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Background Postdural puncture headache (PDPH) is defined as a prolonged orthostatic headache secondary to a lumbar puncture. The mechanism underlying this unpleasant complication and the reasons explaining its higher incidence in the young are not well understood. Here, we speculate on the mechanisms underlying PDPH based on spinal magnetic resonance imaging (MRI) in patients with PDPH and an anatomical study on the size of the intervertebral foramen. Methods Brain and spinal MRI findings were examined in two young women with PDPH. The relationship between age and size of the intervertebral foramen on computed tomography was assessed in 25 female volunteers (22–89 years old) without spinal disease. Results The causative interventions leading to PDPH were epidural anesthesia for painless delivery in a 28-year-old woman and lumbar puncture for examination of the cerebrospinal fluid (CSF) in a 17-year-old woman. These two patients developed severe orthostatic hypotension following the procedure. Brain MRI showed signs of intracranial hypotension, including subdural effusion, in one patient, but no abnormality in the other. Spinal MRI revealed an anterior shift of the spinal cord at the thoracic level and CSF exudation into the paravertebral space at the lumbar level. Treatment involving an epidural blood patch in one patient and strict bed rest with sufficient hydration in the second led to improvement of symptoms and reduction of paravertebral CSF exudation. The size of the intervertebral foramen at the L2–3 level in the 25 volunteers showed a decrease in an age-dependent manner (Spearman's rho −0.8751, p Conclusion We suggest that CSF exudation from the epidural space of the vertebral canal to the paravertebral space through the intervertebral foramen, which is generally larger in the younger population, is the causative mechanism of PDPH.

Objective the advent of BRAF inhibitors for preoperative treatment of craniopharyngioma has necessitated the identification of BRAFV600E status. Hence, we investigated predictors of BRAFV600E mutation in craniopharyngiomas. Methods this retrospective study utilized data from 30 patients who were newly diagnosed with craniopharyngioma between 2011 and 2021. Magnetic resonance imaging (MRI) and computed tomography were performed within 1 week prior to surgery. Genetic analysis for BRAF mutation was performed using the Oncomine next-generation sequencing panel or Sanger sequencing. The relationship between BRAF mutation and demographic data, endocrinological function and tumour characteristics on imaging was assessed. Results tumour tissue carried the BRAFV600E mutation in nine patients. There was no significant difference in age, sex, or presence of hormonal dysfunction amongst patients with and without the BRAFV600E mutation in the tumour. Most tumours with the BRAFV600E mutation were histologically categorized as papillary craniopharyngioma (P = 0.0005), and were solid (P = 0.0002) and supra-diaphragmatic (P = 0.0033) on MRI. BRAFV600E tumours were more frequently associated with optic tract edema than wild-type tumour s (55.6 vs. 0%, P = 0.0009) and all tumour s with optic tract edema carried the BRAFV600E mutation. Optic tract edema was not associated with tumour volume, cysts, or preoperative pituitary function. Conclusions in craniopharyngiomas, the presence of optic tract edema can predict the presence of BRAFV600E mutation with a positive predictive value of 100%. The finding should be verified in larger prospective cohorts and multivariate regression analysis.

Supplementary Figure 1. Metabolic alteration in LSD1-inhibited cancer cells. Supplementary Figure 2. Overall view of the metabolomic analysis in LSD1-KD HepG2 cells. Supplementary Figure 3. GSEA results of the microarray experiment in LSD1-KD HepG2 cells. Supplementary Figure 4. Effect of LSD1-KD on energy metabolism in Huh-7, human hepatocellular carcinoma cells. Supplementary Figure 5. Effect of LSD1-KD on the expression of the glucose transporter GLUT1. Supplementary Figure 6. Overexpression of LSD1 in HepG2 cells. Supplementary Figure 7. Effect of LSD1-KD on the expression of metabolic genes in breast cancer cells. Supplementary Figure 8. Distinct expression of LSD1 in hepatocellular carcinoma and normal hepatic cells. Supplementary Figure 9. LSD1 regulates glycolytic genes through the HIF-1a-mediated pathway. Supplementary Figure 10. LSD1 physically interact with HDACs but not with HIF-1a/HIF-1B in HepG2 cells. Supplementary Figure 11. Effect of LSD1 inhibition in mouse xenograft model. Supplementary Table 1. siRNAs target sequences. Supplementary Table 2. Concentrations of the metabolites indicated in Figure 1E. Supplementary Table 3. Full descriptions of the gene abbreviations used in this study. Supplementary Table 4. Primers used in the study.

The hallmark of most cancer cells is the metabolic shift from mitochondrial to glycolytic metabolism for adapting to the surrounding environment. Although epigenetic modification is intimately linked to cancer, the molecular mechanism, by which epigenetic factors regulate cancer metabolism, is poorly understood. Here, we show that lysine-specific demethylase-1 (LSD1, KDM1A) has an essential role in maintaining the metabolic shift in human hepatocellular carcinoma cells. Inhibition of LSD1 reduced glucose uptake and glycolytic activity, with a concurrent activation of mitochondrial respiration. These metabolic changes coexisted with the inactivation of the hypoxia-inducible factor HIF1α, resulting in a decreased expression of GLUT1 and glycolytic enzymes. In contrast, during LSD1 inhibition, a set of mitochondrial metabolism genes was activated with the concomitant increase of methylated histone H3 at lysine 4 in the promoter regions. Consistently, both LSD1 and GLUT1 were significantly overexpressed in carcinoma tissues. These findings demonstrate the epigenetic plasticity of cancer cell metabolism, which involves an LSD1-mediated mechanism. Cancer Res; 75(7); 1445–56. ©2015 AACR.

The 13th Symposium on Polar Science/Ordinary sessions [OG] Polar geosciences, Wed. 16 Nov.

Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS.Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134 mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups.DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the two groups.The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.

Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913–0.931). Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.

Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors.This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN.In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT.GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.

Adamantinomatous craniopharyngiomas (ACP) are characterized by alterations in the CTNNB1 gene while almost all papillary craniopharyngiomas (PCP) harbor a canonical V600E mutation in the BRAF gene. Although other recurrent driver genes have not been described to date in craniopharyngiomas, the heterogeneous clinical course of these tumors might be associated with the acquisition of further genomic alterations. It is well known that telomerase reverse transcriptase (TERT) promoter (TERTp) alterations, including mutations or methylation, upregulate the expression of TERT and increase telomerase activity, promoting tumorigenesis. We investigated whether TERTp mutations or methylation are associated with tumor relapse in a subset of craniopharyngiomas. Samples from 42 patients with histologically confirmed craniopharyngioma were retrieved. We determined TERTp, BRAF, and CTNNB1 hotspot mutations in all samples using targeted sequencing and the TERTp methylation status by methylation-specific polymerase chain reaction (PCR) in 30 samples. While BRAF V600E mutations and CTNNB1 mutations were detected in 12 (28.6%) and 21 patients (50%) in the initial tumors and subsequent recurrences, respectively, none of the patients in our cohort, including those with multiple relapses, harbored a TERTp mutation. Furthermore, TERTp methylation was detected in 14 out of 24 cases (58.3%) with available primary samples; however, no correlation between TERTp methylation with the pathological subtype, genotype, or tumor aggressiveness was detected. These data suggest that elevated telomerase activity via acquisition of TERTp mutations is an infrequent pathway in the tumorigenesis of craniopharyngiomas, regardless of their clinical course.

Background Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist. Objective To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study. Methods Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr. Results A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively. Conclusion Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.

Thyrotropin-secreting pituitary adenomas (TSPA) are extremely rare pituitary adenomas; their perioperative thyroid hormone dynamics have not been completely elucidated. Here, we investigated the clinical characteristics, perioperative findings, and thyroid hormone dynamics of TSPA at a single institution. We enrolled 11 patients who underwent transsphenoidal surgery (TSS) for TSPA during 2005–2019 at Hiroshima University Hospital (TSPA group) and 24 patients who underwent TSS for nonfunctioning pituitary adenomas (NFPA) in 2019 (NFPA group; for comparison). Their clinical characteristics, operative findings, and thyroid hormone dynamics, including serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were retrospectively analyzed. The NFPA group demonstrated a slight temporary decrease in serum TSH/ FT3/ FT4 levels on day 1 postoperatively and improvement in the levels on day 4 postoperatively. In contrast, the serum TSH level in the TSPA group demonstrated a marked decrease on day 1 postoperatively but improved on day 7 postoperatively. The serum FT3 level was also markedly decreased on day 1 postoperatively but remained within the normal range. The serum FT4 level revealed a gradual decrease until day 21 postoperatively and then recovered within the normal range 3 months postoperatively. There was no significant difference in the frequency of decline in serum FT4 level between the two groups; no patients required thyroid hormonal replacement 3 months postoperatively. Despite a variable degree of transient hypothyroidism, all patients had a normal thyroid function after 3 months follow-up.

OBJECTIVE Rathke’s cleft cysts (RCCs) are relatively common and often detected incidentally. They are usually asymptomatic and managed conservatively. However, little is known about their natural history. Thus, the authors aimed to examine the natural course of RCCs and identify the risk factors for their progression. METHODS This retrospective study examined 229 patients (median age 43.0 years) diagnosed with RCCs by MRI and followed up without surgery (median period 36.6 months). The median cyst height on the initial MRI was 10 mm. Progression or regression of RCC was defined as cyst height changes of ≥ 1 mm. RESULTS In total, 23 (10.0%) RCCs progressed, whereas 73 (31.9%) RCCs spontaneously regressed. The remaining 133 were noted to be stable throughout the follow-up period. Patients with progressed RCCs were significantly older than those with stable RCCs. In patients with acute headache as an initial symptom, RCCs were significantly more likely to spontaneously regress. New symptoms occurred in 6 patients, 5 of whom underwent surgery for RCC progression. Of these 6 patients, 1 patient had persistent adrenocorticotropic hormone deficiency and 1 patient developed diabetes insipidus. Kaplan-Meier analysis results showed RCC progression and new symptom development rates to be 12.0% and 4.1% at 5 years and 13.7% and 5.7% at 10 years, respectively. CONCLUSIONS RCCs rarely progress or cause new symptoms in the long term. Patients with asymptomatic RCC should be followed up for at least 5 years to ensure RCC inactivity. RCCs in older adults may require greater surveillance.

We treated an extremely rare thyroid-stimulating hormone (TSH)-producing pituitary adenoma in a 63-year-old woman with severe hypothyroidism due to autoimmune thyroiditis. She was presented with dizziness and fatigue. The blood level of TSH, prolactin, and fT4 was 288.2 μIU/mL, 72.9 ng/mL, and 0.24 ng/dL, respectively. Magnetic resonance imaging demonstrated a large pituitary tumor, 31 mm in height, and a normal pituitary gland. Preoperative thyroxine replacement reduced the TSH level to 2.05 μIU/mL and produced a significant reduction in the tumor volume. Histopathologically, the surgically removed tumor was a TSH-producing pituitary adenoma.

Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson’s disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD.

OBJECTIVE Recovery from adult growth hormone deficiency (AGHD) after transsphenoidal surgery (TSS) has not been well discussed because of the lack of examinations including pituitary provocation tests (PPTs) before and after the procedure. This study aimed to evaluate the growth hormone (GH) axis function of patients with nonfunctioning pituitary adenoma (NFPA) via pre- and postoperative PPTs. Moreover, the predictive factors for recovery from AGHD after TSS were validated to facilitate surgery for AGHD in patients with NFPA. METHODS In total, 276 patients (median age 60.0 years) who underwent TSS for NFPA were included in this study. PPTs were performed before and 3 months after TSS. Then, the relationships between recovery from AGHD after TSS and clinical, surgical, and hormonal factors, including peak GH level based on PPTs, were evaluated statistically. RESULTS In this study, 114 patients were diagnosed with preoperative AGHD. Approximately 25.4% recovered from AGHD after TSS. In contrast, among the 162 patients without preoperative AGHD, 13 (8.0%) had newly developed postoperative AGHD. The predictive factors for recovery from AGHD were younger age, female sex, initial TSS, and high peak GH level based on preoperative PPT. According to the receiver operating characteristic curve analysis, patients who were aged ≤ 62.2 years and had a peak GH level of ≥ 0.74 μg/L based on preoperative PPT were likely to recover from AGHD (sensitivity: 82.8%, specificity: 72.9%, and area under the curve: 0.8229). CONCLUSIONS AGHD caused by NFPA can improve after initial TSS among young patients with certain peak GH levels assessed by preoperative PPT. Whether TSS for NFPA can promote recovery from AGHD is worth considering in some patients.

Diabetes insipidus (DI) following transsphenoidal surgery (TSS) is a common complication. Although postoperative DI often occurs in patients with craniopharyngioma and Rathke’s cleft cyst, postoperative DI in patients with non-functioning pituitary adenoma (NFPA) has not been fully examined. We clarified the clinical characteristics and magnetic resonance imaging (MRI) findings predicting postoperative DI in NFPAs. A total of 333 patients undergoing initial TSS for NFPA were included in this retrospective study. Hyperintensity (HI) in the posterior pituitary lobe was evaluated on preoperative T1-weighted MRI. Based on the findings of HI patients were divided into three groups as follows: HI was not detected (Disappearance group), HI located intrasellarly (Intrasellar group), and HI located suprasellarly (Suprasellar group). The overall rate of DI was 21.9%, including permanent DI in 0.6%. DI occurred at postoperative day 1 (72.6%) or day 2 (19.2%) and improved within 7 days in most cases (87.7%). Univariable and multivariable analyses showed that the predictive factors of DI were a younger age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, P = 0.0037) and larger tumor diameter (OR 1.04, 95% CI 1.01–1.08, P = 0.0155). The rate of DI was highest in the Disappearance group (43.8%) followed by the Intrasellar group (26.0%). The OR was 2.17 in the Intrasellar group compared with the Suprasellar group (95% CI 1.17–4.02, P = 0.0141). Factors predicting DI following TSS for NFPA were a younger age, larger tumor size, and the location of intrasellar HI on preoperative T1-weighted MRI.

Purpose The safety of transsphenoidal surgery (TSS) for pituitary adenoma in elderly patients is becoming a new topic in our aging society. However, previous studies did not focus on the surgical procedures in elderly patients. We attempted to clarify the safety of TSS and the influence of pseudocapsular resection in elderly patients with non-functioning pituitary adenoma (NFPA). Methods A total of 272 patients undergoing initial surgery for NFPA were categorized into two groups as follows: 1) Elderly group (n = 66; age ≥ 70 years); and 2) Younger group (n = 206; age

Objective Pin-type head frame systems have become a worldwide standard procedure, but they can cause some complications on rare occasions. This study aimed to examine the incidence and associated risk factors of depressed skull fracture and related intracranial hematoma (DSFH) due to the use of head frames in our institute over the past 10 years. Methods This study included 1749 patients who underwent neurosurgical surgeries using pin-type head frames, including the Mayfield (Integra NeuroSciences, Plainsboro, NJ) skull clamp (721 cases) and the Sugita (Mizuho Ikakogyo Co., Ltd., Tokyo, Japan) head frame (1028 cases). We retrospectively reviewed hospital records of our institute to identify cases of DSFH, and documented the type of head frame used, as well as patient characteristics. Results The incidence of DSFH was 0.29% (5 of 1749 cases). All 5 cases had an associated epidural hematoma, with a single case having an additional dural laceration (without subdural damage). All perforation sites, located at the parietal bone near the pterion, occurred by the unilateral horizontal screw of the Sugita head frame. None of the patients experienced postoperative neurological decline. Conclusions Even in the adult population, the DSFH by the pin-type head frame can occur infrequently. Based on our results, we recommend that the following factors should be considered when the pin-type head frame is used for neurosurgical procedures: location of pin application, thickness and fragility of the skull, and adequate control of compressive forces exerted by the head frame.

Objective: Various clinical parameters have been reported to be associated with favorable seizure outcomes after vagus nerve stimulation (VNS); however, none of these parameters have been conclusively validated. Here, we evaluated interpersonal communication skills (IPCS) and seizure outcomes in pediatric patients treated with VNS. Methods: We enrolled 31 Japanese pediatric patients (mean ± SD: 9.0 ± 3.4 years old, range: 3–15 years old) who were treated with VNS and had at least 2 years of follow-up. We divided the patients into two groups: a responder group with ≥50% seizure reduction from the average number of seizures 2 months before VNS; and a nonresponder group with

The Hokkaido Eastern Iburi Earthquake (M = 6.7) occurred on Sep. 6, 2018 in the southern part of Central Hokkaido, Japan. Since Paleogene, this region has experienced the dextral oblique transpression between the Eurasia and North American (Okhotsk) Plates and the subsequent collision between the Northeast Japan Arc and the Kuril Arc due to the oblique subduction of the Pacific Plate. This earthquake occurred beneath the foreland fold-and-thrust belt of the Hidaka Collision zone developed by the collision process, and is characterized by its deep focal depth (~ 37 km) and complicated rupture process. The reanalyses of controlled source seismic data collected in the 1998–2000 Hokkaido Transect Project revealed the detailed structure beneath the fold-and-thrust belt, and its relationship with the aftershock activity of this earthquake. Our reflection processing using the CRS/MDRS stacking method imaged for the first time the lower crust and uppermost mantle structures of the Northeast Japan Arc underthrust beneath a thick (~ 5–10 km) sedimentary package of the fold-and-thrust belt. Based on the analysis of the refraction/wide-angle reflection data, the total thickness of this Northeast Japan Arc crust is only 16–22 km. The Moho is at depths of 26–28 km in the source region of the Hokkaido Eastern Iburi Earthquake. Our hypocenter determination using a 3D structure model shows that most of the aftershocks are distributed in a depth range of 7–45 km with steep geometry facing to the east. The seismic activity is quite low within the thick sediments of the fold–thrust belt, from which we find no indication on the relationship of this event with the shallow (

Background Glioblastoma multiforme (GBM), the most common brain malignancy in adults, is generally aggressive and incurable, even with multiple treatment modalities and agents. Filamins (FLNs) are a group of actin-binding proteins that regulate the actin cytoskeleton in cells. However, the role of FLNs in malignancies—particularly in GBM—is unclear. Methods The relation between FLNC expression and overall survival in GBM was evaluated by the Kaplan−Meier analysis using GBM patients from the Kagoshima University Hospital (n = 90) and data from the Cancer Genome Atlas (TCGA) (n = 153). To assess FLNC function in GBM, cell migration and invasion were examined with Transwell and Matrigel invasion assays using FLNC-overexpressing U251MG and LN299 GBM cells, and ShRNA-mediated FLNC knocked-down KNS81 and U87MG cells. The gelatin zymography assay was used to estimate matrix metalloproteinase (MMP) 2 activity. Results In silico analysis of GBM patient data from TCGA and immunohistochemical analyses of clinical GBM specimens revealed that increased FLNC expression was associated with poor patient prognosis. FLNC overexpression in GBM cell lines was positively correlated with enhanced invasiveness, but not migration, and was accompanied by upregulation of MMP2. Conclusions FLNC is a potential therapeutic target and biomarker for GBM progression.

A geotraverse connecting the Kaligandaki and the Tinau rivers via Pokhara in Western Nepal covers all geologic zones of the Himalayan Orogen from the Tethys Himalayan Zone in the north to the Gangetic Plain in the south. The Student Himalayan Exercise Program has aimed to conduct tours of the above geotraverse, provided for Japanese and Nepalese students. The preparation of the program started in 2008, and the practical content of the tour was decided in December 2010 by collecting ideas from several Himalayan geologists in Japan and Nepal and receiving consent of 17 geoscience-related university departments, committing them to give education points for the participation in the exercise, or to examine the possibility of it. After collecting ideas from and sending call-for-participants to geoscience-related departments of over 60 Japanese universities, and after negotiations with several Nepalese trekking agencies, the first Student Himalayan Exercise Tour (SHET) was conducted in March 2012. Since then the exercise tour was conducted every year in March. We are convinced that the SHETs throughout all 7 years (2012-2018) were successful and meaningful, and we therefore suggest that the program should continue further in future.

An otherwise healthy 22-month-old boy suffered high fever, irritability, nausea, dysphagia, dysarthria and right hemiparesis. Magnetic resonance imaging showed a cystic mass, 15 mm in diameter, with surrounding oedema in the base of the lower pons. The symptoms subsided in about 10 days after onset, followed by a rapid decrease of the cyst size to 5 mm. Thereafter, the patient’s psychomotor growth has been normal. Annual follow-up magnetic resonance imaging scans showed very gradual enlargement of the cyst located on the ventral surface of the pontomedullary junction, reaching 16 mm in diameter in 21 years after onset. It was hyperintense on T1-weighted and isointense on T2-weighted magnetic resonance imaging. No haemosiderin deposition or gadolinium enhancement was seen. This is a rare report of a two decade longitudinal follow-up of a midline prepontine cyst showing asymptomatic and very slow growth. The possible nature of the cyst includes neurenteric, dermoid and epidermoid cyst.

The Cobb angle between the lower endplate of C2 and C7 (C2L-C7L angle) is a traditional parameter used for the assessment of the cervical alignment. However, when the lower cervical column is masked by the shoulder, measurements are difficult. In the present study, we inspected 191 X-ray films, measured the Cobb angle between C2L and the endplates at the several levels of the lower cervical column, and assessed their usefulness of such measurements for the determination of cervical sagittal alignment.We obtained X-ray films on 191 patients ranging in age from 20 to 93 years. The Cobb angle between C2L and the C7 upper (C7U), the C6 lower (C6L), the C6 upper (C6U), and the C5 lower endplate (C5L) was measured and compared with the C2L-C7L angle.C7L was identified in 116 of 191 patients (60.7%). Except for C2L-C7U angle (P = 0.55), the difference in the mean between C2L-C7L angle and the angle between C2L and the other endplates was statistically significant (P0.05). There was a very strong correlation between C2L-C7L angle and C2L-C7U angle (r = 0.99), C2L-C6L angle (r = 0.96), C2L-C6U angle (r = 0.94), and C2L-C5L angle (r = 0.86).To measure the C2L-C7L angle on unclear X-ray films, C7U can be substituted for C7L. Our measurement data for the C6 and C5 endplates were statistically different; however, the correlation between the C2L-C7L angle and C2L-C6U angle, C2L-C6L angle or C2L-C5L angle was very strong. In patients with unclear lower vertebral bodies, cervical sagittal alignment can be predicted by using adjacent endplates.

Background: We previously found the usefulness of dural sac shrinkage signs (DSSSs), which are the anterior shift of the spinal cord and dura mater behind the cord, detected by magnetic resonance imaging (MRI) at the thoracic level for the diagnosis of spontaneous intracranial hypotension (IH). This is a retrospective survey on the usefulness of DSSSs for the early detection of iatrogenic IH caused by overdrainage through a lumboperitoneal shunt (LPS) for patients with idiopathic normal pressure hydrocephalus (INPH). Methods: Forty-five INPH patients had an LPS using a pressure programmable valve equipped with an anti-siphon device. Results: Nine patients complained of orthostatic headache after the LPS, indicating IH due to overdrainage, which persisted for more than a week in three patients and 2–7days in six patients. The headache was transient/ nonorthostatic in ten patients and absent in 26 patients. The DSSSs and accompanying enlargement of the venous plexus were observed in all three patients with prolonged orthostatic headaches. Only the anterior shift of the dura mater was observed in 1 (4%) among 25 patients who had short-term orthostatic headache, transient/ nonorthostatic headache, or absent headache, and underwent spinal MRI. A patient with prolonged severe orthostatic headache with both DSSSs eventually developed intracranial subdural effusion and underwent tandem valve surgery, which provided a quick improvement of symptoms. The DSSSs on thoracic MRI also disappeared promptly. Conclusion: DSSSs may serve as objective signs for the diagnosis of IH due to overdrainage through an LPS for INPH.

Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI.Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed.The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913-0.931).Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999–2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005–2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic–clonic seizures and generalized tonic–clonic seizures were 9, 11 and 11 years (95% CI: 8.170–9.830, 10.170–11.830, and 7.265–14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

Background: Anterior inferior cerebellar artery (AICA) aneurysms in the internal auditory canal (IAC) are rare. We have reported a case of dissecting AICA aneurysm in the IAC presenting initially with the eighth nerve palsy followed by the seventh nerve palsy without hemorrhage. Case Description: A 68-year-old woman presented with a sudden onset of vertigo accompanied by deafness and tinnitus on the right side that was preceded by intermittent right retroauricular pain 2 weeks before. Audiogram showed severe sensorineural hearing loss. Computed tomography and magnetic resonance imaging (MRI) indicated absence of prior subarachnoid hemorrhage. Magnetic resonance angiogram (MRA) suggested a tiny aneurysm at the fundus of the IAC accompanied with thinning of the lateral pontine segment of the AICA. Conservative treatment led to moderate improvement of the symptoms. However, the patient developed the right retroauricular pain again, followed by the right facial paralysis 5 months later but still without signs of hemorrhage on MRI. Digital subtraction angiogram showed dissecting aneurysm in the IAC. The patient was managed with oral steroids and direct intervention was avoided due to a risk of ischemia supposed by large area irrigated by the AICA. Follow-up MRA 18 months after the first presentation showed improvement in the narrowing of the AICA proximal to the aneurysm. The patient was functionally independent despite right-sided hearing loss and slight facial paresis. Conclusion: This report warns physicians that a dissecting AICA aneurysm without subarachnoid hemorrhage may cause eighth and seventh nerve palsy.

Background Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. Objective To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. Methods We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. Results There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. Conclusion In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.

Background: Giant perivascular spaces (PVSs) are very rare condition in the brain and can be associated with neurological symptoms. It often enlarges and causes obstructive hydrocephalus which requires surgical intervention. However, the growth velocity has never been investigated. Case Description: Here, we report a woman in her early eighties with giant PVSs eventually followed up 17 years. She presented with dizziness and mild headache for a week and her neurological examination showed no abnormality. Her brain magnetic resonance imaging (MRI) showed a multiple cystic lesion, 28 mm in maximum diameter as a whole, in the left mesencephalothalamic region. There were no solid part, rim enhancement, or perilesional intensity change suggesting edema or gliosis. Smaller PVSs were also seen in bilateral-hippocampi, basal ganglia, white matter, and left frontal operculum. Retrospectively, five MRI studies over 17 years were analyzed using a 3-D volumetric software and found a very slow growth of the lesion, from 6.54 ml to 9.83 ml indicating gain of 0.1752 ml (2.68%) per year. Conclusion: This is the first report verifying a gradual enlargement of giant PVSs in a natural course. The prospective 3-D volumetric analysis on PVSs may elucidate the true nature of these lesions.

Background Patients with temporal lobe epilepsy (TLE) often report viscerosensory and experiential auras, with substantial epilepsy localization. However, few previous studies have investigated the epileptic preoperative aura, particularly with regard to its effect on surgical outcomes in patients with drug-resistant epilepsy. Objective This study investigated the potential role of preoperative aura in predicting outcomes after surgery for TLE. Material and methods This study included consecutive patients diagnosed with TLE who underwent anterior temporal lobectomy (ATL) for drug-resistant TLE during the period from January 1999 to December 2017. Data pertaining to patient age at the time of surgery, sex, age at initial seizure onset, duration of epilepsy, presence of preoperative aura, comprehensive clinical semiology, side of surgery, and type of pathology were analyzed. Preoperative auras were classified as autonomic, sensory, mental and affective, or multiple manifestations. Patients were followed at 3 and 12 months after surgery and at regular intervals thereafter. Results and conclusions A total of 498 patients were included in the study. Positive preoperative aura was observed in 386 patients (77.51%). The correlation of each variable with seizure outcomes was analyzed, and the only variable found to correlate with seizure outcome was the presence of preoperative aura. Compared with those with negative preoperative aura, those with positive preoperative aura were 1.74-fold more likely to be seizure-free after surgery for TLE. The analysis of patient data suggested a later onset of initial seizure in those with positive preoperative aura, compared with those without (p = 0.04, 95% confidence interval (CI): 0.55–3.24). Patients with a shorter duration of disease prior to TLE surgery were more likely to achieve seizure-free status postoperatively. Preoperative sensory aura was a good predictor that a patient would be seizure-free during follow-up (p = 0.022).

Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly encountered in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. A small group of ATRT stands out clinically, because these tumors are located in the sellar region of adults. To investigate if sellar region ATRT in adults represents a molecular distinct entity, we characterized molecular alterations in 7 sellar region ATRTs in adults as compared with 150 pediatric ATRTs and 47 pituitary adenomas using SMARCB1 sequencing, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization as well as DNA methylation profiling. The median age of the 6 female and 1 male patients was 56 years. On histopathologic examination, all tumors were malignant rhabdoid tumors showing loss of SMARCB1/INI1 protein expression. Two cases displayed compound heterozygous SMARCB1 point mutations, 3 cases showed heterozygous SMARCB1 deletions with point mutations of the other allele and 1 case a homozygous SMARCB1 deletion; in 1 case, underlying SMARCB1 alterations could not be identified. On unsupervised hierarchical cluster analysis of DNA methylation profiles, sellar region ATRTs did not form a distinct group, but clustered with ATRT-MYC, 1 of 3 recently described molecular subgroups of ATRT. On analysis of DNA methylation array intensity data, only 1 sellar region ATRT showed characteristic features of pediatric ATRT-MYC, that is, major copy number losses affecting the SMARCB1 region. In conclusion, these results suggest that sellar region ATRTs in adults form a clinically distinct entity with a different mutational spectrum, but epigenetic similarities with pediatric ATRTs of the ATRT-MYC subgroup.

Background: Accurate diagnosis of brain tumor is crucial for adequate surgical strategy. Our institution follows a comprehensive preoperative evaluation based on clinical and imaging information. Methods: To assess the precision of preoperative diagnosis, we compared the “top three list” of differential diagnosis (the first, second, and third diagnoses according to the WHO 2007 classification including grading) of 1061 brain tumors, prospectively and consecutively registered in preoperative case conferences from 2010 to the end of 2017, with postoperative pathology reports. Results: The correct diagnosis rate (sensitivity) of the first diagnosis was 75.8% in total. The sensitivity of the first diagnosis was high (84–94%) in hypothalamic-pituitary and extra-axial tumors, 67–75% in intra-axial tumors, and relatively low (29–42%) in intraventricular and pineal region tumors. Among major three intra-axial tumors, the sensitivity was highest in brain metastasis: 83.8% followed by malignant lymphoma: 81.4% and glioblastoma multiforme: 73.1%. Sensitivity was generally low (≦60%) in other gliomas. These sensitivities generally improved when the second and third diagnoses were included; 86.3% in total. Positive predictive value (PPV) was 76.9% in total. All the three preoperative diagnoses were incorrect in 3.4% (36/1061) of cases even when broader brain tumor classification was applied. Conclusion: Our institutional experience on precision of preoperative diagnosis appeared around 75% of sensitivity and PPV for brain tumor. Sensitivity improved by 10% when the second and third diagnoses were included. Neurosurgeons should be aware of these features of precision in preoperative differential diagnosis of a brain tumor for better surgical strategy and to adequately inform the patients.

Approximately 26–30% of temporal lobe epilepsy (TLE) cases display a normal-appearing magnetic resonance image (MRI) leading to difficulty in determining the epileptogenic focus. This causes challenges in surgical management, especially in countries with limited resources. The medical records of 154 patients with normal-appearing MRI TLE who underwent epilepsy surgery between July 1999 and July 2019 in our epilepsy centre in Indonesia were examined. The primary outcome was the Engel classification of seizures. Anterior temporal lobectomy was performed in 85.1% of the 154 patients, followed by selective amygdalo-hippocampectomy and resection surgery. Of 82 patients (53.2%), Engel Class I result was reported in 69.5% and Class II in 25.6%. The median seizure-free period was 13 (95% CI,12.550–13.450) years, while the seizure-free rate at 5 and 12 years follow-up was 96.3% and 69.0%, respectively. Patients with a sensory aura had better seizure-free outcome 15 (11.575–18.425) years. Anterior temporal lobectomy and selective amygdala-hippocampectomy gave the same favourable outcome. Despite the challenges of surgical procedures for normal MRI TLE, our outcome has been favourable. This study suggests that epilepsy surgery in normal MRI TLE can be performed in centres with limited resources.