Search

Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation and differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process. In the internodular compartment, we identify proliferating cerebellar granular neuronal precursor-like malignant cells, along with stromal, vascular, and immune cells. In contrast, the nodular compartment comprises postmitotic, neuronally differentiated malignant cells. Both compartments are connected through an intermediate cell stage resembling actively migrating CGNPs. Notably, we also discover astrocytic-like malignant cells, found in proximity to migrating and differentiated cells at the transition zone between the two compartments. Our study sheds light on the spatial tissue organization and its link to the developmental trajectory, resulting in a more benign tumor phenotype. This integrative approach holds promise to explore intercompartmental interactions in other cancers with varying histology. The mechanisms regulating the balance between proliferation and differentiation in medulloblastomas with extensive nodularity (MBEN) remain poorly understood. Here, single cell multi-omics and spatial analysis characterises the spatial tissue organisation of MBEN in the context of the developmental trajectory. [ABSTRACT FROM AUTHOR]

Background Symptomatic cerebellar cyst formation after surgery is rare and the mechanism remains unknown. We describe a cerebellar cyst that gradually expanded, becoming symptomatic, after the removal of a foramen magnum meningioma and discuss the mechanism of cyst formation. Case Description A 76-year-old woman with a tumor at the foramen magnum was treated by posterior fossa craniotomy and C1 hemilaminectomy. The patient suddenly developed cerebellar symptoms and consciousness disturbance approximately 1 week into an otherwise good postoperative course. Imaging showed a subcutaneous pseudomeningocele in the occipital region and cerebellar cyst formation. After resolution by fenestration of the cerebellar cyst and duraplasty, the patient's symptoms gradually improved. No tumor or cerebellar cyst recurrence has been detected in over 5 years since the surgery. Conclusion Postoperative pseudomeningocele appeared crucial for cerebellar cyst formation. Postoperative development of symptomatic cerebellar cysts is rare but should be recognized as a serious, sometimes life-threatening, postoperative complication of posterior fossa surgery. [ABSTRACT FROM AUTHOR]

Background: Acute acquired comitant esotropia caused by prolonged near work, such as the use of digital devices, has been frequently reported in recent years. However, intracranial examination is necessary even for patients with nonparalytic comitant esotropia. Lhermitte–Duclos disease is a rare tumor that grows in layers in the cerebellum. Among those with this disease, cases of esotropia have been reported due to abduction limitation of the eye, but there have been no reports of comitant esotropia. Here, we report the case of a young woman with acute acquired comitant esotropia who was found to have Lhermitte–Duclos disease. Case presentation: A 16-year-old Japanese female patient, whose ethnicity was Asian, was referred to our hospital for acute acquired comitant esotropia. Fundus examination revealed papilledema in both eyes, and magnetic resonance imaging of the head revealed a cerebellar tumor in the right cerebellum with obstructive hydrocephalus. She underwent partial tumor resection, and a histopathological diagnosis of Lhermitte–Duclos disease was obtained. However, comitant esotropia status remained unchanged, and she underwent strabismus surgery. Finally, diplopia disappeared completely. Conclusion: Neurological and intracranial imaging examinations are essential when acute acquired comitant esotropia is observed. Acute acquired comitant esotropia by Lhermitte–Duclos disease did not improve with partial tumor resection and required strabismus surgery, but good surgical results were obtained. [ABSTRACT FROM AUTHOR]

Introduction: Outcomes for pineal region and superior cerebellar tumors in young children often hinge on extent of microsurgical resection, and thus choosing an approach that provides adequate visualization of pathology is essential. The occipital interhemispheric transtentorial (OITT) approach provides excellent exposure while minimizing cerebellar retraction. However, this approach has not been widely accepted as a viable option for very young children due to concerns for potential blood loss when incising the tentorium. The aim of this paper is to characterize our recent institutional experience with the occipital interhemispheric transtentorial approach (OITT) for tumor resection in infants and toddlers. Methods: A retrospective study was performed between 2016 and 2023 of pediatric patients less than 36 months of age who underwent OITT for tumor resection at a high-volume referral center. Patients with at least 3 months of postoperative follow-up and postoperative MRI were included. Primary outcomes included extent of resection, intraoperative and postoperative complications, and neurologic outcome. Secondary outcomes included length of stay and estimated blood loss. Results: Eight patients, five male, were included. The median age at the time of surgery was 10 months (range 5–36 months). Presenting symptoms included macrocephaly, nausea/vomiting, strabismus, gait instability, or milestone regression. Hydrocephalus was present preoperatively in all patients. Average tumor volume was 38.6 cm3, ranging from 1.3 to 71.9 cm3. All patients underwent an OITT approach for tumor resection with stereotactic guidance. No intraoperative complications occurred, and no permanent neurologic deficits developed postoperatively. Gross total resection was achieved in all cases per postoperative MRI report, and no instances of new cerebellar, brainstem, or occipital lobe ischemia were noted. Conclusions: OITT approach for tumor resection in very young children (≤ 36 months) is an effective strategy with an acceptable safety profile. In our series, no significant intraoperative or postoperative complications occurred. To our knowledge, this is the first report describing this technique specifically in patients less than 36 months of age. [ABSTRACT FROM AUTHOR]

Background: Texture analysis extracts many quantitative image features, offering a valuable, cost-effective, and non-invasive approach for individual medicine. Furthermore, multimodal machine learning could have a large impact for precision medicine, as texture biomarkers can underlie tissue microstructure. This study aims to investigate imaging-based biomarkers of radio-induced neurotoxicity in pediatric patients with metastatic medulloblastoma, using radiomic and dosiomic analysis. Methods: This single-center study retrospectively enrolled children diagnosed with metastatic medulloblastoma (MB) and treated with hyperfractionated craniospinal irradiation (CSI). Histological confirmation of medulloblastoma and baseline follow-up magnetic resonance imaging (MRI) were mandatory. Treatment involved helical tomotherapy (HT) delivering a dose of 39 Gray (Gy) to brain and spinal axis and a posterior fossa boost up to 60 Gy. Clinical outcomes, such as local and distant brain control and neurotoxicity, were recorded. Radiomic and dosiomic features were extracted from tumor regions on T1, T2, FLAIR (fluid-attenuated inversion recovery) MRI-maps, and radiotherapy dose distribution. Different machine learning feature selection and reduction approaches were performed for supervised and unsupervised clustering. Results: Forty-eight metastatic medulloblastoma patients (29 males and 19 females) with a mean age of 12 ± 6 years were enrolled. For each patient, 332 features were extracted. Greater level of abstraction of input data by combining selection of most performing features and dimensionality reduction returns the best performance. The resulting one-component radiomic signature yielded an accuracy of 0.73 with sensitivity, specificity, and precision of 0.83, 0.64, and 0.68, respectively. Conclusions: Machine learning radiomic-dosiomic approach effectively stratified pediatric medulloblastoma patients who experienced radio-induced neurotoxicity. Strategy needs further validation in external dataset for its potential clinical use in ab initio management paradigms of medulloblastoma. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to provide an exhaustive analysis of pediatric low-grade gliomas (pLGGs) in the cerebellar hemispheres, focusing on incidence, clinical characteristics, surgical outcomes, and prognosis. It seeks to enhance understanding and management of pLGGs in the pediatric population. Methods: We conducted an observational, descriptive, retrospective, and cross-sectional study at a pediatric hospital, reviewing medical records of 30 patients with cerebellar hemispheric pLGGs treated from December 2014 to January 2023. Data collection included demographics, clinical presentation, imaging findings, surgical approach, postoperative complications, histopathological diagnosis, hydrocephalus management, and follow-up. Molecular markers and adjuvant therapies were also analyzed. Results: The cohort predominantly presented with cerebellar symptoms, with 60% showing hydrocephalus at diagnosis. MRI with gadolinium was crucial for diagnosis. Surgical focus was on achieving gross total resection (GTR), accomplished in 70% of cases. Postsurgical hydrocephalus was less common, and cerebellar mutism was not reported. While a complete molecular analysis was not performed in all cases, available data suggest significant influence of molecular markers on prognosis and therapeutic options of pLGGs. Conclusions: This study highlights the unique clinical and molecular characteristics of cerebellar hemispheric pLGGs in children. The lower incidence of postoperative hydrocephalus and absence of cerebellar mutism are notable findings. Emphasizing a multidisciplinary approach, our findings contribute to a deeper understanding of pediatric pLGGs, underscoring the need for personalized treatment strategies and vigilant follow-up. [ABSTRACT FROM AUTHOR]

Background: Medulloblastoma is one of the common primary central nervous system (CNS) malignancies in pediatric patients. The main treatment is surgical resection preceded and/or followed by chemoradiotherapy. However, their serious side effects necessitate a better understanding of medulloblastoma biology to develop novel therapeutic options. Main body: Circular RNA (circRNA) and long non-coding RNA (lncRNA) regulate gene expression via microRNA (miRNA) pathways. Although growing evidence has highlighted the significance of circRNA and lncRNA-associated competing endogenous RNA (ceRNA) networks in cancers, no study has comprehensively investigated them in medulloblastoma. For this aim, the Web of Science, PubMed, Scopus, and Embase were systematically searched to obtain the relevant papers published before 16 September 2023, adhering to the PRISMA-ScR statement. HOTAIR, NEAT1, linc-NeD125, HHIP-AS1, CRNDE, and TP73-AS1 are the oncogenic lncRNAs, and Nkx2-2as is a tumor-suppressive lncRNA that develop lncRNA-associated ceRNA networks in medulloblastoma. CircSKA3 and circRNA_103128 are upregulated oncogenic circRNAs that develop circRNA-associated ceRNA networks in medulloblastoma. Conclusion: In summary, this study has provided an overview of the existing evidence on circRNA and lncRNA-associated ceRNA networks and their impact on miRNA and mRNA expression involved in various signaling pathways of medulloblastoma. Suppressing the oncogenic ceRNA networks and augmenting tumor-suppressive ceRNA networks can provide ample opportunities for medulloblastoma treatment. [ABSTRACT FROM AUTHOR]

Medulloblastomas are the most common malignant brain tumors in the pediatric population. Based on the idea that tumors with identical radio-genomic features should behave similarly, the 4 molecular subtypes are now widely accepted as a guide for the management and prognosis. The radiological features of medulloblastomas can predict the molecular subtype; thus, anticipating the subsequent disease progression. However, this has not been evaluated comprehensively. We aim to thoroughly study the association between the molecular subtypes and radiological features of medulloblastomas. Moreover, we aim to investigate the efficacy of this correlation with the use of progression-free survival and 5-year survival rates. A retrospective analysis was conducted for all histopathological confirmed medulloblastomas in pediatric patients (<16 years old) that were operated on in Kuwait over the past ten years (n = 44). The radiological, histological, and molecular characteristics were justifiably evaluated and analyzed in our sample. The overall progression-free survival after one year was noticed among 27 cases (≈44%) and the nonspecific 5-year survival was seen in 31 cases (≈70%) after a 5-year follow-up. Sonic Hedgehog and Wingless had the best outcomes, while group 3 showed the worst outcomes. Our findings did not support the association between most of the typical magnetic resonance imaging characteristics and survival rate. We further established that Sonic Hedgehog and Wingless biological types have a better prognosis. There was no association observed between the radiographic features, specifically the location, and the molecular subtype. [ABSTRACT FROM AUTHOR]

Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3–18) and two adult patients (ages 19–75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6–78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusions: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial. [ABSTRACT FROM AUTHOR]

Background: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. Methods: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. Results: Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. Conclusions: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials. [ABSTRACT FROM AUTHOR]

Objective Medulloblastoma is the most common central nervous system embryonal tumor and the most common malignant brain tumor of childhood. This study aims to find out the incidence of the ABO-Rh blood group in medulloblastoma patients of northern India to assess the utility of the blood group as a preclinical non-modifiable risk factor. Materials and Methods The study cohort consisted of 87 pediatric patients (age up to 18 years) who were diagnosed after histopathological examination with medulloblastoma at a university hospital in Lucknow between 2014 and 2019. Hundred random pediatric individuals from the same population who were admitted to the same hospital between 2014 and 2019 for non-tumor cases were selected as the control group. Data concerning characteristics including age, sex, ABO blood group, and Rh factor were collected from hospital records. The distribution of ABO-Rh blood groups in the study population was compared with the general population using the χ 2 test. Statistical analysis of the ABO-Rh blood groups in the study population was done using the IBM SPSS statistics version 24.0. Results Data analysis revealed that blood group A was significantly associated with medulloblastoma cases (odds ratio [OR] = 2.93; 95% confidence interval [CI]: 1.35–6.34). We find that the classical subtype was prevalent with the blood group A (43.8%), while the desmoplastic subtype was associated with the blood group O (38.5%). Conclusion Blood group A has a higher risk for the development of medulloblastoma while blood group O has the least risk. These findings suggest that blood group antigen should be considered as a non-modifiable preclinical risk factor for developing medulloblastoma. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) cerebelli is a common brain tumor of the childhood. MB commonly spreads through cerebrospinal fluid; however, there are several reported cases of extracranial spread. The most common sites of extracranial metastasis are bones and bone marrow followed by peritoneum, liver, and lungs. Here, we report a case of pulmonary metastatic lesions of adult cerebellar MB that were discovered 1 year after the primary surgical treatment. We also tried to highlight similar reported cases in the literature. [ABSTRACT FROM AUTHOR]

Introduction: The role of the cerebellum in emotion regulation involves the integration of cognitive, somatomotor and autonomic activity. It is functionally connected to limbic structures and regulates unconscious emotions through the modulation of autonomic reactions, the autonomic component of emotional learning, and the processing of facial expressions. Survivors of cerebellar pilocytic astrocytoma have a favorable prognosis and require periodic medical monitoring to detect possible suprasegmental autonomic dysfunction. Purpose: To study suprasegmental vegetative dysfunctions in patients operated on with cerebellar tumors in the distant postoperative period. Methods: 30 patients operated on between 2001 and 2022 with pilocytic cerebellar astrocytoma in the vermis, were examined by the following methods: clinical, neurophysiological - cutaneous vegetative evoked potentials (CVEP), neurocognitive and neuropsychological tests. The obtained data were statistically processed through the Quanto program. Results: The average age of the children at the time of the intervention was 14 years, 6 patients with hydrocephalus and clinically unstable neurologically underwent emergency surgery. The tumor volume, the presence of hydrocephalus and postoperative mutism correlate positively with the ICARS score, the results of the CVEP examination and the degree of expression of psychoemotional and cognitive disorders. Conclusions: When there is considerable neuronal loss, none of the existing therapies will completely eliminate the neurological deficit. The recognition and identification of suprasegmental autonomic dysfunctions that affect the quality of life of cerebellar tumor survivors by altering autonomic homeostasis will allow the development of neuromodulation-based treatment methods aimed at improving residual cerebellar function. [ABSTRACT FROM AUTHOR]

Introduction: Brain tumors are a major source of disease burden in pediatric population, with the most common tumor types being pilocytic astrocytoma, ependymoma and medulloblastoma. In every tumor entity, surgery is the cornerstone of treatment, but the importance of gross-total resection and the corresponding patient prognosis is highly variant. However, real-time identification of pediatric CNS malignancies based on the histology of the frozen sections alone is especially troublesome. We propose a novel method based on differential mobility spectrometry (DMS) analysis for rapid identification of pediatric brain tumors. Methods: We prospectively obtained tumor samples from 15 pediatric patients (5 pilocytic astrocytomas, 5 ependymomas and 5 medulloblastomas). The samples were cut into 36 smaller specimens that were analyzed with the DMS. Results: With linear discriminant analysis algorithm, a classification accuracy (CA) of 70% was reached. Additionally, a 75% CA was achieved in a pooled analysis of medulloblastoma vs. gliomas. Discussion: Our results show that the DMS is able to differentiate most common pediatric brain tumor samples, thus making it a promising additional instrument for real-time brain tumor diagnostics. [ABSTRACT FROM AUTHOR]

Objective: Management of emergency care Background: Neurogenic pulmonary edema (NPE) is a rare complication of neurological insults, such as traumatic brain injury and intracranial hemorrhage, in children. NPE frequently accompanies left ventricular (LV) dysfunction mediated via central catecholamine surge and inflammation. A high serum natriuretic (BNP) level was prolonged even after the LV contraction was improved in this case with severe myocardial injury. The overloading stress to the LV wall can last several days over the acute phase of NPE. Case Report: A 6-year-old boy developed NPE after the removal of a brain tumor in the cerebellar vermis, which was complicated by hydrocephalus. Simultaneously, he experienced LV dysfunction involving reduced global contraction with severe myocardial injury diagnosed by abnormally elevated cardiac troponin I level (1611.6 pg/ml) combined with a high serum BNP level (2106 pg/ml). He received mechanical ventilation for 4 days until the improvement of his pulmonary edema in the Intensive Care Unit (ICU). On the next day, after the withdrawal of mechanical ventilation, he was discharged from the ICU to the pediatric unit. Although the LV contraction was restored to an almost normal range in the early period, it took a total of 16 days for the serum BNP level to reach an approximate standard range (36.9 pg/ml). Conclusions: Even in a pediatric patient with NPE, we recommend careful monitoring of the variation of cardiac biomarkers such as BNP until confirmation of return to an approximate normal value because of the possible sustained overloading stress to the LV wall. [ABSTRACT FROM AUTHOR]

Posterior Fossa Syndrome (PFS) is a condition that can develop in children and adults following a cerebellar tumor resection surgery. The syndrome is characterized by multiple symptoms, including mutism, personality changes, and mobility problems. We present a case of a four-year-old boy diagnosed with posterior fossa tumor with secondary hydrocephalus who underwent an uneventful total resection of the tumor and developed posterior fossa syndrome, including mutism, was managed using lorazepam and made a full recovery of almost all of the symptoms he developed. Posterior fossa syndrome has multiple symptoms, most of which are usually transient. The exact pathophysiology and time to recovery are still not fully known. Patients with posterior fossa syndrome are managed with a multidisciplinary approach. Mutism resulting from this syndrome is proven to be successfully managed by lorazepam. [ABSTRACT FROM AUTHOR]

Background: Medulloblastomas (MBs) are one of the most common malignant brain tumor types in children. MB prognosis, despite improvement in recent years, still depends on clinical and biological risk factors. Metastasis is the leading cause of MB-related deaths, which highlights an unmet need for risk stratification and targeted therapy to improve clinical outcomes. Among the four molecular subgroups, sonic-hedgehog (SHH)-MB harbors clinical and genetic heterogeneity with a subset of high-risk cases. Recently, long non-coding (lnc)RNAs were implied to contribute to cancer malignant progression, but their role in MB remains unclear. This study aimed to identify pro-malignant lncRNAs that have prognostic and therapeutic significance in SHH-MB. Methods: The Daoy SHH-MB cell line was engineered for ectopic expression of MYCN, a genetic signature of SHH-MB. MYCN-associated lncRNA genes were identified using RNA-sequencing data and were validated in SHH-MB cell lines, MB tissue samples, and patient cohort datasets. SHH-MB cells with genetic manipulation of the candidate lncRNA were evaluated for metastatic phenotypes in vitro, including cell migration, invasion, sphere formation, and expressions of stemness markers. An orthotopic xenograft mouse model was used to evaluate metastasis occurrence and survival. Finally, bioinformatic screening and in vitro assays were performed to explore downstream mechanisms. Results: Elevated lncRNA LOXL1-AS1 expression was identified in MYCN-expressing Daoy cells and MYCN-amplified SHH-MB tumors, and was significantly associated with lower survival in SHH-MB patients. Functionally, LOXL1-AS1 promoted SHH-MB cell migration and cancer stemness in vitro. In mice, MYCN-expressing Daoy cells exhibited a high metastatic rate and adverse effects on survival, both of which were suppressed under LOLX1-AS1 perturbation. Integrative bioinformatic analyses revealed associations of LOXL1-AS1 with processes of cancer stemness, cell differentiation, and the epithelial-mesenchymal transition. LOXL1-AS1 positively regulated the expression of transforming growth factor (TGF)-β2. Knockdown of TGF-β2 in SHH-MB cells significantly abrogated their LOXL1-AS1-mediated prometastatic functions. Conclusions: This study proved the functional significance of LOXL1-AS1 in SHH-MB metastasis by its promotion of TGF-β2-mediated cancer stem-like phenotypes, providing both prognostic and therapeutic potentials for targeting SHH-MB metastasis. [ABSTRACT FROM AUTHOR]

Constitutional heterozygous pathogenic variants in genes coding for some components of the Fanconi anemia-BRCA signaling pathway, which repairs DNA interstrand crosslinks, represent risk factors for common cancers, including breast, ovarian, pancreatic and prostate cancer. A high cancer risk is also a main clinical feature in patients with Fanconi anemia (FA), a rare condition characterized by bone marrow failure, endocrine and physical abnormalities. The mainly recessive condition is caused by germline pathogenic variants in one of 21 FA-BRCA pathway genes. Among patients with FA, the highest cancer risks are observed in patients with biallelic pathogenic variants in BRCA2 or PALB2. These patients develop a range of embryonal tumors and leukemia during the first decade of life, however, little is known about specific clinical, genetic and pathologic features or toxicities. Here, we present genetic, clinical, pathological and treatment characteristics observed in an international cohort of eight patients with FA due to biallelic BRCA2 pathogenic variants and medulloblastoma (MB), an embryonal tumor of the cerebellum. Median age at MB diagnosis was 32.5 months (range 7–58 months). All patients with available data had sonic hedgehog-MB. Six patients received chemotherapy and one patient also received proton radiation treatment. No life-threatening toxicities were documented. Prognosis was poor and all patients died shortly after MB diagnosis (median survival time 4.5 months, range 0–21 months) due to MB or other neoplasms. In conclusion, MB in patients with biallelic BRCA2 pathogenic variants is a lethal disease. Future experimental treatments are necessary to help these patients. [ABSTRACT FROM AUTHOR]

Introduction: Medulloblastoma is the most common malignant brain tumor in children, often requiring intensive multimodal therapy, including chemotherapy with alkylating agents. However, therapy-related complications, such as therapyrelated myeloid neoplasms (t-MNs), can arise, particularly in patients with genetic predisposition syndromes. This case report presents three pediatric cases of medulloblastoma with subsequent development of t-MNs, highlighting the potential role of genetic predisposition and the importance of surveillance for hematological abnormalities in long-term survivors. Case presentation: We describe three cases of pediatric medulloblastoma who developed t-MNs after receiving chemotherapy, including alkylating agents. Two of the patients had underlying genetic predisposition syndromes (TP53 pathologic variants). The latency period between initial diagnosis of medulloblastoma and the development of secondary cancer varied among the cases, ranging from 17 to 65 months. The three cases eventually succumbed from secondary malignancy, therapy-related complications and progression of primary disease, respectively. Conclusions: This report highlights the potential association between genetic predisposition syndromes and the development of therapy-related myeloid neoplasms in pediatric medulloblastoma survivors. It underscores the importance of surveillance for hematological abnormalities among such patients. [ABSTRACT FROM AUTHOR]

Background: Brain tumors in children can involve different parts of the brain and cause high mortality. These tumors have different types, and they cause different conflicts and complications. So far, limited studies have been conducted in Iran on children's brain tumors. This study aimed to evaluate radiographic, neuropathological, and demographic findings in children aged 1 to 18 years with brain tumors. Materials and Methods: In this descriptive study, which was conducted for children aged 1 to 18 years with brain tumors admitted to the children's ward of Shohada Hospital (Iran-Tehran) in 2012-2018, 64 children were evaluated. Patient information was extracted from patients' files, including basic data radiological and clinical findings. A significance level was considered less than 0.05. Results: Twenty-six patients (40.6%) were girls, and 38 (59.4%) were boys. 96.9% of the children were term, and the mortality rate was 40.6%. 57.8% were diagnosed in less than one month from the onset of symptoms. 47.6% of patients had a positive family history, and none of them had a history of brain infection. The most common clinical complaint was N/V. The most common location of the tumor was the fourth ventricle (31.3%), and acute hydrocephalus was also seen in 19 patients (29.7%). The most common tumor was medulloblastoma (93.8%), and the most common stage was grade 4 (98.4%). Desmoplastic medulloblastoma was the most common form of medulloblastoma. 9.4% of patients were positive for tumor marker P53. None of the patients were positive for Beta-Catenin. Conclusion: The findings have shown that being a boy, involvement of the fourth ventricle and medulloblastoma are the most common characteristics of brain tumor involvement in Iranian children. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common malignant brain tumor in children. This entity in adulthood is rare. The aim of our study is to evaluate therapeutic results and prognostic factors of adult medulloblastoma treated at our institute with post-operative radiotherapy. We retrospectively reviewed a cohort of 55 patients with medulloblastoma who underwent radiation in the department of radiation oncology of institute Salah Azaiz (Tunis) over a 18-year period (1994–2012). The surgery was total or subtotal resection in 73% of cases. Forty-eight patients received radiotherapy to the entire craniospinal axis as part of the curative treatment. The median interval from surgery to the initiation of radiotherapy was 83 days. Etoposide-cisplatin chemotherapy was only performed in metastatic patients (n = 4). The 5-years and 10-years overall survival rates were respectively 53 and 34%. The dose of radiotherapy to the craniospinal axis was a prognostic factor. The 5-years and 10-years event-free-survival rates were 64 and 41%. Reduction in the dose of radiotherapy to the craniospinal axis and fourth ventricular floor involvement were correlated with a worse event-free survival. Our results, compared to those of the literature, conclude that the reduction in the dose of radiotherapy to the craniospinal axis (<34 Gy) in the standard risk group of adult medulloblastoma could not be done without chemotherapy. In the high-risk group of adult medulloblastoma, radiotherapy to the cerebrospinal axis at the dose of 36 Gy with chemotherapy, is required for disease control. [ABSTRACT FROM AUTHOR]

This study aimed to assess the prevalence of neurological symptoms and related imaging findings in patients with von Hippel-Lindau (VHL) at Rasool Akram Hospital from September 2018 to September 2021. This analytical observational study examined eligible patients over the period from September 2018 to September 2021. We collected demographic information (age, gender) along with imaging findings and results of neurological and eye examinations. Comparison between qualitative variables was also done using the Chi-square test or Fisher's exact test. Also, an independent t -test was used to compare quantitative variables between the two groups. SPSS version 22 software was used for statistical analysis of data. A significant level was considered less than or equal to 0.05. Of the 54 examined patients (48.1% were male and 51.9% were female) with an average age of 36.42 ± 13.37 years. A significant majority (87.0%) reported a positive family history of the disease. The most common type of disease was Type 1 observed in 94.4% of cases and Type 2A was the next most frequent (3.7%). The most common pattern of retinal pathological lesions seen in the examination was related to bilateral lesions (79.6%). The most common pathological finding was related to the presence of a mass in cerebellar magnetic resonance imaging (48.1%). Considering the findings of the present study, which highlight a significant frequency of bilateral retinal lesions as well as masses in the central nervous system and endocrine system, it is evident that patients require careful follow-up and various interventions after being diagnosed with the disease. This approach is essential to manage and potentially mitigate the complications associated with these conditions. [ABSTRACT FROM AUTHOR]

Posterior fossa tumors (PFT) are the most common pediatric brain tumors, and the study of the somatic and cognitive status of PFT survivors still remains a critical problem. Since cerebellar damage can affect eye movement centers located in the vermis and hemispheres, such patients suffer from disturbances in visual perception, visual-spatial functions, reading, etc. Our investigation aimed at describing oculomotor impairments in PFT survivors linked to core oculomotor functions assessed through eye tracking method: gaze holding, reflexive saccades, and organization of voluntary saccades and their dependency on age at tumor diagnosis. Also, we investigated the relationship between oculomotor functions and ataxia measured with International Cooperative Ataxia Rating Scale (ICARS). A total of 110 children (patients and age-matched healthy controls, aged 9–17 years old) participated in the study. We found that the earlier the child had a tumor, the more impaired gaze holding (p = 0.0031) and fewer isometric saccades (p = 0.035) were observed at the time of examination. The above-mentioned functions in healthy controls improved with age. Visual scanning was also impaired compared to controls but was not related to age at diagnosis. A positive correlation between ICARS scores and number of hypermetric saccades (r = 0.309, p = 0.039), but no correlation with the number of hypometric saccades (r = − 0.008, p = 0.956). Furthermore, number of hypometric saccades did not differ between patients and controls (p = 0.238). Thus, primarily hypermetric saccades can be considered a prominent oculomotor symptom of cerebellar tumors. Our study provides basis for new methods of PFT diagnosis and rehabilitation procedure evaluation, both playing essential roles in modern pediatric neurooncology. [ABSTRACT FROM AUTHOR]

Medulloblastoma, the most common malignant brain tumor in children, presents a complex treatment challenge due to its propensity for infiltrative growth within the posterior fossa and its potential attachment to critical anatomical structures. Central to the management of medulloblastoma is the surgical resection of the tumor, which is a key determinant of patient prognosis. However, the extent of surgical resection (EOR), ranging from gross total resection (GTR) to subtotal resection (STR) or even biopsy, has been the subject of extensive debate and investigation within the medical community. Today, the impact of neurosurgical EOR on the prognosis of medulloblastoma patients remains a complex and evolving area of investigation. The conflicting findings in the literature, the challenges posed by critical surrounding anatomical structures, the potential for surgical complications and neurologic morbidity, and the nuanced interactions with molecular subgroups all contribute to the complexity of this issue. As the field continues to advance, the imperative to strike a delicate balance between maximizing resection and preserving quality of life remains central to the management of medulloblastoma patients. [ABSTRACT FROM AUTHOR]

A picture naming test (PNT) has long been regarded as an integral part of neuropsychological assessment. In current research and clinical practice, it serves a variety of purposes. PNTs are used to assess the severity of speech impairment in aphasia, monitor possible cognitive decline in aging patients with or without age-related neurodegenerative disorders, track language development in children and map eloquent brain areas to be spared during surgery. In research settings, picture naming tests provide an insight into the process of lexical retrieval in monolingual and bilingual speakers. However, while numerous advances have occurred in linguistics and neuroscience since the classic, most widespread PNTs were developed, few of them have found their way into test design. Consequently, despite the popularity of PNTs in clinical and research practice, their relevance and objectivity remain questionable. The present study provides an overview of literature where relevant criticisms and concerns have been expressed over the recent decades. It aims to determine whether there is a significant gap between conventional test design and the current understanding of the mechanisms underlying lexical retrieval by focusing on the parameters that have been experimentally proven to influence picture naming. We discuss here the implications of these findings for improving and facilitating test design within the picture naming paradigm. Subsequently, we highlight the importance of designing specialized tests with a particular target group in mind, so that test variables could be selected for cerebellar tumor survivors. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common malignant pediatric brain tumor and has been linked to known cancer predisposition syndromes. We report a case of medulloblastoma of a 12-year-old Indo-Trinidadian female with a strong family history of colorectal carcinoma. In collaboration with the SickKids-Caribbean Initiative (SCI), her tumor was confirmed to be a WHO grade 4 medulloblastoma - Wnt subtype. Genetic testing further confirmed the presence of a pathogenic APC gene variant [c.3183_3187del (p.Gln1062*)] which led to a diagnosis of Turcot syndrome type 2. The index patient received multimodal therapy which included surgery, radiation and chemotherapy and is currently post end-oftreatment and in remission. This case report aims to highlight the complexity of diseases and the need for expertise in identifying them in low-and-middle income countries, the need for access to specialized testing and the benefits of collaborating between low-and-middle income and high-income countries when managing complex oncology patients. [ABSTRACT FROM AUTHOR]

Medulloblastoma, the most common childhood malignant brain tumor, has seen significant advancements in diagnosis and treatment over the past few decades. These include improvements in imaging, pathology, molecular biology, neurosurgical techniques, radiotherapy, and systemic therapies. The disease is now recognized as a heterogeneous condition with four broad molecular subgroups, each with distinct characteristics and outcomes. Risk stratification and treatment optimization have become important considerations, with the goal of balancing survival and quality of life for long-term survivors. Ongoing research is focused on refining diagnostic methods, exploring targeted therapies, and improving radiation therapy techniques. [Extracted from the article]

Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma. [ABSTRACT FROM AUTHOR]

Various types of brain tumors occur in both children and adults. These tumors manifest with different characteristics such as malignancy, cellular lineage, location of origin, and genomic profile. Recently, immunotherapy, which manipulates immune cells in the tumor microenvironment (TME) to kill tumor cells, has attracted attention as a treatment strategy for tumors. Here, we analyzed the transcriptomic architecture of the brain tumor microenvironment to provide potential guidelines to overcome the therapeutic vulnerabilities to brain tumors. We decomposed the cellular populations of six brain tumor types (meningioma, pilocytic astrocytoma, ependymoma, medulloblastoma, glioblastoma, and lower-grade glioma) using publicly available microarray data and single-cell RNA sequencing (scRNA-seq) data. Interestingly, transcriptome-based immune cell profiling revealed that infiltrating immune cell types in the brain TME, particularly M2 macrophages, CD8+ T cells, and CD4+ T cells, could be distinguished by tumor type, malignancy, and location. scRNA-seq revealed differences in the proportions of dendritic and mural cells. Unsupervised clustering using immune-related genes divided all samples into two distinct clusters with different characteristics. In addition, immune subpopulations showed disparate reactions after anti-PD-1 therapy for glioblastoma. Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 31-year-old woman who presented with symptoms of headache, dizziness, and phosphenes. Magnetic resonance imaging (MRI) revealed a well-circumscribed mass in the left cerebellar hemisphere. The tumor was diagnosed as a cerebellar liponeurocytoma, a rare and slow-growing tumor that occurs in the cerebellum. The article highlights the diagnostic challenges of distinguishing cerebellar liponeurocytoma from other tumors, such as medulloblastoma, and emphasizes the importance of thorough examination and analysis of histological and immunohistochemical features for accurate diagnosis. The study concludes that cerebellar liponeurocytoma has distinct genetic and epigenetic features that can aid in diagnosis, and that the identification of lipomatous foci is crucial for distinguishing this tumor from other similar tumors. [Extracted from the article]

Purpose: Medulloblastoma is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. Recent transcriptional studies have shown that medulloblastomas comprise at least four molecular subgroups, each with distinct demographics, genetics, and clinical outcomes. Medulloblastoma subtyping has become critical for subgroup-specific therapies. The use of gene expression assays to determine the molecular subgroup of clinical specimens is a long-awaited application of molecular biology for this pediatric cancer. Methods: In the current study, we established a medulloblastoma transcriptome database of 460 samples retrieved from three published datasets (GSE21140, GSE37382, and GSE37418). With this database, we identified a 23-gene signature that is significantly associated with the medulloblastoma subgroups and achieved a classification accuracy of 95.2%. Results: The 23-gene signature was further validated in a long-term cohort of 142 Chinese medulloblastoma patients. The 23-gene signature classified 21 patients as WNT (15%), 41 as SHH (29%), 16 as Group 3 (11%), and 64 as Group 4 (45%). For patients of WNT, SHH, Group 3, and Group 4, 5-year overall-survival rate reached 80%, 62%, 27%, and 47%, respectively (p < 0.0001), meanwhile 5-year progression-free survival reached 80%, 52%, 27%, and 45%, respectively (p < 0.0001). Besides, SHH/TP53-mutant tumors were associated with worse prognosis compared with SHH/TP53 wild-type tumors and other subgroups. We demonstrated that subgroup assignments by the 23-gene signature and Northcott's NanoString assay were highly comparable with a concordance rate of 96.4%. Conclusions: In conclusion, we present a novel gene signature that is capable of accurately and reliably assigning FFPE medulloblastoma samples to their molecular subgroup, which may serve as an auxiliary tool for medulloblastoma subtyping in the clinic. Future incorporation of this gene signature into prospective clinical trials is warranted to further evaluate its clinical. [ABSTRACT FROM AUTHOR]

The cerebellum is involved in motor and non-motor functions. Cerebellar lesions can underlie the disruption of various executive functions. The violation of executive functions in cerebellar lesions is a serious problem, since children, after completing treatment, must return to school, finish their education, and get a profession. One of the important executive functions is working memory, which contributes to academic success. Deficits of verbal working memory in cerebellar tumors have been studied, in contrast to visual-spatial working memory. To assess this issue, 101 patients who survived cerebellar tumors and 100 healthy control subjects performed a visual-spatial working memory test. As a result, in children who survived cerebellar tumors, visual-spatial working memory is impaired compared to the control group. Moreover, with age, and hence the time since the end of treatment, the number of elements that children can retain in visual-spatial working memory increases, but still remains smaller compared to the control group. Our findings complement the idea of cerebellar involvement in visual-spatial working memory and suggest that it is disrupted by cerebellar lesions in children. [ABSTRACT FROM AUTHOR]

Multinodular and vacuolar neuronal tumor (MVNT) is a rare and benign neuroepithelial tumor. Most reports describe tumors located in the cerebral hemisphere. A literature review found that 15 cases were located in the posterior cranial fossa, but all lacked pathological evidence. In this case, a patient sought medical attention due to insomnia and irritability. Neuroepithelial tumors were found in the imaging, and the patient underwent radiation therapy. Three years later, malignant tumors were found upon imaging examination. After surgical resection and pathological testing, MVNT occurring in the cerebellum was diagnosed. MVNT is rare in the cerebellum, and direct imaging diagnosis becomes difficult after treatment. Therefore, our report of this case helps to further accurate understanding of the imaging, pathological, and molecular genetic changes occurring before and after MVNT treatment, and will improve the accuracy of pre-treatment diagnosis and reduce the likelihood of overtreatment. [ABSTRACT FROM AUTHOR]

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expressed genes (DEGs) published for the cortex, hippocampus, and olfactory bulb revealed cerebellar-specific gene signature across these developmental timepoints. Moreover, we conducted a comparative analysis of cerebellar astrocyte gene signatures with gene lists from pediatric brain tumors of cerebellar origin, including ependymoma and medulloblastoma. Notably, genes downregulated at P14, such as Kif11 and HMGB2, exhibited significant enrichment across all pediatric brain tumor groups, suggesting the importance of astrocytic gene repression during cerebellar development to these tumor subtypes. Collectively, our studies describe gene expression patterns during cerebellar astrocyte development, with potential implications for pediatric tumors originating in the cerebellum. [ABSTRACT FROM AUTHOR]

Background: Patients with brain tumors, especially pediatric brain tumors such as cerebellar medulloblastoma, always suffer from the severe side effects of radiotherapy. Regeneration of neural cells in irradiation‐induced cerebellar injury has been reported, but the underlying mechanism remains elusive. Methods: We established an irradiation‐induced developing cerebellum injury model in neonatal mice. Microarray, KEGG analysis and semi in vivo slice culture were performed for mechanistic study. Results: Nestin‐expressing progenitors (NEPs) but not granule neuron precursors (GNPs) were resistant to irradiation and able to regenerate after irradiation. NEPs underwent less apoptosis but similar DNA damage following irradiation compared with GNPs. Subsequently, they started to proliferate and contributed to granule neurons regeneration dependent on the sonic hedgehog (Shh) pathway. In addition, irradiation increased Shh ligand provided by Purkinje cells. And microglia accumulated in the irradiated cerebellum producing more IFN‐γ, which augmented Shh ligand production to promote NEP proliferation. Conclusions: NEP was radioresistant and regenerative. IFN‐γ was increased post irradiation to upregulate Shh ligand, contributing to NEP regeneration. Our study provides insight into the mechanisms of neural cell regeneration in irradiation injury of the developing cerebellum and will help to develop new therapeutic targets for minimizing the side effects of radiotherapy for brain tumors. [ABSTRACT FROM AUTHOR]

Background: Pilocytic astrocytoma (PA) is a benign glial tumor predominately seen in pediatrics and early adolescence with associated overall good outcomes. Very few cases of elderly PA have been reported in the literature, and they are known to display unique anatomic, histologic, and genetic peculiarities distinct from pediatric disease. We report a rare case of vermian PA in an octogenarian with recurrent spontaneous intratumoral hemorrhage as a presenting symptom. Furthermore, a review of the literature on the peculiarities of PA in the elderly will be discussed. Case Description: An 81-year-old woman presented with features suggestive of repeated posterior fossa hemorrhages characterized by headaches, diplopia, and alteration in sensorium occurring about 5 months apart. Brain neuroimaging showed a cerebellar vermian tumor with features suggestive of repeated intratumoral bleeding. She had an initial ventriculoperitoneal shunting for acute hydrocephalus and subsequently had a suboccipital craniotomy and subtotal tumor excision due to morbid adherence to the brainstem. The histologic diagnosis was PA with Ki-67 <1% and negative for isocitrate dehydrogenase-1. There was a slow but progressive clinical improvement, and she has remained symptom-free for 4 years on follow-up. Conclusion: PA in the elderly is a rare disease with distinct histologic and genetic peculiarities. This case review showed one of the oldest cases of cerebellar vermian PA presenting with recurrent spontaneous intratumoral hemorrhage, an extremely rare occurrence in benign glioma. Although complete surgical excision is recommended, partial resection is advocated for morbidly adherent tumors. Overall prognosis is worse in elderly PA. [ABSTRACT FROM AUTHOR]

Background: Gangliogliomas account for 0.4% of primary brain tumors. They mainly occur in the supratentorial compartment and typically affect only children and young adults. We present an especially rare case of cerebellar ganglioglioma in an elderly patient. Case Description: A 76-year-old Japanese woman presented with headache and nausea from 1 month previously. She had been diagnosed with a cerebellar tumor in her childhood, but the lesion was asymptomatic at that time, and there was no evidence of an increase in size, so it had been monitored without surgery. At the time of presentation, she had not been examined for approximately ten years. On admission, magnetic resonance imaging indicated a T2 hypertense cyst in the cerebellar vermis. Post-contrast T1 imaging showed an enhanced mural nodule in the cyst. Cerebral angiography showed that none of the vertebral arteries were significant feeders. The tumor was removed through posterior fossa craniotomy. The histopathological diagnosis was ganglioglioma. The patient's headache and nausea improved after surgery. Conclusion: Our patient presented a very rare case of extremely slow-growing elderly ganglioglioma in the cerebellum. In patients with gangliogliomas, long-term follow-up is important because the disease may become symptomatic at an older age. [ABSTRACT FROM AUTHOR]

Background: Low-grade fibromyxoid tumors are uncommon in children. Their differentiation from high-grade fibromyxoid tumors, as seen in adults, is imperative to diagnosis. Awareness of the entity and its subsequent behavior may guide management and predict outcomes. Case Description: We describe the case of a previously unreported low-grade fibromyxoid tumor of the cerebellum in an 8-year-old male. Extensive immunohistochemical, next-generation sequencing, and attempted DNA methylation profiling are reported. There has been no recurrence during the 6-year follow-up. Screening excluded multiple myxoid tumors, including low-grade fibromyxoid sarcoma. The findings suggest that, with gross total resection, the lesions may not recur. Conclusion: The case of fibromyxoid tumor with 6-year follow-up and the limited literature of similar tumors are reviewed. [ABSTRACT FROM AUTHOR]

A variety of diseases, including gait ataxia, lack of coordination, diminished dexterity, and unsteady posture, can be brought on by cerebellar dysfunction. This case study looks into how a physical therapy program affected a 40-year-old patient's dynamic balance after cerebellar tumour surgery. The patient complained of losing his balance and having uncoordinated motions on the left side of the body. The Timed Up and Go (TUG) test was used to gauge how the Frenkel coordination exercises and balance training affected dynamic balance following cerebellar tumour removal. The patient's muscle strength in the left-side hip extensors, abductors and adductors, knee flexors and extensors, as well as the left-side shoulder, elbow, and wrist flexion and extension, significantly improved. [ABSTRACT FROM AUTHOR]

Objectives: Adult solitary intra-axial cerebellar tumors are uncommon. Their presurgical differentiation based on neuroimaging is crucial, since management differs substantially. Comprehensive full assessment of MR dynamic-susceptibility-contrast perfusion-weighted imaging (DSC-PWI) may reveal key differences between entities. This study aims to provide new insights on perfusion patterns of these tumors and to explore the potential of DSC-PWI in their presurgical discrimination. Methods: Adult patients with a solitary cerebellar tumor on presurgical MR and confirmed histological diagnosis of metastasis, medulloblastoma, hemangioblastoma, or pilocytic astrocytoma were retrospectively retrieved (2008–2023). Volumetric segmentation of tumors and normal-appearing white matter (for normalization) was semi-automatically performed on CE-T1WI and coregistered with DSC-PWI. Mean normalized values per patient tumor-mask of relative cerebral blood volume (rCBV), percentage of signal recovery (PSR), peak height (PH), and normalized time-intensity curves (nTIC) were extracted. Statistical comparisons were done. Then, the dataset was split into training (75%) and test (25%) cohorts and a classifier was created considering nTIC, rCBV, PSR, and PH in the model. Results: Sixty-eight patients (31 metastases, 13 medulloblastomas, 13 hemangioblastomas, and 11 pilocytic astrocytomas) were included. Relevant differences between tumor types' nTICs were demonstrated. Hemangioblastoma showed the highest rCBV and PH, pilocytic astrocytoma the highest PSR. All parameters showed significant differences on the Kruskal–Wallis tests (p < 0.001). The classifier yielded an accuracy of 98% (47/48) in the training and 85% (17/20) in the test sets. Conclusions: Intra-axial cerebellar tumors in adults have singular and significantly different DSC-PWI signatures. The combination of perfusion metrics through data-analysis rendered excellent accuracies in discriminating these entities. Clinical relevance statement: In this study, the authors constructed a classifier for the non-invasive imaging presurgical diagnosis of adult intra-axial cerebellar tumors. The resultant tool can be a support for decision-making in the clinical practice and enables optimal personalized patient management. Key Points: • Adult intra-axial cerebellar tumors exhibit specific, singular, and statistically significant different MR dynamic-susceptibility-contrast perfusion-weighted imaging (DSC-PWI) signatures. • Data-analysis, applied to MR DSC-PWI, could provide added value in the presurgical diagnosis of solitary cerebellar metastasis, medulloblastoma, hemangioblastoma, and pilocytic astrocytoma. • A classifier based on DSC-PWI metrics yields excellent accuracy rates and could be used as a support tool for radiologic diagnosis with clinician-friendly displays. [ABSTRACT FROM AUTHOR]

Background: Acute acquired comitant esotropia (AACE) is an uncommon subtype of esotropia characterized by sudden and usually late onset of a relatively large angle of comitant esotropia with diplopia in older children and adults. Methods: A literature survey regarding neurological pathologies in AACE was conducted using databases (PubMed, MEDLINE, EMBASE, BioMed Central, the Cochrane Library, and Web of Science) in order to collect data for a narrative review of published reports and available literature. Results: The results of the literature survey were analyzed to provide an overview of the current knowledge of neurological pathologies in AACE. The results revealed that AACE with unclear etiologies can occur in many cases in both children and adults. Functional etiological factors for AACE were found to be due to many reasons, such as functional accommodative spasm, the excessive near work use of mobile phones/smartphones, and other digital screens. In addition, AACE was found to be associated with neurological disorders, such as astrocytoma of the corpus callosum, medulloblastoma, tumors of the brain stem or cerebellum, Arnold-Chiari malformation, cerebellar astrocytoma, Chiari 1 malformation, idiopathic intracranial hypertension, pontine glioma, cerebellar ataxia, thalamic lesions, myasthenia gravis, certain types of seizures, and hydrocephalus. Conclusions: Previously reported cases of AACE with unknown etiologies have been reported in both children and adults. However, AACE can be associated with neurological disorders that require neuroimaging probes. The author recommends that clinicians should perform comprehensive neurological assessments to rule out neurological pathologies in AACE, especially in the presence of nystagmus or abnormal ocular and neurological indications (e.g., headache, cerebellar imbalance, weakness, nystagmus, papilloedema, clumsiness, and poor motor coordination). [ABSTRACT FROM AUTHOR]

This study aimed to assess the prevalence of neurological symptoms and related imaging findings in patients with von Hippel-Lindau (VHL) at Rasool Akram Hospital from September 2018 to September 2021. This analytical observational study examined eligible patients over the period from September 2018 to September 2021. We collected demographic information (age, gender) along with imaging findings and results of neurological and eye examinations. Comparison between qualitative variables was also done using the Chi-square test or Fisher’s exact test. Also, an independent t-test was used to compare quantitative variables between the two groups. SPSS version 22 software was used for statistical analysis of data. A significant level was considered less than or equal to 0.05. Of the 54 examined patients (48.1% were male and 51.9% were female) with an average age of 36.42 ± 13.37 years. A significant majority (87.0%) reported a positive family history of the disease. The most common type of disease was Type 1 observed in 94.4% of cases and Type 2A was the next most frequent (3.7%). The most common pattern of retinal pathological lesions seen in the examination was related to bilateral lesions (79.6%). The most common pathological finding was related to the presence of a mass in cerebellar magnetic resonance imaging (48.1%). Considering the findings of the present study, which highlight a significant frequency of bilateral retinal lesions as well as masses in the central nervous system and endocrine system, it is evident that patients require careful follow-up and various interventions after being diagnosed with the disease. This approach is essential to manage and potentially mitigate the complications associated with these conditions.

The article discusses a novel workflow presented by Sanvito et al in European Radiology that allows for the simultaneous quantification of perfusion, permeability, and leakage effects in neurooncology using a single-dose, single-acquisition dual-echo DSC sequence. Traditionally, these measurements require two separate acquisitions, increasing scanning time and contrast agent dose. The new pipeline introduced in this study eliminates the need for a separate acquisition, significantly reducing scanning time and required contrast agent dose. The authors also propose a quantitative biomarker called "Transverse Relaxivity at Tracer Equilibrium" (TRATE) that correlates with cellularity in enhancing gliomas. Additionally, the study explores differences between different types of gliomas and suggests that a metric called ΔR1,ss could potentially serve as a surrogate for the measurement of BBB rupture. The article provides valuable insights and correlations with biological processes, making it useful for both academic and clinical readers interested in DSC imaging. [Extracted from the article]

Purpose: To comprehensively analyze the impact of surgical compliance on the survival of patients with glioma and to explore the factors that influence surgical compliance. Methods: Clinical data of patients with glioma between 2004 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier curves and Cox regression were used to analyze the effect of surgical compliance on overall survival (OS) and disease-specific survival (DSS). Multivariate Cox regression was used to select the prediction variables and construct the nomograms. The predictive power of these models was assessed using Harell's consistency index (C-index), decision curve analysis (DCA), receiver operating characteristic (ROC) curves, and calibration curves. Multivariate logistic regression was performed to analyze the related variables of surgical compliance, and 1:1 propensity score matching (PSM) was applied to evaluate the validity of the results of patients with favorable and poor surgical compliance. Results: Among the 47,573 eligible glioma patients recommended for surgery, 46,380 (97.5%) were in the surgical compliance group, while 1193 (2.5%) were in the noncompliance group. Surgical compliance was an independent prognostic factor for glioma patients, as indicated by multivariate Cox regression analysis that patients with surgical compliance had worse OS (hazard ratio [HR] 1.924; 95% confidence interval [CI] 1.800–2.056, p < 0.001) and DSS (HR 1.718; 95% CI 1.592–1.853, p < 0.001) in comparison to those without surgical compliance. A nomogram was developed and internally validated to be able to predict glioma prognosis. The nomogram can well predict patients' OS (C-index: 0.745) and DSS (C-index: 0.744). ROC curve, DCA curve, and calibration curve were applied to further assess the accuracy of the nomogram. Poor surgical compliance was found to be related to older age, female gender, tumor diameter, grade II or higher, poor grading, tumor location in the cerebellum and brainstem, and low household income. Conclusion: Surgical compliance is an independent prognostic factor for predicting the OS and DSS of patients with glioma, and good surgical compliance was significantly related to good survival. [ABSTRACT FROM AUTHOR]

Background: Medulloblastoma is the most common malignant primary pediatric brain tumor. Over the years, an increase in published research has been observed on this topic. However, there is a lack of analysis on the characteristics and trends and the socioeconomic indicators associated with medulloblastoma research productivity and impact. Methods: The Scopus database was used to search all articles from inception to 2020. Bibliometric information was obtained from Scopus, and bibliometrics diagrams were created using VOSviewer software. Statistical analysis was performed using the GraphPad Prism software version 7. Results: A total of 4058 research articles on medulloblastoma research worldwide were included in this study. There has been an increase in published articles, with a steep increase observed in the last decade. The country with the most publications is the USA, with St. Jude Children's Research Hospital as the most productive institution in medulloblastoma research. The articles mainly focused on molecular biology, diagnosis, treatment, prognostic factors for medulloblastoma, and research on other pediatric tumors. The number of collaborations with other countries showed the strongest positive correlation with scientific productivity. Conclusion: This analysis showed the trend and characteristics of published articles. The results of this study emphasized the need to increase funding for research, support for researchers and physicians, and promote more collaborations with countries and institutions engaged in medulloblastoma research. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common malignant brain tumour in children, while much rarer in adults. Although the prognosis and outcomes have greatly improved in the era of modern multidisciplinary management, long-term treatment-induced toxicities are common. Craniospinal irradiation followed by a boost to the primary and metastatic tumour sites forms the backbone of treatment. Proton therapy has been endorsed over conventional photon-based radiotherapy due to its superior dosimetric advantages and subsequently lower incidence and severity of toxicities. We report here our experience from South-East Asia's first proton therapy centre of treating 40 patients with medulloblastoma (38 children and adolescents, 2 adults) who received image-guided, intensity-modulated proton therapy with pencil-beam scanning between 2019 and 2023, with a focus on dosimetry, acute toxicities, and early survival outcomes. All patients could complete the planned course of proton therapy, with mostly mild acute toxicities that were manageable on an outpatient basis. Haematological toxicity was not dose-limiting and did not prolong the overall treatment time. Preliminary data on early outcomes including overall survival and disease-free survival are encouraging, although a longer follow-up and data on long-term toxicities are needed. [ABSTRACT FROM AUTHOR]

Introduction: the management of genetic diseases is challenging because of their low incidence, diverse etiology, coexisting diseases, and variability in responses to anesthetics. This case presentation provides new insight into how to approach multimodal general anesthetic management in patients with Von Hippel-Lindau disease. Patient information: a 49-year-old female patient is presented for orthopedic surgery with open tibial wound and history of bronchial asthma and Von Hippel-Lindau disease, operated for cerebellar hemangioblastoma and renal carcinoma, with current left meningeal and cerebellar hemangioblastoma with clinical and imaging follow-up, renal and pancreatic cysts, right adrenal nodular lesion of recent appearance (ruling out the possibility of pheochromocytoma) and recent migraine headache unrelated to endocranial hypertension despite the mass effect of the cerebellar tumor. Multimodal general anesthetic management was performed. Conclusions: The possibility of performing multimodal minimally invasive techniques in the surgical intervention of a high surgical risk patient with Von Hippel-Lindau disease with open tibial wound can be considered in order to minimize transoperative morbidity and mortality and to avoid complications. [ABSTRACT FROM AUTHOR]

Purpose: Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%-90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics. Methods: A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively. Results: WNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants. Conclusion: We observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is the most common childhood embryonal malignant tumour in the central nervous system. The diagnosis, prognosis and therapeutic targets of MB depend on the molecular characteristics of the tumor, and it is a great challenge to obtain the tissue samples from the patients with brain tumor. Genomic changes found in cell-free DNA (cfDNA) of cerebrospinal fluid (CSF) can predict genomic changes present in tumor tissue, fluid biopsy of CSF can detect the genomic profile of tumor-associated cfDNA and evaluate cfDNA as a marker of measurable residual disease (MRD) in a relatively noninvasive manner, which provides the evidence of "individualized precision therapy" for MB patients. In this paper, we reviewed the recent studies in medulloblastoma based on cfDNA Liquid Biopsy of CSF. [ABSTRACT FROM AUTHOR]