Proteomic profiling of cerebrospinal fluid reveals TKT as a potential biomarker for medulloblastoma.

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.

Suprasellar teratoma to germinoma recurrence: implications for diagnosis and follow-up.

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.

Challenges in endoscopic third ventriculostomy for patients with achondroplasia: a focus on third ventricle floor anatomy.

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), ß (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 ß (p < 0.001) angles, while there were no significant differences between the control groups (p = 0.947 for α, p = 0.836 for ß). 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 ß 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.

Longitudinal analysis of cranial growth using comprehensive craniometric measurements after fronto-orbital advancement in coronal craniosynostosis.

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.

Identifying Risk Factors for Wound Complications Following Fronto-Orbital Advancement in Patients With Craniosynostosis: 3-dimensional Craniometrics Analysis.

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.

NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors.

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.

Comparison of the Transcranial Approach and Transsphenoidal Approach Based on the Anatomical Location of Origin in Pediatric Craniopharyngiomas.

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.

Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma.

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.

Post-traumatic Transient Neurological Dysfunction: A Proposal for Pathophysiology.

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.

Neurocognitive outcomes and associated clinical factors 5 years after surgery in children with craniosynostosis.

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.

Clinical Features and Treatment of Pediatric Cerebral Cavernous Malformations.

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.

Measurement of the intersiphon distance for normal skull base development and estimation of the surgical window for the endoscopic transtuberculum approach in children.

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.

The Role of Early and Delayed Surgery for Infants with Congenital Brain Tumors.

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.

Surgical treatment of interhemispheric arachnoid cysts.

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.

Interaction of interictal epileptiform activity with sleep spindles is associated with cognitive deficits and adverse surgical outcome in pediatric focal epilepsy.

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.

Survival and Malignant Transformation of Pineal Parenchymal Tumors: A 30-Year Retrospective Analysis in a Single-Institution.

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.

Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains.

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.

The Outcomes of Endoscopic Suturectomy in Syndromic Craniosynostosis.

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.

Neuroepithelial tumor with EWSR1::PATZ1 fusion: A literature review.

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.

Choroid Plexus Hyperplasia : Report of Two Cases with Unique Radiologic Findings.

Choroid plexus hyperplasia (CPH), also known as diffuse villous hyperplasia of choroid plexus, is a rare condition characterized by excessive production of cerebrospinal fluid (CSF), resulting in hydrocephalus. Diagnosing CPH can be challenging due to the absence of clear imaging criteria for choroid plexus hypertrophy and the inability to assess CSF production non-invasively. As a result, many CPH patients are initially treated with a ventriculoperitoneal (VP) shunt, but subsequently require additional surgical intervention due to intractable ascites. In our study, we encountered two CPH patients who presented with significantly enlarged subarachnoid spaces, reduced parenchymal volume, and prominent choroid plexus. Initially, we treated these patients with a VP shunt, but eventually opted for endoscopic choroid plexus cauterization (CPC) to address the intractable ascites. Following the treatment with endoscopic CPC, we observed a gradual reduction in subarachnoid spaces and an increase in parenchymal volume. In cases where bilateral prominent choroid plexus, markedly enlarged subarachnoid spaces, and cortical atrophy are present, CPH should be suspected. In these cases, considering initial treatment with combined endoscopic CPC and shunt may help minimize the need for multiple surgical interventions.