Supratentorial Research Articles

Morphometric Analysis of Neocortical and Infratentorial Structures: Genetic and Environmental Insights from a Twin Neuroanatomical Study

Background and Objective: Brain morphometry is shaped by a complex interplay of genetic and environmental factors, including physiological and neuropsychiatric conditions. These influences can vary across distinct brain regions, yet the precise contributions of genetics and environment to regional variation in healthy brains remain poorly understood. This study examines the heritability of specific brain structures to provide deeper insights into their development. Materials and Methods: We studied 118 healthy adult twins from the Hungarian Twin Registry using T1-weighted magnetic resonance imaging (T1W MRI) and the volBrain pipeline for structural measurements. Results: In all regions, monozygotic (MZ) twins showed a higher resemblance than dizygotic (DZ) twins in total brainstem and cerebellar volumes, with significant heritability (A: 90.5–92.6%) and minimal unique environmental effects (E: <1%). For supratentorial regions, regarding the total gray matter volume, all regions exhibited high heritability (A: 74.5–92.4%) and minimal environmental influence (E: <1.5%). In average cortical thickness analysis, the frontal lobe, temporal lobe, and pre-central gyrus were influenced by shared and unique environmental factors (C: 63–66.5%; E: 33.4–37%), whereas genetics were more prominent in the parietal lobe, occipital lobe, and post-central gyrus (A: 67.7–85%; E: 15–32.3%). Conclusions: Genetics strongly influence cortical gray matter volume in supratentorial regions (both total and regional), as well as the total brainstem volume and the total and cortical gray matter volumes of the cerebellum in infratentorial regions. This genetic influence extends to the average cortical thickness of the parietal lobe, post-central gyrus, and occipital lobe, while the frontal lobe, temporal lobe, and pre-central gyrus are more affected by environmental factors. These findings emphasize the importance of understanding region-specific genetic and environmental contributions to brain structure, which could guide personalized therapeutic and preventive strategies for neurological conditions.

Management of incisional cerebrospinal fluid leak in open cranial surgeries and the "folding technique" in duraplasty.

The aim of this study was to review a series of patients who underwent open cranial surgeries to evaluate the incidence of iatrogenic incisional CSF leaks and discuss its prevention and management. The authors also discuss the utility of the "folding technique" used in duraplasty as an alternative to conventional dural reconstruction techniques. All patients undergoing open cranial surgery were reviewed, and those with incisional CSF leak were included in this study. CSF leakage was managed using either conservative nonsurgical methods or surgical interventions. When the conservative nonsurgical methods failed to curb the leak, surgical procedures such as lumbar external drainage (LED) using lumbar subarachnoid drainage, external ventricular drainage (EVD), a lumboperitoneal or ventriculoperitoneal shunt (VPS), and reexploration of the surgical site were considered. Between 2019 and 2024, 2149 patients underwent open cranial surgeries at our hospital for any cranial pathology; 39 (1.8%) of these patients experienced postoperative incisional CSF leakage. The majority of the pathologies requiring surgeries were located in the supratentorial region (76.9%). Patients were classified according to the type of dural closure technique used. Primary stitching, the patient's fascia, or synthetic dura (resorbable, nonresorbable, or both) were used for dural reconstruction. The median interval between the surgery and the start of the leakage was 19 (IQR 1-79) days in patients with no history of radiotherapy; however, this duration was longer in patients who received radiotherapy (median 45 [IQR 10-540] days). The surgical interventions for CSF leakage were classified as wound resuturing (combined with other conservative approaches such as tightened dressing and elevating the head end of the bed), LED or EVD, or surgical reexploration. The folding technique in duraplasty is a simple way to achieve watertight duraplasty even with autograft or synthetic material. Incisional CSF leakage is a potentially preventable complication with high morbidity. Such cases could be managed via conservative approaches including wound resuturing, LED or EVD, and surgical reexploration. However, the management strategy is beyond any strict algorithm. This folding technique for duraplasty is a worthy replacement for conventional primary suturing for dural repair or reconstruction in cranial and even spinal defects. This study highlights the importance of regaining the watertight nature of the dura in the primary surgery to prevent any further intervention and lower the overall morbidity.

Long-term epidemiological trends in (primary) pediatric central nervous system tumors: a 25-year cohort analysis in Western Mexico.

Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited. This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024. Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.6%) with a mean age at diagnosis of 8.2years. Histological analysis revealed gliomas as the most common type (52.7%), followed by embryonal tumors (28.6%). High-grade tumors (WHO grade 4) comprised 49.8% of cases, demonstrating significantly poorer survival outcomes (median overall survival of 13.5months) compared to lower-grade tumors (up to 57months). The predominance of tumors in the supratentorial region and the notable differences in survival outcomes by tumor type underscore the varied impact of geographical and socioeconomic factors on pediatric oncology in Mexico. This study highlights the critical need for improved healthcare infrastructure and early diagnosis initiatives, as well as the importance of targeted research to address disparities in treatment and outcomes for pediatric CNST in this region.

Analysis of the Molecular Profile of Melanoma Brain Metastases using Immunohistochemistry

AbstractBrain metastases from melanoma represent an advanced and aggressive form of the disease. Understanding their molecular characteristics is crucial for improving diagnosis, prognosis, and treatment. The main objectives of this study were to identify and characterize molecular alterations present in brain metastases from melanoma and to clinically correlate them. The clinical-epidemiological information was anonymously and retrospectively obtained. Brain metastases from melanoma were collected through surgical biopsies, which were processed and analyzed using immunohistochemical markers. A total of 132 samples were initially selected, resulting in 8 samples of metastatic melanoma in the brain region included in this analysis. Regarding the frequency of immunohistochemical markers in brain samples of melanoma metastasis, 75% showed positive BRAF V600R, 62% contained positive SOX10, 37% positive HMB45, and 25% positive Melan-A. Regarding the location, 4 of them were in the frontal lobe, 3 in the parietal lobe, and 1 in the cerebellum. Among the samples, 87.5% originated from the supratentorial region of the brain, while 12.5% came from the infratentorial region. At the time, half of the patients were under 65 years old, with a significant proportion of 25% of individuals being below 40 years old. Moreover, 87.5% had two or more brain lesions at the time of diagnosis. Among the 12.5% that comprised the single lesion group at the time of analysis, the frontal lobe location stands out. The findings indicate heterogeneity among tumors and metastases in different anatomical locations. Further investigations are needed to validate these findings and elucidate their clinical applicability.

Sex differences in brain MRI using deep learning toward fairer healthcare outcomes.

This study leverages deep learning to analyze sex differences in brain MRI data, aiming to further advance fairness in medical imaging. We employed 3D T1-weighted Magnetic Resonance images from four diverse datasets: Calgary-Campinas-359, OASIS-3, Alzheimer's Disease Neuroimaging Initiative, and Cambridge Center for Aging and Neuroscience, ensuring a balanced representation of sexes and a broad demographic scope. Our methodology focused on minimal preprocessing to preserve the integrity of brain structures, utilizing a Convolutional Neural Network model for sex classification. The model achieved an accuracy of 87% on the test set without employing total intracranial volume (TIV) adjustment techniques. We observed that while the model exhibited biases at extreme brain sizes, it performed with less bias when the TIV distributions overlapped more. Saliency maps were used to identify brain regions significant in sex differentiation, revealing that certain supratentorial and infratentorial regions were important for predictions. Furthermore, our interdisciplinary team, comprising machine learning specialists and a radiologist, ensured diverse perspectives in validating the results. The detailed investigation of sex differences in brain MRI in this study, highlighted by the sex differences map, offers valuable insights into sex-specific aspects of medical imaging and could aid in developing sex-based bias mitigation strategies, contributing to the future development of fair AI algorithms. Awareness of the brain's differences between sexes enables more equitable AI predictions, promoting fairness in healthcare outcomes. Our code and saliency maps are available at https://github.com/mahsadibaji/sex-differences-brain-dl.

BIOM-51. MOLECULAR SUBTYPES, CLINICAL CHARACTERISTICS, AND THERAPEUTIC IMPLICATIONS FOR CNS TUMORS WITHBCOR/BCORL1 FUSION/INTERNAL TANDEM DUPLICATION

Abstract Central nervous system (CNS) tumors with either BCOR internal tandem duplication (BCOR ITD) or gene fusions involving BCOR/BCORL1 (BCOR FUS) are recognized as tumor types with characteristic molecular and clinical features but lacking clear therapeutic guidance. In an extensive international effort, we compiled a retrospective cohort of 229 (148 BCOR ITD, 81 BCOR FUS) unique cases via molecular profiling of CNS tumors. By analyzing DNA methylation patterns of 220 tumors we confirmed distinct epigenetic profiles of BCOR ITD versus BCOR FUS. The majority (91 percent) of BCOR FUS primary tumors was localized in the supratentorial region whereas BCOR ITD were localized across all anatomical CNS compartments. Median patient age at diagnosis was 20 years for BCOR FUS and 4 years for BCOR ITD. Metastatic disease was rare in BCOR FUS patients but more common in BCOR ITD tumors where 10 percent presented with metastatic disease and one third showed CNS or (rarely) extra-CNS metastasis in the course of disease. This was also reflected in clinical outcome as 5-year overall survival (OS) was 89 percent in BCOR FUS but 61 percent in BCOR ITD. In contrast, 5-year progression-free survival (PFS) was comparable reaching 27 percent in BCOR FUS and 30 percent in BCOR ITD. Integrating treatment details we found a trend towards benefit of gross-total resection on OS (BCOR FUS, n=18, p<0.08; BCOR ITD, n=67, p<0.12) but not for PFS (BCOR FUS, n=16, p<0.33; BCOR ITD, n=64, p<0.59). Radiotherapy was associated with improved PFS (BCOR FUS, n=18, p<0.01; BCOR ITD, n=70, p<0.001) and OS (BCOR FUS, n=20, p<0.01; BCOR ITD, n=73, p<0.001). Further in-depth analyses of clinical outcome parameters (primary metastatic disease, radiotherapy approach, chemotherapy type, patient age) are currently ongoing. In summary, we provide first robust annotation of CNS BCOR tumor types, clinical outcomes and therapy.

EPCO-30. TRANSCRIPTOMIC ANALYSIS IDENTIFIES REGIONAL BIOLOGY AND OUTCOME HETEROGENEITY IN MEDULLOBLASTOMA AND EPENDYMOMA SUBTYPES

Abstract Medulloblastoma, the most common malignant pediatric brain tumor, includes four distinct subtypes: Wnt, Sonic Hedgehog (Shh), Group 3, and Group 4. In contrast, ependymomas, which account for 10% of pediatric brain tumors and 4% of adult brain tumors, are categorized into three types: supratentorial (ST), posterior fossa (PF), and spinal (SP). While molecular subgrouping has significantly advanced the classification of these diseases, the extent of heterogeneity within these subgroups remains unknown. To address this, we collected bulk RNA sequencing (RNASeq) data from 888 medulloblastoma and 370 ependymoma from various institutions in North America and Europe. Our goal was to establish a comprehensive reference landscape for both medulloblastoma and ependymoma. We also included 42 forebrain and 52 hindbrain fetal samples to contrast against the tumor samples. Our analysis revealed that each disease subtype forms distinct clusters. Previously, subtyping was primarily achieved using methylation data; however, we demonstrate that bulk RNASeq data can also accurately identify disease subtypes. By examining gene expression patterns, gene fusions, and copy number aberrations, we validated existing molecular features and discovered new ones for each subtype. Additionally, we developed an innovative pipeline to identify specific biological patterns for a given region within the landscape. This resource coupled with mapping of new patients’ bulk RNASeq data onto the reference landscape, facilitating accurate disease subtype identification for new patients. This extensive dataset, available through the online tool Oncoscape, will assist the scientific community in uncovering novel therapeutic targets and advancing research in pediatric brain tumors.

The MRI Features of Intracranial Lesions in MOG-IgG Associated Disease

AimTo summarize and analyze the MRI characteristics of patients with Myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD), and to enhance the accuracy of disease diagnosis and advance scientific research. Materials and methodsA retrospective collection of clinical data from 103 patients with MOGAD was conducted. The distribution and signal characteristics of intracranial lesions on MRI were analyzed. Further subgroup statistical analysis based on age was performed to explore differences in lesion locations among different subgroups. Statistical comparisons were made using the χ2 test or Fisher's exact test, with a significance level of p<0.05 considered statistically significant. ResultsMRI revealed variable lesion morphologies in patients with MOGAD. Lesions were predominantly located in the cerebral deep white matter (47.6%), subcortical white matter (38.8%) and cortex (38.8%) of supratentorial region, as well as in the brainstem (35.9%) of infratentorial region. Notably, there was a significantly higher proportion of juvenile patients with thalamic involvement compared to adult patients (p=0.013). Juvenile patients were more likely to have lesions involving both the thalamus and cerebral cortex (p=0.040), thalamus and deep white matter (p=0.026), or thalamus and brainstem (p=0.014). Conversely, lesions involving both the corpus callosum and subcortical white matter were more frequently observed in adult patients, with statistically significant differences (p=0.046). Post-contrast MRI showed mild enhancement in some lesions, with a half of cases exhibiting leptomeningeal enhancement. One rare case presented extensive thickening and enhancement of the falx cerebri. ConclusionThe distribution of intracranial lesions on MRI exhibits distinct characteristics. The differences in the spatial distribution of intracranial lesions between juvenile and adult patients suggest that MOGAD may represent a heterogeneous disease spectrum that varies with age.

Astroblastoma: A molecularly defined entity, its clinico-radiological & pathological analysis of eight cases and review of literature

Astroblastoma, a unique entity of glial tumor, predominantly occur in young women with distinctive MN1 rearrangement, Given its limited documentation in existing literature, we report eight cases of astroblastoma, detailing their clinical, radiological, and histopathological characteristics along with molecular analysis. We conducted a retrospective analysis of our neuropathology archive database spanning the past 8 years. We included all cases that underwent Magnetic Resonance Imaging (MRI), surgical resection, histopathological examination, molecular testing, and follow-up. Histopathological examination involving immunohistochemistry and Fluorescence In Situ Hybridization (FISH) was carried out for all cases. All tumors were found to be located in the supratentorial region (cerebral hemisphere). The median age of the group was 35.1 years, with a female-to-male ratio of 1.6:1. The most common clinical presentation was headache. Morphologically, all tumors exhibited astroblastic features with pseudorosettes and perivascular hyalinization. Immunohistochemistry consistently revealed positivity for EMA and variable immunoreactivity for GFAP, OLIG2, and D2–40. Fluorescence In Situ Hybridization (FISH) analysis conducted for all cases showed MN1 rearrangement in 7 cases. The mean follow-up period was 45 months (ranging from 12 to 105 months). Radiotherapy was administered for high-grade and recurrent astroblastomas. All patients are currently alive and in good health.Astroblastomas are uncommon central nervous system (CNS) tumors with characteristics morphology and molecular signatures. They typically carry a favorable prognosis. High level suspicion is required for their diagnosis and molecular analysis is must to distinguish them from other morphological mimics.

8386 The Evolving Face of The Great Masquerader - Panhypopituitarism Associated with Neurosyphilis

Abstract Disclosure: M. Yabe: None. Z. Lin: None. F. Joseph: None. G. Philip: None. R. Silver: None. L. Callejas: None. J. Giunta: None. Untreated syphilis is on the rise in the United States. The CDC reported syphilis cases in newborns have increased 10-fold over a decade in November 2023, signifying the emergence of untreated infections. Pituitary involvement in syphilis is a very rare phenomenon, and endocrinological investigation is often overlooked. This will be the second reported case of neurosyphilis with pituitary involvement in a non-HIV infected patient. A 45-year-old female with no significant past medical history was admitted to the hospital with progressive neurological symptoms of intermittent left-side headache, hearing loss with tinnitus, and gait instability. Postcontrast MRI Brain revealed multifocal leptomeningeal enhancement involving supratentorial and infratentorial regions. Thickening of the enhanced pituitary infundibulum was also noted. Subsequent RPR titer showed 1:16 and lumbar puncture revealed CSF-VDRL titer 1:32, with pleocytosis 83 cells/uL, CSF-glucose 19 mg/dL, and CSF-protein 370 mg/dL. The patient completed Penicillin G 4 million/units intravenous every 4 hours for 14 days, with repeat MRI showing significant interval decrease in previously described extensive supratentorial and infratentorial leptomeningeal enhancement. However, there is no record of her sexual partner receiving treatment. The patient was readmitted one year later after a fall while displaying dysmetria. MRI Brain with contrast revealed a small subacute infarct along the right frontal corona radiata and pituitary gland measuring up to 1.2 cm in craniocaudal dimension compared to 0.4 cm on the prior exam. This prompted evaluation of pituitary hormones: FSH 0.8 IU/L, LH &amp;lt;0.3 IU/L, and ACTH 6.3 pg/mL, with normal serum growth hormone and prolactin levels. Further investigation revealed morning cortisol 2.5 ug/dL, thyrotropin &amp;lt; 0.2 uIU/mL, and free thyroxine 0.63 ng/dL. Radiological evidence is suspicious of inflammatory etiology of the pituitary gland. The patient was discharged with endocrinology follow-up and plan to perform a pituitary gland biopsy as an outpatient for confirmatory result. The association of neurosyphilis and hypophysitis leading to panhypopituitarism in a non-HIV infected patient was first reported in 2015. Since then, there remains limited research regarding their association due to rarity of pituitary involvement in neurosyphilis. With untreated syphilis on the rise and increased availability of MRI, clinicians should expect to encounter more cases of neurosyphilis with pituitary involvement in the future. Early detection of panhypopituitarism in those with positive CSF-VDRL titer could lead to better clinical outcomes. It is paramount that these cases are documented to emphasize pituitary involvement in neurosyphilis and encourage a low threshold to initiate endocrinological testing in the future. Presentation: 6/3/2024

Demographic Profile and Neuro-Ophthalmic Manifestations in Primary Intracranial Tumours in Adult Patients: An Observational Study from a Tertiary Care Health Centre in Eastern India

Abstract Purpose: To evaluate the demographic profile and neuro-ophthalmic manifestations of primary brain tumours in adult patients presenting to a tertiary care centre in eastern India. Methods: A hospital-based cross-sectional study was conducted on patients with primary intracranial tumours presenting to a tertiary care multi-specialty hospital in eastern India from January 2018 to October 2021. A complete neurosurgical, endocrinal, and ophthalmological evaluation was done in each patient. Results: A total of 106 patients with primary brain tumours were included in the study. The mean age of presentation was 40.98 ± 12.85 years. There were 50 (47.17%) males and 56 (52.83%) females. The tumour location was supratentorial (ST) in 72 (67.92%) patients and infratentorial (IT) in 34 (32.08%) patients. Pituitary adenoma was the most common tumour in the present study (32.07%). The most common tumour was pituitary adenoma in the ST location and cerebellopontine angle schwannoma in the IT location. Headache and hearing loss were the most common presenting symptoms in ST and IT tumours, respectively. Blurring of vision was the most common ocular symptom in 47.16% of cases. Hemianopic field defect was the most common field defect in our study and was seen in 47.72% of cases. Conclusion: Meticulous ophthalmological examination is essential in patients with intracranial tumours. Our study emphasises the importance of a detailed ophthalmological examination and knowledge of associated neurological manifestations in ST and IT tumours.

Occult Amyloid-β-Related Angiitis: Neuroimaging Findings at 1.5T, 3T, and 7T MRI.

Cerebral amyloid angiopathy (CAA) is a progressive neurodegenerative small vessel disease that is associated with intracranial hemorrhage and cognitive impairment in the elderly. The clinical and radiographic presentations have many overlapping features with vascular cognitive impairment, hemorrhagic stroke, and Alzheimer disease (AD). Amyloid-β-related angiitis (ABRA) is a form of primary CNS vasculitis linked to CAA, with the development of spontaneous autoimmune inflammation against amyloid in the vessel wall with resultant vasculitis. The diagnosis of ABRA and CAA is important. ABRA is often fatal if untreated and requires prompt immunosuppression. Important medical therapies such as anticoagulation and antiamyloid agents for AD are contraindicated in CAA. Here, we present a biopsy-proved case of ABRA with underlying occult CAA. Initial 1.5T and 3T MR imaging did not suggest CAA per the Boston Criteria 2.0. ABRA was not included in the differential diagnosis due to the lack of any CAA-related findings on conventional MR imaging. However, a follow-up 7T MR imaging revealed extensive cortical/subcortical cerebral microbleeds, cortical superficial siderosis, and intragyral hemorrhage in extensive detail throughout the supratentorial brain regions, which radiologically supported the diagnosis of ABRA in the setting of CAA. This case suggests an increased utility of high-field MR imaging to detect occult hemorrhagic neuroimaging findings with the potential to both diagnose more patients with CAA and diagnose them earlier.

Clinical characteristics and detection of MYB-QKI fusions in patients with angiocentric glioma

PurposeAngiocentric glioma (AG), a benign tumor identified within the last two decades, was officially included in the 2007 WHO Classification of Tumors of the Central Nervous System, WHO grade I. The tumor is relatively rare, with only approximately 100 cases reported. We aim to complement the characteristics and long-term prognosis of AG, as well as to detect MYB-QKI fusions.MethodsThe characteristics of all cases collected between 1 March 2009 and 1 March 2023 at the Beijing Sanbo Brain Hospital, Capital Medical University, were summarized and analyzed. Additionally, all fourteen patients were tested for MYB-QKI fusions.ResultsAG more predominantly occurs in adolescents (median age 16.5-year-old), and commonly presents with drug-resistant epilepsy. AG is frequently localized in the supratentorial regions and only one patient is in the brainstem. Brain parenchyma atrophy, and stalk-like signs can observe in imaging. Pathologically, tumor cells are perivascular pseudorosettes, presenting immunoreactivity for GFAP, S-100, Vimentin, “dot-like” staining for EMA, and low proliferative activity. Focal cortex dysplasia was observed in four patients. Twelve of fourteen (85.7%) patients were found with MYB-QKI fusions. Completely surgical resection typically has a satisfactory prognosis with long-term follow-up.ConclusionAG is a rare benign tumor with a favorable prognosis after complete resection, characterized by refractory epilepsy, frequently occurring in adolescents. MYB-QKI fusions were detected in most AG patients, as a good defining genetic alteration pathologically. The potential presence of focal cortical dysplasia (FCD) may affect the prognosis of epilepsy.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent adifferential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. We retrospectively analyzed the preoperative imaging of 45patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). Thirty-nine patients were classified as having an ependymoma, 35with aZFTA fusion and four with aYAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), acystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

Prevalence, recovery and phenotype of dysphagia in patients with ischaemic cerebellar stroke.

Swallowing is a complex task, moderated by a sophisticated bilateral network including multiple supratentorial regions, the brainstem and the cerebellum. To date, conflicting data exist about whether focal lesions to the cerebellum are associated with dysphagia. Therefore, the aim of the study was to evaluate dysphagia prevalence, recovery and dysphagia pattern in patients with ischaemic cerebellar stroke. A retrospective analysis of patients consecutively admitted to an academic stroke centre with ischaemic stroke found only in the cerebellum was performed. The presence of dysphagia was the primary end-point and was assessed by a speech-language pathologist, according to defined criteria. Dysphagia pattern was evaluated by analysing the videos of the flexible endoscopic evaluation of swallowing. Brain imaging was used to identify lesion size and location associated with dysphagia. Between January 2016 and December 2021, 102 patients (35.3% female) with a mean age of 52.8 ± 17.3 years were included. Thirteen (12.7%) patients presented with dysphagia. The most frequently observed flexible endoscopic evaluation of swallowing phenotype was premature spillage (n = 7; 58.3%), whilst significant residues or aspiration did not occur. One patient died (7.7%); the other patients showed improvement of dysphagia and one patient (7.7%) was discharged with dietary restrictions. Although the involvement of the cerebellum in deglutition has become increasingly evident, isolated lesions to the cerebellum are less likely to cause clinically relevant and persisting dysphagia compared to other brain regions. The observed dysphagia pattern shows a lack of coordination and control, resulting in premature spillage or fragmented bolus transfer in some patients.

EPEN-29. IS THE OUTCOME OF SUPRATENTORIAL EPENDYMOMA WITH ZFTA FUSION REALLY POOR?

Abstract BACKGROUND Survival of children with intracranial ependymoma is known to depend, in part, on the molecular group of the tumor. Previous studies have linked both PFA and ZFTA molecular group ependymomas to poor outcomes. As part of an unplanned analysis from ACNS0831, we explored outcomes for ZFTA supratentorial (ST) and PFA ependymomas. METHODS Patients were stratified by location, grade and extent of resection. Grade 2, ST tumors with no evidence of disease were observed only, N=37. All other patients were randomized to RT versus RT + maintenance chemotherapy or non-randomly assigned to RT + M if residual disease. A planned “as treated” analysis was performed by actual treatment received for randomized patients, excluding those who did not receive RT. Molecular groups were compared using two-sided log-rank tests stratified by study arms for all and randomized patients. Molecular characterization was achieved in 161/166 (97%) ST and 282/283(99.6%) PF. Among ST, 94% were classified ZFTA and 6% YAP1. Homozygous CDKN2A deletion was detected in 16 tumors, all ZFTA and WHO grade 3. Among posterior fossa ependymomas, 88% were classified as PFA and 12% as PFB. RESULTS There was no statistical difference in outcome according to treatment. Across all study arms, 5-year EFS was 69.6%+4.3 for ZFTA vs. 52.9%+3.4 for PFA (p=0.028). For the randomized cohort, 5-year EFS was 72.1+4.8 for ZFTA vs. 60.1+3.9 for PFA (p=0.076). For the randomized cohort with initial GTR/NTR, 5-year EFS was 74.1+5.1 for ZFTA patients vs. 61.0+4.2 for PFA patients (p=0.045). The 5-year EFS was 66.7+12.2 for ZFTA patients with CDKN2A deletion vs. 69.3+4.7 for ZFTA patients without CDKN2A deletion (p=0.232) CONCLUSION Children with ST ZFTA ependymomas have a significantly better outcome than those with PFA tumors. Homozygous deletion of CDKN2A was present in 12% of ST ependymomas but was not an indicator of poor outcome.

IMG-07. PEDIATRIC CRANIAL INCIDENTALOMAS: A SYSTEMATIC REVIEW UTILIZING MACHINE LEARNING

Abstract BACKGROUND The use of diagnostic neuroimaging in the care of pediatric patients continues to increase, leading to a rise in incidentally discovered lesions. The understanding of appropriate assessment and management of these findings is critical to providing comprehensive and timely care. This review aims to analyze the current literature to characterize diagnostic and prognostic characteristics of incidentally found brain tumors in pediatric patients. METHODS Using the guidelines under the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), Pubmed and Medline (NCBI) databases were searched using selected keyword combinations and machine learning-assisted software. Case reports, case series, and retrospective cohort studies published up to December 2023 were included. RESULTS A total of 20 studies encompassing 627 patients were included in the review. The most common indications for imaging were headache (204; 33%), seizures (96; 15%), and trauma (78; 12%). Of studies providing information regarding localization, lesions were found in the supratentorial region in 327 (52%) cases and infratentorial region in 190 (30%). Of studies reporting imaging characteristics, T1 hypointensity (183/302; 61%), T2 hyperintensity (410/497; 82%), and no contrast enhancement (58/97; 60%) were the most common findings. Four hundred and thirty (68%) patients were observed after diagnosis, 83 (13%) patients underwent surgical intervention at diagnosis, and 40 (6%) patients underwent surgery after observation. Of 91 patients with histopathology data available, pilocytic astrocytoma (19; 21%) was most commonly reported. CONCLUSION In this study, we provide a review of diagnostic characteristics of incidentally discovered brain tumors in the pediatric population. Management of such lesions has changed greatly over the past several decades, and risks of surgical intervention should be weighed against a more conservative management and interval monitoring approach. These results may help guide discussions regarding disclosure of findings and recommendations for additional clinical management.

ETMR-29. PRIMARY CNS SARCOMAS IN CHILDREN AND ADOLESCENTS: EXPERIENCE OF AN INSTITUTION

Abstract BACKGROUND Soft tissue sarcomas represent 6% of childhood cancers, less than 0.2% of CNS tumors are primary intracranial sarcomas. Their origin is pluripotential primitive mesenchymal cells. OBJECTIVE to evaluate clinical and genetic characteristics and report the experience of a rare CNS tumor. METHODS review of CNS tumors database at IOP/GRAACC/UNIFESP for the period 2008-2024, searching for all types of sarcomas that involved the CNS. RESULTS case series included 7 male, 2 female patients; average age at diagnosis 11.3 years. Supratentorial was the most common site of occurrence (66.6%), posterior fossa and intramedulary (2 and 1 cases, respectively) were found. One PF sarcoma presented as a second neoplasm after 2 years finished treatment for medulloblastoma, the other was diagnosed just after metilation. The presenting symptoms varied with tumor location, specially hemiparesis, seizure and headache. Gross total resection was achieved in 7 cases (77.7%), 1 after second look surgery. Histology and immunohistochemistry studies revealed: spinocellular sarcoma, fusocellular and myxoid sarcoma, gliosarcoma, meningeal sarcoma, Ewing sarcoma, condrosarcoma and synovial sarcoma. Work-up excluded other primary tumor origin outside CNS. Analyses for genetic characteristics were performed by Next Generation Sequencing in 6 patients (66.6%) and the following alterations were found: NRAS, TP53, JAK3, NF2, C11orf95-RELA fusion, PDGFRA. Some of these, by now, with no significant meaning for the disease. All patients underwent multimodal treatment. Chemotherapy involved mainly ICE Protocol (55.5%), but also Head Start Protocol and Ewing Sarcoma Protocol. Follow-up ranged from 13 months to 12 years, 90% of patients are alive, 2 (28.5%) dealing with endocrinal issues after focal radiotherapy. The mean overall survival was 61.4 months. CONCLUSION CNS primary sarcomas were mostly observed in the supratentorial region and in older children, with male predilection. Multimodal treatment seems to benefit patients’ outcomes. More patients and longer follow-up periods are needed to further elucidate the biological features of these tumors.

Characteristics of malignant brain tumor-associated epileptic spasms.

Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.

EPEN-17.IN VITRO MODELLING OF PEDIATRIC SUPRATENTORIAL EPENDYMOMAS USING CEREBRAL ORGANOIDS

Abstract BACKGROUND Ependymomas (EPN) are glial tumors of the central nervous system occurring in children and adults. ZFTA-fusion positive and YAP1-fusion positive EPN are the main supratentorial (ST) subgroups in children. While most ST-EPN-YAP1 patients survive, only 50% of ZFTA positive patients survive longer than 5 years. Improving survival of ST-EPN patients requires a better understanding of tumor biology. Human embryonal stem cell-derived (hESC) brain organoids provide a novel opportunity to model ST-EPN and study the impact of oncogenic fusions on tumor development within a healthy brain environment. METHODS hESC-derived cerebral organoids were genetically modified with YAP1 or ZFTA fusion genes and histologically and molecularly analyzed using antibody stainings, bulk and single cell RNA sequencing. RESULTS scRNA-seq analyses showed that our cerebral organoids mimic embryonal brain development and that radial glia, the presumed cell-of-origin of ST-EPN are abundant in 11-day old organoids. At this timepoint, electroporation of oncogenic ZFTA-RELA or YAP1-MAMLD1/YAP1-FAM118B fusions led to ectopic tumor outgrowth. Histological and molecular analyses showed that ZFTA and YAP1 EPN tumor organoids displayed different phenotypes and fusion-specific gene signatures, closely resembling human ZFTA and YAP1 EPN patient samples. ScRNA-seq data of organoid tumors showed a skewed differentiation compared to normal development with ZFTA tumors being more neuronal and YAP1 tumors having a more extracellular matrix-like phenotype. Analysis of the healthy compartment showed that YAP1 tumors influence the differentiation of the healthy cells and in both subtypes a new cell cluster was identified with high expression of tumor associated markers. Intercellular interactions revealed potential targetable tumor(specific) interactions such as YBX1-NOTCH1 in ZFTA or GNAI2-CAV1 in YAP1 tumor organoid models, as well as CD99-CD81 in both. CONCLUSIONS These models contribute to a better molecular and biological understanding of ependymomas and can be used to identify targeted therapies, especially those targeting the tumor microenvironment.