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The robot-assisted catheter system can increase operating distance thus preventing the exposure radiation of the surgeon to X-ray for endovascular catheterization. However, few designs have considered the collision protection between the catheter tip and the vessel wall. This paper presents a novel catheter operating system based on tissue protection to prevent vessel puncture caused by collision. The integrated haptic interface not only allows the operator to feel the real force feedback, but also combines with the newly proposed collision protection mechanism (CPM) to mitigate the collision trauma. The CPM can release the catheter quickly when the measured force exceeds a certain threshold, so as to avoid the vessel puncture. A significant advantage is that the proposed mechanism can adjust the protection threshold in real time by the current according to the actual characteristics of the blood vessel. To verify the effectiveness of the tissue protection by the system, the evaluation experiments in vitro were carried out. The results show that the further collision damage can be effectively prevented by the CPM, which implies the realization of relative safe catheterization. This research provides some insights into the functional improvements of safe and reliable robot-assisted catheter systems.

Background An Internet-based tele-operative robotic catheter operating system was designed for vascular interventional surgery, to afford unskilled surgeons the opportunity to learn basic catheter/guidewire skills, while allowing experienced physicians to perform surgeries cooperatively. Remote surgical procedures, limited by variable transmission times for visual feedback, have been associated with deterioration in operability and vascular wall damage during surgery. Methods At the patient's location, the catheter shape/position was detected in real time and converted into three-dimensional coordinates in a world coordinate system. At the operation location, the catheter shape was reconstructed in a virtual-reality environment, based on the coordinates received. The data volume reduction significantly reduced visual feedback transmission times. Results Remote transmission experiments, conducted over inter-country distances, demonstrated the improved performance of the proposed prototype. The maximum error for the catheter shape reconstruction was 0.93 mm and the transmission time was reduced considerably. Conclusions The results were positive and demonstrate the feasibility of remote surgery using conventional network infrastructures. Copyright © 2015 John Wiley & Sons, Ltd.

Although current treatment advances prolong patient survival, treatment for glioblastoma (GBM) in the elderly has become an emerging issue. The definition of "elderly" differs across articles; GBM predominantly occurs at an age ≥65 years, and the prognosis worsens with increasing age. Regarding molecular markers, isocitrate dehydrogenase (IDH) mutations are less common in the elderly with GBM. Meanwhile, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation has been identified in approximately half of patients with GBM. Surgery should be considered as the first-line treatment even for elderly patients, and maximum safe resection is recommended if feasible. Concurrently, radiotherapy is the standard adjuvant therapy. Hypofractionated radiotherapy (e.g., 40 Gy/15 Fr) is suitable for elderly patients. Studies also supported the concurrent use of temozolomide (TMZ) with radiotherapy. In cases wherein elderly patients cannot tolerate chemoradiation, TMZ monotherapy is an effective option when MGMT promoter methylation is verified. Conversely, tumors with MGMT unmethylated promoter may be treated with radiotherapy alone to reduce the possible toxicity of TMZ. Meanwhile, the efficacy of bevacizumab (BEV) in elderly patients remains unclear. Similarly, further studies on the efficacy of carmustine wafers are needed. Based on current knowledge, we propose a treatment diagram for GBM in the elderly.

Recent studies in animal subarachnoid hemorrhage (SAH) models have reported that dexmedetomidine (DEX) use demonstrates significantly better neurological outcomes. This study aimed to evaluate whether DEX use is associated with favorable neurological outcomes (FO) in SAH patients.We retrospectively reviewed all SAH patients between 2009 and 2017. We calculated the total dosage of DEX administered for the first 24h after admission. All patients were classified into no use, low dosage, and standard dosage group. Multivariate analysis was performed to clarify the association between DEX use and FO (modified Ranking Scale score of 0-2 at hospital discharge).There were 161 patients with 55.3% of FO. On univariate analysis, there were significant differences with regard to age, Hunt and Kosnik (HK) grade, and DEX use. Multivariate analysis showed that age, HK grade, and low dosage DEX (rather than no use) (odds ratio (OR) 3.17; 95% confidence interval (CI), 1.24-8.53; p=0.02) were significantly associated with FO. However, standard dosage DEX was not a significant factor (OR, 0.75; 95% CI, 0.25-2.16; p=0.59).Low dosage DEX during the first 24h after admission was associated with FO in SAH patients.

Introduction In case of cavernous sinus dural arteriovenous fistula (CSDAVF), transvenous embolization (TVE) of the cavernous sinus (CS) via the inferior petrosal sinus (IPS) is generally performed. However, various approach routes have been reported when the accessibility of the IPS is challenging. We herein report a case of CSDAVF treated by TVE with direct puncture of the facial vein. Case report A 70-year-old woman who suffered from tinnitus, chemosis, diplopia and bruit was referred to our hospital. Digital subtraction angiography (DSA) demonstrated CSDAVF. We initially attempted to perform TVE via the IPS route; however, we could not guide a catheter to the CS because of an anatomical difficulty. Then, we performed percutaneous direct puncture of the dilated facial vein, and successfully treated the patient. Conclusion When navigating microcatheter to the CS is difficult because of an anatomical difficulty of the IPS, direct puncture of the facial vein is a feasible route.

Purpose This study assesses the behavior of serial blood lactate measurements during intensive care unit (ICU) stay to identify prognostic factors of unfavorable neurological outcomes (UO) in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods We retrospectively reviewed all patients who were consecutively hospitalized with SAH between 2009 and 2016. Arterial blood lactate levels were routinely obtained on admission and every 6 h in the ICU. Univariate/multivariate analyses were performed to identify independent predictors of UO (modified Rankin scale of 3–6 upon hospital discharge). Results There were 145 patients with 46% of UO. Initially, increased lactate levels reached maximum levels during the first 24 h and then decreased to within the normal range. Then, the levels slightly increased again to within the normal range for the next 24 h, especially in UO. On multiple regression analysis, lactate levels measured at 24 h, and 48 h after admission were strong predictors of UO. Lactate level measured at 48 h after admission demonstrated the greatest accuracy and the highest specificity (area under the curve, 0.716; sensitivity, 40%; specificity, 92.1%). Conclusions The lactate level at 48 h after admission was the most accurate predictor of UO with a high specificity in SAH patients.

The metabolic function of the liver changes sequentially during early life in mammals to adapt to the marked changes in nutritional environment. Accordingly, hepatic fatty acid β-oxidation is activated after birth to produce energy from breast milk lipids. However, how it is induced during the neonatal period is poorly understood. Here we show DNA demethylation and increased mRNA expression of the fatty acid β-oxidation genes in the postnatal mouse liver. The DNA demethylation does not occur in the fetal mouse liver under the physiologic condition, suggesting that it is specific to the neonatal period. Analysis of mice deficient in the nuclear receptor peroxisome proliferator–activated receptor α (PPARα) and maternal administration of a PPARα ligand during the gestation and lactation periods reveal that the DNA demethylation is PPARα dependent. We also find that DNA methylation of the fatty acid β-oxidation genes are reduced in the adult human liver relative to the fetal liver. This study represents the first demonstration that the ligand-activated PPARα-dependent DNA demethylation regulates the hepatic fatty acid β-oxidation genes during the neonatal period, thereby highlighting the role of a lipid-sensing nuclear receptor in the gene- and life-stage–specific DNA demethylation of a particular metabolic pathway.

The present study investigates the neuroprotective effects of d-allose, a rare sugar, against ischemia/reperfusion injury in a gerbil model. Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. D-Allose was intravenously injected before and after ischemia (200 mg/kg). Extracellular glutamate and lactate release from the gerbil brain, and PO₂ profiles were monitored during ischemia and reperfusion. We also examined neuronal death and oxidative damage in the hippocampus one week after ischemia reperfusion, and investigated functional outcome. D-Allose administration suppressed glutamate and lactate release compared to vehicle controls. Brain damage, 8-OHdG levels (a marker of oxidative stress) and locomotor activities were significantly decreased by D-allose treatment. The present results suggest that d-allose reduces delayed neuronal death and behavioral deficits after transient ischemia by changing cerebral metabolism and inhibiting oxidative stress.

Background: Pain is regarded as one of the most common nonmotor symptoms in Parkinson's disease (PD). In particular, musculoskeletal pain has been reported as the most common type of PD-associated pain. Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Case Presentation: This report describes the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity, gait disturbance and neck pain. Laboratory examination revealed marked elevations of white blood cells (10,100/µl) and C-reactive protein (CRP; 8.63 mg/dl). She was primarily diagnosed with severe and untreated PD, corresponding to Hoehn and Yahr scale score IV, with musculoskeletal pain and urinary tract infection. The patient was treated with antiparkinsonism drugs, antibiotic agents and nonsteroidal anti-inflammatory drugs, but they had only limited effects. Cervical plain computed tomography (CT) scanning detected remarkable crown-like calcification surrounding the odontoid process. Based on CT findings, the patient was diagnosed as having CDS with PD, and was immediately treated with corticosteroid. The severe neck rigidity with pain and the serum CRP level (0.83 mg/dl) of the patient were drastically improved within a week by the additional corticosteroid therapy. Conclusion: Severe neck rigidity and bradykinesia in this patient might have strengthened the chondrocalcinosis around the odontoid process. Cervical plain CT scan is necessary and useful for the definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for musculoskeletal pain related to rigidity and bradykinesia in PD.

Purpose Hypoxia and its consequences at the molecular level promote tumour progression and affect patient prognosis. One of the main early cellular events evoked by hypoxia is induction of hypoxia-inducible factor 1 (HIF-1) and subsequent upregulation of vascular endothelial growth factor (VEGF). In this study we sought to determine whether hypoxia detected by 18F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas.

OBJECTIVE Neuronavigation systems with MRI and multiple PET examinations (methionine [MET], fluorothymidine [FLT], and fluoromisonidazole [FMISO]) have become our standard techniques for glioma surgeries. Residual tumors are identified and removed using intraoperative MRI (IoMRI) to maximize tumor removal. This time, we performed tumor removal after Bevacizumab (Bev) therapy for glioblastoma with low KPS at admission and compared extraction rate and residual volume of MRI and PET examinations, and prognosis between with and without Bev therapy. METHODS We selected 12 glioblastoma patients with low KPS at admission and performed multiple PET examinations and IoMRI from January 2016 to July 2019. We divided them into the pre-Bev group that performed tumor removal after neoadjuvant Bev therapy and the non-Bev group that did not use Bev. We compared the extraction rate and residual volume of MRI and PET examinations, and prognosis between the pre-Bev group and the non-Bev group. RESULTS The pre-Bev group was 6 cases and the non-Bev group was 6 cases. The number of KPS for the pre-Bev group just before surgery was (90; 3 cases, 80; 2 cases, 70; 1 case) and (50; 2 cases, 40; 4 cases) for the non-Bev group. For comparison between the pre Bev group and the non-Bev group, the extraction rate (%) was T1-Gd (97.6, 91.5), MET (95.4, 99.9), FLT (96.2, 90.2), FMISO (97, 92), residual volume (ml) was T1-Gd (0.6, 1.7), MET (1.2, 2.9), FLT (1.0, 2.1), FMISO (0.5, 1.1), and for prognosis, median PFS (month) is (10.1, 4.9) and median OS (months) was (15.7, 13.3). CONCLUSIONS For glioblastoma patients with low KPS at admission, the neoadjuvant Bev therapy improved KPS just before surgery. The neoadjuvant Bev therapy improved the extraction rate and reduced residual volume of MRI and PET examinations and leads to the prolonged prognosis of PFS and OS.

OBJECTIVE After WHO 2016 Classification of Tumors of the Central Nervous System have published, molecular diagnosis became part of the diagnostic criteria. In this study, we investigated the correlation between PET images and molecular diagnosis of glioma. METHODS We performed retrospective review of newly diagnosed supratentorial glioma patients who preoperatively underwent all four PET examinations (18F-FDG, 11C-MET, 18F-FLT and 18F-FMISO) from April 2009 to March 2019. The standardized uptake value (SUV) from the accumulation of each PET tracers, TNR (tumor to contralateral normal tissue ratio) of 18F-FDG,11C-MET and 18F-FLT, TBR (tumor to blood values ratio) of 18F-FMISO were measured. We investigated the correlation between these PET images and molecular diagnosis of glioma. RESULTS Data from total of 79 patients which were 42 cases of IDH wild type glioblastoma, 2 cases of IDH mutated glioblastoma, 9 cases of IDH wild type astrocytoma, 13 cases of IDH mutated astrocytoma and 13 cases of IDH mutated and 1p/19q co-deleted oligodendroglioma were included in this study. Both TNR of 11C-MET(p CONCLUSION Preoperative PET evaluation of each PET tracers may be useful for the molecular diagnosis of glioma.

Pilomyxoid astrocytoma (PMA) is a recently identified type of pilocytic astrocytoma (PA) with shorter progression-free and overall survival, higher rate of recurrence, and higher risk of leptomeningeal spread compared to pilocytic tumors (WHO grade 2 designation). A case is presented here in which intraoperative imprint smears of a pineal region tumor in a 14-year-old girl revealed cytologic monomorphism, elongated cells with bland nuclei embedded in a myxoid background. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic fibrillary processes and angiocentric arrangement were observed but Rosenthal fibers or eosinophilic granular bodies were absent. A cytologic diagnosis of PMA of the pineal region was suggested by intraoperative smear preparation. Histology and immunohistochemical results confirmed the final diagnosis. This report shows that smear preparation can be trustworthy for the intraoperative diagnosis of PMA, helping to determine the appropriate neurosurgical procedure and therapeutic implications.

The aim of this study was to investigate the neuroprotective effects of yokukansan, a traditional Kampo medicine, on the behavioral dysfunction induced by cerebral ischemia/reperfusion injury in gerbils. Gerbils were treated with yokukasan by oral gavage for 30 days, once per day, until the day before induction of ischemia, which was induced by occluding the bilateral common carotid artery for 5 min. The effects of yokukansan (50, 100 and 300 mg/kg) were examined by measuring neuronal damage and behavioral deficits (locomotor activity, 8-arm radial maze task). The anti-inflammatory and anti-oxidant properties of yokukansan were also examined. Administration of yokukansan at 300 mg/kg significantly reduced hippocampal neuronal death after brain ischemia, inhibited the ischemia-induced inflammatory response and DNA oxidative damage. Yokukansan also reduced ischemia-induced locomotor hyperactivity and improved memory impairment. These findings suggest that yokukansan can inhibit the inflammatory response, oxidative damage and subsequent neuronal death induced by cerebral ischemia/reperfusion injury, and also can contribute to improvement in neurological deficits following such injury.

Traumatic brain injury (TBI) is an epigenetic risk factor for Alzheimer's disease (AD) and amyloid β (Aβ) deposition is observed histopathologically in the traumatized brain. This study was conducted to detect cerebral Aβ deposition using amyloid positron emission tomography (PET) in patients with neuropsychological impairment after TBI.Twelve patients with post-traumatic neuropsychological impairment (11 men and one woman, age range = 21-78 years) were examined using Pittsburgh Compound B ((11)C-PIB) PET at the chronic stage after TBI (range = 5-129 months).(11)C-PIB was positive in three patients and negative in the other nine patients. There was no correlation between (11)C-PIB deposition and the severity of injury; initial CT findings; elapsed time from the injury; and neuropsychological test scores.The absence of Aβ deposition in many patients with chronic neuropsychological impairment after TBI does not support the premise that Aβ pathology progresses over time in the traumatized brain. Early and sequential (11)C-PIB PET examination may clarify the time course of Aβ deposition in the traumatized brain and the relationship between traumatic brain insult and subsequent neuropsychological impairment.

Manual operation of the catheter is inaccurate in minimally invasive surgery, requires dexterous and efficient manipulation for the catheter and exposes the surgeons to intense radiation. A novel robotic catheter manipulating system has been developed with remote navigation to reduce the performance error and irradiation to surgeons. In addition, unlike the conventional technique which requires surgeons to manipulate the catheter using their hands, remote systems always have removed surgeons’ hands and replaced from joystick and handle, thus withdrawing their unique skills and experience. The proposed novel robotic catheter manipulating system presented that surgeon could manipulate the catheter that is same to the surgeons’ often use. The surgeon console (the master side) used to measure the axial and radial motions of input catheter transferred to the catheter manipulator (the slave side). Also, we designed the haptic device in the surgeon console and proximal measurement mechanism of resistance force in the catheter manipulator to provide the force feedback feeling and get the resistance force during input catheter. Performance evaluation of system was conducted to test both the dynamic and static performance of manipulation and synchronization between master and slave side. Finally, tele-operation has been done by endovascular evaluator (EVE) simulator. The experimental results showed the system has the ability to be a training system for neurosurgeons and to complete the clinical interventional surgery in the future.

The authors report on a case of concurrent herpes simplex encephalitis (HSE) and malignant glioma. The co-occurrence of HSE and malignant glioma is very rare, but it can occur during glioma treatment. Both radiotherapy and chemoradiation with temozolomide can induce viral reactivation, leading to HSE relapse. Careful observation for HSE is necessary when administering chemoradiation to patients with a history of HSE. Antiviral therapy for HSE must be initiated immediately, and the chemoradiation for glioma should be stopped; however, it is not clear what antitumor therapy is optimal when HSE co-occurs during the treatment of glioma.

D-allose, a type of rare sugar, can produce inhibitory effects on activated leukocytes in various organs, including immunosuppressive effects and anti-inflammatory effects, as well as anti-oxyradical effects. The present experiment was performed to investigate the potential anti-inflammatory effects of D-allose in acute cerebral ischemia/reperfusion (I/R) injury. Transient middle cerebral artery occlusion model was applied in rats. D-allose was administered two times via a tail vein (300 mg/kg, 1 hour before ischemia and 10 hours after reperfusion). After 22 hours of reperfusion following 2 hours of ischemia, brain damage was evaluated by cerebral infarct volume. Myeloperoxidase (MPO) activity assay by enzyme-linked immunosorbent assay, and protein expression of MPO and cyclooxygenase-2 (COX-2) by immunohistochemistry were evaluated to investigate the potential mechanisms of D-allose. The experimental results showed that D-allose exhibited significant neuroprotective effects against acute cerebral I/R injury. The infarct volume in D-allose-treated rats (90.9 ± 13.5 mm(3)) was significantly smaller than that in vehicle rats (114.9 ± 15.3 mm(3), p < 0.01). D-allose treatment significantly suppressed the MPO activity and the number of MPO-positive cells compared with those in the vehicle group, suggesting that treatment with D-allose can reduce the infiltration of leukocytes into the ischemic tissue. Treatment of D-allose also significantly decreased the number of COX-2-positive cells and microglial activation in the ischemic tissue. The present results demonstrate that D-allose exerts potent neuroprotective effects against acute cerebral I/R injury, and constitute the first evidence of anti-inflammatory effects of D-allose which considerably contributes to the beneficial effects. Treatment with D-allose might provide a new strategy and clinically beneficial outcome for acute ischemic stroke.

Background Several studies using trauma data banks and registers showed that age, Glasgow Coma Scale (GCS), Injury Severity Score, and intraventricular hemorrhage were independent factors for neurologic outcomes in geriatric patients with traumatic brain injury (TBI). However, these analyses did not comprehensively evaluate factors particularly associated with geriatric patients. We aimed to identify factors particularly associated with geriatric patients that affect neurologic outcomes in TBI. Methods Patients aged ≥65 years who were hospitalized consecutively in Kagawa University Hospital with severe TBI between 1 January 2008 and 31 October 2015 were retrospectively reviewed. We evaluated background factors particularly associated with geriatric patients, including comorbidities (Charlson Comorbidity Index [CCI]), nutritional status (serum albumin level), and presence/absence of antiplatelet and anticoagulant drugs, in addition to baseline characteristics. Multivariate analyses were performed to identify independent predictors of unfavorable neurologic outcomes (UO), as defined as a Glasgow Outcome Scale score of 1–3 at discharge from hospital. The association between CCI and UO was evaluated in a subgroup analysis. Results UO occurred in 65.0% of 140 patients. Multivariate analyses showed that the CCI (odds ratio, 1.91; 95% confidence interval, 1.21–3.29; P = 0.011), age, and GCS were independent predictors of UO. In subgroup analyses of patients with an initial GCS score of 13–15, the rate of UO significantly increased with CCI score (CCI 0, 35.5%; CCI 1 or 2, 39.4%; CCI >2, 83.3%; P Conclusions CCI was an independent predictor of UO in geriatric patients with severe TBI.

This paper presents a robotic catheter system with force sensors, monitor and a master-slave remote control system. We developed micro force sensors and applied them in the system to guarantee the operation safety in intravascular neurosurgery applications, and employed a camera to monitor the operation. Two kinds of force information are obtained through force sensors when the catheter contacted the blood vessel. The experiment shows that the proposed force sensors-based catheter system works well through force feedback and remote control. The system can facilitates the operation and avoid potential damages.

Accumulating evidence indicates that VEGF and matrix metalloproteinase-9 (MMP-9) play a central role in the development of peritumoral brain edema (PTBE) associated with human brain tumors. However, the roles of these proteins, particularly of MMP-9, in PTBE associated with benign meningiomas have not been elucidated. We investigated the association between clinical features and biological factors, such as VEGF and MMP-9, and the incidence of PTBE and edema index (EI) in 60 patients with benign meningiomas. In this study, supratentorial lesions were examined for evaluating the extent of PTBE in the surrounding normal brain tissue. VEGF and MMP-9 expression was immunohistochemically examined. Multivariate analysis revealed that the presence of pial blood supply (odds ratio [OR] 12.250; P = 0.0096) and VEGF (OR 7.683; P = 0.0155), but not MMP-9 (OR 1.178; P = 0.8113), expression are significant factors that independently predict the incidence of PTBE and influence EI. VEGF (P = 0.0397) and MMP-9 (P = 0.0057) expression correlates with the presence of pial blood supply. Moreover, tumors with high VEGF and MMP-9 expression had higher EIs than those with high expression of either (P = 0.030). Our findings suggest that MMP-9 expression was positively related to VEGF expression and pial blood supply and promoted the occurrence of PTBE by inducing the disruption of the arachnoid membrane and formation of pial blood supply.

A 53-year-old man suffered from pulsating headache for 2 months. Magnetic resonance imaging with gadolinium revealed a linear or nodular mass along the left fronto-parietal convexity. Positron emission tomography (PET) with L-[methyl-11C]methionine (11C-MET) demonstrated increased uptake in the enhanced lesion. Biopsy, obtained by craniotomy, demonstrated granulation with lymphocyte and plasma cell infiltration, suggesting inflammatory changes, and a diagnosis of idiopathic hypertrophic cranial pachymeningitis (IHCP) was made. Steroid therapy resulted in improvement of the clinical symptoms and shrinkage of the enhanced lesion in a week. Follow-up 11C-MET PET study, after 18 months of steroid therapy, demonstrated significantly decreased uptake in the lesion, so the steroid therapy was discontinued. Neither clinical nor radiological recurrence was observed one year after discontinuation of the steroid therapy. This case of IHCP with increased 11C-MET uptake, which then decreased after steroid therapy suggests that 11C-MET PET is a useful monitoring modality for therapeutic efficacy against IHCP, and can indicate the appropriate timing of therapy discontinuation.

This study was conducted to identify the regional neuronal damage occurring in patients with neuropsychological impairment following diffuse traumatic brain injury (TBI) compared with normal control subjects. In addition, measures of the neuropsychological tests were correlated with regional 11C-flumazenil (FMZ) binding potential (BP) reductions to clarify the relationship between cognitive impairment and regional neuronal damage. We performed 11C-flumazenil positron emission tomography (FMZ-PET) studies using three-dimensional stereotactic surface projection (3D-SSP) statistical image analysis in eight diffuse axonal injury (DAI) patients (mean age 29.1 ± 11.1 years, range 19–46 years). All patients underwent assessment with the Wechsler Adult Intellectual Scale-Third Edition (WAIS-III) to evaluate general intelligence. Twenty healthy control subjects (mean age 24.4 ± 2.8 years, range 22–30 years) were also studied to obtain a normal database for 3D-SSP. Group comparisons showed significant regi...

BACKGROUND: Comorbidity is a common problem in the treatment of elderly patients, but there is no standard method of the evaluation in glioblastoma patients. Gagne comorbidity index (GCI) has been proposed to be an integrated prognostic index of the Charlson comorbidity index and Elixhauser index, associating with the short-term survival of various diseases. We examined the relationship between GCI and prognosis of elderly patients with glioblastoma. METHODS: 31 patients over 70 years treated at our hospital from Dec.2006 to Aug.2017. 16 males and 15 females. Mean age 76.8 years (70–86 years old). Relationship to overall survival (OS) was examined focusing on the age, GCI at hospitalization(low:≤1, intermediate:2–4, high:≥5), Karnofsky Performance Status (KPS), surgery, radiotherapy (standard and hypofractionated), and temozolomide-based chemotherapy. RESULT: Median OS of entire cohort was 13.0 months. There was no significant correlation between age and GCI, but a negative correlation between KPS and GCI (r=-0.427). Median OS was longer in the resection group (resection; 13.5m vs non-resection; 8.6m), and in chemo-radiotherapy (standard radiotherapy+TMZ: 13.5m and hypofractionated radiotherapy+TMZ: 10.1m), though, GCI has no relationship to such treatment option. Nevertheless, high GCI indicated poor prognosis with a median OS in the group of low GCI:13.0m, intermediate GCI:14.5m and high GCI:5.3m (p=0.002). DISCUSSION: The presence of comorbidities is one of the factors related to prognosis, and glioblastoma affecting the brain is in a disadvantageous condition due to cognitive dysfunction and paralysis. Since surgical excision and radiation chemotherapy lead to improvement in prognosis even in the elderly, it is important to complete the treatment paying maximum attention to the management of comorbidities. GCI would be useful to evaluate comorbidities. Further examination is needed in large cohort.

A capillary hemangioma with hydrocephalus in the posterior fossa of a fetus was detected on ultrasonography at 38 weeks and 4 days of gestation. A well-defined, round tumor with a mixed pattern occupied the posterior fossa, and the normal cerebellum was significantly compressed by this tumor. No other anomaly was detected. Delivery was induced because of rapidly progressive hydrocephalus, and an otherwise healthy female infant weighing 2800 g was delivered vaginally at 39 weeks and 4 days of gestation. Histologic examination of the lesion through biopsy demonstrated capillary hemangioma. The tumor spontaneously decreased in size, and disappeared six months later. The child is now 2 years of age, and is developing normally.

The diagnosis of primary central nervous system lymphoma (PCNSL) in immunocompetent patients with atypical magnetic resonance (MR) findings such as disseminated lesions or no (non-enhancing) lesion is sometimes difficult because of mimicking other tumorous and non-tumorous diseases. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) and (11)C-methionine (MET) can measure the glucose and amino acid metabolism in the lesions and may provide useful information for diagnosing PCNSL in patients with such subtle MR findings.We performed PET studies with FDG and MET in 17 histologically proven PCNSL and compared the uptake of FDG and MET qualitatively and quantitatively in the tumors between 12 typical and 5 atypical MR findings.All typical PCNSL showed strong uptake of FDG and MET; however, visual analysis of FDG and MET uptake in atypical PCNSL was not very useful for finding lesions in the brain. Semiquantitative FDG and MET uptake values (SUVmax) and quantitative FDG influx rate constant (K ( i )) in the tumors are significantly lower in atypical PCNSL compared with those in typical PCNSL. These values obtained in the lesions with atypical MR findings were also not useful for differentiating PCNSL from other tumorous and non-tumorous diseases. The k (3) values evaluated by FDG kinetic analysis in atypical PCNSL were similar to those obtained in typical PCNSL.Visual analysis of FDG and MET uptake in atypical PCNSL was not useful for finding the lesions in the brain. Semiquantitative and quantitative values obtained in the lesions with atypical MR findings were also not useful for differentiating PCNSL from other tumorous and non-tumorous diseases. The k (3) values evaluated by FDG kinetic analysis in atypical PCNSL may provide valuable information in the diagnosis of PCNSL.

A 63-year-old man was found with confusion and right limb monoparesis. He was taken to the emergency center under suspicion of stroke. Head computed tomography and magnetic resonance (MR) imaging and MR angiography were immediately conducted, which revealed no abnormality, but diffusion-weighted imaging showed increased intensity areas in the splenium of the corpus callosum and the left posterior limb of the internal capsule with decreased apparent diffusion coefficient (ADC) in the same areas. Immediately after the head scan, blood sugar level was measured, which revealed hypoglycemia (23 mg/dl). He quickly became lucid after intravenous administration of 20 ml of 50% glucose solution, and the paresis disappeared. Follow-up brain MR imaging was conducted 3 days later, but no clearly abnormal findings were seen on T(2)-weighted, fluid-attenuated inversion recovery, diffusion-weighted, or ADC images. Reports of reversible high intensity area in the splenium of the corpus callosum on diffusion-weighted imaging due to transient hypoglycemia are rare. Hemiparesis is one of the manifestations of hypoglycemia, so verifying the blood sugar level is important. Since MR imaging can be conducted easily now, we may need to consider the imaging findings in the differential diagnosis of hypoglycemia.

It is expected that human neural stem/progenitor cells (hNS/PCs) will some day be used in cell replacement therapies. However, their availability is limited because of ethical issues, so they have to be expanded to obtain sufficient amounts for clinical application. Moreover, in-vitro-maintained hNS/PCs may have a potential for tumorigenicity that could be manifested after transplantation in vivo. In the present study, we demonstrate the in vitro and in vivo properties of long-term-expanded hNS/PCs, including a 6-month bioluminescence imaging (BLI) study of their in vivo tumorigenicity. hNS/PCs cultured for approximately 250 days in vitro (hNS/PCs-250) exhibited a higher growth rate and greater neurogenic potential than those cultured for approximately 500 days in vitro (hNS/PCs-500), which showed greater gliogenic potential. In vivo, both hNS/PCs-250 and -500 differentiated into neurons and astrocytes 4 weeks after being transplanted into the striatum of immunodeficient mice, and hNS/PCs-250 exhibited better survival than hNS/PCs-500 at this time point. We also found that the grafted hNS/PCs-250 survived stably and differentiated properly into neurons and astrocytes even 6 months after the surgery. Moreover, during the 6-month observation period by BLI, we did not detect any evidence of rapid tumorigenic growth of the grafted hNS/PCs, and neither PCNA/Ki67-positive proliferating cells nor significant malignant invasive features were detected histologically. These findings support the idea that hNS/PCs may represent a nontumorigenic, safe, and appropriate cell source for regenerative therapies for neurological disorders. © 2008 Wiley-Liss, Inc.

There is accumulating evidence indicating the role of aldosterone in the pathogenesis of hypertension and renal injury. In this study, we investigated the role of the Rho-kinase dependent signaling pathway in aldosterone-induced myofibroblastic transdifferentiation and collagen gene expression in rat mesangial cells (RMCs). Stimulation with aldosterone (1 nmol/L) significantly increased phosphorylation of myosin phosphatase target subunit-1 (MYPT-1), a marker of Rho-kinase activity, with a peak at 20 min in RMCs. Pre-incubation with a selective mineralocorticoid receptor antagonist, eplerenone (10 micromol/L), or a specific Rho-kinase inhibitor, Y27632 (10 micromol/L), attenuated the aldosterone-induced increase in MYPT-1 phosphorylation. Aldosterone also induced hypertrophy in RMCs, accompanied by an increase in actin polymerization and expression of alpha-smooth muscle actin (alpha-SMA), a myofibroblastic transdifferentiation marker. Collagen type I, III and IV mRNA levels were also increased with aldosterone stimulation. Pre-treatment with eplerenone or Y27632 prevented the aldosterone-induced cell hypertrophy, actin polymerization, the increase in alpha-SMA expression and the increases of collagen type I, III, IV mRNA levels in RMCs. These results suggest that aldosterone-induced mesangial cell hypertrophy is associated with cell transformation, leading to an increase in collagen gene expression via the Rho-kinase dependent signaling pathway.

Secondary consequences of intracerebral hemorrhage (ICH) including inflammation, edema, and oxidative damage all contribute to cell death after ICH. Brain hypothermia (BH) has been used as an effective neuroprotective treatment in experimental brain ischemia and traumatic brain injury. In this study, we first attempted to evaluate the effect of delayed mild BH (35 degrees C) on brain edema formation 48 hours after ICH. BH was started 3, 6, 12, and 24 hours after the induction of 100 muL of autologous blood into the basal ganglia (hypothermic [HT]; HT3: n = 4, HT6: n = 6, HT12: n = 11, HT24: n = 6) in rats. To examine the protective mechanism of BH, blood-brain barrier (BBB) permeability to Evans blue, accumulation of polymorphonuclear leukocyte, and oxidative DNA damage in the lesion were compared between normothermic (NT) (37 degrees C) and HT6 rats 48 hours after ICH. Finally, neurologic recovery was assessed using behavioral tests in NT and HT6 rats 48 hours after ICH. Brain water content in the ispilateral basal ganglia was significantly reduced with delayed BT compared with NT (n = 7, 81.8 +/- 0.7% v HT3: 78.9 +/- 0.8%, P < .01; HT6: 78.7 +/- 0.6%, P < .01; HT12: 79.4 +/- 1.1%, P < .01; HT24: 80.3 +/- 0.6%, P < .01). The BBB disruption to Evans blue was significantly reduced with BH (HT6: n = 6) compared with NT (n = 6) rats in the ipsilateral basal ganglia (23.0 +/- 5.2 v 42.3 +/- 4.0 ng/g wet tissue, P < .05). HT6 treatment (n = 6) significantly inhibited the accumulation of polymorphonuclear leukocyte compared with NT treatment (n = 6) (0.43 +/- 0.22 v 1.49 +/- 0.61 DeltaAbs/mg tissue, P < .05). HT6 treatment (n = 3) also significantly reduced oxidative DNA damage determined with 8-hydroxyl-2'-deoxyguanosine compared with NT treatment (n = 3) (92 +/- 18 v 40 +/- 7 pg 8-hydroxyl-2'-deoxyguanosine/mug DNA, P < .05). Furthermore, HT6 treatment (n = 5) significantly improved neurologic recovery assessed with forelimb placing score compared with NT treatment (42.0 +/- 5.8 v 12.0 +/- 3.7, P < .05). In conclusion, mild BH significantly reduces the brain edema formation after ICH, even when the BH is applied 24 hours after hematoma induction in rats. Several neuroprotective mechanisms, including reduced BBB disruption, inflammation and oxidative damage, are suggested in this study.

OBJECTIVE: Some recent reports have described the endoscopic endonasal removal of orbital tumors. However, the surgical anatomy for an endoscopic endonasal approach has not yet been clearly described. The first aim of this study is to examine the anatomic relationship between the paranasal and orbital structures with the use of computed tomographic imaging and to find useful landmarks for a transethtrioidal approach to the orbital retrobulbar space. The second aim is to determine a procedure to minimize the possibility of bleeding via the endonasal transethmoidal approach, METHODS: One hundred axial and coronal computed tomographic scans obtained between January 2004 and December 2005 were evaluated. RESULTS: The third lamella was located posteriorly to the posterior end of the eyeball on all axial computed tomographic scans, thus indicating that it may be a useful landmark for the localization of the retrobulbar space. There was a large variation in the relationship among the inferior and medial rectus muscles and the ethmoid-maxillary plate regarding their location. These results demonstrate that the route into the orbit via the ethmoid-maxillary plate gains no access to the medial side of the medial rectus muscle, the region with abundant blood vessels. CONCLUSION: These results suggest that the third lamella and ethmoid-maxillary plate are the most important anatomic landmarks for an endoscopic endonasal transethmoidal approach to the orbital retrobulbar space.

We developed a novel catheter operating system with an integrated force sensor for medical applications which included a highly precise master-slave remote control system. This paper explains the system design and control system in detail. As part of our research, we designed a micro force sensor and included it in the system to ensure safe operation in intravascular neurosurgery applications. We performed operation simulation experiments and analyzed the operating errors. The experimental results indicated that the proposed force sensor-based catheter operating system works well and can be controlled remotely, and the force feedback can effectively improve operability at an aneurysm.

Background and Purpose— Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury. Methods— These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 μL autologous whole blood (ICH), FeCl 2 , or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2′-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron- and thrombin-induced brain injury. Results— Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle ( P P Conclusions— Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. It also reduces iron- and thrombin-induced brain injury. These results suggest that edaravone is a potential therapeutic agent for ICH.

Several pathological and epidemiological studies have demonstrated a possible relationship between traumatic brain injury (TBI) and Alzheimer's disease (AD). However, the exact contribution of TBI to AD onset and progression is unclear. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in triple transgenic (3×Tg)-AD model mice. Five- to seven-month-old 3×Tg-AD model mice were subjected to either TBI by the weight-drop method or a sham treatment. In the 3×Tg-AD mice subjected to TBI, the spatial learning was not significantly different 7 days after TBI compared to that of the sham-treated 3×Tg-AD mice. However, 28 days after TBI, the 3×Tg-AD mice exhibited significantly lower spatial learning than the sham-treated 3×Tg-AD mice. Correspondingly, while a few amyloid-β (Aβ) plaques were observed in both sham-treated and TBI-treated 3×Tg-AD mouse hippocampus 7 days after TBI, the Aβ deposition was significantly greater in 3×Tg-AD mice 28 days after TBI. Thus, we demonstrated that TBI induced a significant increase in hippocampal Aβ deposition 28 days after TBI compared to that of the control animals, which was associated with worse spatial learning ability in 3×Tg-AD mice. The present study suggests that TBI could be a risk factor for accelerated AD progression, particularly when genetic and hereditary predispositions are involved.

A 75-year-old man with a recent history of transient left hemiparesis and dysarthria was referred to our hospital. Angiography showed right internal carotid artery (ICA) occlusion and left ICA 89% stenosis. Positron emission tomography (PET) showed decreased cerebral blood flow (CBF), and increased oxygen extraction fraction (OEF) and cerebral blood volume (CBV) in the right hemisphere. In the left hemisphere, CBV was increased, but CBF and OEF remained normal. One month after the transient ischemic attack, left carotid artery stenting (CAS) was performed without complications. Diffusion-weighted magnetic resonance imaging (MRI) on the day after CAS showed no fresh ischemic lesion. PET on the second day after CAS showed increased CBF and decreased OEF and CBV in the right hemisphere as compared with those before CAS. In the left hemisphere, decreased CBV was observed and CBF was slightly increased as compared with those before CAS. The postoperative course was uneventful, but on the fifth day after CAS, the patient suddenly showed a focal seizure and right motor weakness. Emergency computed tomography scanning showed massive intracranial hemorrhage with severe brain edema in the left hemisphere. Although CBF study is useful to predict the hyperperfusion syndrome, we cannot disregard the possibility of intracerebral hemorrhage after CAS for carotid artery stenosis when there is no evidence of hyperperfusion on postoperative CBF study.

Background/Aims: The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation. Methods: In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas. Results: The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). The IRS of MSP58 in the tumor showed a highly significant positive correlation with corresponding FLT uptake value (r = 0.61, P < 0.001). The correlation between MSP58 expression and glioma malignancy was also confirmed by immunofluorescence, RT-PCR and western blot analysis. FLT uptake value also exhibited a highly significant positive correlation with the Ki-67 index (r = 0.59, P < 0.001). Kaplan-Meier analysis revealed that MSP58 expression has a significant prognostic ability for the overall survival time similar to that found in the uptake value of FLT-PET. Conclusion: These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy.

Endovascular surgery benefits patients because of its superior short convalescence and lack of damage to healthy tissue. However, such advantages require the operator to be equipped with dexterous skills for catheter manipulation without resulting in collateral damage. To achieve this goal, a training system is in high demand.A training system integrating a VR simulator and a haptic device has been developed within this context. The VR simulator is capable of providing visual cues which assist the novice for safe catheterization. In addition, the haptic device cooperates with VR simulator to apply sensations at the same time. The training system was tested by non-medical subjects over a five days training session.The performance was evaluated in terms of safety criteria and task completion time. The results demonstrate that operation safety is improved by 15.94% and task completion time is cut by 18.80 s maximum. Moreover, according to subjects' reflections, they are more confident in operation.The proposed training system constructs a comprehensive training environment that combines visualization and force sensation. Copyright © 2016 John WileySons, Ltd.

Background The present study investigates the effects of d -allose, a rare sugar, on the inflammatory response after transient forebrain ischemia in the gerbil and whether it reduces oxidative stress (8-hydroxyl-2′-deoxyguanosine levels) and behavioral deficits. Methods Transient forebrain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 minutes. d -Allose was intraperitoneally injected immediately after ischemia (400 mg/kg). Inflammatory cytokines and oxidative damage in the hippocampus and behavioral deficits were examined 3 days after ischemia. Results d -Allose administration reduced ischemia-induced cytokine production, oxidative stress, and behavioral deficits (motor and memory related). Conclusions The present results suggest that d -allose reduces brain injury after transient global ischemia by suppressing inflammation as well as by inhibiting oxidative stress.

There has been no clinical observation about histopathological changes in human gliomas under control of the anti-angiogenic treatment, and the tissue-based observation is likely crucial to understand mechanism of action of these treatment. We collected 4 glioblastomas resected under control of neoadjuvant bevacizumab (Bev). Histopathological investigation was performed by hematoxilyn- eosin staining and immunohistochemistry for CD34, VEGF, VEGFR1/2, HIF-1α, and Nestin as compared to 6 control glioblastomas to assess changes in histological features, microvessel density, expression of VEGF and its receptors, tumor hypoxic condition, and cancer stem cells. Tumor resection under control of Bev was uneventful in all of the 4 cases. Intraoperatively, the tumors were clearly less vasculized than usual. Histopathologically, vascular morphology was quite different from usual glioblastomas with universal disappearance of microvascular proliferation. Microvessel density was significantly decreased in the 4 tumors as compared to control tumors. The expression of VEGF and its receptors was decreased in 2 cases of partial response, suggesting possible correlation with radiologic response. The expression of HIF-1α was similar or somewhat decreased in the 4 tumors. The expression of Nestin was significantly decreased in the 4 tumors as compared to control tumors, but there still remained numerous Nestin-positive cells especially around vessels. We provide the first clinicopathological evidence that the anti-angiogenic therapy induces vascular normalization and decrease of microvessel density in glioblastomas. These in situ observation will help to elucidate the mechanism of resistance to Bev and to optimize therapy.

OBJECT: Neuroendocrine carcinoma (NEC) is a malignant tumor that usually arises in the lung, pancreas and gastrointestinal tract. Brain metastasis of NEC is merely reported. Herein, we report two cases of NEC in the brain mimicking glioblastoma (GBM). CASES: Both patients were in their 60s, cystic lesions with peritumoral edema affected the temporal lobe. Cyst walls were thin but hyperintense in diffusion weighted images implying increased cellularity. Positron emission tomography (PET) revealed malignant nature by strong uptake of methionine (MET), fluorothymidine (FLT) and fluoromisonidazole likewise GBM. However, fluorodeoxyglucose (FDG) indicated relatively weak uptakes compared as GBM. Both tumors were resected under the preoperative diagnosis of GBM, however, pathological diagnoses were NEC by immunohistochemical finding of negative GFAP and positive markers of neuroendocrine differentiation. Systemic examination failed to reveal the origin. Both cases underwent radiotherapy. One case was lost by spinal dissemination 11 months after the operation. DISCUSSION: FDG-PET of neuroendocrine tumor in the extracranial lesion does not always demonstrate strong uptake. FDG-PET for NEC in the brain could be less accumulated than GBM, while it should be evaluated keeping in mind that the background level of FDG would be high in the brain tissue. In case of malignant tumors endorsed by other tracer such as MET and FLT, inconsistent FDG-PET finding might be useful for the diagnosis of NEC in the brain.