Whole-exome sequencing reveals the genetic causes and modifiers of moyamoya syndrome.

Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause.

"Apathetic look" is a valuable indicator of intraoperative supplementary motor area syndrome during awake craniotomy.

Resection of a glioma from the dorsomedial frontal lobe, including the supplementary motor area (SMA), can result in postoperative SMA syndrome. SMA syndrome may occur during awake craniotomies. However, it is often difficult to intraoperatively distinguish between motor dysfunction due to pyramidal tract damage from that due to SMA syndrome. Patients with suspected intraoperative SMA syndrome are indifferent to their surroundings, have stiff facial muscles, and maintain a fixed gaze. We defined this condition as "apathetic look." The present study aimed to investigate whether intraoperative "apathetic look" is useful for identifying intraoperative SMA syndrome in patients with glioma close to motor-related areas, including the SMA, during awake craniotomy. This study included 33 consecutive patients with glioma included in the SMA. We excluded patients whose tumors extended to motor-related areas. We also assessed whether intraoperative SMA syndrome occurred in each patient. We evaluated the correlation between the occurrence of intraoperative SMA syndrome and various clinical factors, including intraoperative "apathetic look." Of the 33 patients, 12 had intraoperative SMA syndrome. Intraoperative "apathetic look" showed strong correlation with intraoperative SMA syndrome (p < 0.0001). Additionally, higher extent of resection (EOR) and resection of the corpus callosum showed a significantly higher incidence of intraoperative "apathetic look." All 12 patients with intraoperative SMA syndrome showed intraoperative "apathetic look" and recovered from SMA syndrome with high EOR. In conclusion, intraoperative "apathetic look" shows strong correlation with intraoperative SMA syndrome. Therefore, "apathetic look" may be a valuable indicator of intraoperative SMA syndrome during awake craniotomy.

Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

Solitary isolated disseminations of glioblastoma to sellar and suprasellar regions: two case reports.

Herein, we present two cases of isolated suprasellar dissemination of glioblastoma in patients with well-controlled primary lesions. A 22-year-old woman and a 56-year-old woman developed rapid growth of suprasellar glioblastoma dissemination 26 and 17 months after initial surgery, respectively. Both patients presented with acute visual impairment (decreased acuity and visual field disturbances) but lacked severe pituitary dysfunction. During surgery for the disseminated tumors, gross total tumor resection was difficult due to intraoperative findings suggesting optic pathway invasion. Both patients developed further intracranial dissemination within several months post-surgery. The presence of solitary sellar and suprasellar dissemination may indicate a terminal stage.

The Future of Sustainable Neurosurgery: Is a Moonshot Plan for Artificial Intelligence and Robot-Assisted Surgery Possible in Japan?

Japanese neurosurgery faces challenges such as a declining number of neurosurgeons and their concentration in urban areas. Particularly in rural areas, access to neurosurgical care for patients with conditions, such as stroke, is limited, raising concerns about the collapse of regional healthcare. Robot-assisted surgical technologies have advanced in recent years, contributing to the improved precision and safety of deep brain surgery. This study proposes the "Artificial Intelligence (AI) and Robot-Assisted Surgery Moonshot Plan" for Japan, comprising 5 pillars: 1) establishment of regional medical centers, 2) development of remote surgery systems, 3) enhancement of robotic-assisted surgery training programs, 4) integration of AI technologies, and 5) promotion of industry-academia-government collaboration. In addition, strengthening the approach to spinal surgery is expected to revitalize regional medical centers, optimize the number of neurosurgeons, improve surgical skills, and promote minimally invasive surgery. This study analyzed the current status and challenges of Japanese neurosurgery through a literature review and statistical analysis. AI is used in various aspects of neurosurgery, including diagnostic support, surgical planning and navigation, treatment outcome prediction, intraoperative monitoring, robot-assisted surgery, and rehabilitation. However, challenges, such as data bias, ethical issues, costs, and regulations, remain. In Japan, issues such as the uneven distribution and decline of neurosurgeons, collapse of regional healthcare, and increase in the number of patients with spinal disorders due to aging have been highlighted. The "AI and Robot-Assisted Surgery Moonshot Plan" serves as a guide to overcome the challenges of neurosurgery in Japan and establish a sustainable medical system.

Pediatric craniopharyngioma with significantly increased intraoperative visual evoked potential amplitude and postoperative visual acuity improvement: a case report.

Visual evoked potential (VEP) is an established modality that allows safe brain tumor resection and preservation of optical function. We herein present a case of a pediatric craniopharyngioma with significant improvement in the VEP amplitude detected during endoscopic transsphenoidal surgery (ETS) and obvious postoperative improvement in visual acuity. A 13-year-old boy presented with visual acuity disturbance in his right eye and was followed up for 5 months by an ophthalmologist. His visual acuity rapidly worsened, and a suprasellar lesion with calcification was found on brain computed tomography. The patient underwent tumor resection during ETS with intraoperative transcranial VEP monitoring. Gross total tumor resection was achieved without injury to the perforators, including the superior hypophyseal arteries. The VEP amplitude was unstable, and significant waves were not detectable before tumor resection; however, a positive wave was detected after removing most of the tumor and exposing the bilateral optic nerves and optic chiasm. Subsequently, negative and positive VEP waves were continuously detected. Visual acuity improved remarkably on postoperative day 10. This case demonstrated both a significant increase in the intraoperative VEP amplitude and rapid postoperative improvement in visual acuity. We surmised that the preoperative rapid worsening of visual dysfunction, intraoperative increase in the VEP amplitude, and significant postoperative improvement in visual acuity were associated with the compression of the optic nerves by the internal carotid artery, anterior cerebral artery, and tumor.

A case of bilateral vertebral artery dissection treated by bilateral surgical occlusion and low-flow bypass.

Background: Bilateral vertebral artery dissection aneurysm (VADA) is a rare condition that leads to severe stroke. However, the surgical strategy for its treatment is controversial because the pathology is very complicated and varies in each case. Here, we report a case of bilateral VADA that was successfully treated with staged bilateral VADA occlusion and low-flow bypass. Case Description: A Japanese man in his 40s presented with bilateral VADA with subarachnoid hemorrhage. He had only mild headaches without any other neurological deficits. Subsequently, the ruptured left VADA was surgically trapped. However, on postoperative day 11, the contralateral VADA enlarged. The right VADA was then proximally clipped via a lateral suboccipital approach. Furthermore, a superficial temporal artery-superior cerebellar artery bypass was performed through a subtemporal approach in advance to preserve cerebral flow in the posterior circulation. The bilateral VADA was obliterated, and the patient had an uneventful postoperative course during the 1-year and 6-month follow-up period. Conclusion: Bilateral VADA can be successfully treated with staged bilateral VADA obstruction and low-flow bypass. In this case, as the posterior communicating arteries were the fetal type and the precommunicating segments of the posterior cerebral arteries (P1) were hypoplastic, a low-flow bypass was used to supply the basilar and cerebellar arteries, except the posterior cerebral and posterior inferior cerebellar arteries. Furthermore, low-flow bypass is a less invasive option than high-flow bypass.

A case of a pineal parenchymal tumor of intermediate differentiation with bifocal lesions differentiated by negative placental alkaline phosphatase in the spinal fluid.

Placental alkaline phosphatase (PLAP) in the spinal fluid is helpful for the diagnosis of intracranial germinomas. Bifocal lesions involving the pineal and pituitary regions have also been reported as characteristic findings of intracranial germinomas. We present a rare case of a 15-year-old boy with a pineal parenchymal tumor of intermediate differentiation (PPTID) with bifocal lesions negative for PLAP. Magnetic resonance imaging of the brain revealed bifocal mass lesions in the pineal and suprasellar regions and non-communicating hydrocephalus. We initially suspected a germinoma based on imaging findings, but all tumor markers, including PLAP, in the spinal fluid were negative. Based on these results, germinoma was considered less likely, and an endoscopic third ventriculostomy and endoscopic tumor biopsy were performed for diagnosis. The histopathological diagnosis was PPTID, corresponding to World Health Organization grade 3, in both pineal and suprasellar specimens. A craniotomy for tumor removal was performed, resulting in total resection. PLAP is known to have high sensitivity and extremely high negative predictive value for germinomas. Although bifocal lesions highly suggest germ cell tumors, there are exceptions, as in the present case. This case suggests that PLAP measurements are useful for differentiation, leading to appropriate treatment strategies.

Brainstem cavernous hemangioma with improvement of Holmes tremor on excision.

An 8-year-old boy presenting with left-angle paralysis, tremor in upper and lower extremities, and diplopia was diagnosed with hemorrhage from a mesencephalic cavernous hemangioma. He underwent hemangiomectomy through the occipital transtentorial approach 4 weeks post-hemorrhage, after which Holmes tremor (HT) markedly reduced. A year later, hemangioma has not recurred; he is now independent in his daily activities. Early intervention in the subacute stage allows for the complete removal of brainstem cavernomas (BSCs), with minimal risk of complications or sequelae. Proper timing and surgical approach for BSCs can prevent re-bleeding and improve HT after an initial hemorrhage, without any lasting negative consequences.

Association Between Pretreatment 11C-Methionine Positron Emission Tomography Metrics, Histology, and Prognosis in 125 Newly Diagnosed Patients with Adult-Type Diffuse Glioma Based on the World Health Organization 2021Classification.

OBJECTIVE: To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. METHODS: A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients. RESULTS: The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2-3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values. CONCLUSIONS: MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.

Perioperative Management of Spinal Arteriovenous Malformation Embolization: Delayed Venous Thrombosis and Implications for Severe Back Pain.

BACKGROUND AND PURPOSE: The prognosis of untreated spinal arteriovenous malformations (SAVMs) is poor. Embolization plays an important role in the management of intramedullary SAVMs. Delayed aggravation due to spinal venous thrombosis following successful embolization has been reported; however, perioperative management strategies to prevent thrombosis have not been explored. We present our single-center experience of SAVM embolization and perioperative management, including anticoagulation. MATERIAL AND METHODS: We retrospectively evaluated 18 patients with SAVMs who underwent transarterial embolization. Perioperative anticoagulation therapy was administered to selected patients. We compared the characteristics of the patients, including perioperative management procedures, between those with and without postoperative worsening following embolization. RESULTS: Acute postoperative worsening within 1 week occurred in 4 (22.2%) patients. Of these, immediate worsening was observed in one patient as a procedure-related complication. Delayed worsening after 24 h was observed in 3 patients, caused by delayed venous thrombosis with severe back pain. Rescue anticoagulation for delayed worsening improved symptoms in two patients. A comparison between patients with and without acute postoperative worsening revealed significant differences in age (median 46.5 vs. 26.5 years, p = 0.009) and the presence of postoperative back pain (75.0% vs. 0%, p = 0.005); however, there was no significant difference in use of selective anticoagulation (p = 0.274). CONCLUSION: The results of this study suggest that SAVM embolization can cause acute worsening due to postoperative venous thrombosis with severe back pain, which may be reversed by anticoagulation therapy. Back pain is an important finding that suggests venous thrombosis, and anticoagulation should be urgently administered.

DNA hypomethylator phenotype reprograms glutamatergic network in receptor tyrosine kinase gene-mutated glioblastoma.

DNA methylation is crucial for chromatin structure and gene expression and its aberrancies, including the global "hypomethylator phenotype", are associated with cancer. Here we show that an underlying mechanism for this phenotype in the large proportion of the highly lethal brain tumor glioblastoma (GBM) carrying receptor tyrosine kinase gene mutations, involves the mechanistic target of rapamycin complex 2 (mTORC2), that is critical for growth factor signaling. In this scenario, mTORC2 suppresses the expression of the de novo DNA methyltransferase (DNMT3A) thereby inducing genome-wide DNA hypomethylation. Mechanistically, mTORC2 facilitates a redistribution of EZH2 histone methyltransferase into the promoter region of DNMT3A, and epigenetically represses the expression of DNA methyltransferase. Integrated analyses in both orthotopic mouse models and clinical GBM samples indicate that the DNA hypomethylator phenotype consistently reprograms a glutamate metabolism network, eventually driving GBM cell invasion and survival. These results nominate mTORC2 as a novel regulator of DNA hypomethylation in cancer and an exploitable target against cancer-promoting epigenetics.

Reconsideration of Surgical Indication for Prolactin-producing Pituitary Tumor Focusing on Visual Impairment.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.

Information-guided Surgery Centered on Intraoperative Magnetic Resonance Imaging Guarantees Surgical Safety with Low Mortality.

Neurosurgery is complex surgery that requires a strategy that maximizes the removal of tumors and minimizes complications; thus, a safe environment during surgery should be guaranteed. In this study, we aimed to verify the safety of brain surgery using intraoperative magnetic resonance imaging (iMRI), based on surgical experience since 2000. Thus, we retrospectively examined 2,018 surgical procedures that utilized iMRI performed in the operating room at Tokyo Women's Medical University Hospital between March 2000 and October 2019. As per our data, glioma constituted the majority of the cases (1,711 cases, 84.8%), followed by cavernous hemangioma (61 cases, 3.0%), metastatic brain tumor (37 cases, 1.8%), and meningioma (31 cases, 1.5%). In total, 1,704 patients who underwent glioma removal were analyzed for mortality within 30 days of surgery and for reoperation rates and the underlying causes within 24 hours and 30 days of surgery. As per our analysis, only one death out of all the glioma cases (0.06%) was reported within the 30-day period. Meanwhile, reoperation within 30 days was performed in 37 patients (2.2%) due to postoperative bleeding in 17 patients (1.0%), infection in 12 patients (0.7%), hydrocephalus in 6 patients (0.4%), cerebrospinal fluid (CSF) leakage in 1 patient, and brain edema in 1 patient (0.06%). Of these, 14 cases (0.8%) of reoperation were performed within 24 hours, that is, 13 cases (0.8%) due to postoperative bleeding and 1 case (0.06%) due to acute hydrocephalus. Mortality rate within 30 days was less than 0.1%. Thus, information-guided surgery with iMRI can improve the safety of surgical resections, including those of gliomas.

Long-term follow-up of task-specific tremor after thalamotomy: a retrospective observational study.

OBJECTIVE: This study aimed to report the long-term results of thalamotomy in 23 patients with task-specific tremor. METHODS: Data of 23 patients with task-specific tremor who underwent ventralis intermedius nucleus and posterior part of ventro-oral nucleus thalamotomy at the Tokyo Women's Medical University Hospital between 2010 and 2022 were retrospectively analyzed. To evaluate neurological conditions, the severity of task-specific tremor was divided into 0 (no tremor), 1 (slightly tremulous), 2 (moderately tremulous), 3 (accomplishing tasks with great difficulty), and 4 (unable to complete tasks). We also used the subscores "handwriting" (0-4) and "spiral drawing" (0-4) of the Clinical Rating Scales for Tremor. Evaluation scales were presented as medians and interquartile ranges. RESULTS: The severities of task-specific tremor were 3.0 (3.0-4.0) preoperatively and 0.0 (0.0-0.0, p < 0.0001) at the last available evaluation. The writing and spiral drawing of the Clinical Rating Scales for Tremor significantly improved from 3.0 (3.0-4.0) and 3.0 (2.0-3.0) preoperatively, respectively, to 0.0 (0.0-0.0, p < 0.0001) and 0.0 (0.0-0.0, p < 0.0001) at the last available evaluation, respectively. The mean clinical follow-up period was 62.7 ± 26.0 months. Seven (30.4%) patients had focal hand dystonia, which newly developed on the ipsilateral side of the tremor at 2-45 months after the surgery. No serious complications were observed. INTERPRETATION: Thalamotomy significantly improves task-specific tremor with high long-term efficacy, and long-term follow-up is important because focal hand dystonia can develop postoperatively.

Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels.

Context: GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. Objective: We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. Methods: We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Results: Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (ß = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [ß] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (ß = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. Conclusion: The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

Endoscope-assisted Trans-lamina Terminalis Resection of Chordoid Glioma at the Third Ventricle: A Case Report.

As per the 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System, chordoid glioma (CG) is defined as a slow-growing glial neoplasm categorized as grade II tumor. This tumor is primarily located in the anterior part of the third ventricle, often adheres to important surrounding structures, and is hemorrhagic in nature. Therefore, dissecting this tumor is extremely difficult. In this study, we present the case of a 44-year-old man who initially complained of mild headache and was diagnosed with a homogeneous gadolinium-enhanced lesion in the third ventricle via magnetic resonance imaging. The pathological diagnosis based on his biopsy at the previous hospital was CG. The patient demonstrated no neurological deficit at that time, but the tumor had gradually grown, hydrocephalus appeared 2 years after the tumor was detected, and the patient developed short memory disorder and daytime sleepiness. We resected the tumor via the anterior interhemispheric trans-lamina terminalis approach using a microscope and an endoscope. The residual tumor at the blind spot of the microscopic view was resected under an angled rigid endoscopic view using dedicated tools for transsphenoidal surgery. The tumor was grossly resected, and the histopathological diagnosis was CG. Postoperative neurological findings included slight memory disorder and hypothalamic adrenal dysfunction. No tumor recurrence was reported 3 years post resection. The endoscope-assisted anterior interhemispheric trans-lamina terminalis approach was determined useful for CG resection with minimal surgical complications and without tumor recurrence.

Systemic Metastasis of Pediatric Diffuse High-grade Astrocytoma: A Case Report.

Extracranial brain tumor metastases are extremely rare. The etiology, pathophysiology, and clinical progression of systemic metastatic brain cancer remain to be elucidated. We encountered a case of pediatric diffuse high-grade astrocytoma in a four-year-old girl with subcutaneous and lymph node metastases. Numerous metastatic lesions emerged, progressed rapidly, and were difficult to manage despite temozolomide (TMZ) administration. The patient underwent repeated surgical resection for these lesions. Conversely, the primary intracranial lesions responded well to TMZ for some time. However, the patient died 15 months after the initial diagnosis. Extracranial metastasis and highly varying effects of chemotherapy were the characteristic clinical features in this case. Our analysis did not reveal definitive histopathological and molecular factors contributing to this presentation. The lack of notable molecular pathological features illustrates the unpredictability of glioma metastasis, and the treatment for extracranial metastasis remains unknown. A gene panel analysis revealed several genetic aberrations, including PDGFRA, PIK3CA, and NBN mutations. As it is impossible to resect all frequently and rapidly progressing lesions, we stress that the prognosis of metastatic brain tumors is undoubtedly poor if these tumors are refractory to existing treatments, including chemotherapy.