide useful information regarding the surgical risks when surgical intervention is being considered for intracranial meningiomas. Surgery is an important option for asymptomatic meningiomas as the mortality rate and complication rate in the current study were sufficiently low.

DOI： 10.2176/nmc.oa.2020-0304

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Gliomas are sometimes difficult to differentiate from strokes and are often misdiagnosed on magnetic resonance imaging (MRI); thus, the terms "stroke mimics" and "stroke chameleons" have been introduced. In this study, we analyzed stroke mimics and stroke chameleons in glioma and discussed the diagnostic perplexity.We retrospectively reviewed cases that were removed from lesions that were considered to be brain tumors. This study enrolled 214 patients who underwent tumor resection for suspected glioma. Clinical characteristics and radiological findings of the patients were compared between the masquerade findings group, which was further divided into two groups: the stroke chameleons and stroke mimics according to their final diagnosis, and the intelligible findings group.Stroke chameleons and stroke mimics were significantly higher in age and smaller in lesion size than the intelligible findings group. In the multivariate analysis, the predictive factor of the masquerade finding group was higher age and smaller size. Stroke mimics group has a tendency to be higher rate of hyperintensity lesion on diffusion-weighted imaging (DWI) compared with stroke chameleons group. The average period from initial diagnosis to pathological diagnosis was 13.50 days in the stroke chameleons and 61.50 days in the stroke mimics, which proved significantly different.Proper diagnosis of glioma and stroke affects a patient's prognosis, and should be diagnosed as soon as possible. However, stroke mimics and stroke chameleons caused by glioma can occur. Thus, the diagnosis of a stroke should take into consideration the possibility of a glioma in real clinical situations.

DOI： 10.2176/nmc.oa.2020-0309

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BACKGROUND: The large number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into fear in recent times. In Japan, 18,769 novel coronavirus disease 2019 (COVID-19) cases have been reported as of June 30, 2020. This study aimed to assess whether cluster infection prevention is possible by evaluating the association between viral transmission and meteorological factors. METHODS: This study included 1263 people who were successively diagnosed with COVID-19 in Hokkaido, Japan between January 24, 2020 and June 30, 2020. After obtaining the values from the Japanese Meteorological Agency, the average scores of air temperature and humidity were calculated and compared with COVID-19 reproduction numbers, and the association between COVID-19 incidence or reproduction number and meteorological factors was assessed. RESULTS: The COVID-19 reproduction number in Hokkaido had three peaks that came several days before the surge in COVID-19 cases. The peaks are indicative of cluster infections. There was a strong negative correlation between the kinematic viscosity of atmospheric air and the reproduction number. DISCUSSION AND CONCLUSION: Analysis of the reproduction number is important for predicting or suppressing COVID-19 infection clusters. The authors found a strong association between meteorological factors, such as kinematic viscosity of atmospheric air and the incidence of COVID-19 infection. Meteorological forecasts could provide foreknowledge about COVID-19 infection clusters in the future.

DOI： 10.1016/j.virusres.2020.198259

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Awake craniotomy has been widely performed in patients with glioma in eloquent areas to minimize postoperative brain dysfunction. However, neurological examination in awake craniotomy is sometimes problematic due to communication difficulties during the intraoperative awake period. We evaluated preoperative predictors of these difficulties in awake craniotomy for patients with glioma. In all, 136 patients with glioma who underwent awake craniotomy at our institution between January 2012 and January 2020 were retrospectively evaluated. Patients were divided into two groups (appropriately awake group and inappropriately awake group) depending on their state during the intraoperative awake period, and the relationship between communication difficulties in awake craniotomy and both clinical and radiological characteristics were assessed. The appropriately awake group included 110 patients, and the inappropriately awake group included 26 patients. Reasons for inclusion in the inappropriately awake group were insufficient wakefulness in 15 patients, restless state in 6, and intraoperative seizures in 5. In multivariate analysis, the likelihood of being inappropriately awake was inversely correlated with preoperative seizures (odds ratio [OR], 0.23; 95% confidence interval [CI], 0.06-0.89; p = 0.033) and positively correlated with left-sided lesions (OR, 7.31; 95% CI, 1.54-34.62; p = 0.012). Both lack of preoperative seizures and left-sided lesions were identified as risk factors for intraoperative difficulties in awake craniotomy for patients with glioma. Understanding these risk factors may lead to more appropriate determination of eligibility for awake craniotomy.

DOI： 10.2176/nmc.oa.2020-0232

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OBJECTIVES: Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass operation is an effective treatment for patients with Moyamoya disease, and the hemodynamic parameters are reported to be improved after operation. However, there is no report concerning hemodynamic changes from the viewpoint of the preoperative anatomical structure of grafts. In this study, we evaluated the correlation between the preoperatively estimated blood flow of the graft obtained through image-based computational fluid dynamics (CFD) analysis and the hemodynamic changes in the acute phase after revascularization. MATERIALS AND METHODS: A total of 30 hemispheric sides of 23 patients were examined. The blood flow, that is, flow rate (FR) of the STA branches that were anastomosed to the MCA was evaluated using CFD analysis based on computed tomography (CT) angiography imaging data. The correlations between the FR and the hemodynamic changes in the acute phase after revascularization obtained through CT perfusion were assessed. RESULTS: The preoperatively estimated FR of the graft was moderately correlated with the changes in the mean transit time significantly and weakly correlated with those in the cerebral blood flow and cerebral blood volume. In addition, the FR was strongly correlated with age and the diameter of the STA from the origin to the bifurcation. CONCLUSION: The preoperatively estimated FR of the graft obtained through image-based CFD analysis contributed to the improvement of the mean transit time after revascularization. Because the FR of the graft was associated with the diameter of the STA, the size of the STA might be an important factor in postoperative hemodynamic changes. This might lead to the risk assessment of acute drastic hemodynamic changes as cerebral hyperperfusion, and consequently, better surgical outcomes might be expected.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105450

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BACKGROUND: Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion? METHODS: Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI). RESULTS: A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI. CONCLUSION: CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.

DOI： 10.1093/noajnl/vdab086

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OBJECTIVE: Grade 2 meningioma is more likely to recur than grade 1 meningioma. Recurrence decreases overall survival in patients with grade 2 meningioma. However, the clinical course of grade 2 meningioma with several repeated recurrences is poorly understood. The purpose of this study was to clarify the clinical characteristics of grade 2 meningioma with repeated recurrences. METHODS: This study included 28 patients with grade 2 meningioma treated at our institution from January 1994 to December 2017. The relationship between survival and factors including age, sex, number of recurrences, malignant transformation, radiation therapy, tumor location, MIB-1 labeling index, Simpson grade, Karnofsky Performance Status, and surgical interval were analyzed. RESULTS: The average age at the initial operation was 53.4 years. The number of recurrences was 3.7 times on average during the follow-up of 113.9 months after the initial operation. An increasing number of recurrences resulted in shortening of the surgical interval, increase in the MIB-1 labeling index, and decrease in Karnofsky Performance Status. In fatal cases, the average surgical interval before death was approximately 1 year. Three factors were related to poor prognosis: number of recurrences (odds ratio, 1.620; P = 0.030), malignant transformation (odds ratio, 10.625; P = 0.019), and high MIB-1 labeling index (odds ratio, 1.089; P = 0.044). CONCLUSIONS: Shortening of the surgical interval within 1 year because of multiple recurrences led to death in patients with grade 2 meningioma. Malignant transformation was the most potent among the poor prognostic factors.

DOI： 10.1016/j.wneu.2020.05.145

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OBJECTIVES: Moyamoya disease is a unique cerebrovascular disorder that is characterized by chronic bilateral stenosis of the internal carotid arteries and by the formation of an abnormal vascular network called moyamoya vessels. In this stury, the authors inspected whether differentiation between patients with moyamoya disease and those with atherosclerotic disease or normal controls might be possible by using deep machine learning technology. MATERIALS AND METHODS: This study included 84 consecutive patients diagnosed with moyamoya disease at our hospital between April 2009 and July 2016. In each patient, two axial continuous slices of T2-weighed imaging at the level of the basal cistern, basal ganglia, and centrum semiovale were acquired. The image sets were processed by using code written in the programming language Python 3.7. Deep learning with fine tuning developed using VGG16 comprised several layers. RESULTS: The accuracies of distinguishing between patients with moyamoya disease and those with atherosclerotic disease or controls in the basal cistern, basal ganglia, and centrum semiovale levels were 92.8, 84.8, and 87.8%, respectively. CONCLUSION: The authors showed excellent results in terms of accuracy of differential diagnosis of moyamoya disease using AI with the conventional T2 weighted images. The authors suggest the possibility of diagnosing moyamoya disease using AI technique and demonstrate the area of interest on which AI focuses while processing magnetic resonance images.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105322

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OBJECTIVES: Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to assess cerebral perfusion. When tissue perfusion is impaired, such as in Moyamoya disease, a hyperintense band called the arterial transit artifact (ATA) may occur, which interferes with accurate measurements on ASL-MRI. In this study, we evaluated the correlation of ATAs with magnetic resonance angiography (MRA) and single-photon emission computed tomography (SPECT) imaging results in Moyamoya disease. The aim of our study was to elucidate the pathophysiology of ATAs and risk factors for high ATA scores. MATERIALS AND METHODS: This retrospective study included 28 patients (56 hemispheres) with Moyamoya disease treated at our institution. MRI, MRA, ASL perfusion, and N-isopropyl-[123I] b-iodoamphetamine (123I-IMP) SPECT were performed. In order to semi-quantitatively evaluate the degree of ATA, the ATA scores were measured according to the number of hyperintense signal bands in the cerebral cortex. The relationship between the ATA scores and clinical and radiological factors were analyzed. RESULTS: Regional cerebral blood flow (rCBF) determined with ASL weakly correlated with that determined by 123I-IMP SPECT (ρ=0.31, p=0.027). There was no significant association between the ATA scores and rCBF values determined with 123I-IMP SPECT (p=0.872, 0.745, 0.743 at PLD1000 (post-labeling delay), 1500, and 2000, respectively). However, there was a significant correlation between ATA scores and MRA scores (ρ=0.427 p=0.001; ρ=0.612 p=0.001; ρ=0.563 p=0.001 at PLD1000, 1500, and 2000, respectively). An analysis of patient background characteristics revealed a significantly higher incidence of high ATA scores in female patients, patients with high MRA scores, and patients with a distinguishable ivy sign. A multivariate analysis confirmed that female sex, high MRA score, and presence of an ivy sign were risk factors for high ATA scores. CONCLUSION: ATA scores were moderately correlated with MRA scores, and presence of an ivy sign was the most predictive factor for high ATA scores. A high ATA score determined using ASL in a patient with Moyamoya disease might suggest an advanced disease stage and a reduction in cerebrovascular reserve capacity.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105058

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Giant thrombosed middle cerebral artery (MCA) aneurysms are difficult to treat and sometimes require complex revascularization using allografts. We describe a technical method using revascularization with a natural Y-shaped graft that provides a normal variation for a complex MCA aneurysm. A 65-year-old man with a giant thrombosed MCA aneurysm presented with right hemiparesis and aphasia. The patient had a history of clipping surgery for the ipsilateral side of the MCA aneurysm 25 years before, and a de novo aneurysm developed over the previous 18 years. For the giant thrombosed aneurysm, trapping and revascularization were performed. A natural radial artery Y-graft was used as the graft and anastomosed to both M2 trunks. The symptoms improved after surgery, and the patient was discharged 3 weeks later. This is the first report of a double-barrel bypass using a natural Y-graft. This method attained a normal variation, and the flow of the Y-graft was physiological. For the radical cure of giant thrombosed MCA aneurysms, multiple revascularizations might be required. With this natural Y-graft, complex transpositions could be avoided.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104853

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OBJECTIVES: Balloon test occlusion (BTO) is performed to evaluate ischemic tolerance for large and giant cerebral aneurysms and head and neck tumors that may require parent artery occlusion. However, ischemic tolerance for the temporary test occlusion does not always guarantee a tolerance for permanent occlusion. In this study, we evaluated the utility of computed tomography (CT) perfusion during BTO to quantify ischemic tolerance for detecting delayed ischemic stroke. MATERIALS AND METHODS: Forty-one patients who underwent BTO for the internal carotid artery were included. The correlations between the parameters of CT perfusion and collateral angiographic appearance or stump pressure during BTO were evaluated. The cerebral blood flow (CBF), cerebral blood volume, mean transit time (MTT), and time to peak (TTP) were obtained through CT perfusion, and the asymmetry ratios were determined. Collateral angiographic appearances were categorized into 5 grades (0-4). RESULTS: The collateral angiographic appearance showed moderate correlations with CBF, MTT, and TTP that was significant. Of these, the absolute value of the correlation coefficient was the highest for MTT. MTT also showed a moderate correlation with stump pressure. CBF and MTT were significantly different between the poor collateral group (grades 2 and 3) and the good collateral group (grade 4). Based on the MTT, the good collateral group was identified with high sensitivity (75.0%) and specificity (81.2%). CONCLUSIONS: In BTO, the MTT obtained through CT perfusion showed a correlation with collateral angiographic appearance and stump pressure. Thus, the MTT might be useful to quantify ischemic tolerance for detecting delayed ischemic stroke.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104807

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The purpose of this study was to investigate whether and how vagus nerve stimulation (VNS) reduces the epileptogenic activity in the bilateral cerebral cortex in patients with intractable epilepsy. We analyzed the electrocorticograms (ECoGs) of five patients who underwent callosotomy due to intractable epilepsy even after VNS implantation. We recorded ECoGs and analyzed power spectrum in both VNS OFF and ON phases. We counted the number of spikes and electrodes with epileptic spikes, distinguishing unilaterally and bilaterally hemispherically spread spikes as synchronousness of the epileptic spikes in both VNS OFF and ON phases. There were 24.80 ± 35.55 and 7.20 ± 9.93 unilaterally spread spikes in the VNS OFF and ON phases, respectively (P = 0.157), and 35.8 ± 29.21 and 10.6 ± 13.50 bilaterally spread spikes in the VNS OFF and ON phases, respectively (P = 0.027). The number of electrodes with unilaterally and bilaterally spread spikes in the VNS OFF and ON phases was 3.84 ± 2.13 and 3.59 ± 1.82 (P = 0.415), and 8.20 ± 3.56 and 6.89 ± 2.89 (P = 0.026), respectively. The ECoG background power spectra recordings in the VNS OFF and ON phases were also analyzed. The spectral power tended to be greater in the high-frequency band at VNS ON phase than OFF phase. This study showed the reduction of epileptogenic spikes and spread areas of the spikes by VNS as immediate effects, electrophysiologically.

DOI： 10.2176/nmc.oa.2019-0221

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Extracranial-to-intracranial (EC-IC) bypass surgery is an effective treatment for patients with moyamoya disease and other conditions. Some patients with moyamoya disease have a risk of acute thrombogenesis at the anastomotic site just after bypass surgery. The purpose of this study was to study risk factors of acute thrombogenesis and determine effective countermeasures. This study included 48 patients (66 EC-IC bypass procedures) with moyamoya disease and 52 controls (54 procedures) without moyamoya disease. The development of acute thrombogenesis was compared between the moyamoya disease and control groups. In the moyamoya disease group, clinical and radiological characteristics were assessed with respect to acute thrombogenesis. In the patients with acute thrombogenesis, causes of technical problems were retrospectively examined. The incidence of acute thrombogenesis was significantly higher in the moyamoya disease group than those in the control group. In the moyamoya disease group, acute thrombogenesis was observed in seven patients. In the moyamoya disease group, the magnetic resonance angiography (MRA) scores were significantly higher in patients with acute thrombogenesis than those in the patients without acute thrombogenesis. In the multivariate analysis, the predictive factor of acute thrombogenesis in moyamoya disease was a high MRA score (odds ratio, 2.336; p = 0.009). During EC-IC bypass surgery for moyamoya disease, acute thrombogenesis should be considered to obtain a high patency rate, particularly in patients with high MRA scores. Acute thrombogenesis will not influence morbidity if proper countermeasures are followed; therefore, the prediction and recognition of white thrombus are important for a successful bypass surgery.

DOI： 10.1007/s10143-019-01086-4

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Diffuse astrocytic and oligodendroglial tumors are frequently associated with symptomatic epilepsy, and predictive seizure control is important for the improvement of patient quality of life. To elucidate the factors related to drug resistance of brain tumor-associated epilepsy from a pathological perspective. From January 2012 to October 2017, 36 patients diagnosed with diffuse astrocytic or oligodendroglial tumors were included. Assessment for seizure control was performed according to the Engel classification of seizures. Patient clinical, radiological, and pathological data were stratified based on the following 16 variables: age, sex, location of tumor, existence of the preoperative seizure, extent of resection, administration of temozolomide, radiation therapy, recurrence, Karnofsky performance scale, isocitrate dehydrogenase 1, 1p/19q co-deletion, Olig2, platelet-derived growth factor receptor alpha, p53, ATRX, and Ki67. These factors were compared between the well-controlled group and drug-resistant seizure group. Twenty-seven patients experienced seizures; of these, 14 cases were well-controlled, and 13 cases were drug-resistant. Neither clinical nor radiological characteristics were significantly different between these two groups, though p53 immunodetection levels were significantly higher, and the frequency of 1p/19q co-deletion was significantly lower in the group with drug-resistant seizures than in the well-controlled group. In the multivariate analysis, only one item was selected according to stepwise methods, and a significant difference was observed for p53 (OR, 21.600; 95% CI, 2.135-218.579; P = 0.009). Upregulation of p53 may be a molecular mechanism underlying drug resistant epilepsy associated with diffuse astrocytic and oligodendroglial tumors.

DOI： 10.2176/nmc.oa.2019-0218

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Postoperative visual function is a major concern in transsphenoidal surgery (TSS). Although several reports have demonstrated the importance of visual evoked potential (VEP) monitoring during TSS, the usefulness of VEP monitoring have been controversial because of its reproducibility. Efficacy of VEP was analyzed in 20 consecutive cases of patients who underwent endoscopic endonasal TSS surgery. We adapted a high-power light-emitting diode stimulator with electroretinography using venous anesthesia. In addition, we used black shield patch and braided codes to obtain reproducible VEP amplitudes. Stable and reproducible VEP waveforms were obtained in 38 of 39 eyes (97.4%) before surgery. Fifteen eyes had deteriorated VEP amplitude during operation, and nine eyes had improved VEP amplitude at the end of surgery, and six eyes had not improved VEP amplitude. But no postoperative visual impairment was observed in all cases by temporary halting the surgical manipulation when the VEP was deteriorated. In conclusion, VEP monitoring could be a warning sign to avoid postoperative visual dysfunction. We recommend VEP as a routine monitoring in TSS.

DOI： 10.1007/s10143-018-1024-3

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BACKGROUND: Intraventricular schwannoma is extremely rare, with only 35 cases reported to date in the literature. Consequently, its etiology and pathogenesis are still unclear, and therefore require further investigations. Here, we report on and discuss a rare case of intraventricular schwannoma to elucidate on this matter. CASE DESCRIPTION: A 26-year-old man was admitted to our institution with a 1-month history of headaches and left hemianopsia. At diagnosis, magnetic resonance imaging of the brain revealed a well-demarcated mass with surrounding edema in the right lateral ventricle. Total resection of the tumor was performed by a transsulcal approach through the right parietal lobe. In surgery, it was observed that the tumor was attached to the choroid plexus without invading the wall of the right lateral ventricle. The respective histologic examination confirmed the diagnosis of intraventricular schwannoma. Six months after the surgery, there was no recurrence. Additionally, during this follow-up period, the patient did not develop any neurologic deficit, including visual field narrowing or parietal symptoms, such as acalculia and right-left, finger, and space agnosias. CONCLUSIONS: Although intraventricular schwannomas are rare, 35 cases have already been reported to date. We emphasize the importance of diagnosing such cases correctly to increase knowledge on the origin and pathogenesis of intraventricular tumors, which would facilitate disease management.

DOI： 10.1016/j.wneu.2019.09.137

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To describe the far-anterior interhemispheric transcallosal approach for the treatment of a central neurocytoma at the roof of the lateral ventricle. In comparison to the view obtained during the usual anterior transcallosal approach, the far-anterior approach allowed for a higher view of the lateral ventricle to be obtained without further injury or retraction of the corpus callous. Two patients with central neurocytoma in the lateral ventricle were treated with the far-anterior interhemispheric transcallosal approach. Gross-total resections were achieved in both the patients without any postoperative neurological impairments by only 2-3 cm incisions of the corpus callosum. With the anterior transcallosal approach, which was usually used for the intraventricular tumors, the surgical view was relatively downward into the lateral ventricle and suitable for the resection of the tumors located at the base of the lateral ventricle or even in the third ventricle through the foramen of Monro. However, it was relatively difficult to reach the roof of the lateral ventricle using this approach. In contrast, the surgical corridor of the far-anterior transcallosal approach reaches upward to the roof of the lateral ventricle. The far-anterior transcallosal approach provides an alternative to reach the lesions, especially those located in the upper region of the lateral ventricle near important structures, such as the pyramidal tracts.

DOI： 10.2176/nmc.tn.2019-0130

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DOI： 10.1007/s10143-019-01184-3

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Adult orbital xanthogranuloma is rare and usually associated with systemic disease. There are several options available to treat this disorder. Periorbital lesions are treated with steroids, chemotherapy, radiotherapy, or local excision; however, there is still no consensus regarding optimal treatment. Here, we report a rare case of orbital xanthogranuloma that was not associated with systemic disease and was treated by transcranial surgery. The patient was a 52-year-old man who presented with a 2-year history of unilateral eye symptoms. A computed tomography scan revealed a well-defined mass in the right orbit. The mass was completely removed via a transcranial orbital approach. The histopathologic diagnosis was xanthogranuloma. No recurrence was observed during 15 months of postoperative follow-up. Complete surgical resection might be an effective treatment option for locally growing sporadic adult xanthogranulomatous disease of the orbit, and allows systemic steroids, chemotherapy, and irradiation to be avoided.

DOI： 10.2176/nmccrj.cr.2018-0304

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BACKGROUND: Primary extracranial meningiomas are uncommon neoplasms. In particular, meningioma involving the hypoglossal canal is extremely rare, with only 4 cases reported in the literature so far. Given that each of these meningiomas originated in the juxtacondyle region with involvement of the hypoglossal canal, to the best of our knowledge, a meningioma that exists only within the hypoglossal canal has yet to be reported. CASE DESCRIPTION: We present a case of primary extracranial meningioma arising solely from the hypoglossal canal. A 62-year-old woman presented with long-term difficulty in tongue movement. Her tongue was deviated to the right, and neurologic examination revealed fasciculation and muscle wasting on the right side of the tongue. Computed tomography revealed a calcification in the right hypoglossal canal. Magnetic resonance imaging further demonstrated a hypointense tumor on both T1-weighted and T2-weighted images, with contrast enhancement in the right condyle. Total tumor removal was performed via a transcondylar approach, and histopathologic examination confirmed the presence of a transitional meningioma. No recurrence was observed at 14 months of follow-up. The patient's tongue atrophy was slightly improved, and the deviation completely disappeared. CONCLUSIONS: In this extremely rare case of hypoglossal canal meningioma, total tumor removal via a transcondylar approach resulted in the recovery of hypoglossal nerve function.

DOI： 10.1016/j.wneu.2019.04.084

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BACKGROUND: Previous studies have reported the usefulness of intraoperative corticocortical evoked potentials (CCEPs) for preserving language function during brain surgery. OBJECTIVE: This study aimed to assess the influence of depth of anesthesia on CCEP to establish its clinical utility. METHODS: Twenty patients with brain tumors or epilepsy who underwent awake craniotomy were included in this study. Before resection, the electrode plates were placed on the frontal and temporoparietal cortices, and 1-Hz alternating electrical stimuli were delivered to the pars opercularis/pars triangularis in a bipolar fashion. Electrocorticograms from the temporoparietal cortices time-locked to stimuli were averaged to obtain CCEP responses from a state of deep anesthesia until the awake state. The correlation between CCEP waveforms and bispectral index (BIS) was evaluated. RESULTS: CCEP amplitude increased with the increase in the BIS level. CCEP latency decreased in 5 patients and increased in 15 patients under anesthesia compared with the awake state. CCEP amplitudes decreased by 11.3% to 75.2% (median 31.3%) under anesthesia with <65 BIS level. These differences were statistically significant (P < 0.01, Wilcoxon signed-rank test). With respect to CCEP latencies, there was no significant difference between the awake and anesthetic states. CONCLUSIONS: CCEP amplitudes were correlated with depth of anesthesia, whereas CCEP latencies were not affected by anesthesia. The influence of anesthesia should be considered when applying this technique to intraoperative monitoring.

DOI： 10.1016/j.wneu.2018.11.253

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BACKGROUND: Scalp tissue shrinkage and volume contraction is a major problem in cranioplasty, and sometimes a tissue expander must be set before cranioplasty. The procedure for placing scalp expanders is cumbersome. In this study, we present a method for flattening the curvature of synthetic materials to relieve scalp skin tension and discuss the feasibility and limitations of the method. METHODS: A total of 25 cranioplasty patients were included in this study. The optimal degree of curvature flattening for each piece of bone substitute material was determined based on cosmetic considerations and the extent of encephalomalacia or atrophy due to primary disease. In this series, the correlation between the degree of curvature flattening and the size or location of the bone flap was considered, and the amount of scalp surface area that could be obtained through curvature flattening was estimated. RESULTS: The median degree of curvature flattening was 5.0 mm. The degree of curvature flattening showed moderate correlation with the rate of change in the area of synthetic material achieved through curvature flattening (p < 0.001). The 21 cases of fronto-temporal craniectomy were divided into two groups according to the distance from the midline. There was a statistically significant difference between these two groups in degree of flattening curvature. CONCLUSIONS: In the present cranioplasty series using synthetic materials, curvature flattening was a non-invasive and convenient method for skin closure. This method can be beneficial especially in patients requiring a larger craniotomy including convexity regions.

DOI： 10.1016/j.jocn.2018.10.032

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kowsar Medical Publishing Company  

DOI： 10.5812/ijp.68869

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DOI： 10.1016/j.inat.2018.07.011

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BACKGROUND: Microvascular anastomosis is an essential procedure in neurosurgery, but the opportunity to perform the surgery has gradually decreased for neurosurgeons. Therefore, training is necessary for obtaining and maintaining the skills required for the procedure. We describe the detailed anatomy of cervical and femoral regions in rats and discuss the advantages for practicing microvascular anastomosis. METHODS: Cervical regions of Sprague-Dawley rats were dissected under intraperitoneal anesthesia. The step-by-step anatomic description was documented using a high-resolution charge-coupled device image sensor and recording systems. Using this model, temporal occlusion time and patency were measured, and these measures were compared between the trainee and trainer groups. The number of times the training needs to be completed to attain competency in the bypass procedure was estimated. RESULTS: After exposing the carotid triangle, a half-ring was created by end-to-side anastomosis. Anastomosis was performed at the common carotid artery using the contralateral side of the carotid artery as a graft. The cutoff value for the temporal occlusion time was 79.3 minutes in the receiver operating characteristic curve based on a target temporal occlusion time for beginners determined during the training. CONCLUSIONS: Using a living animal model, a trainee has the opportunity to learn not only anastomotic techniques but also hemostatic control as well as overcoming mental strain during surgery. Living animal models are important in training because the fidelity of a living animal model is superior to nonliving models. Applying training using a half-ring model contributes to safe and efficient surgery.

DOI： 10.1016/j.wneu.2018.09.071

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

DOI： 10.1016/j.wneu.2018.08.137

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Aneurysms of the internal carotid artery (ICA) arising from the petrous portion are extremely rare, and most cases are asymptomatic or cause a mass effect leading to palsy of the adjacent cranial nerves. In rupture cases, massive nasal and ear bleeding occurs, which may cause death. We describe a 73-year-old man with a giant ICA aneurysm arising from the petrous portion and presenting as epistaxis. The patient had no history of trauma or clotting disorders. Computed tomography angiography demonstrated a giant petrous carotid aneurysm and erosion of a part of the left temporal bone. The patient was treated by trapping of the aneurysm with high-flow bypass using a radial artery. From an anatomical view point, rupture of ICA aneurysms of this portion might be caused by thinness of the bone partition between the ICA and the sphenoidal sinus. It should be noted that petrous carotid aneurysms are usually asymptomatic but may cause massive epistaxis in cases of rupture.

DOI： 10.1016/j.jocn.2018.10.007

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

Ichushi

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BACKGROUND: Recurrence is inevitable in glioblastomas (GBMs) and requires multifactorial processes. One of the factors that cause recurrence is the strong migratory capacity of GBM cells. We recently reported that actin, alpha, cardiac muscle 1 (ACTC1) could serve as a marker to detect GBM migration in clinical cases. OBJECTIVE: This study aimed to clarify whether the knockdown of highly expressed ACTC1 can inhibit the migratory capacity of cells in the GBM cell line. METHODS: ACTC1 expression was examined using immunocytochemistry and droplet digital polymerase chain reaction. The motility of GBM cells that were either treated with siRNA to knock down ACTC1 or untreated were investigated using a time-lapse study in vitro. RESULTS: The relatively high ACTC1 expression was confirmed in a GBM cell line, i.e., U87MG. The ACTC1 expression in U87MG cells was significantly inhibited by ACTC1-siRNA (p < 0.05). A cell movement tracking assay using time-lapse imaging demonstrated the inhibition of U87MG cell migration by ACTC1 knockdown. The quantitative cell migration analysis demonstrated that the distance traversed during 72 h was 3607 ± 458 (median ± SD) μm by untreated U87MG cells and 3570 ± 748 μm by negative control siRNA-treated cells. However, the distance migrated by ACTC1-siRNA-treated cells during 72 h was significantly shorter (1265 ± 457 μm, p < 0.01) than the controls. CONCLUSION: ACTC1 knockdown inhibits U87MG cell migration.

DOI： 10.1016/j.jns.2018.07.013

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Language：Japanese   Publisher：(一社)日本てんかん学会  

Ichushi

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BACKGROUND: Hypertrophic pachymeningitis (HP) is a rare disorder characterized by diffuse thickening of the dura mater with resultant neurologic deficits. HP develops secondary to various conditions or idiopathically usually in adults but rarely in children. CASE REPORT: We describe a 3-year-old female child with idiopathic HP. Her HP involved the entire central nervous system with progression into the brainstem. The lesion responded poorly to pulsed steroids or any immunosuppressants. The brainstem lesion grew rapidly and formed various nodules that ultimately resulted in brain death. This is the first fatal case of HP in a child.

DOI： 10.1007/s00381-018-3819-5

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In blunt cerebrovascular injury, reported traumatic basilar artery occlusions have involved dissection of the basilar artery, distal embolization due to traumatic vertebral artery dissection, or entrapment of the basilar artery into the clivus fracture. To date, however, there are no reports of traumatic basilar artery entrapment without a clivus fracture. Here, we report the first case of traumatic basilar artery occlusion caused by entrapment into an originally existing bone defect. A 67-year-old man with a history of treatment for intracranial aneurysm suffered multiple traumatic injuries in a fall. On arrival at our hospital, he presented with neurogenic shock with quadriplegia. Computed tomography (CT) showed small epidural hematoma, C4-6 cervical spinous process fracture, and Th2-3 vertebral body fracture. CT angiography revealed occlusion of the basilar artery trunk. As vertebrobasilar artery dissections and clivus fracture were not observed; however, we could not elucidate the pathology of the basilar artery occlusion. On day 4, after surgery for the cervical and thoracic lesions, he exhibited consciousness disturbance. Diffusion-weighted imaging on day 5 showed hyperintensities in the brainstem and cerebellum. Basi-parallel anatomic scanning magnetic resonance imaging showed that the basilar artery, while lacking vascular wall injuries, was tethered into the clivus. Antithrombotic therapy was performed, but the patient progressed to a locked-in state. Previous head CT before the trauma revealed a bone defect already present in the clivus. We speculated basilar artery entrapment into this preexisting bone defect. We must look for basilar artery injury in trauma patients even in the absence of clivus fracture.

DOI： 10.2176/nmc.cr.2018-0041

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BACKGROUND: Preoperative evaluation of malignancy in gliomas is important for surgical planning, particularly to determine whether a 1,3-bis-2-chloroethyl-1-nitrosourea wafer should be placed into the tumor cavity. In some cases, the intraoperative pathologic diagnosis of World Health Organization grade differs from the final diagnosis. Supplemental methods in addition to the routine contrast tomography or magnetic resonance imaging sequences may provide a more accurate preoperative diagnosis. Because tumor vascularity has been useful in distinguishing between low- and high-grade gliomas, we evaluated the accuracy of the arterial spin labeling (ASL) method, which could measure the cerebral blood flow (CBF) without using contrast medium, to determine the malignancy of gliomas. METHODS: This study included 102 patients with glioma (grade II, n = 40; grade III, n = 18; grade IV, n = 44). All patients underwent ASL to determine the tumor blood flow (TBF) and CBF in the middle cerebral region. The relative tumor vascular index (tVI), which is calculated as TBF divided by CBF in the contralateral middle cerebral region, was used to avoid dispersion of the absolute TBF value. RESULTS: tVI was significantly greater (1.46 ± 0.751) in high-grade gliomas than in low-grade gliomas (1.05 ± 0.343) (P = 0.003). As for each grade, tVI was statistically higher in grade IV than in grade II (P = 0.03) gliomas. CONCLUSIONS: The noninvasive ASL method provides additional information to distinguish high-grade glioma from low-grade gliomas without using contrast medium.

DOI： 10.1016/j.wneu.2018.03.015

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OBJECTIVE: To retrospectively determine the safety and efficacy of combined chemotherapy with carmustine (BCNU) wafer, bevacizumab, and temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma (GBM). METHODS: A total of 54 consecutive newly diagnosed GBMs were resected at our institution between 2010 and 2016. Twenty-nine patients underwent BCNU wafer implantation into the resection cavity followed by standard radiochemotherapy with temozolomide (TMZ, Stupp regimen) plus additional bevacizumab treatment between 2013 and 2016. Twenty-five patients who underwent resection without BCNU implantation between 2010 and 2012 were enrolled as a control group; these patients were treated with the Stupp regimen and did not receive bevacizumab. This retrospective study included evaluation of progression-free survival and overall survival, plus comparisons between the combined therapy group and the control group. RESULTS: There were no significant differences in age, sex, Karnofsky Performance Status on admission, isocitrate dehydrogenase 1/2 mutation ratio, or resection rate between the combined and standard therapy groups. The median overall survival in the combined therapy group and control group was 24.2 months and 15.30, respectively (P = 0.027). The median progression-free survival was 16.8 months and 7.30 months, respectively (P = 0.009). Overall, the incidence of adverse events leading to discontinuation of the study drug was similar between the treatment groups, except for infection, which was more common in the combined treatment group and required repeat surgery. CONCLUSIONS: The combined therapy showed higher efficacy compared with standard therapy in patients with GBM. Therefore, combined therapy seems to be effective with an acceptable toxicity profile.

DOI： 10.1016/j.wneu.2018.02.070

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In neurosurgery, extracranial-to-intracranial (EC-IC) bypass surgery is necessary for patients who have undergone surgery in which the superficial temporal artery (STA) was already used for a different bypass procedure or was damaged. Here we report our experience with EC-IC bypass using the occipital artery (OA) in patients in whom the STA was unavailable, and discuss the technical considerations and pitfalls. Five patients with ischemic-onset moyamoya disease and atherosclerotic disease were included. Two patterns of skin incisions were planned according to the OA pathway and recipient artery location. In one of these methods, a skin incision is made above the OA, and a craniotomy is performed under this incision after OA dissection. In the other method, a skin incision is made above the OA to enable its dissection, and a craniotomy is performed via a separate skin incision. No major perioperative complications developed in any of the 5 cases, and bypass patency was confirmed in all patients. There was a significant difference between the preoperative and postoperative asymmetry ratios of the mean transit time values. Our findings suggest that OA-to-middle cerebral artery (MCA) bypass is a simple and effective technique in patients in whom the STA was already used or was damaged by previous intracranial revascularization or craniotomy. This procedure could be an alternative to STA-MCA bypass in patients without an available STA.

DOI： 10.1016/j.wneu.2018.01.103

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BACKGROUND: Ultrasonic bone curettes have been used as with high-speed drills. However, the amount of heat generated by the ultrasonic bone curette is not well known. This study quantitatively assessed the heat generated by an ultrasonic bone curette and compared it to that by a high-speed drill. METHODS: The thermal change in a swine skull during bone curetting using an ultrasonic device and a high-speed drill were assessed. The investigation focused on the type of surgical manipulation (brush-like strokes vs. pushing motion) and irrigation (room temperature vs. cold water; low-volume irrigation vs. high-volume irrigation). RESULTS: The thermal elevation during drill use was suppressed when using brush-like strokes compared to pushing motion (brush-like strokes, 44.7 °C; pushing motion, 69.2 °C; p < 0.01). Cold-water irrigation while drilling had a small effect compared to room temperature (RT) water (RT, 44.7 °C; cold, 35.2 °C; p = 0.12). The temperature generated by the curette was higher than that generated by the drill (curette, 72.5 °C; drill, 44.7 °C; p < 0.01). High-volume irrigation was required to reduce the heat generated by the curette (no irrigation, 88.6 °C; low-volume, 72.5 °C; high-volume, 60.5 °C; p < 0.01). CONCLUSIONS: The ultrasonic bone curate generated more heat than the high-speed drill. During surgical manipulation, the use of brush-like strokes by both the high-speed drill and the ultrasonic bone curette is necessary to avoid excess thermal elevation. Irrigation with RT water is sufficient to avoid heat generation. High-volume irrigation is required to reduce the heat generated by the curette.

DOI： 10.1007/s00701-017-3445-0

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BACKGROUND: Glioblastoma, also known as glioblastoma multiforme, is the most common primary malignant cerebral tumor in adults. Although glioblastoma multiforme is one of the most aggressive tumors in the brain, propagation through the dura mater is rare. CASE DESCRIPTION: A 59-year-old man presented with progressive headache and aphasia. Magnetic resonance imaging identified an abnormal mass extending transcranially through the widened foramen rotundum into the infratemporal fossa and cavernous sinus. Emergency surgery was performed because of the patient's disturbed consciousness and uncal herniation. The pathologic diagnosis was glioblastoma with isocitrate dehydrogenase 1 (IDH-1) wild type arising in the left temporal region of the brain, penetrating the dura mater and propagating to the middle fossa with enlargement of the foramen rotundum. The tumor was resected, and radiochemotherapy with temozolomide was administered. CONCLUSION: Although the mechanism of tumor spread is unknown, we hypothesized that originally there may have been spontaneous dural defects or thinning, such as a meningoencephalocele in the middle fossa, and the tumor coincidentally occurred there.

DOI： 10.1016/j.wneu.2017.12.097

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BACKGROUND: SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1, including the relationship with prognosis, has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of messenger RNA expression from formalin-fixed paraffin-embedded (FFPE) tissues. OBJECTIVE: In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR, and we analyzed its relationship with prognosis. METHODS: Twenty-nine FFPE surgical samples from patients with HGGs (7 of World Health Organization [WHO] grade III and 22 of WHO grade IV), and human glioblastoma cell lines, U87 and U118, were used for analysis. A qualitative assessment using immunostaining and quantitative assessment using digital PCR were performed to assess the expression of SERPINA1. RESULTS: The expression of SERPINA1 was demonstrated in glioma tissues and glioblastoma multiforme cell lines by immunostaining. Digital PCR analysis showed that SERPINA1 was expressed in 14.3% and 63.6% of the tissues from patients with grade III and grade IV HGG, respectively (P = 0.035). The median overall survival of 38.8 months in the low SERPINA1 expression group was longer than that of 15.3 months in the high expression group (P = 0.030). CONCLUSIONS: The frequency and the amount of SERPINA1 expression were higher in grade IV than in grade III HGGs. The high expression of SERPINA1 indicates a poor prognosis of HGGs.

DOI： 10.1016/j.wneu.2017.12.166

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BACKGROUND: Three-dimensional (3D) graphics are used in the medical field, especially during surgery. Although 3D monitoring is useful for medical education, its effectiveness needs to be objectively evaluated. The aim of this study was to investigate the efficacy of 3D monitoring in the surgical education of medical students. METHODS: A questionnaire on high-definition 3D monitoring was given to fifth-year medical students in a 6-year program. Sixty-four students wore polarized glasses and observed a microsurgical operation through a 3D monitor. The questionnaire contained questions on stereopsis, neurosurgical interest, visual impact, comprehension of surgical anatomy and procedures, optical sharpness, active learning enhancement, and eye exhaustion. These parameters were evaluated on a 5-point scale that spanned negative and positive scores. RESULTS: The average score of each parameter ranged from 3.13 to 3.78, except for eye exhaustion, which was 0.88. The items for which the students reported positive perceptions (scores of 4 or 5) were stereopsis (67.2% of students), neurosurgical interest (62.5%), visual impact and optical sharpness (60.9% for both), active learning enhancement (57.8%), and comprehension of surgical anatomy (50.0%) and procedures (42.2%). By contrast, only eye exhaustion was evaluated negatively (26.6%). CONCLUSION: The use of 3D monitoring systems in medical education offers the advantage of stereopsis and contributes to surgical training. However, improvements are required to decrease eye exhaustion.

DOI： 10.1016/j.wneu.2017.09.113

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Due to the recent development of multidetector row computed tomography (CT), hemodynamic parameters can now be conveniently obtained with CT perfusion. The purpose of this study is to characterize the hemodynamic parameters of CT perfusion in moyamoya disease, and to discuss the differences in collateral circulation between moyamoya disease and atherosclerotic disease. A total of 16 hemispheric sides of 15 patients with moyamoya disease and 10 hemispheric sides of 9 patients with atherosclerotic disease who underwent bypass surgery were included. CT perfusion was performed with 123I-IMP SPECT. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values obtained by CT perfusion using standard singular value decomposition as the deconvolution algorithm in moyamoya disease were calculated. Preoperative values of these parameters were compared with those of atherosclerotic disease. Then, the postoperative changes of these parameters were analyzed. In the impaired side, CBF as measured by CT perfusion was correlated with that measured by 123I-IMP SPECT. In moyamoya disease, CBV as measured by CT perfusion was significantly increased compared to in atherosclerotic disease, yet CBF was significantly decreased in atherosclerotic disease. Postoperatively, the asymmetry ratios of MTT were significantly improved, especially in atherosclerotic disease compared with moyamoya disease. On CT perfusion, the parameters included transit time and arrival time. CBV increase in moyamoya disease and postoperative improvement of MTT, especially in atherosclerotic disease, were unique characteristics in each. This might be due to the difference of collateral circulation and compensatory mechanisms between moyamoya disease and atherosclerotic disease.

DOI： 10.1016/j.jocn.2017.09.020

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BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. CASE REPORT 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. CASE REPORT 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. CONCLUSION: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.

DOI： 10.1159/000495344

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

DOI： 10.1016/j.wneu.2017.07.166

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Intraoperative monitoring of the motor evoked potential (MEP) during cerebral aneurysm surgery has been widely used to confirm surgical safety. In this study, we retrospectively analyzed the influence of the MEP amplitude resulting from temporal occlusion of the parent artery, and appropriate judgement in the surgery was discussed. Ten patients underwent temporal occlusion of the parent artery during aneurysm surgery, and five of these patients showed a decrease in the MEP amplitude following temporal arterial occlusion. Clinical factors in patients with and without MEP decrease were compared. The time gap between the surgical procedure and the MEP change and recovery was then investigated. A decrease in the MEP amplitude caused by temporal occlusion had a significantly higher occurrence compared with permanent clip failure. The time from the release procedure to MEP amplitude recovery was relatively longer than the time from the occlusion procedure to the decrease in MEP amplitude. The time from release procedure to MEP amplitude recovery showed a weak correlation with the parent artery occlusion time. There is a time gap between releasing the temporal arterial occlusion and MEP recovery that is similar to temporal parent arterial occlusion and the MEP decrease. The cause of MEP amplitude should be judged carefully, and influence of parent artery temporal occlusion should be taken into consideration during aneurysm clipping.

DOI： 10.1016/j.jocn.2017.06.002

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BACKGROUND: Dilatation of the microvascular diameter is recognized in moyamoya disease and referred to as microvascularization. The purpose of this study was to characterize the cortical microvascularization in moyamoya disease using imaging analysis, and to explore the developmental mechanism of the collateral network around the cortical surface. METHODS: A total of 20 hemispheric sides of 14 patients with moyamoya disease were included in this study. From the intraoperative images, cortical surface images were extracted, and binary images were subsequently created. Then the ratio of the microvessels of the brain surface (vascular fraction; VF) and the box-counting fractal dimension (Db) values were calculated. The VF and Db values in the moyamoya disease group were then compared with those in atherosclerotic disease and nonischemic disease groups, and assessed in terms of clinical and radiologic factors. RESULTS: VF was significantly higher in the moyamoya disease group compared with the atherosclerotic disease group, and Db was significantly higher in the moyamoya disease group compared with the atherosclerotic disease and nonischemic disease groups. In the moyamoya disease group, VF showed a moderate correlation with magnetic resonance angiography (MRA) score. Moreover, Db was significantly higher in the pediatric patients, in the presence of ischemic symptoms, and in the presence of ivy sign, and Db showed a moderate correlation with MRA score and cerebral blood flow in moyamoya disease. CONCLUSIONS: In the patients with moyamoya disease, the cortical microvascularization exhibited increased Db and dilatation of the pial arteries. In moyamoya disease, cortical microvascularization is associated with clinical and radiologic factors. This microvascularization might be a compensatory mechanism in the ischemic condition in moyamoya disease.

DOI： 10.1016/j.wneu.2017.06.124

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Language：Japanese   Publisher：(一社)日本てんかん学会  

Ichushi

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BACKGROUND: Spinal subdural hematoma is a rare clinical entity marked by the onset of pain and paralysis, which is usually associated with hemorrhagic disorders, trauma, and iatrogenic causes such as lumbar puncture or epidural anesthesia. CASE DESCRIPTION: A 71-year-old man was admitted to our hospital with 2 weeks' history of bilateral lower leg pain, dysesthesia, paraparesis, and urinary disturbance. Magnetic resonance imaging showed characteristic findings at the thoracolumbar spine, and surgical evacuation successfully treated this condition. The postoperative course was uneventful. The patient gradually recovered from paraparesis and was discharged 4 weeks after operation. CONCLUSIONS: We report an extremely rare case of chronic spinal subdural hematoma associated with antiplatelet therapy. Spinal subdural hematoma should be considered as the differential diagnosis of gait disturbance in patients undergoing antiplatelet therapy. Early diagnosis and identification of the extent of the hematoma are necessary for successful treatment.

DOI： 10.1016/j.wneu.2016.11.128

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OBJECTIVE: To evaluate motor function during neuroendoscopic resectioning of deep-seated brain tumors using endoscopically guided depth electrodes. METHODS: For 12 cases of thalamic tumors, including high-grade gliomas, germinomas, and malignant lymphomas, depth electrodes were inserted using endoscopic guides between the tumor and the pyramidal tract in the thalamus. Motor-evoked potentials (MEPs) were continuously recorded during neuroendoscopic resectioning of the tumors. RESULTS: Monitoring of MEP responses using depth electrodes in all 12 cases was successful. The minimum stimulus intensity threshold required to induce MEP responses was 3 mA. Gross total or subtotal resections were successful with this technique for all patients with glioma. No additional neurologic impairments were found after surgery in any of the cases. CONCLUSIONS: Continuous MEP measurement using depth electrodes can serve as a new monitoring technique for endoscopic resectioning of deep-seated brain tumors.

DOI： 10.1016/j.wneu.2017.05.048

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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OBJECTIVE Medullary streaks detected on fluid-attenuated inversion recovery (FLAIR) imaging have been considered to be reflected ischemic regions in pediatric moyamoya disease. The purpose of this study was to evaluate these medullary streaks both clinically and radiologically and to discuss associated pathophysiological concerns. METHODS The authors retrospectively reviewed data from 14 consecutive pediatric patients with moyamoya disease treated between April 2009 and June 2016. Clinical and radiological features and postoperative imaging changes were analyzed. In 4 patients, hyperintense medullary streaks on FLAIR imaging (HMSF) at the level of the centrum semiovale were detected. RESULTS The HMSF were coincident with hyperintense medullary streaks on a T2-weighted image, though they were not completely coincident with the vasculature on either a T2*-weighted image or contrast-enhanced CT. Analysis revealed significantly higher values in terms of MR angiography scores, number of flow voids of the basal ganglia, and the presence of the medullary artery in the group with HMSF than in those without. In contrast, the presence of white matter damage was significantly less frequent in the HMSF group. All HMSF disappeared after surgery, and the mean apparent diffusion coefficient at the same level was significantly reduced postoperatively. CONCLUSIONS Although HMSF should be associated with collateral circulation in moyamoya disease, other factors may be involved, including stagnated cerebrospinal fluid or vasogenic edema that is relevant to the impaired state of the white matter. Findings in this study provide insight into the pathophysiological basis of the perivascular space in moyamoya disease.

DOI： 10.3171/2017.1.PEDS16541

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DOI： 10.3171/2016.1.JNS152075

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The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1-5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70-100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12-35%) and 8% (95% CI, 4-15%). Median PFS was 13 months (95% CI, 9.2-17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67-89%) and 49% (95% CI, 33-57%). Median OS was 11.8 months (95% CI, 8.2-14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS.

DOI： 10.2176/nmc.oa.2016-0162

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OBJECTIVE Motor evoked potentials (MEPs) are a critical indicator for monitoring motor function during neurological surgery. In this study, the influence of depth of anesthesia on MEP response was assessed. METHODS Twenty-eight patients with brain tumors who underwent awake craniotomy were included in this study. From a state of deep anesthesia until the awake state, MEP amplitude and latency were measured using 5-train electrical bipolar stimulations on the same site of the precentral gyrus each minute during the surgery. The depth of anesthesia was evaluated using the bispectral index (BIS). BIS levels were classified into 7 stages: < 40, and from 40 to 100 in groups of 10 each. MEP amplitude and latency of each stage were compared. The deviation of the MEP measurements, which was defined as a fluctuation from the average in every BIS stage, was also considered. RESULTS A total of 865 MEP waves in 28 cases were evaluated in this study. MEP amplitude was increased and latency was decreased in accordance with the increases in BIS level. The average MEP amplitudes in the > 90 BIS level was approximately 10 times higher than those in the < 40 BIS level. Furthermore, the average MEP latencies in the > 90 BIS level were 1.5-3.1 msec shorter than those in the < 60 BIS level. The deviation of measured MEP amplitudes in the > 90 BIS level was significantly stabilized in comparison with that in the < 60 BIS level. CONCLUSIONS MEP amplitude and latency were closely correlated with depth of anesthesia. In addition, the deviation in MEP amplitude was also correlated with depth of anesthesia, which was smaller during awake surgery (high BIS level) than during deep anesthesia. Therefore, MEP measurement would be more reliable in the awake state than under deep anesthesia.

DOI： 10.3171/2015.11.JNS151291

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Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a "coated artery," which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient's condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation.

DOI： 10.2176/nmccrj.cr.2015-0331

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BACKGROUND: Pleomorphic xanthoastrocytomas (PXAs) in the tectal region are exceedingly rare and have distinctive clinicopathological features. CASE PRESENTATION: A 17-year-old man was admitted to our hospital owing to headache and diplopia. Magnetic resonance imaging showed a mass lesion in the tectal gland accompanied by obstructive hydrocephalus. A biopsy and third ventriculostomy were performed. Pathological examination revealed a PXA. Total excision of the lesion was achieved via an occipital transtentorial procedure performed 6 weeks after the biopsy. A pathological examination at that time showed a PXA with anaplastic features and a high mitotic index in surgical specimens. The patient's symptoms improved after the second operation, and radiation and temozolomide-based chemotherapy were administered. No recurrence was found at 24 months after the second operation. CONCLUSIONS: Maximum resections are recommended in cases with anaplastic features such as a high mitotic index in biopsy specimens because of the likelihood of recurrence and the low overall survival rate. We administered radiotherapy and temozolomide-based chemotherapy because of the high mitotic activity detected in surgical specimens. The postoperative course in this case is currently deemed acceptable.

DOI： 10.1016/j.wneu.2016.07.110

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DOI： 10.1016/j.jns.2016.07.013

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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BACKGROUND: Meningioma is a hypervascular tumor of the central nervous system. Angiographic disappearance of tumor blush after preoperative feeder embolization allows qualitative, but not quantitative, assessment of flow reduction. Pseudocontinuous arterial spin labeling (PCASL), which has evolved from magnetic resonance imaging techniques, allows noninvasive measurement of cerebral blood flow (CBF) using water protons in the arterial blood flow. OBJECTIVE: We applied PCASL for assessment of blood flow in meningioma and its reduction on preoperative embolization. METHODS: Forty-one consecutive patients (11 males, 30 females) with histologically proven meningioma were evaluated by PCASL. Quantitative assessment by an absolute value of tumor blood flow (TBF) and a relative value of tumor vascular index (tVI; calculated as TBF divided by CBF) were calculated. In 8 cases, in which preoperative embolization was achieved, flow reduction rate was evaluated. RESULTS: TBF of meningiomas, 155.8 mL/100 g·min(-1) on average, was 2.6 times higher than CBF, 59.9 mL/100 g·min(-1) (P < 0.001). Patients who underwent feeder embolization showed statistically greater flow reduction rate, which was calculated as 42.7% (P < 0.05). Mean tVI before embolization was 4.1, which was reduced to 2.1 after embolization. CONCLUSION: PCASL could yield quantitative assessment of blood flow in meningioma including flow reduction rate in cases of feeder embolization.

DOI： 10.1016/j.wneu.2016.06.004

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OBJECTIVE: A 3-dimensional temporal bone model for skull base surgical training was reconstructed via the use of a selective laser sintering technique, which is one of the 3-dimensional printing technologies. METHODS: The temporal bone model was created in 2 pieces to remove powder material in the mastoid air cells and to place dye into the semicircular canal and the Fallopian canal. RESULTS: The powder material was minimal, and the decisive structures were identified in color. CONCLUSIONS: This artificial model will pave the way to a "new era" in surgical training and medical education.

DOI： 10.1016/j.wneu.2016.03.084

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BACKGROUND: Damage to the motor division of the lower cranial nerves that run into the jugular foramen leads to hoarseness, dysphagia, and the risk of aspiration pneumonia; therefore, its functional preservation during surgical procedures is important. Intraoperative mapping and monitoring of the motor rootlets at the cerebellomedullary cistern using endotracheal tube electrodes is a safe and effective procedure to prevent its injury. OBJECTIVE: To study the location of the somatic and autonomic motor fibers of the lower cranial nerves related to vocal cord movement. METHODS: Twenty-four patients with pathologies at the cerebellopontine lesion were studied. General anesthesia was maintained with fentanyl and propofol. A monopolar stimulator was used at amplitudes of 0.05 to 0.1 mA. Both acoustic and visual signals were displayed as vocalis muscle electromyographic activity using endotracheal tube surface electrodes. RESULTS: The average number of rootlets was 7.4 (range, 5-10); 75% of patients had 7 or 8 rootlets. As many as 6 rootlets (2-4 in most cases) were responsive in each patient. In 23 of the 24 patients, the responding rootlets congregated on the caudal side. The maximum electromyographic response was predominantly in the most caudal or second most caudal rootlet in 79%. CONCLUSION: The majority of motor fibers of the lower cranial nerves run through the caudal part of the rootlets at the cerebellomedullary cistern, and the maximal electromyographic response was elicited at the most caudal or second most caudal rootlet. ABBREVIATION: EMG, electromyographic.

DOI： 10.1227/NEU.0000000000001109

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OBJECTIVE: During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. METHODS: We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. RESULTS: The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. CONCLUSIONS: SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas.

DOI： 10.1016/j.wneu.2015.10.043

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OBJECTIVE: In patients with severe traumatic brain injury (TBI), a randomized controlled trial revealed that outcomes did not significantly improve after therapeutic hypothermia (TH) or normothermia (TN). However, avoiding pyrexia, which is often associated with intracranial disorders, might improve clinical outcomes. The objective of this study was to compare neurological outcomes among patients with moderate and severe TBI after therapeutic temperature modulation (TTM) in the absence of other interventions. METHODS: Data from 1091 patients were obtained from the Japan Neurotrauma Data Bank Project 2009, a cohort observational study. Patients with cardiac arrest, those with a Glasgow Coma Scale score of 3 and dilated fixed pupils, and those whose cause of death was injury to another area of the body were excluded, leaving 687 patients aged 16 years or older in this study. The patients were divided into 2 groups: the TTM group underwent TN (213 patients) or TH (82 patients), and the control group (392 patients) did not receive TTM. The primary end point for this study was the rate of poor outcome at hospital discharge, and the secondary end point was in-hospital death. Out of the 208 total items in the database, 29 variables that could potentially affect outcome were matched using the propensity score (PS) method in order to reduce selection bias and balance the baseline characteristics. RESULTS: From each group, 141 patients were extracted using the PS-matching process. Among the patients in the TTM group, 29 had undergone TH and 112 had undergone TN. In a log-rank test using Kaplan-Meier survival curves, no significant differences in patient outcome or death were observed between the 2 groups (poor outcome, p = 0.83; death, p = 0.18). A Cox proportional-hazards regression analysis established the HR for poor outcome and mortality at 1.03 (95% CI 0.78-1.36, p = 0.83) and 1.34 (95% CI 0.87-2.07, p = 0.18), respectively. CONCLUSIONS: There was no clear improvement in neurological outcomes after TTM in patients with moderate or severe TBI. To elucidate the role of TTM in patients with these injuries, a prospective study is needed with long-term follow-up using specific target temperatures.

DOI： 10.3171/2015.3.JNS141895

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OBJECTIVES: Decreased cortical and subcortical vascular signals in gradient echo T2* weighted imaging have been reported in acute stroke due to major artery occlusion. The purpose of this study was to evaluate this cortical and subcortical vascular hypointensity (CSVH) in patients with moyamoya disease. METHODS: Subjects were 20 consecutive patients with moyamoya disease. The numbers of CSVH in each hemisphere were counted and the numbers were compared between patients with moyamoya disease and controls. The distribution of CSVH, clinical features of cases exhibiting large numbers of CSVH and post-operative changes were analysed. RESULTS: Patients with moyamoya disease had significantly more CSVH in the middle cerebral artery territory (p < 0.001) and the anterior cerebral artery territory (p < 0.001) compared with controls. The number of CSVH was correlated significantly with regional cerebral blood flow, as shown through simple regression analysis (R = 0.461, p = 0.006), and the numbers of CSVH were significantly higher in patients with higher magnetic resonance angiography scores (p = 0.017). A given patient's total number of CSVH per hemisphere was significantly decreased after surgery (p = 0.018). CONCLUSION: CSVH on T2* WI may be a useful tool for diagnosing and evaluating the extent of moyamoya disease. Our small series study shows that revascularization surgery can decrease the number of CSVH.

DOI： 10.1080/01616412.2015.1136117

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Cases of intracranial germinoma with granulomatous reaction are rare, so a pathological diagnosis of this disease is difficult. In this report, we describe the case of a 13-year-old boy with a bilateral thalamic germinoma which initially mimicked tumefactive demyelinating disease with inflammation, based on the clinical symptoms, imaging results and histology of a biopsy specimen obtained endoscopically. Upon examination of the cerebrospinal fluid, oligoclonal bands were detected. Although his symptoms and radiological findings improved following steroid pulse treatment, they worsened dramatically almost 1 year after the first surgery and even after an additional steroid pulse treatment. Prompted by the clinical course, a second biopsy was performed, and a pathological examination of the specimen showed a two-cell pattern. The diagnosis was changed to intracranial germinoma. After chemotherapeutic treatment with etoposide and cisplatin, the patient's symptoms and radiological findings dramatically improved. We conclude that it is very challenging to distinguish germinomas with a granulomatous reaction due to other inflammatory diseases, especially when only small specimens can be obtained. Stereotactic or endoscopic biopsies should be performed using samples from several different points even if the lesions are associated with eloquent brain regions.

DOI： 10.1159/000439028

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BACKGROUND: Cavernomas frequently are associated with intractable epilepsy. When cavernomas located in the temporal lobe are associated with intractable epilepsy, the hippocampus also may have an epileptic focus. The objective in the present study was to clarify the importance of evaluation of the posterior hippocampal epileptogenicity during epilepsy surgery for posteromedial temporal lobe cavernoma. CASE DESCRIPTIONS: In this study, we describe 2 rare cases of medically intractable epilepsy in patients with posteromedial temporal lobe cavernomas who underwent surgery via the occipital approach. Using longitudinal insertion of depth electrodes into the hippocampus, we evaluated epileptogenicity in both patients from the cavernoma cavity and its surrounding hemosiderin, as well as from the posterior hippocampus near the cavernoma. We show that the transoccipital approach to the posteromedial temporal lobe is compatible with depth electrode insertion and subdural electrode placement on the temporal lobe, enabling an accurate evaluation of potential epileptogenic zones in the posterior part of the hippocampus. Both patients did not experience any seizures and had no postoperative neurologic deficits, and their cognitive functions were intact. CONCLUSIONS: The transoccipital approach enables the optimization of the extent of posterior hippocampectomy while avoiding unnecessary resection for seizure control. We suggest resecting the posterior part of the hippocampus in addition to the cavernoma and surrounding areas in patients with medically refractory epilepsy due to a posteromedial temporal cavernoma. Tailored systematic resection guided by intraoperative electrocorticography and electroencephalography with a depth electrode was important and necessary in the present cases.

DOI： 10.1016/j.wneu.2015.04.047

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OBJECTIVES: A positive (outward) remodelling pattern in patients with typical atherosclerotic disease was recognised using magnetic resonance imaging (MRI). In this report, the outer diameter of the circle of Willis was evaluated in patients with moyamoya disease, and its remodelling pattern was verified. METHODS: A total of 18 consecutive patients with moyamoya disease were included in this analysis. The diameter of the terminal portion of the internal carotid artery (ICA) (C1), proximal portion of the middle cerebral artery (MCA) (M1) and proximal portion of the anterior cerebral artery (A1) was evaluated using fast imaging employing steady-state acquisition (FIESTA) imaging. The outer diameter was estimated using these images, and compared with the control group, and the correlation with magnetic resonance angiography (MRA) scores was calculated for patients with moyamoya disease. RESULTS: The mean diameter of the moyamoya patient group on FIESTA was significantly lower than that of the control group in the C1, M1 and A1 (P < 0.0001). The M1 diameter on the FIESTA image showed a strong correlation with the moyamoya disease MRA score (y = (0.53x+2.31; R = 0.72), whereas the C1 diameter on the FIESTA image showed only a weak correlation (y = (0.16x+2.47; R = 0.21). CONCLUSION: We found that the outer diameter of all the vessels around the C1 was generally reduced in patients with moyamoya disease. Diameter of the MCA especially decreases as the disease progresses, similar to the negative (constrictive) remodelling pattern.

DOI： 10.1179/1743132815Y.0000000069

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We report a case of an optic nerve mass lesion associated with IgG4-related disease. A 39-year-old man presented with right blurred vision and proptosis 8 years before admission. Magnetic resonance imaging showed a mass lesion in the center of the right orbit, which was diagnosed as optic nerve sheath meningioma by neuroradiologists and neurosurgeons. Irradiation was selected for treatment of the lesion on the basis of the radiological diagnosis; subsequently, the lesion gradually reduced in size. However, regrowth of an optic nerve mass lesion observed during the previous 2 years caused remarkable exophthalmos, and removal of the orbital mass lesion was performed via a transcranial orbital approach. Pathological examinations resulted in a diagnosis of IgG4-related disease, and hematological tests revealed an elevated level of serum IgG4. Additional radiological examinations showed mass lesions in the left maxillary nerve, bilateral inferior alveolar nerves, paravertebral tissue, and left kidney. Treatment with oral steroids has produced a reduction in the size of these lesions.

DOI： 10.1007/s10014-015-0223-7

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An intraorbitalsubperiosteal hematoma is a rare clinical entity that is usually caused by head trauma. The authors experienced a patient involving an intraorbital hemorrhage that was associated with minor injury in the forehead and that required surgical decompression. The authors describe this rare case involving an intraorbitalsubperiosteal hematoma that occurred in a conscious young boy who had no remarkable head injury and who had sudden onset of proptosis. Three-dimensional computed tomography, which was conducted with a volume-rendering method, was very useful, and the transorbital approach that was used to remove the hematoma was very effective. The patient showed good recovery. The pathogenesis of the intraorbitalsubperiosteal hemorrhage could not be fully explained, and, thus, the authors suggest that a possible pathogenesis involved the migration of the hemorrhage from the forehead into the intraorbital region.

DOI： 10.1097/SCS.0000000000002036

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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BACKGROUND: Meningiomas or solitary fibrous tumors arising from the cavernous sinus (CS) are usually treated with radiosurgery to control growth. Surgical removal of cavernous tumors is indicated only for tumors extending outside the CS. However, even after adequate treatment, the tumor may exhibit recurrence or malignant transformation. We report a treatment option for recurrent meningeal tumors of the CS. METHODS: In 4 patients with CS tumors that exhibited regrowth after multiple operations and radiosurgery, radical removal in combination with high-flow bypass was performed, and a vascularized muscle flap was used for reconstruction. One patient had a radiation-induced atypical meningioma, 2 patients had transformed atypical meningiomas, and 1 patient had a frequently recurring solitary fibrous tumor. RESULTS: No local recurrence was observed in any patients during a follow-up period of 13-41 months. In all patients, a Karnofsky performance scale score of >80 on admission was maintained at >70 at the final follow-up evaluation. CONCLUSIONS: Radical removal in combination with high-flow bypass provides favorable results and maintains quality of life in patients with recurrent CS meningeal tumors.

DOI： 10.1016/j.wneu.2015.01.019

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Mitochondrial autophagy eliminates damaged mitochondria and decreases reactive oxygen species (ROS). The autophagy inhibitor chloroquine (CQ) potentiates temozolomide (TMZ) cytotoxicity in glioma cells, but it is not known whether CQ does this by inhibiting mitochondrial autophagy. The effects of CQ and TMZ on MitoSOX Red fluorescence, a mitochondrial ROS indicator, and cell death were examined in rat C6 glioma cells. Mitochondrial autophagy was monitored by the colocalization of MitoTracker Red fluorescence and EGFP-LC3 dots. Mitochondrial content was measured by MitoTracker Green fluorescence and immunoblotting for a mitochondrial protein. Finally, CQ's effects on tumor cells derived from a glioblastoma patient and human U87-MG glioblastoma cells were assessed. TMZ (100-1,000 μM) alone did not affect mitochondrial ROS or cell death in C6 cells, but when administered with CQ (10 μM), it increased mitochondrial ROS and cell death. Antioxidants significantly suppressed the CQ-augmented cell death in TMZ-treated cells, indicating that mitochondrial ROS were involved in this cell death. TMZ treatment reduced MitoTracker Green fluorescence and mitochondrial protein levels, and these effects were inhibited by CQ. TMZ also increased the colocalization of EGFP-LC3 dots with mitochondria, and CQ enhanced this effect. CQ potentiated TMZ-induced cytotoxicity in patient-derived glioblastoma cells as well as human U87-MG glioblastoma cells. These results suggest that CQ increases cellular ROS and augments TMZ cytotoxicity in glioma cells by inhibiting mitochondrial autophagy.

DOI： 10.1007/s11060-014-1686-9

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Rigid endoscopic resection using a thick sheath (ViewSite) may be a viable method for the resection or biopsy of selected deep-seated brain tumors, such as thalamic gliomas and malignant lymphomas. Neuroendoscopic biopsy is one technique used for the histological verification of suspected brain tumors. There are a number of advantages to using this technique. For example, under direct vision, it is possible to carefully observe the tumor surface and avoid vessels during tumor resections. It is also possible to collect enough specimens for a pathological diagnosis. Eighteen consecutive patients safely underwent rigid endoscopic resection or biopsy using a thick sheath (ViewSite). The two-handed endoscopic technique that utilized a mounted rigid endoscope proved very useful and safe, since it enabled easy stanching of hemorrhages. The aim of this study was to demonstrate how to use a thick sheath for deep-seated or intraventricular tumors. The rigid endoscopic approach with a thick sheath provides an alternative medial approach with improved visualization and a wider working space.

DOI： 10.1179/1743132814Y.0000000439

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BACKGROUND: Epilepsy cannot always be recognized in patients with moyamoya disease. In this report, the clinical features of patients with epilepsy were evaluated for assessing the predictive factors of epilepsy in moyamoya disease. METHODS: A total of 64 consecutive patients with moyamoya disease were included in this study. During their follow-up periods, 7 patients were diagnosed with epilepsy. Then, the patients with epilepsy were compared with the patients without epilepsy regarding their clinical features. RESULTS: Analysis of patient background characteristics revealed a significantly higher incidence of epilepsy in patients with high modified Rankin Scale (mRS) scores, high cerebrovascular attack scores, onset age of 3 years or less, early seizures, cortical involvement, stroke subtype, and diffuse brain atrophy. A logistic analysis of epilepsy data revealed significant differences between the 2 groups in mRS score, cerebrovascular attack score, onset age 3 years or less, early seizure, cortical involvement, stroke subtype, and diffuse brain atrophy. Of these, significant differences were noted in 3 items (mRS score, early seizure, and diffuse brain atrophy) on multivariate analysis. These 3 items were selected as the basis of our new moyamoya disease epilepsy risk scale (MDERS), which we then evaluated. The cutoff value estimated by the receiver operating characteristic curve was set at 1 (sensitivity, .857; specificity, .825) or 2 (sensitivity, .571; specificity, 1.000). CONCLUSIONS: Epilepsy in moyamoya disease is associated with clinical factors and is not an independent category. For prediction of epilepsy in moyamoya disease, MDERS is a simple and convenient assessment scale.

DOI： 10.1016/j.jstrokecerebrovasdis.2014.07.050

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Congress of Neurological Surgeons  

DOI： 10.7887/jcns.24.92

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Maximum tumor extirpation with preservation of the facial and cochlear nerve function is the goal of surgery for vestibular schwannoma. To preserve cochlear nerve function, the surgeon must employ a detailed knowledge of microanatomy, precise microsurgical techniques, and persistence. This paper describes the "pearls" of surgical techniques based on the anatomical study inside the mastoid from the view of the retrosigmoid transmeatal approach. A total of 592 consecutive patients underwent surgical removal of unilateral vestibular schwannoma (VS) between January 1994 and December 2009. The hearing preservation rate was 53.7 % for large vestibular schwannomas (>20 mm in diameter) and 74.1 % for tumors of all sizes. The key procedures for hearing preservation surgery are as follows: bloodless microdissection, sufficient coring-debulking, capsular elevation to locate the facial and cochlear nerves both electrophysiologically and by visual observation, sharp dissection of the facial and cochlear nerves, and avoidance of heat and mechanical injury to the nerves, the internal auditory artery, and the brain stem. Besides these techniques, appropriate instruments are essential to preserve hearing. The function of the facial and cochlear nerves should be the foremost concern. Meticulous techniques and the knowledge of microsurgical anatomy lead to hearing preservation with maximum tumor removal.

DOI： 10.1007/s10143-014-0543-9

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Congress of Neurological Surgeons  

DOI： 10.7887/jcns.23.802

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In patients with vascular compression syndromes, the preoperative recognition of the cranial nerves and compressed vessels will contribute to improved surgical results. The aim of this study was to clarify the pathophysiology of hemifacial spasm (HFS) associated with the vertebral artery (VA) and to assess the value of preoperative imaging. Fifty-three consecutive patients with HFS underwent microvascular decompression (MVD). Of these, 18 cases of HFS were associated with the VA; this case series was compared with the remaining non-VA-associated HFS. For preoperative assessment, magnetic resonance imaging (MRI) was performed. Since January 2006, fusion imaging has been performed by combining MRI and computed tomography angiography. Of the 18 cases of VA-associated HFS, 17 (94.4 %) were on the left side; this was significantly higher than in the non-VA-associated HFS cases (p < 0.0001). The VA was attached to the root exit zone (REZ) directly in three cases. In the other 15 cases, the VA was compressing the REZ indirectly as a result of other intervening vessels. In all cases, preoperative imaging fully simulated the status of the REZ. The symptom disappeared in 17 cases (94.4 %) after MVD, and there was no significant difference in the surgical results between the VA-associated group and the non-VA-associated group (p = 0.9925). HFS associated with VA is not a rare condition. Preoperative recognition is thus important to the improvement of surgical results. Fusion imaging is useful to determine the status of the REZ, especially in indirect VA-associated HFS.

DOI： 10.1007/s10143-012-0425-y

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Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein.

DOI： 10.1007/s10014-012-0094-0

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BACKGROUND: Decision-making during the management of unruptured cerebral aneurysms is a delicate process for both neurosurgeons and patients. Guidelines are evidence-based references that can aid in making decisions. However, neurosurgeons do not always follow guidelines in clinical practice. The purpose of this study is to verify the hypothesis that there is substantial dissociation between treatment guidelines and practical decision-making due to a bias in treatment selection for unruptured cerebral aneurysms. This bias is dependent upon clinician-driven factors such as experience and specialty, and patient-driven factors such as patient preference. METHODS: This study was performed using internet questionnaires. A total of 282 randomly selected, qualified Japanese neurosurgeons (out of approx. 6,000 registered neurosurgeons), including 45 endovascular specialists, participated in this study. Radiological and demographic data from 88 cases of unruptured cerebral aneurysm were opened on the Web. Participating neurosurgeons decided on the treatment for each case (clipping, coiling or observation). RESULTS: Variations in treatment selection were not significant between neurosurgeons and endovascular specialists, except for aneurysms such as anterior choroidal artery aneurysm. However, contrary to the guidelines, aneurysms larger than 10 mm tended to be treated conservatively because the risk of treatment is high, while aneurysms smaller than 5 mm in diameter were often selected for intervention (clipping or coiling). CONCLUSIONS: This study revealed that in real-world clinical practice, physicians are not always faithful to the current guidelines. In making practical treatment decisions for unruptured cerebral aneurysms, the patient's will and the recognition of unavoidable, treatment-related risks seriously influence neurosurgeons' decisions.

DOI： 10.1159/000317087

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The sensitivity of susceptibility-weighted magnetic resonance (MR) imaging was compared with conventional MR sequences, including T(2)*-weighted imaging, and computed tomography for the detection of cerebral hemorrhages in 15 patients with head injury. Susceptibility-weighted imaging detected a mean of 76+/-52 (total 1132) hypointense spotty lesions, compared to a mean of 21+/-19 (total 316) detected by T(2)*-weighted imaging (p<0.0001, paired t-test). Susceptibility-weighted imaging is extremely sensitive for the visualization and detection of microhemorrhages.

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DOI： 10.1097/WNO.0b013e318183c633

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DOI： 10.1136/jnnp.2007.133959

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：3  

DOI： 10.1016/j.ijcard.2006.07.024

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A 38-year-old man presented with a dysplastic cerebellar gangliocytoma associated with a paraspinal arteriovenous fistula (AVF) at the upper cervical portion. Neuroimaging examination indicated the diagnosis of Lhermitte-Duclos disease. The patient was treated by embolization of the AVF followed by partial resection of the cerebellar tumor. Genetic examination showed a mutation of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene. Histological examination confirmed the diagnosis. Lhermitte-Duclos disease is a rare dysplastic gangliocytoma manifesting as a slowly growing mass in the cerebellum and is usually asymptomatic. This case of Lhermitte-Duclos disease associated with paraspinal AVF and mutation of the PTEN gene suggests a relationship between Lhermitte-Duclos disease and Cowden disease.

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Transplantation of cell suspensions containing olfactory ensheathing cells (OECs) has been reported to remyelinate demyelinated axons in the spinal cord with a Schwann cell (SC)-like pattern of myelination. However, questions have been raised recently as to whether OECs can form SC-like myelin. To address this issue we prepared SCs and OECs from transgenic rats in which a marker gene, human placental alkaline phosphatase (hPAP), is linked to the ubiquitously active promoter of the R26 gene. SCs were prepared from the sciatic nerve and OECs from the outer nerve-fiber layer of the olfactory bulb. Positive S100 and p75 immunostaining indicated that >95% of cells in culture displayed either SC or OEC phenotypes. Suspensions of either SCs or OECs were transplanted into an X-irradiation/ethidium bromide demyelinating lesion in the spinal cord. We observed extensive SC-like remyelination following either SC or OEC transplantation 3 weeks after injection of the cells. Alkaline phosphatase (ALP) chromagen reaction product was associated clearly with the myelin-forming cells. Thus, cell suspensions that are enriched in either SCs or OECs result in peripheral-like myelin when transplanted in vivo.

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DOI： 10.1006/exnr.2000.7539

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Language：Japanese   Publisher：The Japanese Congress of Neurological Surgeons  

Introduction: To identify the risks in managing unruptured cerebral aneurysms in Japan, we conducted a prospective multi-center study. Method: Patients with newly diagnosed UCA during January 2006 to January 2007 in 31 institutions were prospectively registered. Patients were regularly followed up and registered at 3 months, 12 months and at 60 months (scheduled) after registration. At the same time, three dimensional images, periodic health related quality of life (SF-8, EQ5D) and cognitive function data were collected. Source documents were confirmed by outside reviewers. Results: 1,056 patients were registered. The 3 months registration was recorded in 1007, 12 months in 946 cases. Aneurysms were repaired in 558 patients; by clipping in 81% and coiling in 19% of cases. Severe morbidity (Modified Rankin scale worse than 1) was observed in 4.5% of cases and was significantly related with the size, location and history of the subarachnoid hemorrhage. Management morbidity was most frequently caused by perforator injury of the parent artery occlusion. Conclusion: With multiple prospective studies conducted in Japan, we can now delineate high risk UCA group for management. With such data, adequate risk communication with the patient can be achieved.

DOI： 10.7887/jcns.20.484

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Language：Japanese   Publisher：(一社)日本脳神経外傷学会  

Ichushi

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本脳神経外傷学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本脳卒中学会  

Ichushi

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Language：Japanese   Publisher：The Japanese Society on Surgery for Cerebral Stroke  

Other Link:： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2008&ichushi_jid=J02079&link_issn=&doc_id=20080410160004&doc_link_id=%2Fcp4strok%2F2008%2F003602%2F004%2F0088-0094%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcp4strok%2F2008%2F003602%2F004%2F0088-0094%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

DOI： 10.2335/scs.36.88

Ichushi

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Language：Japanese   Publisher：(一社)日本脳神経外科学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本脳神経外科救急学会  

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

Ichushi

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

Ichushi

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Language：English   Publishing type：Research paper, summary (international conference)  

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J-GLOBAL

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Language：Japanese   Publisher：日本脳腫瘍病理学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本小児神経外科学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本脳卒中学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本脳卒中学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本脳神経外科救急学会  

Ichushi

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Language：Japanese   Publisher：(NPO)日本脳神経外科救急学会  

Ichushi

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DOI： 10.1016/j.neulet.2005.06.073

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DOI： 10.1016/j.brainres.2004.09.062

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DOI： 10.1089/089771504323004584

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DOI： 10.1002/glia.10102

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