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Frameless stereotactic brain biopsy (FSB) with navigation system has been widely used. We reported preliminary experience of FSB with intraoperative computed tomography (iCT) and examined the usefulness of this novel adjuvant technique and real target registration error (rTRE) of FSB. The FSB with 5-aminolevulinic acid (5-ALA) and iCT was performed on 10 patients. The gadolinium-enhanced lesions on magnetic resonance image were defined as the biopsy target. In the procedure, iCTs were scanned twice, for autoregistration of the navigation system and for confirmation of the position of the actual inserted biopsy needle. The red fluorescence of the samples was observed under excitation with violet-blue light through a low-cut filter of neurosurgical microscope. The distance between the planned target and the tip of the biopsy needle in the image of iCT was calculated in a workstation for the assessment of rTRE. The median volume of the target was 12.13 mL (0.06-39.15 mL). We performed the surgical procedure in a prone position in four patients. None to faint 5-ALA-induced fluorescence was observed in six samples. There existed no sampling errors. The mean target distance between the planned and real targets of the mean rTRE of FSB was 2.7 ± 0.56 mm. The real TRE of FSB was first reported and was larger than the reported rTRE exactly calculated from the fiducial registration error. iCT guarantees accurate tumor sampling with autoregistration regardless of the surgical position and prevents inaccurate biopsy to occur even with ALA fluorescence assistance.

Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

Boron neutron capture therapy (BNCT), which uses the capture reaction between neutrons and boron-10, an isotope of boron, is rapidly gaining interest. The reason for this is the successful development of a compact accelerator-type neutron generator that can be installed in a hospital and launched into the clinical setting. BNCT, which provides selective radiotherapeutic effects at the cellular level, is expected to be effective against invasive cancer. We have been investigating BNCT applications in various types of malignant brain tumors, especially malignant gliomas, as medical applications. Recently, we have conducted clinical trials using the developed accelerator neutron source. Research on pharmaceutical applications of compounds that transport boron to cancer cells is expected to be in even greater need. Currently, the only boron agent used in cancer therapy is BPA (Borofaran 10B), which takes advantage of the demand for essential amino acids, but the research and development of boron agents are an absolutely key technology to further improve the precision of this treatment modality. This chapter summarizes and discusses the results of BNCT in the treatment of brain tumors.

The ORBEYE (ORB), an innovative 3-dimensional digital exoscope, is an equipped system for fluorescence-guided surgery with 5-aminolevulinic acid. Therefore, this study aimed to verify the characteristics of fluorescence-guided surgery with 5-aminolevulinic acid and excitation light source with ORB.The same operative field of glioblastoma was recorded under blue light (BL) excitation using a conventional microscope (MS) and ORB. For in vitro studies, the energy of 405-nm wavelength light in white light and BL modes of each scope was examined in various focal lengths. To examine the degree of photobleaching with BL for each scope, protoporphyrin IX-soaked filter papers were continuously exposed with BL of an MS and ORB, and the video-recorded red fluorescence intensity was analyzed.The color tone of tumor-induced red fluorescence was remarkably different under each scope. Furthermore, nonfluorescent normal structures without red fluorescence were well recognized under ORB. The energy of 405-nm wavelength light in BL was significantly higher in ORB than that in an MS, especially in the short focal length. With continuous BL excitation to filter papers, the relative red fluorescence intensity of filter papers was significantly decreased over time in ORB than in an MS. In low protoporphyrin IX concentration, the difference was more significant.With ORB, the good visibility due to BL energy as compared with an MS might improve the surgical manipulation even in BL mode. However, the weak fluorescent tissue and short focal length should be carefully considered because photobleaching might be critical for FGS.

Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT).Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (OHypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs.Hypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.

Background Although most patients with Rathke's cleft cysts (RCCs) remain asymptomatic throughout their lives, visual impairment in RCCs usually indicates surgical interventions, including endoscopic drainage of the cyst. We report a case of RCC with unique findings in the optic nerve root (ONR) by magnetic resonance imaging (MRI). Case Description A 58-year-old man admitted to our hospital complained of progressive left visual impairment. Preoperative computed tomography MRI revealed a suprasellar cystic lesion that extended anteriorly, and the bilateral ONRs were lateralized with the cyst and were partially enhanced with gadolinium administration. The cyst content was drained, and the cyst wall was partially removed by endoscopic transsphenoidal surgery. Postoperatively, the patient was administered corticosteroid intravenously for 3 days, and his visual acuity improved dramatically. Postoperative MRI revealed that the volume of the cyst decreased, and the position of the bilateral ONRs normalized. Additionally, enhancement of the ONRs with gadolinium administration was not observed. Histological examination of the surgical specimen revealed a ciliated single-layer columnar epithelium with inflammatory cell infiltration. Conclusions To our knowledge, we report the first case of a patient with RCC with ONR enhancement with gadolinium administration on MRI. This unique finding might prove that inflammation is one of the causes of visual impairment in RCC as in optic neuritis.

Background Endovascular embolization of the middle meningeal artery (MMA) is effective for recurrent chronic subdural hematoma (CSDH). CSDH associated with dural metastasis is generally refractory to burr hole surgery and has poor prognosis even if any interventions are applied. To the best of our knowledge, this study is the first to report a case of refractory CSDH associated with dural metastasis that was successfully treated with embolization of the MMA. Case Description A 66-year-old man with a 1-year history of lung adenocarcinoma had also undergone whole-brain irradiation for multiple brain metastases 5 months before presentation, surgical removal of relapse of brain metastases 3 months prior, and stereotactic radiotherapy for the relapses 1 month prior. He was admitted to our institution with speech disturbance, severe headache, and right-sided motor weakness. Head computed tomography on admission revealed left-sided CSDH, and emergency burr hole irrigation surgery was performed. However, CSDH recurred twice in a short period after hospitalization. Histological examination revealed adenocarcinoma cells in the dura mater and in hematoma samples during the first surgery; therefore, the patient was diagnosed with refractory CSDH associated with dural metastasis of lung adenocarcinoma. We performed endovascular embolization of the MMA, followed by systemic chemotherapy at 1 month after embolization, and no recurrence of the CSDH was observed. Conclusions Embolization of the MMA has few surgical risks and could be a treatment option for refractory CSDH associated with dural metastasis because it might prolong the therapeutic time window until radical therapies are administered.

This article reviews the existing approaches to determining the

Cancer cells with stem cell-like features are generally more resistant to chemotherapy and radiotherapy than differentiated tumor cells. Thus, these cells tend to increase the propensity for tumor recurrence and metastasis. This study investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in destructing glioma stem cells (GSCs), including the mesenchymal subtype (MES-GSCs) demonstrated to have the lowest radio- and chemosensitivity.Five high-grade glioma (HGG) GSC lines and derived differentiated glioma cell (DGC) lines were examined for protoporphyrin-IX (PpIX) expression using fluorescence-activated cell sorting (FACS) and then assessed for ALA-PDT sensitivity using cell viability assays. MES-GSCs surviving ALA-PDT were then isolated and evaluated for stem cell and mesenchymal marker expression levels (CD44, ALDH1A3, KLF4, nestin) by qRT-PCR. The ability of these surviving cells to form tumors was then examined using colony forming and by xenograft tumor assays in athymic mice. Finally, the relationship between PpIX expression level (high versus low) and ALA-PDT sensitivity was examined by FACS and colony forming assays.ALA-PDT was effective against all GSC lines including MES-GSCs. MES-GSC lines exhibited higher PpIX expression than derived DGCs. Surviving MES-GSCs demonstrated lower stem cell marker expression and tumor forming potential than naive MES-GSCs. Higher PpIX production capacity by MES-GSCs was associated with greater colony forming ability, and ALA-PDT was more effective against MES-GSCs with greater PpIX accumulation.ALA-PDT may be clinically effective against HGG by targeting GSCs, including MES-GSCs.

Background Glioblastoma is a highly malignant brain tumor refractory to standard treatment and its refractoriness is attributed to the presence of a small number of glioma stem cells (GSCs) that survive in a harsh microenvironment. The aim of this study was to investigate the effect of hypoxic conditions on the sensitivity of GSCs to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). Materials and Methods Six human GSClines: three GSCs classified as Mesenchymal subtype and three GSCs classified as Proneural subtype, were divided into normoxia-GSCs (O2: 21%) and hypoxia-GSCs (O2: 5%) groups. To compare the effects of different oxygen partial pressures on protoporphyrin-IX (PpIX) biosynthetic activity, the expression levels of PpIX biosynthetic enzymes and transporters were examined by qRT-PCR and intracellular PpIX concentration was measured by flow cytometry. In addition, the sensitivity of these two cell groups to ALA-PDT was assessed in vitro. Results Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpIX to haem, compared to Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpIX from exogenous ALA in Hypoxia-GSCs was reduced compared to in Normoxia-GSCs. Despite this, no Hypoxia-GSC lines showed significantly reduced sensitivity to ALA-PDT compared to Normoxia-GSCs. Conclusion Hypoxia-GSCs had lower intracellular PpIX accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA- PDT was reduced less, despite accumulating lower concentrations of PpIX. ALA-PDT is at least a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.

Background We previously reported a phase II trial of accelerator-based boron neutron capture therapy (BNCT) for patients with malignant glioma, which showed a long median overall survival of 18.9 months. However, median progression-free survival was 0.9 months. In this trial, bevacizumab was permitted to use after progressive disease. The reason of discrepance between a short progression-free survival and a long overall survival was speculated that progression disease included pseudoprogression. But, efficacy of add-on bevacizumab on overall survival was not ignored. Methods The present study was approved by the Osaka Medical and Pharmaceutical University certificated review board and registered for Japan Registry of Clinical Trial (jRCTs051220019). Twenty-one patients who had malignant glioma refractory to bevacizumab treatment were planned to enroll in the study. The primary endpoint was a response rate of boronophenylalanine positron emission tomography. The secondary endpoints were a response rate of magnetic resonance image and safety. Conclusion Patients have been enrolled from June 2022. The efficacy of BNCT for malignant glioma could be elucidated by PET evaluation of tumor viability after BNCT.

Background Glioblastoma is a highly malignant brain tumor refractory to standard treatment and its refractoriness is attributed to the presence of a small number of glioma stem cells (GSCs) that survive in a harsh microenvironment. The aim of this study was to investigate the effect of hypoxic conditions on the sensitivity of GSCs to 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). Materials and Methods Six human GSClines: three GSCs classified as Mesenchymal subtype and three GSCs classified as Proneural subtype, were divided into normoxia-GSCs (O2: 21%) and hypoxia-GSCs (O2: 5%) groups. To compare the effects of different oxygen partial pressures on protoporphyrin-IX (PpIX) biosynthetic activity, the expression levels of PpIX biosynthetic enzymes and transporters were examined by qRT-PCR and intracellular PpIX concentration was measured by flow cytometry. In addition, the sensitivity of these two cell groups to ALA-PDT was assessed in vitro.Results:Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpIX to haem, compared to Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpIX from exogenous ALA in Hypoxia-GSCs was reduced compared to in Normoxia-GSCs. Despite this, no Hypoxia-GSC lines showed significantly reduced sensitivity to ALA-PDT compared to Normoxia-GSCs.Conclusion:Hypoxia-GSCs had lower intracellular PpIX accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA- PDT was reduced less, despite accumulating lower concentrations of PpIX. ALA-PDT is at least a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.

Boron neutron capture therapy (BNCT) is a particle therapy that can target tumors at the cellular level. BNCT has been developed for the treatment of malignant gliomas with widely infiltrated tumors, but as the indication for BNCT was expanded to include the whole body, the focus shifted to borophalan-10B (BPA), which is based on the essential amino acid phenylalanine, as a candidate agent. We started BNCT for brain tumors in 2002 with a protocol combining two compounds (BPA, BSH) that had been clinically used, but later, with the development of an accelerator-based system, we conducted a clinical study of a single agent of BPA with a modified administration protocol in a nuclear reactor. In this report, we analyze the clinical studies of BNCT for recurrent malignant glioma using the reactor as a neutron source, and discuss the possibility of BNCT using multiple drugs in combination. The median survival with BSH+BPA was 11.0 months (n=29) overall, and the MST with BPA alone was 11.1 months (n=24), with similar results for BPA alone. The blood boron levels at the time of irradiation were 46.3 and 27.3 μg/ml, respectively, which were higher with the addition of BSH. The irradiation doses converted to X-rays (Gy) equivalent were calculated to be 69 and 76 Gy-Eq for the maximum tumor, 37 and 40 Gy-Eq for the minimum, and 10.9 and 10.5 Gy-Eq for the normal brain, respectively. The biological effectiveness ratios for tumor and normal tissue from neutron capture reactions with boron compounds and tissue boron concentrations were factored into these calculations, and since BPA and BSH have different target systems (BPA in the infiltration zone and BSH in the contrast zone, respectively), we believe that their combined use may improve therapeutic efficacy and attenuate adverse events.

Background Virtual reality (VR) and mixed reality (MR) are now widely applied for preoperative simulation and intraoperative navigation. Methods We developed an MR-based simulator for endoscopic transnasal surgery (ETNS) with a head-mounted display HoloLens and evaluated its usefulness. This simulator consisted of MR images of patients and an MR endoscope. HoloLens was used for projection of MR images and recognition of markers. The MR images were reconstructed from the preoperative images of patients and superimposed onto the endoscopic training model of the head. The MR endoscope was superimposed onto a three-dimensional (3D) printed replica of an endoscope. The MR endoscopic images from the replica of the endoscope were projected in the operator’s visual field. The MR images followed the manipulation of the replica of the endoscope through a nasal cavity on the training model. To evaluate the developed simulator, the MR endoscopic images were compared with video-recorded actual operative endoscopic views. And face validity and content validity of the simulator were evaluated by senior residents, using a 5-point Likert scale. Result The 3D MR images through HoloLens correlated well with the actual intraoperative views. Although there was an innate learning curve with the simulator, the face validity and the content validity demonstrated effective simulation of an operative field of view with real-time characteristics of the surgical procedure. Conclusions Our developed simulator for ETNS will contribute to learning the unique and the limited surgical fields through the narrow surgical corridor with endoscope, particularly for novice surgeons.

Background Glioblastoma (GBM) is a highly malignant lethal brain cancer. Accumulated evidence suggests that elevated resistance of GBM to both chemo- and radio-therapy is, at least in part, due to the presence of a small population of glioma stem cells (GSC). In the present study, we aimed to determine the sensitivity of GSCs to 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). Methods For this purpose, we established GSC-enriched cell cultures (termed glioma stem-like cells or GSLCs) from A172 human GBM cell line. Under our cultivation conditions, GSLCs formed floating spheroid clusters that contained increased population of CD133/Sox2 expressing cells. Firstly, to compare the activity of protoporphyrin IX (PpIX) biosynthesis in the GSLCs and the parental A172 glioma cells, we examined the expression levels of biosynthesis enzymes and transporters for PpIX using qRT-PCR, and investigated the intracellular levels of PpIX with use of flow cytometry analysis. Then, we evaluated the sensitivity of these cells to ALA-PDT in vitro. Finally, to confirm the therapeutic impact of ALA-PDT on GSLCs with more clinically relevant model, we performed the same experiment using three different patient-derived glioma sphere lines, which cultivated them either in stem cell media or under differentiation conditions in the presence of serum. Results and Conclusion GSLCs expressed higher mRNA levels of PpIX biosynthesis enzymes and its transporters PEPT1/2 and ABCB6, when compared to the parental A172 glioma cells. Consistently, flow cytometry analysis revealed that upon incubation with ALA, GSLCs accumulate a higher level of PpIX. Finally, we showed that GSLCs were more sensitive to ALA-PDT than the original A172 cells, and confirmed that all patient-derived glioma sphere lines also showed significantly increased sensitivity to ALA-PDT if cultivated under the pro-stem cell condition. Our data indicate that ALA-PDT has potential as a novel clinically useful treatment that might eliminate GBM stem cells that are highly resistant to current chemo- and radio-therapy.

Background: This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy for malignant brain tumors affect the recurrence and progression of glioma. Methods: 3 months after the same 65-Gy irradiation had been applied to the right hemisphere. Irradiated Fisher rats were divided into three groups for in vitro assay as follows. IR/Ipsi-brain; the right-hemisphere tissue was used for experiments. IR/Contra-brain; the left-hemisphere tissue was used. Sham-IR/Brain; sham-irradiation was applied to the brain, and the right-hemisphere tissue was used. The effects of proteins extracted from the brains directly or indirectly affected by irradiation on the growth of F98 cells, the effect on tube formation, the influence on tumor biology, and the influence on cytokine production were investigated. Additionally, irradiated animals were divided into three groups for in vivo assay as follows. IR/Ipis-tumor; F98 cells (a glioma cell line) were transplanted to the right hemisphere. IR/Contra-tumor; F98 cells were transplanted to the left hemisphere. Sham-IR/Tumor; F98 cells were transplanted to the right hemisphere without irradiation. The median survival time of F98 transplanted rats was also examined. Results: X-ray irradiation promoted the secretion of cytokines such as TNFα, TGF-β1, VEGF-A, and CXCL12 from the irradiated brain. F98 glioma cells implanted in the irradiated brains showed significantly high proliferation and angiogenesis ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group.Conclusions: These results indicate that the up-regulation of CXCL12-CXCR4 axis by radiotherapy could promote tumor proliferation. Radiation therapy is a standard treatment for malignant gliomas including glioblastoma multiforme, but the current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.

Malignant gliomas are highly invasive tumors. Accurate identification of tumor tissue is essential for enabling tumor resection as much as possible without damaging important neurological functions. One of the methods is intraoperative fluorescence imaging. This method visualizes in real time the boundary between the tumor and normal brain, which cannot be identified using conventional surgical microscope under white light. Although many fluorescent dyes have been reported for intraoperative fluorescence imaging of brain tumors, only 5-aminolevulinic acid(5-ALA)is approved by Ministry of Health, Labour and Welfare in Japan. After the oral administration of 5-ALA, fluorescence is emitted by protoporphyrin Ⅸ, a metabolite of 5-ALA in tumor cells(red fluorescence with a peak at 635 nm, induced by an excitation light of 405 nm). The intensity of fluorescence is correlated with tumor cell density, proliferation rate, and vascular density. In a multicenter randomized controlled study in Germany, compared with white light imaging, fluorescence imaging with 5-ALA increased the tumor resection rate and significantly prolonged progression-free survival at 6 months. However, no difference was observed in overall survival. Regarding other fluorescent substances, fluorescein sodium is a dye that leaks from tumor vessels without the blood-brain barrier, like contrast media used for computed tomography and magnetic resonance imaging(green fluorescence with a peak at 520 nm, induced by an excitation light of 493 nm). This dye spreads in the interstitial tissue of the tumor to visualize the tumor area. Indocyanine green emits a near-infrared light of 820-920 nm, induced by an excitation light of 760- 810 nm. This dye was expected to be useful for visualizing deep tumors as it emits light with high tissue permeability; however, it does not leak out of blood vessels because of its large molecular weight. Subsequently, this dye is used for intraoperative angiography of highly vascularized tumors. Talaporfin sodium was originally developed for photodynamic therapy in Japan and is readily taken up by tumor cells. This substance is also used for intraoperative fluorescence imaging because it emits the fluorescence of 672 nm, induced by an excitation light of 664 nm. Here, we review various fluorescent dyes used for intraoperative imaging of brain tumors.

BACKGROUNDCalcifications in pituitary adenomas are rare, being found in only 5.4%–25% of reported cases. These are divided into eggshell-like calcifications around the tumor and nodular calcifications at the center of the tumor, the latter of which are called “pituitary stones” (PSs).OBSERVATIONSThe authors report the case of a 60-year-old male with a nonfunctional pituitary adenoma with PSs and asymptomatic ventricular dilatation who presented with spontaneous cerebrospinal fluid (CSF) rhinorrhea and rapid visual aggravation without an increase in tumor size over the course of 4 years. After endoscopic transnasal surgery, his visual acuity immediately improved temporarily. It was believed that the increased intracranial pressure due to secondary hydrocephalus resulted in visual aggravation; thus, a ventriculoperitoneal (VP) shunt was created. After creation of the VP shunt, the patient’s visual acuity improved gradually and completely. Histological findings showed that adenoma cells were observed among the lamellar bone trabeculae. To the best of the authors knowledge, this is the first report of osteoid metaplasia–type PSs in nonfunctioning pituitary adenoma.LESSONSPSs formed near the sellar floor and caused spontaneous CSF rhinorrhea due to direct mechanical stress on the dura mater and optic nerves, which may have caused meningitis and secondary hydrocephalus that resulted in visual impairment independent of tumor size.

The long-term prognosis of cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH) remains unclear. This study aimed to determine the long-term prognosis of cognitive function in patients with iNPH, as well as the factors related to it. It included 48 patients with iNPH who were treated with cerebrospinal fluid shunting between January 2015 and December 2017 at Osaka Medical College Hospital, with follow-up evaluation of their cognitive function for >2 years. Cognitive function was measured using the Mini-Mental State Examination (MMSE) preoperatively and at 3 months, 1 and 2 years post-operatively. The mean MMSE score (22.4 ± 5.4 preoperatively) improved at 3 months [23.8 ± 5.0 (p = 0.0002)] and 1 year [23.7 ± 4.8 (p = 0.004)] post-operatively. At 2 years post-operatively, they were able to maintain their preoperative level (22.6 ± 5.3). The patients were classified in to the cognitive decline group [11 (23%) patients; a decrease in the MMSE score by ≥ 2 points 2 years after surgery] and the maintenance/improvement group [37 (77%) patients]. Univariate and receiver operating characteristic analyses were performed for the two groups to identify factors associated with cognitive prognosis. In both groups, the patients who were younger (p = 0.009) or had milder symptoms (p = 0.035) had a better long-term prognosis of cognitive function. The cutoffs for age and disease severity (idiopathic normal-pressure hydrocephalus grading scale; INPHGS) were 78 years (area under the curve = 0.77) and 5 points (area under the curve = 0.71), respectively. In conclusion, most patients (77%) were able to improve and maintain cognitive function for at least 2 years after surgery. The fact that disease severity and age are associated with cognitive prognosis suggests that early iNPH intervention is desirable to improve cognitive prognosis.

Background: Nocardia is an aerobic Gram-negative bacillus belonging to actinomycetes and has been reported to be an infectious disease in healthy individuals. However, more than 60% have some underlying illnesses and are said to be opportunistic infections. Case Description: The case was a 69-year-old man who had been on long-term steroids for systemic lupus erythematosus. He developed with nausea and gait disturbance and was suspected of having a brain abscess by imaging. Abscess drainage detects actinomycetes that appear to belong to the genus Nocardia and brain abscess by Nocardia thailandica using matrix-assisted laser desorption/ionization time-of-flight mass analysis (MALDITOFMS) I was diagnosed. He died during the course of the treatment, and his organs did not detect his N. thailandica at necropsy, so he concluded that bacterial death from long-term administration of antibiotics was the cause of death. Conclusion: N. thailandica is a very rare bacterium belonging to Nocardia asteroides and is said to easily form brain lesions. In immunocompromised patients, prophylaxis with antibiotics and detailed examination of lung lesions for surveillance were considered necessary. This paper is the first report of a brain abscess caused by N. thailandica, including a review of the literature.

BACKGROUND Spinal catheter insertion in lumboperitoneal (LP) shunt surgery for idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with technical difficulties especially in patients with obesity and elderly patients with vertebral deformities. OBJECTIVE To elucidate the accuracy and safety of image-guided spinal catheter placement using a paramedian approach (PMA). METHODS We retrospectively analyzed 39 consecutive iNPH patients treated by LP shunting with spinal catheter insertion via the PMA. The success rate of catheter placement and the number of changes in puncture location were evaluated. Accuracy of catheter insertion was assessed by measuring both vertical and horizontal deviations in the point of catheter dural penetration from the center of the interlaminar space. RESULTS The success rate of catheter placement was 100% (39/39). The difficulty rate for catheter insertion, measured by the number of changes in puncture location, was 2.6% (1/39). No bloody punctures or surgical infections were observed. Accuracy of catheter insertion, measured as the degree of deviation, was 0.5 ± 1.9 mm horizontally and 0.0 ± 2.4 mm vertically. The rates of minor complications, including caudal catheter insertion, transient low-pressure headache, and root pain, were 5.1% (2/39), 10.4% (4/39), and 0% (0/43), respectively. Subdural hematoma requiring surgical intervention occurred in 1 case (2.6%). During the mean follow-up period of 36 mo, spinal catheter rupture at the level of the spinous processes was not observed. CONCLUSION Fluoroscopic-guided spinal catheter placement via the PMA was safe, accurate, and reliable, even for use in geriatric and obese patients.

This study is intended to objectively clarify the relationship between the fluorescence intensity emitted by protoporphyrin IX (PpIX), which is a metabolite of 5-aminolevulinic acid (ALA), and histological findings during glioblastoma surgery.ALA is widely used for the intraoperative detection of tumors. There are several reports about the fluorescence of PpIX and the histological findings of tumors, but judgments about the fluorescence intensity depend largely on the subjective sense of each surgeon.We quantified the PpIX fluorescence intensity emitted from tissue specimens using a spectroradiometer and evaluated the relationship between a spectral radiance of 635 nm and the histopathological features of surgical specimens of glioblastoma. Surgical samples from glioblastoma patients consist of a strongly fluorescent area (SFA) or vaguely fluorescent area (VFA). Hematoxylin and eosin staining, immunohistochemical Ki-67, and CD31 staining were performed to evaluate the cell density, MIB-1 index, and vascularity, respectively. The fluorescence intensities of each sample were compared with each histopathological parameter.Cell density, MIB-1 index, and total vascular area were significantly correlated with PpIX fluorescence radiance. 87.5% of SFA were judged to be tumor bulk consisting mostly of tumor cells and 12.5% peritumoral invaded brain. In the VFA, 100% of specimens were judged to be peritumoral invaded brain.ALA-induced PpIX fluorescence has quantitatively correlated well with histopathological malignant features both in SFA and VFA. These findings suggest that not only SFA but also VFA should be removed to the highest extent that does not cause neurological symptoms.