Background: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Pathogenic germline variants (PGVs) are increasingly recognized as critical elements in pediatric cancer predisposition. Determining the pathogenicity of germline variants is a dynamic process, with advancements in next-generation sequencing and expanding genome databases reshaping our understanding of cancer genomics. This article reviews the role of PGVs in key oncogenic pathways, including RTK (receptor tyrosine kinase)/RAS/MAPK (mitogen-activated protein kinase), PI3K (phosphatidylinositol 3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog 1), WNT (wingless-type), and Hedgehog signaling, highlighting their associations with specific cancer predisposition syndromes and neurosurgical implications. Most PGVs are inherited in an autosomal dominant pattern and are frequent in tumor suppressor genes, while autosomal recessive conditions like Ataxia-telangiectasia and Fanconi anemia are less common. Germline variants in proto-oncogenes such as PTPN11, KRAS, and HRAS are associated with RASopathies, including Noonan and Costello syndromes, which show variable cancer risks. Similarly, PTEN PGVs, linked to Cowden syndrome, and DICER1 PGVs, responsible for DICER1 syndrome, exemplify the diverse clinical presentations and risks of pediatric cancer predisposition syndromes. Medulloblastoma, a pediatric-specific brain tumor, shows an increasing proportion of PGVs, with approximately 12% of all medulloblastomas harboring PGVs in APC, PTCH1, SUFU, and ELP1 in the WNT-activated and sonic hedgehog-activated subtypes. Emerging evidence suggests that approximately 8.5–20% of pediatric cancer patients harbor PGVs, with a substantial proportion arising de novo. Routine germline screening for pediatric cancer patients is increasingly recommended, as many PGVs lack family history. Programs like STREAM (Solid Tumor REsearch And Magic) in Korea underscore the importance of comprehensive pediatric genome databases for personalized precision medicine. As neurosurgeons are frequently the first to encounter central nervous system tumor manifestations, a robust understanding of genomic medicine is essential. This review emphasizes the need for international collaboration to develop actionable insights into pediatric cancer genomics, ultimately improving diagnostic, therapeutic, and preventive strategies.

Background: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Pathogenic germline variants (PGVs) are increasingly recognized as critical elements in pediatric cancer predisposition. Determining the pathogenicity of germline variants is a dynamic process, with advancements in next-generation sequencing and expanding genome databases reshaping our understanding of cancer genomics. This article reviews the role of PGVs in key oncogenic pathways, including RTK (receptor tyrosine kinase)/RAS/MAPK (mitogen-activated protein kinase), PI3K (phosphatidylinositol 3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog 1), WNT (wingless-type), and Hedgehog signaling, highlighting their associations with specific cancer predisposition syndromes and neurosurgical implications. Most PGVs are inherited in an autosomal dominant pattern and are frequent in tumor suppressor genes, while autosomal recessive conditions like Ataxia-telangiectasia and Fanconi anemia are less common. Germline variants in proto-oncogenes such as PTPN11, KRAS, and HRAS are associated with RASopathies, including Noonan and Costello syndromes, which show variable cancer risks. Similarly, PTEN PGVs, linked to Cowden syndrome, and DICER1 PGVs, responsible for DICER1 syndrome, exemplify the diverse clinical presentations and risks of pediatric cancer predisposition syndromes. Medulloblastoma, a pediatric-specific brain tumor, shows an increasing proportion of PGVs, with approximately 12% of all medulloblastomas harboring PGVs in APC, PTCH1, SUFU, and ELP1 in the WNT-activated and sonic hedgehog-activated subtypes. Emerging evidence suggests that approximately 8.5–20% of pediatric cancer patients harbor PGVs, with a substantial proportion arising de novo. Routine germline screening for pediatric cancer patients is increasingly recommended, as many PGVs lack family history. Programs like STREAM (Solid Tumor REsearch And Magic) in Korea underscore the importance of comprehensive pediatric genome databases for personalized precision medicine. As neurosurgeons are frequently the first to encounter central nervous system tumor manifestations, a robust understanding of genomic medicine is essential. This review emphasizes the need for international collaboration to develop actionable insights into pediatric cancer genomics, ultimately improving diagnostic, therapeutic, and preventive strategies.

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Objective: In this study, changes in treatment methods and patient prognosis were analyzed using a Korean nationwide medical insurance information database. Methods: Patients with subarachnoid hemorrhage who received surgical treatment for cerebral aneurysm from 2005 to 2020 were included. The specific surgery type was classified using the surgical code and according to whether stents were used. Yearly trends in mortality rates and poor prognosis, using tracheostomy as proxy, were analyzed by a simple regression analysis. A multistep logistic regression analysis was performed to evaluate the risk factors of mortality and poor prognosis. Results: Overall, 83,587 patients were included. Females were predominant (64.5%). Microsurgical clip usage rate decreased by approximately two-thirds from 78.8% in 2005 to 24.4% in 2020. Contrarily, endovascular treatment proportion gradually increased, and stent-assisted coil embolization rate surpassed microsurgical clip usage rate in 2020 (24.6% vs. 24.4%). In the multivariate analysis, endovascular treatment correlated positively with 3-month mortality (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 1.07–1.19, P<0.0001), although correlated negatively with poor prognosis (tracheostomy) (HR: 0.93, 95% CI: 0.89–0.98, P=0.0050). Conclusions According to the treatment trend analysis, during the 16 years studied, for patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm, the endovascular treatment rate increased rapidly and stent-assisted coil embolization rate surpassed that of microsurgical clip ligation. Diversification of treatment methods has led to a decrease in mortality and improved prognosis.

Background: While the clinical course of radiation-induced meningioma (RIM) is considered to be more aggressive than that of sporadic meningioma (SM), the genetic predisposition for RIM is not established well. The present study aimed to analyze the clinical and genetic characteristics of RIMs to increase understanding of the tumorigenesis and prognosis of RIMs. Methods: We investigated a database of 24 patients who met the RIM criteria between January 2000 and April 2023. Genetic analysis through next-generation sequencing with a targeted gene panel was performed on 10 RIM samples. Clinical, radiological, and pathological parameters were evaluated with genetic analyses. Results: The median ages for receiving radiotherapy (RT) and RIM diagnosis were 8.0 and 27.5 years, respectively, with an interval of 17.5 years between RT and RIM diagnosis. RIMs tended to develop in non-skull bases and multifocal locations. Most primary pathologies included germ cell tumors and medulloblastoma. The tumor growth rate was 3.83 cm 3 per year, and the median doubling time was 0.8 years. All patients underwent surgical resection of RIMs. The histological grade of RIMs was World Health Organization grade 1 (64%) or 2 (36%). RIMs showed higher incidences in young-age (63%), high-dose (75%), and extendedfield (79%) RT groups. The recurrence rate was 21%. Genetic analysis revealed NF2 one copy loss in 90% of the patients, with truncating NF2 mutations and additional copy number aberrations in grade 2 RIMs. TERT promoter mutation and CDKN2A/B deletion were not identified. Notably, loss of H3K27me3 was identified in 26% of RIMs. H3K27me3 loss was associated with a higher prevalence of grade 2 RIMs (67%) and high recurrence rates (33%). Conclusion The study reveals a higher prevalence of high-grade tumors among RIMs with more rapid growth and higher recurrences than SMs. Genetically, RIMs are primarily associated with NF-2 alterations with chromosomal abnormalities in grade 2 tumors, along with a higher proportion of H3K27me3 loss.

Pathogenic germline variants (PGVs) are increasingly recognized as critical elements in pediatric cancer predisposition. Determining the pathogenicity of germline variants is a dynamic process, with advancements in next-generation sequencing and expanding genome databases reshaping our understanding of cancer genomics. This article reviews the role of PGVs in key oncogenic pathways, including RTK (receptor tyrosine kinase)/RAS/MAPK (mitogen-activated protein kinase), PI3K (phosphatidylinositol 3-kinase)/AKT (v-akt murine thymoma viral oncogene homolog 1), WNT (wingless-type), and Hedgehog signaling, highlighting their associations with specific cancer predisposition syndromes and neurosurgical implications. Most PGVs are inherited in an autosomal dominant pattern and are frequent in tumor suppressor genes, while autosomal recessive conditions like Ataxia-telangiectasia and Fanconi anemia are less common. Germline variants in proto-oncogenes such as PTPN11, KRAS, and HRAS are associated with RASopathies, including Noonan and Costello syndromes, which show variable cancer risks. Similarly, PTEN PGVs, linked to Cowden syndrome, and DICER1 PGVs, responsible for DICER1 syndrome, exemplify the diverse clinical presentations and risks of pediatric cancer predisposition syndromes. Medulloblastoma, a pediatric-specific brain tumor, shows an increasing proportion of PGVs, with approximately 12% of all medulloblastomas harboring PGVs in APC, PTCH1, SUFU, and ELP1 in the WNT-activated and sonic hedgehog-activated subtypes. Emerging evidence suggests that approximately 8.5–20% of pediatric cancer patients harbor PGVs, with a substantial proportion arising de novo. Routine germline screening for pediatric cancer patients is increasingly recommended, as many PGVs lack family history. Programs like STREAM (Solid Tumor REsearch And Magic) in Korea underscore the importance of comprehensive pediatric genome databases for personalized precision medicine. As neurosurgeons are frequently the first to encounter central nervous system tumor manifestations, a robust understanding of genomic medicine is essential. This review emphasizes the need for international collaboration to develop actionable insights into pediatric cancer genomics, ultimately improving diagnostic, therapeutic, and preventive strategies.