Aging and Sex Differences in Brain Volume and Cerebral Blood Flow.

How do regional brain volume ratios and cerebral blood flow (CBF, mL/min) change with aging, and are there sex differences? This study aimed to comprehensively evaluate the relationships between regional brain volume ratios and CBF in healthy brains. The study participants were healthy volunteers who underwent three-dimensional T1-weighted MRI, time-of-flight MR angiography, and four-dimensional (4D) flow MRI between 2020 and 2022. The brain was automatically segmented into 21 brain subregions from 3D T1-weighted MRI, and CBF in 16 major intracranial arteries were measured by 4D flow MRI. The relationships between segmented brain volume ratios and CBFs around the circle of Willis were comprehensively investigated in each decade and sex. This study included 129 healthy volunteers (mean age ± SD, 48.2 ± 16.8; range, 22-92 years; 43 males and 86 females). The association was strongest between the cortical gray matter volume ratio and total outflow of the intracranial major arteries distal to the circle of Willis (Pearson's correlation coefficient, r: 0.425). In addition, the mean flow of the total inflow and outflow around the circle of Willis were significantly greater in women than men, and significant left-right differences were observed in CBFs even on the peripheral side of the circle of Willis. Moreover, the correlation was strongest between the left cortical gray matter volume ratio and the combined flows of the left anterior and posterior cerebral arteries distal to the circle of Willis (r: 0.486). There was a trend toward greater total intracranial CBF, especially among women in their 40s and younger, who had a larger cortical gray matter volume. This finding may be one of the reasons for the approximately twofold higher incidence of cerebral aneurysms and subarachnoid hemorrhage, and a threefold higher incidence of migraine headaches.

Aging-related volume changes in the brain and cerebrospinal fluid using artificial intelligence-automated segmentation.

OBJECTIVES: To verify the reliability of the volumes automatically segmented using a new artificial intelligence (AI)-based application and evaluate changes in the brain and CSF volume with healthy aging. METHODS: The intracranial spaces were automatically segmented in the 21 brain subregions and 5 CSF subregions using the AI-based application on the 3D T1-weighted images in healthy volunteers aged > 20 years. Additionally, the automatically segmented volumes of the total ventricles and subarachnoid spaces were compared with the manually segmented volumes of those extracted from 3D T2-weighted images using the intra-class correlation and Bland-Altman analysis. RESULTS: In this study, 133 healthy volunteers aged 21-92 years were included. The mean intra-class correlations between the automatically and manually segmented volumes of the total ventricles and subarachnoid spaces were 0.986 and 0.882, respectively. The increase in the CSF volume was estimated to be approximately 30 mL (2%) per decade from 265 mL (18.7%) in the 20s to 488 mL (33.7%) in ages above 80 years; however, the increase in the volume of total ventricles was approximately 20 mL (< 2%) until the 60s and increased in ages above 60 years. CONCLUSIONS: This study confirmed the reliability of the CSF volumes using the AI-based auto-segmentation application. The intracranial CSF volume increased linearly because of the brain volume reduction with aging; however, the ventricular volume did not change until the age of 60 years and above and then gradually increased. This finding could help elucidate the pathogenesis of chronic hydrocephalus in adults. KEY POINTS: • The brain and CSF spaces were automatically segmented using an artificial intelligence-based application. • The total subarachnoid spaces increased linearly with aging, whereas the total ventricle volume was around 20 mL (< 2%) until the 60s and increased in ages above 60 years. • The cortical gray matter gradually decreases with aging, whereas the subcortical gray matter maintains its volume, and the cerebral white matter increases slightly until the 40s and begins to decrease from the 50s.

Incidental diffuse low-grade gliomas: A systematic review and meta-analysis of treatment results with correction of lead-time and length-time biases.

Background: Better overall survival (OS) reported in patients with incidental diffuse low-grade glioma (iLGG) in comparison to symptomatic LGG (sLGG) may be overestimated by lead-time and length-time. Methods: We performed a systematic review and meta-analysis of studies on adult hemispheric iLGGs according to the PRISMA statement to adjust for biases in their outcomes. Survival data were extracted from Kaplan-Meier curves. Lead-time was estimated by 2 methods: Pooled data of time to become symptomatic (LTs) and time calculated from the tumor growth model (LTg). Results: We selected articles from PubMed, Ovid Medline, and Scopus since 2000. Five compared OS between patients with iLGG (n = 287) and sLGG (n = 3117). The pooled hazard ratio (pHR) for OS of iLGG to sLGG was 0.40 (95% confidence interval [CI] {0.27-0.61}). The estimated mean LTs and LTg were 3.76 years (n = 50) and 4.16-6.12 years, respectively. The corrected pHRs were 0.64 (95% CI [0.51-0.81]) by LTs and 0.70 (95% CI [0.56-0.88]) by LTg. In patients with total removal, the advantage of OS in iLGG was lost after the correction of lead-time. Patients with iLGG were more likely to be female pooled odds ratio (pOR) 1.60 (95% CI [1.25-2.04]) and have oligodendrogliomas (pOR 1.59 [95% CI {1.05-2.39}]). Correction of the length-time bias, which increased the pHR by 0.01 to 0.03, preserved the statistically significant difference in OS. Conclusions: The reported outcome in iLGG was biased by lead-time and length-time. Although iLGG had a longer OS after correction of biases, the difference was less than previously reported.

Usefulness of the Three-step Simple Binostril Approach in Endoscopic Endonasal Transsphenoidal Surgery.

We describe a three-step, simple binostril approach to endoscopic endonasal transsphenoidal surgery in cases of sellar/parasellar lesions. In the first step, the mucosa of the lower third of the ethmoid bulla on the outside was coagulated with monopolar microdissection needle and opened to create space on the outside of the middle turbinate. The middle turbinate was moved outward using this space, and the natural ostium of the sphenoid sinus could be confirmed easily. In the second step, a less than 10 mm incision was made from the right natural ostium of the sphenoid sinus to the right nasal septal mucosa. The anterior wall of the sphenoid sinus was removed to free the sphenoid sinus. In the third step, the instrument was inserted through the left nostril using a hole connected to the natural ostium of the sphenoid sinus to reach the sellar floor via both nostrils. It took longer for the trainee than for the instructor to reach the sellar floor in the first four cases. However, there was no significant difference in the approach time after the fifth case. Approach-related postoperative complications were observed in 52 cases of sellar/parasellar lesions performed. This approach was considered to provide sufficient space and was simple and less burdensome to the patient.

Usefulness and problems of Y-Stent and T-Stent assisted coiling for unruptured cerebral aneurysms.

INTRODUCTION: We are going to discuss about usefulness and problems of Y-stent and T-stent assisted coiling for unruptured cerebral aneurysms. METHODS: A retrospective review was performed to identify patients who were treated using Y-stent or T-stent assisted coiling (Y-SAC, T-SAC) for 25 unruptured cerebral aneurysms from April 2017 to September 2021. Fifteen cases were treated using Y-SAC, 10 were done using T-SAC. Only a case was treated with Low-profile Visualized Intraluminal Support (LVIS; MicroVention TRUMO, Aliso Viejo, California, USA) and Neuroform ATLAS (Striker, Kalamazoo, Michigan, USA), Others were done with two Neuroform ATLAS stents. RESULTS: Y-SAC and T-SAC were succeeded in all cases. In two cases that were treated using Y-SAC, ischemic complications were observed. A patient received additional embolization because subarachnoid hemorrhage (SAH) was appeared after discharge. On follow-up imaging, complete occlusion (CO) was confirmed in all cases. CONCLUSION: The position of deployment of stents was the most important issue. In particular, the second stent should be deployed as to contact the first stent, as possible. The case that the position of the second stent was shifted, and neck was not covered was observed. In the cases that are treated by using T-SAC, microcatheter must be navigated to distal position as possible. In that point, Y-SAC is more applicable. The familiarization of Y-SAC or T-SAC will expand the indication of endovascular treatment for unruptured cerebral aneurysms.

Successful use of an LVIS device to treat unruptured distal aneurysm of the superior cerebellar artery at a vascular bifurcation.

Background: Aneurysms of the distal superior cerebellar artery (SCA) account for only a small proportion of all cerebral aneurysms. Reports of the use of flow diverters (FDs) started to appear in 2013. We obtained good results from placement of a low-profile visualized intraluminal support device (LVIS) to treat unruptured distal aneurysm of the SCA at a vascular bifurcation. Case Description: A 65-year-old man presented at our hospital with sudden peripheral facial nerve palsy and suspected subarachnoid hemorrhage. Investigational cerebral angiography revealed an aneurysm at the bifurcation of the caudal and rostral trunks of the SCA. An LVIS was placed with the aim of obtaining flow diversion, and cerebral angiography 6 months after this procedure showed disappearance of aneurysm with preservation of the distal SCA. Conclusion: Twelve cases of the use of FDs to treat aneurysms of the SCA have been reported previously. However, none of those reports described FD use to treat an aneurysm at a vascular bifurcation, as in the present case. Our results suggested that LVIS placement with the aim of obtaining flow diversion may be useful for the treatment of aneurysms at such sites.

Usefulness of endoscope-assisted surgery under exoscopic view in skull base surgery: A technical note.

BACKGROUND: The use of the exoscope has been increasing in the field of neurosurgery, as it can set the visual axis freely, enabling the surgeon to operate in a comfortable posture. Although endoscope-assisted surgery for compensation of insufficient surgical field is useful under the microscope, we report that using an endoscope in exoscopic surgery is safer and more useful. METHODS: The exoscope used was ORBEYE. All surgical procedures were performed exoscopically from the beginning of the surgery. When endoscopic observation was required during the operation, the endoscope was inserted under observation by an exoscope. The exoscopic screen was 4K-3D and endoscopic screen was 4K-2D, the operation was performed while observing both screens at the same time. The endoscope was held manually or by a mechanical holder. RESULTS: Twenty-two cases, including 14 requiring microvascular decompression (MVD) and eight requiring tumor removal, were performed by endoscopic-assisted exoscopic surgery. The endoscope could be inserted safely because its relationship with the surrounding structure could be observed under the exoscope, and the operator could observe both screens without moving the head. Fourteen of 22 patients required additional endoscopic treatment. Satisfactory two-handed operation was performed in 13 cases. Symptomatology disappeared in all cases of MVD, and sufficient tumor resection was achieved. CONCLUSION: Exoscopic surgery provides excellent surgical view that is not inferior to conventional microsurgery. As a large space can be secured between the scope and the surgical field, it is safer and easier to manipulate the endoscope under the exoscope.

Iatrogenic Middle Meningeal Arteriovenous Fistula During Embolization: Two Case Reports and Literature Review.

Objective Dural arteriovenous fistulae of the middle meningeal artery are rare. There are few reports of complications associated with endovascular therapy. This report describes two cases of iatrogenic middle meningeal arteriovenous fistula due to vascular injury sustained during endovascular treatment. Case description Case 1 was that of a 46-year-old woman. She was treated for an incidentally discovered dural arteriovenous fistula of the cerebellar tentorium by transarterial embolization. During the procedure, a middle meningeal arteriovenous fistula occurred because of vessel laceration by the forced advancement of the distal access catheter (DAC). After the intervention, she developed tinnitus. Follow-up angiography revealed a middle meningeal arteriovenous fistula. The fistula was treated by coil embolization of the affected middle meningeal artery. The second case was that of a 56-year-old woman who developed a middle meningeal arteriovenous fistula from the perforation caused by the microguidewire during tumor embolization. The fistula was treated by occluding the proximal segment of the affected artery with coils. Both patients were discharged without neurological complications after the endovascular procedures. Conclusion Endovascular surgeons should be aware of the possibility of middle meningeal arteriovenous fistula as a potential complication of endovascular procedures.

Primary Central Nervous System T-cell Lymphoma as Methotrexate-associated Lymphoproliferative Disorders: Case Report.

We report a rare case of primary central nervous system (CNS) lymphoma as methotrexate-associated lymphoproliferative disorders (MTX-LPD). A 75-year-old woman who had been treated for rheumatoid arthritis (RA) with MTX for 3 years was admitted to our hospital complaining of unsteady gait, nausea, and vomiting. T2-weighted image of magnetic resonance imaging (MRI) showed multiple high intensity mass-like lesions including right lateral, frontal and temporal lobes, and right cerebellar hemisphere. We performed surgical biopsy, and the pathological and immunohistochemical examinations identified T-cell lymphoma. The tumor regressed and the symptoms were resolved soon after MTX withdrawal. Primary CNS lymphoma due to MTX-LPD is a rare disease and only eight cases including ours are reported.

Brainstem Venous Congestion Due to Transverse-sigmoid Sinus Dural Arteriovenous Fistula: Case Report and Literature Review.

Brainstem venous congestion due to dural arteriovenous fistula (dAVF) can mimic brainstem glioma and infarction. We report a case of a 56-year-old woman with a transverse-sigmoid sinus (TS) dAVF. On MRI, she presented with brainstem edema that was difficult to distinguish from brainstem glioma and infarction. She was referred to our hospital for mild dysarthria with right hemiparesis and a suspected left pontine glioma. On MRI, contrast enhancement of the lesion was demarcated by the pontine raphe, and the ipsilateral vein of Rosenthal was dilated. Cerebral angiography revealed TS dAVF with an isolated sinus. Transarterial followed by transvenous coil embolization was performed to reduce shunt flow, resulting in symptom improvement and normal findings on MRI and cerebral angiography. Brainstem venous congestion due to TS dAVF is as rare as adult brainstem glioma. Differentiating the above-mentioned three diseases on the basis of diagnostic imaging findings and clinical course is necessary for appropriate and timely treatment.

Distal Embolic Protection by Manual Compression of the Vertebral Artery in Subclavian Artery Stenting.

Objective: There is no established method for preventing vertebral artery embolization in percutaneous transluminal angioplasty (PTA) for subclavian artery stenosis. We manually compressed the supraclavicular fossa outside the sternocleidomastoid muscle to disrupt vertebral artery blood flow and prevent embolism. We report the usefulness of this procedure. Case Presentations: Between April 2017 and July 2018, three patients with severe stenosis of the subclavian artery of 80% or higher were examined. For these patients, subclavian artery stenting was performed. The approach was via the left brachial artery in one patient and right femoral artery in two patients. After crossing the lesion, the vertebral artery was manually compressed and angiography confirmed that blood flow was blocked. In all patients, stent placement was successfully performed and good dilatation was confirmed by angiography. There were no neurological complications and no findings suggestive of acute cerebral infarction were found on magnetic resonance imaging (MRI). Conclusion: Prevention of distal embolism by manual compression is simple, does not require multiple catheters, and is useful for subclavian artery stenting.

Primary pericranial Ewing's sarcoma on the temporal bone: A case report.

BACKGROUND: Primary Ewing's sarcoma originating in the pericranium is an extremely rare disease entity. CASE DESCRIPTION: A 9-year-old female patient was admitted to our department due to a left temporal subcutaneous mass. The mass was localized under the left temporal muscle and attached to the surface of the temporal bone. Head computed tomography revealed a mass with bony spicule formation on the temporal bone, however, it did not show bone destruction or intracranial invasion. F-18 fluorodeoxyglucose positron emission tomography showed no lesions other than the mass on the temporal bone. Magnetic resonance imaging showed that the mass was located between the temporal bone and the pericranium. The mass was completely resected with the underlying temporal bone and the overlying deep layer of temporal muscle, and was diagnosed as primary Ewing's sarcoma. Because the tumor was located in the subpericranium, we created a new classification, "pericranial Ewing's sarcoma," and diagnosed the present tumor as pericranial Ewing's sarcoma. CONCLUSION: We herein present an extremely rare case of primary pericranial Ewing's sarcoma that developed on the temporal bone.

Straight sinus thrombosis during neurosurgical operation.

BACKGROUND: Perioperative straight sinus thrombosis is extremely rare. CASE DESCRIPTION: A 59-year-old female was admitted to our department because of incidentally found small anterior cerebral artery (A1) aneurysm with microbleeding. After clipping the cerebral aneurysm, she had delayed emergence from anesthesia, total aphasia, and right hemiparesis. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) of the head showed hyperintensity in the bilateral caudate nuclei, putamina, and thalami, and computed tomography of the head showed a hyperdense straight sinus, suggesting straight sinus thrombosis. Her neurologic symptoms improved gradually, and she achieved a full clinical recovery, with radiological evidence of recanalization of the straight sinus at follow-up. CONCLUSION: The possibility of straight sinus thrombosis should be considered in postoperative patients with unexplained postoperative deficits when MRI demonstrates hyperintensity in the bilateral basal ganglia and thalami on FLAIR signal images.

Improvement in treatment results of glioblastoma over the last three decades and beneficial factors.

BACKGROUND: The purpose of this study is to elucidate the trend of glioblastoma outcome and scrutinize the factors contributing to better outcome over three decades. METHODS: Survival time and the influencing factors were retrospectively analyzed in 223 newly diagnosed primary glioblastoma patients during 1980-2010. Appraised factors included age, sex, tumor site, year of surgery, extent of resections, use of surgery supporting system, Karnofsky Performance Status (KPS), chemotherapy, conventional external beam radiotherapy (EBRT), and CyberKnife stereotactic radiotherapy (CK-SRT) use. RESULTS: The median survival time (MST) in all patients was 13.6 months. The MSTs for 4 periods were 9.8 (1980-1990), 13.7 (1991-2000), 12.9 (2001-2005), and 15.8 months (2006-2010), respectively (p=0.0047). Total resection, subtotal resection, partial resection, and biopsy had MSTs of 31.8, 13.9, 11.4, and 7.0 months, respectively (p<0.0001). Regarding chemotherapy, MSTs of the temozolomide base group and nimustine hydrochloride (ACNU) base group were 16.9 and 14.6 months, respectively, whereas the MST of patients without chemotherapy was only 9.8 months (p<0.0001). The MSTs for 40-Gy EBRT plus CK-SRT and 60-Gy EBRT were 19.1 and 10.7 months, respectively (p<0.0001). But in sub-selected patients, treated during 2001-2010, whose resection rate was total resection or subtotal resection, EBRT was completed and postoperative KPS was greater than or equal to 70, the MST with and without CK-SRT was 26.6 and 18.3 months, respectively (p=0.1529). According to the Cox proportional hazards model, degree of resection, KPS, ACNU use, temozolomide use, bevacizumab use, EBRT dose, and CK-SRT use were good prognostic factors. Use of neuronavigation and use of intraoperative magnetic resonance imaging were related to higher resection rate, but not determined as prognostic factors. CONCLUSIONS: We observed a gradual improvement in glioblastoma outcome, presumably because of improvements in therapeutic modalities for surgery, anticancer agents, and radiation, but the efficacy of CK-SRT remains unclear.

Identification of CD133+ cells in pituitary adenomas.

Stem-like cells in tumors are capable of self-renewal and pluri-differentiation; they are thought to play important roles in tumor initiation and maintenance. Stem-like cells in malignant glioma express CD133. We examined samples from human pituitary adenoma, a generally benign neoplasm, for CD133 expression using routine immunohistochemical and biochemical methods. Our study of 70 pituitary adenomas (clinically nonfunctioning adenomas and growth hormone-, prolactin-, adrenocorticotropic hormone-, and thyroid-stimulating hormone-producing adenomas) showed that 18 (25.7%) expressed CD133. This rate was higher in clinically nonfunctioning (33.3%) than functioning adenomas (12.0%) (p = 0.085). Real-time PCR assay revealed the expression of CD133 mRNA in samples immunohistochemically positive for CD133. Neither the patient age and gender, nor the tumor size or postoperative recurrence rate correlated with CD133 positivity. CD133+ cells ubiquitously coexpressed CD34, nestin, and VEGFR2 (KDL1). S-100 and GFAP were not coexpressed with CD133. Chromogranin A, Pit-1, SF-1, and NeuroD1 were immune-negative, indicating that CD133+ cells did not have the potential to differentiate into functional endocrine cells. Our data suggest that the expression of CD133 in pituitary adenomas is related to immature endothelial progenitor cells that may play a role in the neovascularization of pituitary adenomas. Further studies are needed to elucidate the significance of CD133+ cells with respect to neovascularization and their sustainable growth in pituitary adenomas.

Role of sonic hedgehog signaling in migration of cell lines established from CD133-positive malignant glioma cells.

The sonic hedgehog (SHH) signaling pathway is essential for normal development and embryogenic morphogenesis. In malignant neoplasms its inappropriate activation correlates with tumorigenesis, proliferation, and migration. However, the role of SHH in infiltrative growth of glioblastoma remains to be elucidated. CD133 is a marker of tumor stem cells in glioblastoma, which are thought to play important roles in tumorigenesis, drug resistance, and tumor recurrence. We investigated the role of the SHH signaling pathway in migration of glioblastoma cell lines derived from CD133-positive cells. Two cell lines, GBM1 and GBM2, were established from CD133-positive cells sorted on an automagnetic cell separator from dispersed human glioblastoma cells. Both cell lines exhibited sphere-like growth in serum-free medium containing growth factor. Expression of patched (PTCH)-, a receptor of SHH, of smoothened (SMO)-, a 7 transmembrane receptor, and of GLI1- and GLI2, PTCH cascade signal proteins, was evaluated by reverse-transcription polymerase chain reaction (RT-PCR). The effects of recombinant SHH in the medium, and of knockdown of SMO-, GLI1- or GLI2 messenger RNA (mRNA) on the migratory ability of neoplastic cells were evaluated by scratch assays. RT-PCR revealed the presence of PTCH-, SMO-, GLI1-, and GLI2 mRNA in these cells. Their migratory ability was significantly enhanced (P < 0.05) by addition of recombinant SHH to the medium. Knockdown of SMO-, GLI1- or GLI2 mRNA resulted in significant decrease in the mobility of the neoplastic cells. Our study suggests that the SHH pathway plays an important role in the migratory ability of cells derived from CD133-positive human glioblastoma cells.

[Three pediatric cases with choroid plexus papilloma in the fourth ventricle].

Choroid plexus papillomas are rare; they comprise less than 1% of all intracranial tumors. In children, most of these neoplasms arise in the lateral ventricle while in adults they are primarily located in the fourth ventricle. We report 3 children with choroid plexus papilloma in the fourth ventricle; they were one 5-month-old girl and 2 boys aged 8-and 15-years. The baby girl presented with macrocephaly and signs of raised intracranial pressure, the 2 boys exhibited cerebellar signs. On magnetic resonance imaging (MRI) the tumors were well-enhanced with a cauliflower-like contour and hydrocephalus. In one case, diffusion weighted images (DWIs) showed an isointense tumor signal clearly different from the well-known hyperintensity of medulloblastomas, Via suboccipital craniotomy we succeeded in the total or subtotal surgical resection of these tumors and there were no sequela. None of the tumors have recurred in the intervening 2-9 years. In conclusion, choroid plexus papilloma should be included as a differential diagnosis in children presenting with tumors in the fourth ventricle. The contour of the tumor on MRI and its intensity on DWI may be clues for a correct preoperative diagnosis.