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Mature teratoma is a subtype of intracranial germ cell tumors (GCTs), distinguished from malignant GCTs by its benign nature and excellent prognosis. Typically, no adjuvant therapy is recommended following gross total resection (GTR). We report a case of a prepubertal girl with a suprasellar mature teratoma that recurred as a germinoma 6 months post-GTR. A 7-year-old girl presented with headache and polydipsia. Imaging revealed a suprasellar mass. The patient underwent GTR, and pathological diagnosis confirmed a mature teratoma without other GCT components. Six months later, MRI identified a newly developed suprasellar mass adjacent to the optic chiasm. A second surgery confirmed the mass as a germinoma. The patient subsequently underwent adjuvant chemotherapy combined with proton therapy, resulting in complete remission. The diagnosis of mature teratoma must be approached with caution, and thorough follow-up is imperative, particularly in cases involving female patients, prepubertal age, or non-pineal locations., Competing Interests: Declarations. Ethics approval: Not applicable Conflict of interest: The author has no potential conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cerebrospinal fluid (CSF) plays an important role in brain tumors, including medulloblastoma (MBL). Recent advancements in mass spectrometry systems and 'Omics' data analysis methods enable unbiased, high proteome depth research. We conducted proteomic profiling of the total CSF in MBL patients with the purpose of finding a potential diagnostic biomarker for MBL. We quantified 1112 proteins per CSF sample. Feature selection identified four elevated soluble proteins (SPTBN1, HSP90AA1, TKT, and NME1-NME2) in MBL CSF. Validation with ELISA confirmed that TKT was significantly elevated in MBL. Additionally, TKT-positive extracellular vesicles were significantly enriched in MBL CSF and correlated with the burden of leptomeningeal seeding. Our results provide insights into the proteomics data of the total CSF of MBL patients. Furthermore, we identified the significance of TKT within the total CSF and its presence within circulating EVs in the CSF. We suggest that TKT may serve as a biomarker for MBL., (© 2024. The Author(s).)

Background: Various clinical classifications of craniopharyngiomas (CRPs) have been proposed to suggest optimal surgical planning. We aimed to evaluate the clinical outcomes of pediatric CRPs and the clinical significance of anatomical classification in relation to the diaphragm sellae., Methods: A retrospective review was conducted on patients below 18 years of age who underwent surgery for CRPs from July 1998 to August 2022. The patients were divided into transcranial approach (TCA), and transsphenoidal approach (TSA) groups, which included microscopic TSA and endoscopic endonasal approach (EEA) groups. EEA has been adopted at our institute since 2011. CRPs were classified by their origin and relationship with the diaphragm sellae., Results: A total of 132 pediatric CRP patients were included in this study, 117 of whom underwent surgery for primary CRP and 15 for recurrent CRP. Among them, 89 (67.4%) underwent TCA, 9 (6.8%) had microscopic TSA, and 34 (25.8%) had EEA. In subdiaphragmatic CRPs with competent diaphragm sellae, TSA tended to yield better outcomes than TCA did in terms of stalk preservation and ophthalmologic outcomes. After the introduction of EEA, the proportion of supradiaphragmatic CRPs treated via the TSA increased from 0% to 50% (P<0.001). Gross total resection (HR=0.194; 95% CI=0.102-0.367, P<0.001) and adjuvant therapy (HR=0.208; 95% CI=0.048-0.897, P=0.035) were found to be positive prognostic factors for long-term tumor control., Conclusions: Over time, with the adoption of EEA at our institute, the impact of anatomical classification on the surgical approach has decreased. Nevertheless, an individualized surgical approach should be employed to improve long-term outcomes and minimize complications for pediatric CRPs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Hydrocephalus is one of the neurological risks occurring in patients with achondroplasia. Ventriculoperitoneal shunt (VPS) insertion is the most common treatment. However, reports of successful endoscopic third ventriculostomy (ETV) suggest that ETV may be a good alternative to VPS insertion in achondroplasia. However, it has been stated that ETV in achondroplasia patients is technically demanding to perform. The current study examined the anatomical variations of the third ventricle and the brainstem in achondroplasia patients and correlated the findings with the difficulty of performing ETV., Methods: A retrospective analysis of 51 patients with achondroplasia and 138 hydrocephalus patients without achondroplasia (48 patients had tumor-related hydrocephalus and 90 patients had hydrocephalus of nontumorous origin) who have visited the authors' institution since 2012 was performed. Preoperative T2-weighted sagittal MR images were used to measure α (steepness of the third ventricle floor), β (endoscopic angle of incidence), d1 (vertical distance between the dorsum sellae and basilar bifurcation), and d2 (horizontal distance between the dorsum sellae and basilar artery). Each value was compared using the Tukey multicomparison test., Results: Achondroplasia patients showed significantly smaller α (p < 0.001) and β (p < 0.001) angles, while there were no significant differences between the control groups (p = 0.947 for α, p = 0.836 for β). The d1 value was significantly larger in achondroplasia patients (p < 0.001), and d2 was smaller (p < 0.001). The control groups showed similar d1 and d2 values (p = 0.415 for d1, p = 0.154 for d2). Smaller α and β values meant that in achondroplasia patients the third ventricle floor stood more vertically than in other patients with hydrocephalus, and the endoscopic contact angles were small, increasing the risk of ventriculostomy devices slipping down into the infundibular recess. Additionally, a large d1 meant that the basilar artery was shifted upward and a small d2 indicated that the basilar artery was located closer to the dorsum sellae, potentially increasing the risk of basilar artery damage., Conclusions: Achondroplasia patients' skull and brain anatomies were significantly different from those of other hydrocephalus patients, with steeper third ventricle floors and basilar arteries closer to the dorsum sellae. Because these anatomical differences lead to difficulties in performing ETVs in achondroplasia patients, such differences should be considered when ETV is planned for the patients.

This study aims to identify 3-dimensional (3D) craniometric predictors of wound complications following fronto-orbital advancement (FOA) surgery in craniosynostosis patients. The authors conducted a retrospective review of medical records for 43 patients (25 female, 18 male) who underwent open FOA between 2006 and 2023, with an average follow-up duration of 91.8 months. The data collected included age at surgery, sex, whether the craniosynostosis was syndromic, involvement of multiple sutures, history of suturectomy, wound complications (categorized as minor or major), and preoperative and postoperative 3D CT scans. The authors quantified relative changes in intracranial volume (ICV), cranial area above the Frankfurt Horizontal plane, anteroposterior diameter (APD), and cranial height (CH) using Mimics software. A logistic regression analysis was performed to identify predictors of wound complications post-FOA. Among the 43 patients who underwent FOA, 10 experienced postoperative wound complications (4 minor, 6 major), revealing significant associations with multisuture involvement and changes in △cranial area, △APD, and △CH (all P<0.05). In the multivariable analysis with backward elimination, △cranial area, and △CH were identified as significant risk factors for wound complications (OR 1.17, 95% CI: 1.01-1.36, P=0.032; and OR 0.59, 95% CI: 0.38-0.92, P=0.019, respectively). The cutoff values for △cranial area and △APD were 5.95% and 7.93%, respectively. This study identified measurable craniometric changes, especially in the cranial area, as risk factors for wound complications following FOA. It underscores the necessity for personalized surgical planning and meticulous postoperative wound care in FOA to enhance patient outcomes through risk-aware strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: The objective of this study was to investigate the longitudinal changes in cranial growth following fronto-orbital advancement (FOA) surgery in patients with unilateral and bilateral coronal craniosynostosis., Methods: This retrospective review analyzed head circumference (HC) and CT data during preoperative (T0), immediate postoperative (T1), and final follow-up (T2) visits in 40 patients (23 female, 17 male) who underwent FOA using either the open approach or distraction osteogenesis (DO) between 1987 and 2018. The mean follow-up period was 90.62 months. The z-scores of HC, CT-based intracranial volume, anteroposterior diameter (APD), biparietal diameter (BPD), and cranial height (CH) were calculated using sex- and age-specific standards. Logistic regression analysis was performed., Results: While the z-scores of HC, intracranial volume, and BPD remained within the normal range, the z-scores of APD fluctuated between -2 and -1, and the z-scores of CH were > 2, indicating a substantial elevation compared with norms from T0 to T2. Age at surgery significantly influenced the z-scores of HC, BPD, and CH at T2 (all p < 0.05). Delayed surgical timing was correlated with increased BPD and CH z-scores from T1 to T2 (p = 0.007 and 0.019, respectively). The DO for FOA resulted in elevated HC z-scores at T2 and increased APD from T0 to T1, followed by a significant APD relapse from T1 to T2., Conclusions: These findings suggest that delayed surgical timing may support better cranial growth, as indicated by increased HC at long-term follow-up. However, delayed timing is also associated with worsening abnormally elevated CH. Despite the immediate APD expansion and long-term HC increase with DO, potential relapse warrants caution. While intentional overcorrection of APD is recommended, careful consideration of surgical timing and planning is essential.

Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood-brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1-15 years) and six adults (aged 27-72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions., (© 2024. The Author(s).)

Unexplained neurological deterioration is occasionally observed in patients with traumatic brain injuries (TBIs). We aimed to describe the clinical features of post-traumatic transient neurological dysfunction and provide new insight into its pathophysiology. We retrospectively collected data from patients with focal neurological deterioration of unknown origin during hospitalization for acute TBI for 48 consecutive months. Brain imaging, including computed tomography, diffusion-weighted imaging and perfusion-weighted imaging, and electroencephalography were conducted during the episodes. Fourteen (2.0%) patients experienced unexplained focal neurological deterioration among 713 patients who were admitted for traumatic intracranial hemorrhage during the study period. Aphasia was the predominant symptom in all patients, and hemiparesis or hemianopia was accompanied in three patients. These symptoms developed within 14 days after trauma. Structural imaging did not show any significant interval change, and electroencephalography showed persistent arrhythmic slowing in the corresponding hemisphere in most patients. Perfusion imaging revealed increased cerebral blood flow in the symptomatic hemisphere. Surgical intervention and anti-seizure medications were ineffective in abolishing the symptoms. The symptoms disappeared spontaneously after 4 h to 1 month. Transient neurological dysfunction (TND) can occur during the acute phase of TBI. Although TND may last longer than a typical transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we postulate that this is a manifestation of spreading depolarization occurring in the injured brain, which is analogous to migraine aura.

Purpose: The present study aimed to evaluate the role of early and delayed surgery in congenital brain tumors and analyze the clinical outcomes of infantile brain tumors., Materials and Methods: We performed a retrospective cohort study on 69 infantile brain tumors at a single institution from January 2008 to June 2023. Outcomes were assessed as early mortality (within 30 days following surgery) to evaluate the risk of early surgery in congenital brain tumors. Outcomes of recurrence and overall survival were analyzed in infantile brain tumors., Results: Surgery-related early mortality appeared to occur in young and low-body-weight patients. Cut-off values of age and body weight were found to be 1.3 months and 5.2 kg to avoid early mortality. Three patients (3/10, 30%) showed early mortality in the early surgery group, and early mortality occurred in one patient (1/14, 7.14%) in the delayed surgery group, whose tumor was excessively enlarged. Younger age at diagnosis (< 3 months of age; hazard ratios [HR], 7.1; 95% confidence intervals [CI], 1.4 to 35.6; p=0.018) and leptomeningeal seeding (LMS; HR, 30.6; 95% CI, 3.7 to 253.1; p=0.002) were significant independent risk factors for high mortality in infantile brain tumors., Conclusion: We suggest delaying surgery until the patient reaches 1.3 months of age and weighs over 5.2 kg with short-term imaging follow-up unless tumors grow rapidly in congenital brain tumors. Younger ages and the presence of LMS are independent risk factors for high mortality in infantile brain tumors.

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level., (© 2024. The Author(s).)

Cerebral cavernous malformation (CCM) is a vascular anomaly commonly found in children and young adults. Common clinical presentations of pediatric patients with CCMs include headache, focal neurological deficits, and seizures. Approximately 40% of pediatric patients are asymptomatic. Understanding the natural history of CCM is crucial and hemorrhagic rates are higher in patients with an initial hemorrhagic presentation, whereas it is low in asymptomatic patients. There is a phenomenon known as temporal clustering in which a higher frequency of symptomatic hemorrhages occurs within a few years following the initial hemorrhagic event. Surgical resection remains the mainstay of treatment for pediatric CCMs. Excision of a hemosiderin-laden rim is controversial regarding its impact on epilepsy outcomes. Stereotactic radiosurgery is an alternative treatment, especially for deepseated CCMs, but its true efficacy needs to be verified in a clinical trial.

Objective: In children, interhemispheric arachnoid cysts (IHACs) are rare lesions often associated with corpus callosum dysgenesis. It is still controversial about surgical treatments for IHACs. We aim to report our experience with pediatric IHAC patients and evaluate surgical courses and neurological developments., Methods: Pediatric IHACs treated between 2001 and 2021 were reviewed retrospectively. IHAC was observed until they represented rapid cyst enlargement or neurological symptoms. Cyst fenestration was done by microscope or endoscope, depending on the IHAC's location. Cyst size and corpus callosum dysgenesis were evaluated with neuroimaging. Neurological development was assessed from medical records at the last follow-up., Results: Fifteen children received cyst fenestration surgery (mean age 11.4 months). Eleven patients (73.3%) under observation showed rapid cyst enlargement in a short period (median 5 months). Cysto-ventriculostomy (CVS) and cysto-cisternostomy (CCS) regressed the cyst size significantly (p = 0.003). The median follow-up duration was 51 months (range 14-178 months). Corpus callosum dysgenesis was observed in eleven patients (73.3%, complete = 5, partial = 6). Among eight patients (53.3%) having developmental delay, five patients (33.3%) showed speech delay, including one patient with intractable seizures., Conclusion: Pediatric IHACs frequently present within 1 year after birth, with rapid cyst enlargement. CVS and CCS were effective in regressing the cyst size. Corpus callosum dysgenesis accompanied by IHAC might have a risk of language achievement; however, development delay could rely on multifactorial features, such as epilepsy or other brain anomalies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Craniosynostosis involves early closure of one or more sutures, which is known to limit normal cranium growth and interfere with normal brain development. Various surgical methods are used, ranging from minimally invasive strip craniectomy to more extensive whole-vault cranioplasty. This study aimed to evaluate neurocognitive outcomes 5 years after surgical treatment in children with craniosynostosis and to evaluate relevant clinical factors., Methods: After exclusion of genetically confirmed syndromic craniosynostosis patients, a retrospective review was conducted on 112 nonsyndromic craniosynostosis patients who underwent surgical treatment and follow-up neurocognitive assessment. Ninety-seven patients underwent strip craniectomy with postoperative orthotic helmet therapy, and 15 received other surgical treatment: 4 with distraction osteotomy and 11 with craniofacial reconstruction. Neurocognitive assessment using the Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), was performed 5 years postoperatively. Clinical factors were assessed regarding neurocognitive outcomes., Results: The mean age at surgery was significantly younger in the strip craniectomy group (strip craniectomy 4.6 months vs other surgical treatment 18.6 months, p < 0.01). Patients with 2 or more sutures involved were more likely to receive more extensive surgical treatment (16.5% in the strip craniectomy group vs 53.8% in the other group, p < 0.01). Four (3.5%) patients who showed evidence of increased intracranial pressure (ICP) also underwent more extensive surgical treatment. Multivariable linear regression revealed a significant correlation of age at neurocognitive testing (-3.18, 95% CI -5.95 to -0.40, p = 0.02), increased ICP (-34.73, 95% CI -51.04 to -18.41, p < 0.01), and the level of maternal education (6.11, 95% CI 1.01-11.20, p = 0.02) with the Full-Scale Intelligence Quotient (FSIQ). Age at surgery, involvement of 2 or more sutures, and type of operation demonstrated no correlation with FSIQ. Among the 97 patients who underwent strip craniectomy, the FSIQ ranged from mean ± SD 100.2 ± 10.2 (bicoronal) to 110.1 ± 12.7 (lambdoid), and there was no significant difference between the suture groups (p = 0.41). The 5 index scores were all within average ranges based on their age norms., Conclusions: Age at neurocognitive assessment, increased ICP, and maternal education level showed significant correlations with the neurocognitive function of craniosynostosis patients. Although children with craniosynostosis exhibited favorable 5-year postoperative neurocognitive outcomes across various synostosis sutures, longer follow-up is needed to reveal the incidence of neurocognitive dysfunction in these patients.

Objective: Endoscopic suturectomy is a widely practiced surgical option for infants with craniosynostosis. But the efficacy and safety of the procedure remain unclear in syndromic patients. This study aims to evaluate the efficacy and safety of endoscopic suturectomy for patients with syndromic craniosynostosis., Methods: From January 2013 to December 2020, 242 patients underwent endoscopic suturectomy at our institution. The surgical outcome was determined to be favorable or unfavorable based upon the necessity of an additional cranial surgery upon the last follow-up. First, we analyzed the outcomes of 26 syndromic craniosynostosis patients who have followed up for over a year. Second, we compared the outcomes between the syndromic (N=12) and nonsyndromic (N=11) patients with bilateral coronal synostosis who have followed up for over a year., Results: Twenty-three out of 26 syndromic craniosynostosis patients (88%) showed favorable outcomes without significant complications. In the analysis for bilateral coronal synostosis patients, 11 of 12 syndromic patients (92%) presented favorable outcomes, and all nonsyndromic patients showed favorable outcomes. No significant differences were observed in various anthropometric indices (cranial index, intracranial volume, anterior cranial height, anterior cranial base length, and cranial height-length index) and surgical outcomes between syndromic and nonsyndromic groups., Conclusions: Endoscopic suturectomy has the potential to be a surgical option for syndromic craniosynostosis. Even for patients with unfavorable outcomes, endoscopic suturectomy could serve as a bridge treatment for infants to counter cranial deformation before additional extensive surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objective: Due to the underdeveloped skull base in children, it is crucial to predict whether a sufficient surgical window for an endoscopic endonasal approach can be achieved. This study aimed to analyze the presumed surgical window through measurement of the intersiphon distance (ISD) and the planum-sella height (PSH) on the basis of age and its correlation with the actual surgical window for the endoscopic transtuberculum approach., Methods: Twenty patients of each age from 3 to 18 years were included as the normal skull base population. ISD and PSH were measured and compared among consecutive ages. Additionally, 42 children with craniopharyngiomas or Rathke's cleft cysts who underwent treatment via the endoscopic transtuberculum approach were included. ISD and PSH were measured on preoperative images and then correlated with the dimensions of the surgical window on postoperative CT scans. The intraoperative endoscopic view was classified as narrow, intermediate, or wide based on operative photographs or videos, and relevant clinical factors were analyzed., Results: In the normal skull base population, both ISD and the estimated area of the surgical window increased with age, particularly at 8 and 11 years old. On the other hand, PSH did not show an incremental pattern with age. Among the 42 children who underwent surgery, 24 had craniopharyngioma and 18 had Rathke's cleft cysts. ISD showed the strongest correlation with the actual area of the surgical window [r(40) = 0.69, p < 0.001] rather than with age or PSH. The visual grade of the intraoperative endoscopic view was narrow in 17 patients, intermediate in 21, and wide in 4. Preoperative ISD was 14.58 ± 1.29 mm in the narrow group, 16.13 ± 2.30 mm in the intermediate group, and 18.09 ± 3.43 mm in the wide group (p < 0.01). There were no differences in terms of extent of resection (p = 0.41); however, 2 patients in the narrow group had postoperative complications., Conclusions: Normal skull base development exhibited age-related growth. However, in children with suprasellar lesions, the measurement of the ISD showed a better correlation than age for predicting the surgical window for the endoscopic transtuberculum approach. Children with a small ISD should be approached with caution due to the limited surgical window.

Objective: Temporal coordination between oscillations enables intercortical communication and is implicated in cognition. Focal epileptic activity can affect distributed neural networks and interfere with these interactions. Refractory pediatric epilepsies are often accompanied by substantial cognitive comorbidity, but mechanisms and predictors remain mostly unknown. Here, we investigate oscillatory coupling across large-scale networks in the developing brain., Methods: We analyzed large-scale intracranial electroencephalographic recordings in children with medically refractory epilepsy undergoing presurgical workup (n = 25, aged 3-21 years). Interictal epileptiform discharges (IEDs), pathologic high-frequency oscillations (HFOs), and sleep spindles were detected. Spatiotemporal metrics of oscillatory coupling were determined and correlated with age, cognitive function, and postsurgical outcome., Results: Children with epilepsy demonstrated significant temporal coupling of both IEDs and HFOs to sleep spindles in discrete brain regions. HFOs were associated with stronger coupling patterns than IEDs. These interactions involved tissue beyond the clinically identified epileptogenic zone and were ubiquitous across cortical regions. Increased spatial extent of coupling was most prominent in older children. Poor neurocognitive function was significantly correlated with high IED-spindle coupling strength and spatial extent; children with strong pathologic interactions additionally had decreased likelihood of postoperative seizure freedom., Significance: Our findings identify pathologic large-scale oscillatory coupling patterns in the immature brain. These results suggest that such intercortical interactions could predict risk for adverse neurocognitive and surgical outcomes, with the potential to serve as novel therapeutic targets to restore physiologic development., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Brain abscess is medically challenging. In this study, we applied nanopore sequencing for 16S rRNA analysis and investigated its efficacy and diagnostic value for patients with brain abscesses. Genomic DNA was extracted from the pus samples (n = 27) of brain abscess, and 16S rRNA genes were amplified by PCR. Sequencing libraries were generated using a rapid barcoding kit, and the generated reads were analyzed using the EPI2ME16S workflow. A conventional culture study was performed. More sensitive identification of pathogens was made by 16S sequencing, faster than the culture study. The proportion of anaerobic bacteria identified by 16S sequencing was higher (75%) than that obtained by culturing (32%). Polymicrobial infections were identified in 10 cases (40%) by 16S sequencing, while the culture study identified multiple bacteria in only 2 cases (8%). 16S sequencing was useful for identifying the composition of polymicrobial infections, including rare pathogens, and for the initial diagnosis of space-occupying lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the spontaneous recovery of bone deformity after surgical excision of craniofacial dermoid cysts in pediatrics. Pediatric patients who underwent excision of a dermoid cyst were included in the study. A prospective analysis was conducted to evaluate the amount of bone recovery by comparing the depth of bony concavity in the preoperative and postoperative (6 months) ultrasonography. In 145 of 187 patients with preoperative imaging available, the mean size of dermoid cysts was 1.4 cm 3 (range, 0.1 to 9.5), and 41.4% (60/145 cases) showed cranial bone depression. In the comparison of preoperative and postoperative ultrasonography of 30 patients, the mean depth of bony cavity decreased significantly from 4.0 to 0.9 mm (p<0.001) after a mean of 6.7 months postoperatively. There was 13.3% (4/30) of mild (≤2.0 mm), 40.0% (12/30) of moderate (>2.0 to ≤4.0 mm), and 46.7% (14/30) of severe (>4.0 mm) depression, and the concavity depth significantly decreased in all groups (p = 0.028, mild; p<0.001, moderate; p<0.001 severe). Within the limitations of the study it seems that significant recovery of cranial bone depression does take place within 6 months after excision of craniofacial dermoid cysts in pediatric patients, saving the need for immediate reconstruction., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: Endothelial colony-forming cells (ECFCs) have been reported to play an important role in the pathogenesis of moyamoya disease (MMD). We have previously observed stagnant growth in MMD ECFCs with functional impairment of tubule formation. We aimed to verify the key regulators and related signaling pathways involved in the functional defects of MMD ECFCs., Methods: ECFCs were cultured from peripheral blood mononuclear cells of healthy volunteers (normal) and MMD patients. Low-density lipoproteins uptake, flow cytometry, high content screening, senescence-associated β-galactosidase, immunofluorescence, cell cycle, tubule formation, microarray, real-time quantitative polymerase chain reaction, small interfering RNA transfection, and western blot analyses were performed., Results: The acquisition of cells that can be cultured for a long time with the characteristics of late ECFCs was significantly lower in the MMD patients than the normal. Importantly, the MMD ECFCs showed decreased cellular proliferation with G1 cell cycle arrest and cellular senescence compared to the normal ECFCs. A pathway enrichment analysis demonstrated that the cell cycle pathway was the major enriched pathway, which is consistent with the results of the functional analysis of ECFCs. Among the genes associated with the cell cycle, cyclin-dependent kinase inhibitor 2A (CDKN2A) showed the highest expression in MMD ECFCs. Knockdown of CDKN2A in MMD ECFCs enhanced proliferation by reducing G1 cell cycle arrest and inhibiting senescence through the regulation of CDK4 and phospho retinoblastoma protein., Conclusion: Our study suggests that CDKN2A plays an important role in the growth retardation of MMD ECFCs by inducing cell cycle arrest and senescence.

The aim of this study is to investigate the genetic profiles and methylation-based classifications of Embryonal tumor with multilayered rosettes (ETMR), with a specific focus on differentiating between C19MC amplified and C19MC-not amplified groups, including cases with DICER1 mutations. To achieve this, next-generation sequencing using a targeted gene panel for brain tumors and methylation class studies using the Epic850K microarray were performed to identify tumor subclasses and their clinicopathological characteristics. The study cohort consisted of four patients, including 3 children (a 4-months/F, a 9-months/M, and a 2 y/F), and one adult (a 30 y/Male). All three tumors in the pediatric patients originated in the posterior fossa and exhibited TTYH1:C19MC fusion and C19MC amplification. The fourth case in the adult patient involved the cerebellopontine angle with biallelic DICER1 mutation. Histopathological examination revealed typical embryonal features characterized by multilayered rosettes and abundant neuropils in all cases, while the DICER1 -mutant ETMR also displayed cartilage islands in addition to the classic ETMR pathology. All four tumors showed positive staining for LIN28A. The t-SNE clustering analysis demonstrated that the first three cases clustered with known subtypes of ETMR, specifically C19MC amplified, while the fourth case clustered separately to non-C19MC amplified subclass. During the follow-up period of 6~12 months, leptomeningeal dissemination of the tumor occurred in all patients. Considering the older age of onset in DICER1 -mutant ETMR, genetic counseling should be recommended due to the association of DICER1 mutations with germline and second-hit somatic mutations in cancer.

We present the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET), EWSR1::PATZ1 fusion-positive with a literature review. This fusion has recently been discovered in rare central nervous system tumors and soft tissue sarcomas and was not included in the fifth edition of the WHO classifications. We identified this fusion in 2 NETs. The first case involved a 7-year-old girl and the second case occurred in a 53-year-old man; both presented with headaches and vomiting. The pediatric case initially showed an intermediate grade of the tumor, but upon recurrences, it transformed into a high-grade tumor with 2 relapses in 8.3 years. This case exhibited high mitotic activity (20/10 high-power fields), and a high Ki-67 index (21%). The TERT promoter (TERTp) mutation was present in both initial and recurrent tumors. In contrast, the adult case was a low-grade tumor with no mitotic activity or recurrence over 13.5 months after subtotal resection and gamma knife surgery. Interestingly, the pediatric case demonstrated a longer survival time compared to conventional glioblastoma. The TERTp mutation, similar to being a molecular signature in adult-type glioblastoma, could also be an indicator of high-grade behavior in PATZ1 fusion NET., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Achondroplasia is an autosomal dominant disorder mainly affecting bony growth, typically resulting in markedly short stature. From a neurosurgical viewpoint, patients sometimes develop spinal cord compression at the narrowed foramen magnum and hydrocephalus. This study aims to construct growth references for height, weight, and head circumference (HC) of young achondroplasia patients in Korea and to evaluate the predictability of the necessity and timing of neurosurgical procedures through growth patterns., Methods: Growth data were collected from achondroplasia patients who visited our institution between January 2002 and August 2022. First, we constructed percentile growth curves of height, weight, and HC for the patients under 3 years of age with the generalized additive model for location, scale, and shape (GAMLSS). Second, the growth patterns of the patients with hydrocephalus who underwent neurosurgical procedures such as foramen magnum decompression (FMD) and ventriculoperitoneal (VP) shunt were analyzed., Results: There were 125 achondroplasia patients, including 67 males and 58 females. Among 125 patients, 46 underwent FMD, and 5 underwent VP shunt. As short stature and macrocephaly were typical characteristics of achondroplasia, the height of achondroplasia was lower than that of the general population, and HC in achondroplasia showed accelerated growth postnatally. There were no significant changes in HC in hydrocephalus patients before they underwent neurosurgical procedures. The influence of hydrocephalus on the growth patterns of HC in achondroplasia seemed insignificant., Conclusion: Growth references for height, weight, and HC in young achondroplasia patients were constructed. It is the first report of growth patterns of achondroplasia in Korea. Unlike other pediatric patients, the diagnosis of hydrocephalus and the necessity of neurosurgical procedures are hard to be predicted with HC in achondroplasia. Neuroimaging should be considered for achondroplasia patients with neurological symptoms., (© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).)

Background and Objectives: Moyamoya disease (MMD) is a steno-occlusive disease treated with revascularization surgery. Craniotomy and multiple burr hole encephalogaleoperiosteal-synangiosis (EGPS) are used for revascularization of the anterior cerebral artery territory. The aim of this study was to compare the clinical outcome between the 2 surgical methods in pediatric patients with MMD., Methods: A retrospective review of patients with MMD who underwent bifrontal indirect bypass surgery was performed. Clinical features, perioperative data, and angiographic, perfusion, and functional outcomes were compared between the 2 groups. Propensity score matching was performed to compare the perioperative characteristics and clinical outcomes., Results: A total of 346 patients were included in this study, 111 patients underwent bifrontal craniotomy EGPS, and 235 patients had bifrontal multiple burr hole EGPS. An insignificant higher rate of postoperative infarction (11.7% vs 5.5%, P = .072) and more postoperative hemorrhage occurred in the craniotomy EGPS group (3.6% vs 0%, P = .004). Of the 83 patients selected with propensity score matching for each group, the duration of operation was shorter ( P < .001) and the amount of intraoperative bleeding was significantly less in the multiple burr hole EGPS group ( P = .008). There was no difference in clinical outcomes between the 2 groups., Conclusion: Bifrontal multiple burr hole EGPS has benefits over craniotomy with shorter surgical time, less intraoperative bleeding, fewer postoperative complications, and comparable perfusion and functional outcomes. Multiple burr hole EGPS is a safe and effective method that might be considered for revascularization of the anterior cerebral artery territory in pediatric patients with MMD., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: The prognosis of moyamoya disease (MMD) in young children (younger than 4 years) is worse than that of older adults. The effectiveness of surgery is still inconclusive., Objective: To evaluate long-term outcomes after indirect bypass in young children with MMD., Methods: A total of 1417 MMD children underwent indirect bypass from August 1988 to October 2020. This study included 135 patients who were younger than 4 years at the time of surgery. The clinical features and surgical outcomes of these patients were assessed. We analyzed the long-term outcome of 102 children who were followed up for more than 5 years (mean: 18.8 years, range: 5-27.3 years). Cross-sectional analysis was performed to evaluate overall outcomes based on the Lansky Play Performance Scale (LPS). The annual risk of symptomatic stroke after surgery was calculated with a person-year method, and the event-free survival rate was evaluated using the Kaplan-Meier method., Results: The overall clinical outcome was favorable (LPS ≥ 80) in 88% of the patients. The overall postoperative adverse event rate was 15%, including 1 death. At the last follow-up, 86% of patients who had seizures at diagnosis were seizure-free. During the follow-up, there were 3 symptomatic infarctions on the operated hemisphere (postoperative 3, 3, and 10 months each). There was no hemorrhagic event. The annual infarction rate was 0.16% per person-year. The 20-year event-free survival rates for symptomatic infarction were 97%., Conclusion: Indirect bypass could provide a satisfactory long-term outcome and prevent recurrent stroke in young children with MMD., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: This study aims to elucidate clinical features, therapeutic strategies, and prognosis of pineal parenchymal tumors (PPT) by analyzing a 30-year dataset of a single institution., Methods: We reviewed data from 43 patients diagnosed with PPT at Seoul National University Hospital between 1990 and 2020. We performed survival analyses and assessed prognostic factors., Results: The cohort included 10 patients with pineocytoma (PC), 13 with pineal parenchymal tumor of intermediate differentiation (PPTID), and 20 with pineoblastoma (PB). Most patients presented with hydrocephalus at diagnosis. Most patients underwent an endoscopic third ventriculostomy and biopsy, with some undergoing additional resection after diagnosis confirmation. Radiotherapy was administered with a high prevalence of gamma knife radiosurgery for PC and PPTID, and craniospinal irradiation for PB. Chemotherapy was essential in the treatment of grade 3 PPTID and PB. The 5-year progression-free survival rates for PC, grade 2 PPTID, grade 3 PPTID, and PB were 100%, 83.3%, 0%, and 40%, respectively, and the 5-year overall survival rates were 100%, 100%, 40%, and 55%, respectively. High-grade tumor histology was associated with lower survival rates. Significant prognostic factors varied among tumor types, with World Health Organization (WHO) grade and leptomeningeal seeding (LMS) for PPTID, and the extent of resection and LMS for PB. Three patients experienced malignant transformations., Conclusion: This study underscores the prognostic significance of WHO grades in PPT. It is necessary to provide specific treatment according to tumor grade. Grade 3 PPTID showed a poor prognosis. Potential LMS and malignant transformations necessitate aggressive multimodal treatment and close-interval screening., Competing Interests: Seung-Ki Kim, Ji Hoon Phi, Chul-Kee Park, and Sung-Hye Park, contributing editors of Brain Tumor Research and Treatment, were not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Background: Craniofacial computed tomography (CT) is the diagnostic investigation of choice for craniosynostosis, but high radiation dose remains a concern., Objective: To evaluate the image quality and diagnostic performance of an ultra-low-dose craniofacial CT protocol with deep learning reconstruction for diagnosis of craniosynostosis., Materials and Methods: All children who underwent initial craniofacial CT for suspected craniosynostosis between September 2021 and September 2022 were included in the study. The ultra-low-dose craniofacial CT protocol using 70 kVp, model-based iterative reconstruction and deep learning reconstruction techniques was compared with a routine-dose craniofacial CT protocol. Quantitative analysis of the signal-to-noise ratio and noise was performed. The 3-dimensional (D) volume-rendered images were independently evaluated by two radiologists with regard to surface coarseness, step-off artifacts and overall image quality on a 5-point scale. Sutural patency was assessed for each of six sutures. Radiation dose was compared between the two protocols., Results: Among 29 patients (15 routine-dose CT and 14 ultra-low-dose CT), 23 patients had craniosynostosis. The 3-D volume-rendered images of ultra-low-dose CT without deep learning showed decreased image quality compared to routine-dose CT. The 3-D volume-rendered images of ultra-low-dose CT with deep learning reconstruction showed higher noise level, higher surface coarseness but decreased step-off artifacts, comparable signal-to-noise ratio and overall similar image quality compared to the routine-dose CT images. Diagnostic performance for detecting craniosynostosis at the suture level showed no significant difference between ultra-low-dose CT without deep learning reconstruction, ultra-low-dose CT with deep learning reconstruction and routine-dose CT. The estimated effective radiation dose for the ultra-low-dose CT was 0.05 mSv (range, 0.03-0.06 mSv), a 95% reduction in dose over the routine-dose CT at 1.15 mSv (range, 0.54-1.74 mSv). This radiation dose is comparable to 4-view skull radiography (0.05-0.1 mSv) and lower than previously reported effective dose for craniosynostosis protocols (0.08-3.36 mSv)., Conclusion: In this pilot study, an ultra-low-dose CT protocol using radiation doses at a level similar to skull radiographs showed preserved diagnostic performance for craniosynostosis, but decreased image quality compared to the routine-dose CT protocol. However, by combining the ultra-low-dose CT protocol with deep learning reconstruction, image quality was improved to a level comparable to the routine-dose CT protocol, without sacrificing diagnostic performance for craniosynostosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Rathke's cleft cyst (RCC) is the most commonly encountered pituitary incidentaloma in children. Because RCC is not frequently diagnosed in children, there are few reports on pediatric RCCs. The natural course of the disease and appropriate treatments are still obscure. The present study aimed to elucidate the natural history and surgical indications of RCCs in children., Methods: The authors retrospectively reviewed the clinical presentations, imaging features, ophthalmological evaluations, endocrine evaluations, and surgical outcomes of pediatric RCCs at a single institution from January 2000 to October 2022. Clinical outcomes between the surgery and observation groups were compared., Results: Among 93 patients, there were 41 patients in the surgery group and 52 patients in the observation group. The mean age at diagnosis was 10.9 years, and the mean follow-up period was 5.6 years. Headache fully or partially improved after surgery (86.2%), but the rate of improvement was not different from that of the observation group (70.0%). Ophthalmological abnormalities were effectively improved by surgical treatment (93.3%). Both the improvement and deterioration rates of endocrine abnormalities were significantly higher in the surgery group (p = 0.026 and p < 0.001, respectively), but the deterioration rate (43.9%) was higher than the improvement rate (14.6%). In the surgery group, the recurrence rate was 17.1% and the reoperation rate was 4.9%. Compared with total cyst wall resection, cyst fenestration with partial wall resection was associated with a higher recurrence rate (26.9%, p = 0.035) but a lower rate of endocrine abnormalities (30.8%, p = 0.049)., Conclusions: Pediatric RCCs of ≥ 10 mm in size were analyzed. Ophthalmological abnormalities are the major surgical indications for pediatric RCCs. Headache and partial endocrine abnormalities may be improved with surgery, but they are not absolute indications for surgery. Cyst fenestration with partial wall resection via an endoscopic endonasal approach is the most recommended surgical method. Follow-up is essential to monitor for the occurrence of visual field defects and the recurrence of cysts.

Introduction: The pineal region is a challenging area for neurosurgeons due to its innate anatomical features, such as its deep location, surrounding large draining veins, and adjacent critical neural structures., Discussion: There is a high proportion of malignant tumors in the pineal gland, especially in children, and they are frequently accompanied by obstructive hydrocephalus. These cases require that surgical procedures can make a pathological diagnosis to guide further treatment strategies and immediately resolve increased intracranial pressure. Simultaneous endoscopic third ventriculostomy and biopsy have been regarded as the first-line surgical intervention before establishing a definite treatment plan. However, it is not always successful because various factors affect the surgical procedures, such as the location and extent of the tumor, degree of ventriculomegaly, location and size of the massa intermedia, and size of the foramen of Monro., Conclusion: Here, we briefly reviewed the points to be considered in endoscopic biopsy of pineal tumors and introduced an alternative surgical procedure, the endoscopic endonasal trans-tuber cinereum approach, to surmount the anatomical hurdles., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Central neurocytoma (CN) is a low-grade neuronal tumor that mainly arises from the lateral ventricle (LV). This tumor remains poorly understood in the sense that no driver gene aberrations have been identified thus far. We investigated immunomarkers in fetal and adult brains and 45 supratentorial periventricular tumors to characterize the biomarkers, cell of origin, and tumorigenesis of CN. All CNs occurred in the LV. A minority involved the third ventricle, but none involved the fourth ventricle. As expected, next-generation sequencing performed using a brain-tumor-targeted gene panel in 7 CNs and whole exome sequencing in 5 CNs showed no driver mutations. Immunohistochemically, CNs were robustly positive for FGFR3 (100%), SSTR2 (92%), TTF-1 (Nkx2.1) (88%), GLUT-1 (84%), and L1CAM (76%), in addition to the well-known markers of CN, synaptophysin (100%) and NeuN (96%). TTF-1 was also positive in subependymal giant cell astrocytomas (100%, 5/5) and the pituicyte tumor family, including pituicytoma and spindle cell oncocytoma (100%, 5/5). Interestingly, 1 case of LV subependymoma (20%, 1/5) was positive for TTF-1, but all LV ependymomas were negative (0/5 positive). Because TTF-1-positive cells were detected in the medial ganglionic eminence around the foramen of Monro of the fetal brain and in the subventricular zone of the LV of the adult brain, CN may arise from subventricular TTF-1-positive cells undergoing neuronal differentiation. H3K27me3 loss was observed in all CNs and one case (20%) of LV subependymoma, suggesting that chromatin remodeling complexes or epigenetic alterations may be involved in the tumorigenesis of all CNs and some ST-subependymomas. Further studies are required to determine the exact tumorigenic mechanism of CN., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The goal of this study was to analyze the clinical outcomes of endoscopic third ventriculostomy (ETV) and endoscopic septostomy when shunt malfunction occurs in a patient who has previously undergone placement of a ventriculoperitoneal shunt., Methods: From 2001 to 2020 at Seoul National University Children's Hospital, patients who underwent ETV or endoscopic septostomy for shunt malfunction were retrospectively analyzed. Initial diagnosis (etiology of hydrocephalus), age at first shunt insertion, age at endoscopic procedure, magnetic resonance or computed tomography image, subsequent shunting data, and follow-up period were included., Results: Thirty-six patients were included in this retrospective study. Twenty-nine patients, 18 males and 11 females, with shunt malfunction underwent ETV. At the time of shunting, the age ranged from 1 day to 15.4 years (mean, 2.4 years). The mean age at the time of ETV was 13.1 years (range, 0.7 to 29.6 years). Nineteen patients remained shunt revision free. The 5-year shunt revisionfree survival rate was 69% (95% confidence interval [CI], 0.54-0.88). Seven patients, three males and four females, with shunt malfunction underwent endoscopic septostomy. At the time of shunting, the age ranged from 0.2 to 12 years (mean, 3.9 years). The mean age at the time of endoscopic septostomy was 11.9 years (range, 0.5 to 29.5 years). Four patients remained free of shunt revision or addition. The 5-year shunt revision-free survival rate was 57% (95% CI, 0.3-1.0). There were no complications associated with the endoscopic procedures., Conclusion: The results of our study demonstrate that ETV or endoscopic septostomy can be effective and safe in patients with shunt malfunction.

Background: Toxocariasis is a common parasitic infection worldwide. Although it can present as several clinical syndromes, neurological manifestation is rare. Only a few reports are available on spinal cord involvement of toxocariasis. We report a case that presented with gait disturbance due to progressive lower limb spasticity. The patient had had visceral toxocariasis infection 8 years before. A spine magnetic resonance image (MRI) showed syringomyelia along the entire thoracic cord with small nodular enhancing lesions in the mid-portion of the syrinx, which led to the suspicion of ependymoma. Surgical mass removal was performed. However, histopathological examination of the mass did not show any malignant cells; instead, there were numerous axonal retraction balls with an eosinophilic granular body-like appearance. The serum antibody titer against toxocariasis was borderline high. Taken together, these observations led to a diagnosis of Toxocara infection, and the patient was treated with albendazole., Conclusion: To the best of our knowledge, this is the first case report of tumor-like spinal toxocariasis involving extensive lesions. A solid enhancing mass with accompanied syrinx and hemorrhage might be a Toxocara infection. It can easily be diagnosed with serologic tests and simply be treated with oral albendazole if suspected., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Pilocytic astrocytoma is a slow-growing tumor that predominantly develops in children, but has a broad age spectrum. A notable characteristic of pilocytic astrocytoma is that the tumor arises in diverse locations and the clinical course is not always benign. Therefore, it is necessary to elucidate the clinical spectrum of the disease and analyze the relevant prognostic factors., Methods: Demographic and treatment-related factors were retrospectively reviewed in a cohort of 254 patients with histologically confirmed pilocytic astrocytoma. Clinical features were compared between the pediatric group (N = 208; age < 18 years) and the adult group (N = 46; age ≥ 18 years). Cox regression analysis was performed to identify relevant prognostic factors., Results: There was no difference in progression-free survival (PFS) between the pediatric and adult groups (p = 0.36); however, patients under 8 years of age exhibited worse PFS (p < 0.01). Leptomeningeal seeding at diagnosis and pilomyxoid histology was observed only in pediatric patients. In the pediatric group, nine patients experienced recurrence after complete resection. Increasing age (hazard ratio (HR) = 0.89, p < 0.01) and adjuvant therapy (HR = 0.32, p < 0.01) were protective factors against tumor progression. In the adult group, no progression occurred after complete resection. Age and adjuvant therapy were not significant factors in the adult group., Conclusion: Pilocytic astrocytoma presents with a diverse clinical spectrum. Complete resection is of utmost importance, and appropriate adjuvant treatment is recommended if complete resection cannot be achieved. Children with younger age are associated with more aggressive tumors, and recurrence may occur even after complete resection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The MYB/MYBL1::QKI fusion induces the protooncogene, MYB, and deletes the tumor suppressor gene, QKI. MYB/MYBL1::QKI rearrangement was previously reported only in angiocentric glioma (AG) and diffuse low-grade glioma. This report compares 2 tumors containing the MYB/MYBL1::QKI fusion: a diffuse pediatric-type high-grade glioma (DPedHGG) in an 11-year-old boy and an AG in a 46-year-old woman. We used immunohistochemistry, next-generation sequencing, and methylation profiling to characterize each tumor and compare our findings to the literature on AG and tumors with the MYB/MYBL1::QKI rearrangement. Both tumors were astrocytic with angiocentric patterns. The MYB::QKI fusion-positive DPedHGG, which recurred once, was accompanied by TP53 mutation and amplification of CDK6 and KRAS, suggesting malignant transformation secondary to additional genetic aberrations. The second case was the adult AG with MYBL1::QKI fusion, which mimicked ependymoma based on histopathology and its dot- and ring-like epithelial membrane antigen positivity. Combined with a literature review, our results suggest that MYB/MYBL1 alterations are not limited to low-grade gliomas, including AG. AG is most common in the cerebra of children and adolescents but exceptional cases occur in adults and the acquisition of additional genetic mutations may contribute to high-grade glioma. These cases further demonstrate that molecular characteristics, morphologic features, and clinical context are essential for diagnosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)

Patients with Crouzon syndrome have increased risks of cerebrospinal fluid rhinorrhea and meningoencephalocele after LeFort III osteotomy. We report a rare case of meningoencephalocele following LeFort III midface advancement in a patient with Crouzon syndrome. Over 10 years since it was incidentally found during transnasal endoscopic orbital decompression, the untreated meningoencephalocele eventually led to intermittent clear nasal discharge, frontal headache, and seizure. Computed tomography and magnetic resonance imaging demonstrated meningoencephalocele in the left frontal-ethmoid-maxillary sinus through a focal defect of the anterior cranial base. Through bifrontal craniotomy, the meningoencephalocele was removed and the anterior cranial base was reconstructed with a pericranial flap and split calvarial bone graft. Secondary frontal advancement was concurrently performed to relieve suspicious increased intracranial pressure, limit visual deterioration, and improve the forehead shape. Surgeons should be aware that patients with Crouzon syndrome have the potential for an unrecognized dural injury during LeFort III osteotomy due to anatomical differences such as inferior displacement and thinning of the anterior cranial base., Competing Interests: Conflict of Interest None declared., (The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Dysembryoplastic neuroepithelial tumor (DNET) is a low-grade brain tumor commonly associated with drug-resistant epilepsy. About half of DNETs are accompanied by tiny nodular lesions separated from the main mass. The existence of these satellite lesions (SLs) has shown a strong association with tumor recurrence, suggesting that they are true tumors. However, it is not known whether SLs represent multiple foci of progenitor tumor cell extension and migration or a multifocal development of the main DNET. This study was designed to elucidate the histopathology and pathogenesis of SLs in DNETs. Separate biopsies from the main masses and SLs with DNET were analyzed. We performed comparative lesion sequencing and phylogenetic analysis. FGFR1 K656E and K655I mutations or duplication of the tyrosine kinase domain was found in all 3 DNET patients and the main masses and their SLs shared the same FGFR1 alterations. The phylogenic analysis revealed that the SLs developed independently from their main masses. It is possible that the main mass and its SLs were separated at an early stage in oncogenesis with shared FGFR1 alterations, and then they further expanded in different places. SLs of DNET are true tumors sharing pathogenic mutations with the main masses. It is plausible that multifocal tumor development takes place in the dysplastic cortex containing cells with a pathogenic genetic alteration., (© 2023. The Author(s).)

Introduction: Patients with moyamoya disease (MMD) often have headaches after successful revascularization surgery. We aimed to characterize headache in surgically treated MMD patients and elucidate its clinical meaning and pathophysiology., Methods: Headache and related symptoms were surveyed using structured questionnaires in pediatric MMD patients with follow-up for 6 months or longer after indirect revascularization surgery. Clinical information including initial presentation, surgical method, and outcome was collected from medical records. Surgical outcomes were assessed clinically and by perfusion imaging. We defined "headache associated with MMD" as the headache accompanied by a transient ischemic attack or provoked by hyperventilation. Other headaches were further classified based on the diagnostic criteria of the International Headache Society-3. We analyzed the characteristics of "headache associated with MMD" and newly developed headache after surgery., Results: Among 90 participants, 65 (72.2%) had headaches within the last year before survey, including 28 (43.1%) with "headaches associated with MMD," 10 (15.3%) with probable migraines, 2 (3.1%) with infrequent episodic tension-type headaches, and 4 (6.2%) with probable tension-type headaches. Headache quality was pulsatile in 27 (41.5%) patients and pressing or tightening in 27 (41.5%) patients. Nausea or vomiting was accompanied in 30 (46.2%) patients. Headache upon awakening was reported in 37 (57.8%) patients. Headache disturbed daily life in 12 (18.5%) patients. Among the 32 (35.6%) patients who suffered headache during both the pre- and postoperative period, the headache quality was similar in 27 (84.4%) patients, and its severity decreased in 24 (75.0%) and did not change in 8 (25.0%) patients. Twelve (13.3%) patients experienced newly developed headaches after surgery. Among them, six (50.0%) were classified as having "headaches associated with MMD." They were predominantly electric shock-like or stabbing in 5 (45.6%) patients and nondisturbing in all patients. All 90 patients achieved improvement of ischemic symptoms after surgery., Conclusion: Headaches often persist or newly develop after revascularization surgery in MMD patients. Accompanying nausea or vomiting and occurrence upon awakening are characteristic features. Postoperative headache does not necessarily imply insufficient disease control., (© 2023 S. Karger AG, Basel.)

Purpose: Dysembryoplastic neuroepithelial tumors (DNETs) are slow-growing epilepsy-associated tumors. Low or normal 11C-methionine (MET) PET uptake helps to differentiate DNETs from other low-grade gliomas. However, diverse MET-PET uptake in DNETs has been observed. The aim of this study is to measure the clinical significance and prognostic value of MET-PET in DNET management., Patients and Methods: Retrospective review of 26 DNET patients was done. Clinical characteristics, radiologic findings, and visual and quantitative MET-PET results were analyzed. PET uptake was calculated as the tumor-to-homotopic mirror ratio (TNRm) and tumor-to-contralateral cortex ratio (TNRc). The clinical activity of the tumors at the time of PET was classified into active and quiescent groups. The surgical outcome was defined as a composite of 2 different aspects: tumor progression and/or clinical events such as seizure recurrence or tumor bleeding., Results: Twenty-seven MET-PET examinations (20 initial MET-PET and 7 MET-PET during follow-up) were included. Clinically active tumors at the time of PET presented significantly higher values of TNRm and TNRc than quiescent tumors. High MET-PET uptake by visual grading, TNRm ≥ 1.90, and TNRc ≥ 1.85 exhibited poor prognosis for event-free survival., Conclusions: MET-PET uptake correlates well with the clinical behavior of DNETs at the time of PET examination. Moreover, High MET-PET uptake is closely related to seizure recurrence if tumors are not entirely resected. Efforts to achieve gross total resection should be made for DNETs with high MET-PET uptake., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This study was jointly supported by a grant from the Seoul National University Hospital (no. 26-2019-0010; to J.H.P.) and Creative-Pioneering Researchers Program through Seoul National University (no. 800-20210571; to J.H.P.)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Molecular subgrouping of medulloblastoma has become important due to its impact on risk group stratification. Immunohistochemistry (IHC) has been widely used but it has innate limitations. The NanoString assay has been proposed as an alternative method. This study aims to present the characteristics of medulloblastoma subgrouped by the NanoString assay and to compare the subgrouping results with the IHC method., Methods: Pediatric patients with histological diagnosis of medulloblastoma who underwent surgery from 2007 to 2021 were included. Clinical characteristics, pathological findings were reviewed. Molecular subgrouping was performed by IHC and by NanoString nCounter Elements TagSets assay. Test for concordance between two methods was made., Results: Among a total of 101 patients analyzed, subgrouping using the NanoString assay resulted in 14 (13.8%) WNT, 20 (19.8%) SHH, 18 (17.8%) Group 3, and 39 (38.6%) Group 4 subgroup cases. Survival analysis revealed the following from best to worse prognosis: WNT, Group 4, SHH, and Group 3. In SHH subgroup the large cell/anaplastic histology was present in 30% of cases. Seventy-one cases were analyzed for concordance between NanoString and IHC. Cohen's kappa value indicated moderate agreement but identification of Groups 3 and 4 with IHC using NPR3 and KCNA1 markers exhibited poor results., Conclusions: The NanoString assay of Korean medulloblastoma patients revealed a more aggressive clinical course in the SHH subgroup which may be explained by a higher proportion of large cell/anaplastic histology being present in this subgroup. IHC did not distinguish Group 3 or 4 accurately. The NanoString assay may represent a good alternative method for practical use in the clinical field., (© 2022. The Author(s).)

Purpose: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs., Methods: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan)., Results: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or β-human chorionic gonadotropin (β-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated β-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum β-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS., Conclusion: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Optic pathway and hypothalamic gliomas (OPHGs) are challenging to surgically remove owing to their anatomical relationship. We previously reported on surgical treatment outcomes over a 10-year time frame. The purpose of this study was to update the OPHG clinical outcomes for cases in which chemotherapy has become the primary treatment option. The role of surgery was also revisited., Methods: Patients with a diagnosis of OPHG who underwent treatment at Seoul National University Children's Hospital from February 1999 to July 2019 were included. A multidisciplinary approach was used to determine the patients' treatment plans. Chemotherapy was the first-line treatment for all patients. When symptoms of hydrocephalus existed, debulking surgery was performed to reopen the flow of cerebrospinal fluid., Results: The study included 47 patients with OPHGs. The mean age was 6.9 years. Neurofibromatosis 1 was diagnosed in 3 patients. The extent of removal was none or biopsy in 13 (28%) cases, partial resection in 23 (49%) cases, and subtotal to gross total resection in 11 (23%) cases. In 32 (68%) patients, chemotherapy was first-line treatment. Ascites after ventriculoperitoneal shunt occurred in 3 cases, and 2 cases were successfully managed with debulking surgery. Treatment outcomes showed a 5-year overall survival rate of 97.7% and a 5-year progression-free survival rate of 47.7%., Conclusions: OPHG management using less invasive operations and chemotherapy as first-line treatment is feasible. Debulking surgery in patients with OPHGs may be considered in cases with cerebrospinal fluid pathway obstruction, progression despite chemotherapy or radiation, and refractory shunt-related ascites., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: One-fourth of cerebral cavernous malformation (CCM) patients are children, but studies on these patients are scarce. This study aimed to identify the clinical presentation of pediatric CCM patients and to investigate clinical outcomes according to the treatment modalities applied on the basis of our institution's treatment strategy., Methods: The authors performed a retrospective analysis of 124 pediatric CCM patients with a follow-up of more than 1 year from 2000 to 2019. They performed resection (n = 62) on lesions causing intractable seizure, rebleeding, or mass effect and observed the clinical courses of patients with lesions in deep or eloquent areas without persistent symptoms (n = 52). Radiosurgery (n = 10) was performed when the patient refused resection or strongly desired radiosurgery. The authors investigated the clinical characteristics, performance status (modified Rankin Scale [mRS] score), and rebleeding rate at the 1-year and last follow-up examinations and compared these among 3 groups classified on the basis of treatment applied. The authors evaluated seizure outcomes at the 1-year and last follow-up examinations for the surgery (n = 32) and observation (n = 17) groups. Finally, the authors drew cumulative incidence curves for the discontinuation of antiepileptic drugs (AEDs) for patients in the surgery (n = 30) and observation (n = 9) groups., Results: The 3 groups showed slight differences in initial symptoms, lesion locations, and rates of recent hemorrhage. The proportion of patients with improved mRS score at the 1-year follow-up was significantly greater in the surgery group than in the other groups (67% of the surgery group, 52% observation group, and 40% radiosurgery group; p = 0.078), as well as at the last follow-up (73% surgery group, 54% observation group, and 60% radiosurgery group; p = 0.097). The surgery group also had the lowest rebleeding rate during the follow-up period (2% surgery group, 11% observation group, and 20% radiosurgery group; p = 0.021). At the 1-year follow-up, the proportion of seizure-free patients without AEDs was significantly higher in the surgery group than the observation group (88% surgery group vs 53% observation group, p < 0.001), and similar results were obtained at the last follow-up (91% surgery group vs 56% observation group, p = 0.05). The 5-year AED-free rates for the surgery and observation groups were 94% and 50%, respectively, on the cumulative incidence curve (p = 0.049)., Conclusions: The clinical presentation of pediatric CCM patients was not significantly different from that of adult patients. Lesionectomy may be acceptable for pediatric CCM patients with indications of persistent seizures despite AED medications, rebleeding, and mass effects.

According to the new 2021 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) the classification of the primary intramedullary spinal cord tumors (IM-SCT) follows that of CNS tumors. However, since the genetics and methylation profile of ependymal tumors depend on the location of the tumor, the 'spinal (SP)' should be added for the ependymoma (EPN) and subependymoma (SubEPN). For an evidence-based review, the authors reviewed SCTs in the archives of the Seoul National University Hospital over the past decade. The frequent pathologies of primary IM-SCT were SP-EPN (45.1%), hemangioblastoma (20.0%), astrocytic tumors (17.4%, including pilocytic astrocytoma [4.6%] and diffuse midline glioma, H3 K27-altered [4.0%]), myxopapillary EPN (11.0%), and SP-subEPN (3.0%) in decreasing order. IDH-mutant astrocytomas, oligodendrogliomas, glioneuronal tumors, embryonal tumors, and germ cell tumors can occur but are extremely rare in the spinal cord. Genetic studies should support for the primary IM-SCT classification. In the 2021 WHO classifications, extramedullary SCT did not change significantly but contained several new genetically defined types of mesenchymal tumors. This article focused on primary IM-SCT for tumor frequency, age, sex difference, pathological features, and genetic abnormalities, based on a single-institute experience.

Background: The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues., Methods: Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups., Results: We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression., Conclusions: This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies., (© 2022. The Author(s).)

Background: This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes., Methods: A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken., Results: From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had β-human chorionic gonadotropin values <50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%)., Conclusions: Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dysembryoplastic neuroepithelial tumor (DNET) is a distinct type of low-grade glioneuronal tumor. Clinically, DNET is highly associated with intractable epilepsy in young children and adolescents. Therefore, the burden of the tumor comprises oncological concerns (recurrence), seizure control, and quality of life. The pathology of DNET is characterized by glioneuronal elements and floating neurons. Grossly, many DNETs harbor separate nodules on the medial side of the mass. Some of the satellite lesions are bone fide tumor nodules that grow during the follow-up. Therefore, removing all satellite lesions may be important to prevent tumor progression. Seizure control is highly dependent on the complete removal of tumors, and the presence of satellite lesions also exerts a negative impact on seizure outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Background: Advances in surgical techniques based on in-depth anatomical knowledge of the skull base have broadened the indications for endoscopic skull base surgery (ESS) with the advantage of wide and direct surgical exposure while minimizing invasiveness. However, the low incidence of the indicated diseases and narrow surgical corridors in children have limited the popularization of ESS. In addition, surgical complications and preventive interventions are not yet well known. Therefore, we retrospectively investigated the complications and prevention methods of ESS in children with a comprehensive review., Methods: We retrospectively analyzed the medical records of pediatric patients who underwent ESS for sellar and parasellar tumors at Seoul National University Children's Hospital from July 2010 to December 2020. Visual and endocrine status, extent of resection, complications, and recurrences were investigated depending on the pathology of the tumor. In addition, a comprehensive literature review regarding the complications of pediatric ESS was performed., Results: A total of 98 patients were enrolled. The median age of the patients was 12 years, and 52 patients were male. Preoperative visual disturbance was found in 53 patients, anterior pituitary function deficit in 69, and diabetes insipidus in 32. Gross total resection was attempted in 67 patients and achieved in 62 (93%). Biopsy and cyst fenestration were the goals of surgery in 26 patients, and all were achieved as planned. Regarding outcomes, visual disturbance worsened in two patients (2%), endocrine status was aggravated in 34 (35%) patients, and new-onset diabetes insipidus occurred in 27 (41%) patients. The overall surgical complication rate (other than aggravation of visual or endocrine status) was 17%. Postoperative meningitis (12%) was the most common complication, followed by cerebrospinal fluid leakage (2%), vasospasm, hemorrhage and infarction. By pathological diagnosis, craniopharyngioma had the highest complication rate of 29%. All but one patient with postoperative hemorrhage showed no permanent deficits., Conclusion: ESS in children is feasible and relatively safe. More attention and different postoperative management protocols are required in children to avoid complications, especially in craniopharyngiomas. However, the complications can be mostly managed conservatively without permanent neurologic deficits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Kim, Phi, Kim and Wang.)