Background: Chordoma is a rare primary tumor originating from embryonic notochord remnants, with limited systemic therapeutic options due to a poor understanding of its genomic landscape. This study aims to characterize the genetic alterations in chordoma using a large national patient-level genomic repository, the AACR Project GENIE, to identify potential therapeutic targets and improve disease modeling. Methods: A retrospective analysis of chordoma samples was conducted using the AACR Project GENIE database. Targeted sequencing data were analyzed for recurrent somatic mutations, tumor mutational burden, and chromosomal copy number variations, with significance set at p < 0.05. Results: Frequent mutations were observed in genes associated with SWI/SNF complex affecting chromatin remodeling (SETD2, PBRM1, ARID1A). Mutations were also common among the TERT promoter regions, and cell cycle regulation (CDKN2A). Significant co-occurrences were identified among PBRM1, BRCA2, and KMT2D mutations. CDKN2A/B deletions were enriched in metastatic tumors, and pediatric cases demonstrated distinct mutation profiles compared to adults. Conclusions: This study provides a genomic profile of chordoma, identifying key mutations and potential therapeutic targets. These findings highlight the roles of chromatin remodeling and cell cycle pathways in chordoma biology, offering insights for future precision medicine approaches and therapeutic interventions.

Purpose Herein lies a brief historical review of the practice of artificial cranial deformation (ACD) in Tiwanaku, Bolivia, a pre-Columbian archeological ruin once regarded as one of the most powerful pre-Inca regions whose influence extended into present-day Peru and Chile from 600 to 1000 AD. We describe the history, purpose, and implications of ACD from both a neuroanatomical and cultural perspective. Methods A literature review was conducted through PubMed on the history of artificial cranial deformation in South America, concentrating on the Tiwanaku region. The authors searched all available data with no specific time reference, using the mentioned keywords: ACD, neuroanatomical implications of ACD, cultural and social functions of ACD, Tiwanaku society, and Andean civilization. Results Early Andean civilization was hierarchical and stratified. In Tiwanaku, the practice of ACD served to delineate one’s social class, caste, lineage, and vocation. This was especially useful for warriors, who distinguished their fellow combatants from insurgents by differences in their cranial structure. ACD was usually conducted within the first few months of an infant’s life before morphogenetic features became permanent. Two popular cranial styles—tabular and annular—were achieved by applying various mechanical apparatus and resulted in several cranial shapes (conical, box-like, flattened, etc.). Neuroanatomically, each deformation technique and the duration for which mechanical stress was applied influenced the solidification of cranial bones and shaped the frontal, occipital, parietal, and temporal bones differently. Cognitive deficits and plagiocephalic defects were recorded in limitation and may have been overlooked as the era’s occupational demands were more labor-intensive than knowledge-driven. Conclusion In Tiwanaku, the custom of ACD was used to demonstrate group identity, with alterations of the cranial shape corresponding to a particular headdress. ACD was used to distinguish an individual’s social identity, separating different groups of society into castes, classes, and slaves (Brain, 1979). The custom has also been used to mark territory and emphasize ethnic differences among groups, with potential cognitive implications that were largely unrecorded.

Purpose: To evaluate for predictive neuroimaging features of pediatric brain tumor development and quantify tumor growth characteristics in patients who had neuroimaging performed prior to a diagnosis of a brain tumor.Methods: Retrospective review of 1098 consecutive pediatric patients at a single institution with newly diagnosed brain tumors from January 2009 to October 2021 was performed to identify patients with neuroimaging prior to the diagnosis of a brain tumor. Pre-diagnostic and diagnostic neuroimaging features (e.g., tumor size, apparent diffusion coefficient (ADC) values), clinical presentations, and neuropathology were recorded in those patients who had neuroimaging performed prior to a brain tumor diagnosis. High- and low-grade tumor sizes were fit to linear and exponential growth regression models.Results: Fourteen of 1098 patients (1%) had neuroimaging prior to diagnosis of a brain tumor (8 females, mean age at definitive diagnosis 8.1 years, imaging interval 0.2-8.7 years). Tumor types included low-grade glioma (n = 4), embryonal tumors (n = 2), pineal tumors (n=2), ependymoma (n = 3), and others (n = 3). Pre-diagnostic imaging of corresponding tumor growth sites were abnormal in four cases (28%) and demonstrated higher ADC values in the region of high-grade tumor growth (p = 0.05). Growth regression analyses demonstrated R²-values of 0.92 and 0.91 using a linear model and 0.64 and 0.89 using an exponential model for high- and low-grade tumors, respectively; estimated minimum velocity of diameter expansion was 2.4 cm/year for high-grade and 0.4 cm/year for low-grade tumors. High-grade tumors demonstrated faster growth rate of diameter and solid tumor volume compared to low-grade tumors (p = 0.02, p = 0.03, respectively).Conclusions: This is the first study to test feasibility in utilizing pre-diagnostic neuroimaging to demonstrate that linear and exponential growth rate models can be used to estimate pediatric brain tumor growth velocity and should be validated in a larger multi-institutional cohort.

The opioid epidemic has become a significant public health crisis worldwide. With the rise in popularity of fentanyl, opioid overdoses continue to rise at unprecedented rates. Unfortunately, young children have become collateral damage in the face of the opioid epidemic. Accidental exposures and ingestions are the leading cause of opioid overdose in this age group and can result in significant acute complications, long-term sequelae and even death. We present the case of a toddler with accidental fentanyl ingestion who experienced seizures and required intubation for respiratory distress. He was found to have notable diffusion restriction cerebellar changes on MRI and ultimately discharged with normal neurological function. Our case adds to the growing literature of the clinical presentation and neuroimaging features associated with opioid toxicity in young children.

We present 4 children (diagnosed between 1 and 8 y, 3 females and 1 male) with molecularly distinct tectal gliomas (2 KRAS mutant, 1 EGFR mutant, 1 SRGAP3-RAF-1 fusion) that contributes to the growing literature of this uncommonly biopsied tumor. The patient with EGFR R222C mutation had a more severe course, earlier diagnosis, subsequent leptomeningeal metastatic disease, required more aggressive therapies, and died 9 years after diagnosis. Patients with KRAS mutations and SRGAP3-RAF-1 fusion had a more indolent course. Our series expands the molecular phenotype of tectal glioma with the potential for leptomeningeal dissemination. Future studies on establishing genotypic/phenotypic correlation from those who undergo biopsy are needed.