Consensus guidelines for the management of posterior fossa tumour for low- and middle-income countries.

The posterior fossa is a limited compartment therefore lesions compressing its structures can result in devastating outcomes. It can cause significant neurological deficit due to mass effect on critical structures and hydrocephalus. Due to the nature of the infratentorial region, urgent surgical intervention is often the first-line option. Surgical neuro-oncologists guide patients and caregivers through the course of this disease and to inform them about the various options for management and long-term outcome optimisation. There is currently conflicting data; however, institutional experiences can guide us towards achieving improvements in surgical outcomes and quality of life. Advances in molecular classifications coupled with highdose radiation treatment improve our capacity for improving overall survival in these patients. Common childhood tumours are ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, while adults often present with metastases, and less commonly, cerebellar haemangioblastomas and gliomas. This paper outlines management strategies with consideration for multidisciplinary care and resourcelimited settings.

Surgical outcome of sinodural meningiomas.

INTRODUCTION: Meningiomas located in the posterior fossa and involving the sinodural angle at the junction of the transverse and sigmoid sinuses are uncommon and present unique challenges due to their complex anatomical location. Despite their distinctive features, they are frequently categorized with tentorial meningiomas in the literature. MATERIALS AND METHODS: This retrospective study conducted at a tertiary care center involved 64 patients with sinodural meningiomas who underwent surgical treatment between 2010 and 2023. The analysis covered demographics, clinical presentation, radiological characteristics, surgical approaches, histopathological findings, and outcomes. RESULTS: The cohort predominantly comprised females (83 %) with a mean age of 47.64 years. Headache (92.2 %) and gait disturbances (62.5 %) were the most common presenting symptoms. Preoperative imaging showed sinus involvement in 57.8 % of cases, predominating Sindou's type 1 and type 6. Gross total resection (Simpson grades 1-2) was achieved in 40.6 % of cases. Postoperative complications included pseudomeningocele (9.4 %), especially in patients with hydrocephalus. CONCLUSION: Sinodural meningiomas represent a distinct subset of posterior fossa tumors, necessitating meticulous preoperative planning and intraoperative decision-making regarding sinus management. The study underscores the importance of individualized surgical strategies and highlights the role of radiosurgery in managing residual disease effectively.

Posterior Fossa Craniopharyngioma Arising from the Inferior Medullary Velum.

We report the case of a 63-year-old man with a midline posterior fossa tumor and peculiar imaging features where we were unsure of the nature of the lesion preoperatively. Histopathology revealed it to be a craniopharyngioma. It appeared to arise from the inferior medullary velum, a site not described before in the literature. The previous four cases mentioned in literature and speculations on the origins in this uncommon site are discussed.

Doing more with less: surgical results of pediatric posterior fossa tumors from a single center in Latin America.

OBJECTIVE: We aim to report the epidemiology, surgical outcomes, and survival rates of pediatric patients with posterior fossa tumors in a large single-center case series. METHODS: A retrospective analysis was conducted on pediatric patients who underwent surgical treatment for posterior fossa tumors between January 2011 and January 2019. RESULTS: A total of 135 pediatric patients, with an average age of 7.5 years at diagnosis and a mean follow-up of 35.7 months, were included in the study. Most tumors were located within the midline, with ventriculomegaly observed in 71.4% of the patients. Pilocytic astrocytomas encompassed the majority of tumors (34.1%), followed by medulloblastomas (27.4%) and ependymomas (11.8%). Gross total resection (GTR) was achieved in 71.8% of the patients, with a recurrence rate of 20%. Surgical complications were observed in 25.9% of the patients. GTR significantly impacted 5-year overall survival (OS) and 4-year progression-free survival (PFS) in patients with posterior fossa tumors. Patients who underwent GTR had a 5-year OS of 89.7%, compared to 72.7% for near-total resection and 70.8% for subtotal resection. The 4-year PFS for patients who underwent GTR was 82.5%, whereas it was 63.6% for patients who underwent near-total resection and 54.2% for patients who underwent subtotal resection. CONCLUSION: Surgical resection remains the main treatment for pediatric posterior fossa tumors, and higher resection rates are linked to better survival outcomes. Despite limited resources for molecular diagnosis, our institution has demonstrated that a specialized neurooncological center with a high surgical volume can still achieve favorable survival outcomes for these patients.

TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

Exploring Memory Systems After Pediatric Posterior Fossa Tumor: From Memory Profile Comparisons in Nonirradiated Versus Irradiated Patients to Episodic Memory Tests Capable of Detecting Radiation-induced Hippocampal Damage.

AIMS: Pediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. MATERIALS AND METHODS: A total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SDs as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. RESULTS: PBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. CONCLUSION: Memory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation.

Prevalence of dysphagia following posterior fossa tumor resection: a systematic review and meta­analysis.

OBJECTIVE: Dysphagia is common in individuals who have undergone posterior fossa tumor (PFT) resection and negatively impacts on the individual's quality of life, nutritional status, and overall health. We aimed to quantitatively synthesize data from studies of the prevalence of dysphagia following PFT resection. METHODS: PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cross-sectional studies that evaluated the prevalence of dysphagia after PFT surgery. Meta-analyses were performed to determine the prevalence of dysphagia. Subgroup and meta-regression analyses were performed to determine the sources of heterogeneity among the studies. RESULTS: A total of 22 studies were included, involving 20,921 cases. A meta-analysis of the random-effects model showed that the pooled global prevalence of dysphagia following PFT resection was 21.7% (95% confidence interval: 16.9-26.6). The subgroup and meta-regression analyses demonstrated that participant age (P < 0.001), assessment methods (P = 0.004), and geographical region of the study participants (P = 0.001) were sources of heterogeneity among the studies. CONCLUSIONS: Dysphagia has a high prevalence following PFT resection. Individuals with PFTs who are at a high risk for dysphagia should be identified early through screening. Multidisciplinary diagnosis and treatment of dysphagia are required to improve the outcomes in the early stages after PFT resection.

Cortical and subcortical structural changes in pediatric patients with infratentorial tumors.

PURPOSE: This study aimed to detect supratentorial cortical and subcortical morphological changes in pediatric patients with infratentorial tumors. METHODS: The study included 24 patients aged 4-18 years who were diagnosed with primary infratentorial tumors and 41 age- and gender-matched healthy controls. Synthetic magnetization-prepared rapid gradient echo images of brain magnetic resonance imaging were generated using deep learning algorithms applied to T2-axial images. The cortical thickness, surface area, volume, and local gyrification index (LGI), as well as subcortical gray matter volumes, were automatically calculated. Surface-based morphometry parameters for the patient and control groups were compared using the general linear model, and volumes between subcortical structures were compared using the t-test and Mann-Whitney U test. RESULTS: In the patient group, cortical thinning was observed in the left supramarginal, and cortical thickening was observed in the left caudal middle frontal (CMF), left fusiform, left lateral orbitofrontal, left lingual gyrus, right CMF, right posterior cingulate, and right superior frontal (P < 0.050). The patient group showed a volume reduction in the pars triangularis, paracentral, precentral, and supramarginal gyri of the left hemisphere (P < 0.05). A decreased surface area was observed in the bilateral superior frontal and cingulate gyri (P < 0.05). The patient group exhibited a decreased LGI in the right precentral and superior temporal gyri, left supramarginal, and posterior cingulate gyri and showed an increased volume in the bilateral caudate nucleus and hippocampus, while a volume reduction was observed in the bilateral putamen, pallidum, and amygdala (P < 0.05). The ventricular volume and tumor volume showed a positive correlation with the cortical thickness in the bilateral CMF while demonstrating a negative correlation with areas exhibiting a decreased LGI (P < 0.05). CONCLUSION: Posterior fossa tumors lead to widespread morphological changes in cortical structures, with the most prominent pattern being hypogyria. CLINICAL SIGNIFICANCE: This study illuminates the neurological impacts of infratentorial tumors in children, providing a foundation for future therapeutic strategies aimed at mitigating these adverse cortical and subcortical changes and improving patient outcomes.

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

Management of Neurogenic Respiratory Alkalosis and Concomitant Lactatemia After Resection of a Posterior Fossa Meningioma: A Case Report.

Central neurogenic hyperventilation (CNH) is a rare disease, caused by chemical or mechanical disturbance of respiratory centers. It is characterized by the absence of extracerebral respiratory stimuli. A woman developed severe respiratory alkalosis and lactatemia after resection of a posterior fossa meningioma despite lack of cardio-respiratory or metabolic alterations. Cerebral computed tomography (cCT) revealed edema of the pontomedullary area. Treatment with mannitol and dexamethasone reestablished normal breathing patterns. Lactatemia was likely due to reduced splanchnic lactate utilization. Intracranial pathologies should be suspected in case of hyperventilation without overt reasons. cCT to confirm edema or ischemia and prompt treatment is suggested.

Tension Subdural Hygroma Following Resection of Posterior Fossa Tumour in a Child: A new clinico-radio-pathological entity.

Persistent hydrocephalus is common in children after resection of posterior fossa tumours. However, occurrence of subdural hygroma is very rare. We report the case of a 14-month-old child who presented at a paediatric neurology clinic in Muscat, Oman in 2021 who developed a tense subdural hygroma with stable hydrocephalus, in the early postoperative period, following posterior fossa tumour resection. We describe the distinctive clinical, radiological and pathological features associated with the development of a tense subdural hygroma. We also discuss the management by cerebrospinal fluid diversion, which includes either a ventriculoperitoneal or subduroperitoneal shunt. This unique condition is distinguished from external hydrocephalus by features that are critical to the management strategy.

Predictors of Acute Cerebellar Bulge Prior to Posterior Fossa Lesion Resection.

OBJECTIVE: A cerebellar bulge prior to posterior fossa resection is an emergency condition during surgery. Intraoperative cerebellar bulging not only increases the difficulty of lesion resection but also brings additional postoperative complications. Currently, there are few systematic reports on this topic. The predictors of cerebellar bulge and how to effectively prevent intraoperative cerebellar bulge are discussed in this article. METHODS: The clinical and imaging data of 527 patients with posterior fossa lesions who underwent resection at our hospital were retrospectively collected and analyzed. Perioperative clinical and imaging data were assessed. Variables were analyzed using univariate and multivariate regression analyses. RESULTS: Overall, 10.4% (55/527) of patients had intraoperative acute bulges. Multivariate analysis revealed that age <60 years, body mass index ≥24, lesion size ≥30 (mm), cerebellar tonsillar herniation and/or hydrocephalus, and perilesional edema (moderate-severe) were predictors of cerebellar bulging. Relief of the cerebellar bulge can be accomplished by excising the lesion, releasing cerebrospinal fluid, and removing the cerebellum (the outer one-third). Obvious cerebellar-related complications occurred in 4 patients postoperatively, and the symptoms disappeared after 6 months of follow-up. CONCLUSIONS: Cerebellar bulging during intraoperative posterior fossa resection deserves attention. Through the analysis of multiple factors related to cerebellar bulge, comprehensive evaluation and early intervention during the perioperative period are necessary. The incidence of cerebellar bulges can be reduced, and surgical complications related to cerebellar bulges can be avoided.

Impact of Molecular Subgroups on Prognosis and Survival Outcomes in Posterior Fossa Ependymomas: A Retrospective Study of 412 Cases.

BACKGROUND AND OBJECTIVES: Posterior fossa ependymomas (PFEs) are rare brain tumors classified as PF-EPN-A (PFA) and PF-EPN-B (PFB) subgroups. The study aimed to evaluate the prognosis and survival outcomes in PFEs, with a focus on the impact of molecular subgroups. METHODS: A retrospective study was conducted on 412 patients with PFEs. Kaplan-Meier survival analyses were conducted to evaluate the overall survival (OS) and progression-free survival. Cox regression analyses were conducted to assess the prognostic factors. A nomogram was developed to predict the OS rates of PFEs. RESULTS: The study revealed significant differences between PFA and PFB in patient and tumor characteristics. PFAs were associated with poorer OS (hazard ratios [HR] 3.252, 95% CI 1.777-5.950, P < .001) and progression-free survival (HR 4.144, 95% CI 2.869-5.985, P < .001). World Health Organization grade 3 was associated with poorer OS (HR 2.389, 95% CI 1.236-4.617, P = .010). As for treatment patterns, gross total resection followed by radiotherapy or the combination of radiotherapy and chemotherapy yielded the most favorable OS for PFA ( P = .025 for both), whereas gross total resection followed by radiotherapy rather than observation showed improved OS for PFB ( P = .046). The nomogram demonstrated a high degree of accuracy and discrimination capacity for the prediction of OS rates for up to 10 years. In addition, 6 cases of PFA (3.51%) with H3K27M mutations were identified. CONCLUSION: PFAs demonstrate worse prognosis and survival outcomes compared with PFBs. Both PFAs and PFBs necessitate maximal resection followed by intensive adjuvant therapies in long-term effects.

Effects of cognitive-motor intervention for pediatric posterior fossa tumor survivors: results of a pilot study.

The purpose of this prospective pilot study was to evaluate the feasibility and effects of cognitive-motor intervention on the cognitive and motor abilities of pediatric survivors of posterior fossa tumors. The study involved patients aged 7 to 18 years with cognitive deficits who had completed primary treatment for posterior fossa tumors. 25 participants (Mage=11.3 ± 2.93, 64% male; 17 medulloblastoma, 1 ependymoma, 1 desmoplastic medulloblastoma, 6 piloid astrocytoma; 22 in remission (Mmonths =45), 3 in stabilization (Mmonths=49)) were recruited from the Research Institute for Brain Development and Peak Performance. The intervention consisted of two phases with a 3-month break for home training, and a total duration of 6 months. Each phase lasted 7 weeks and included two assessment procedures (pre- and post-intervention) and 10 training sessions over a period of 5 weeks (two 3-hour sessions per week). At baseline and pre- and post-intervention, all participants underwent a battery of cognitive and motor tests. Each training session included gross motor training (GMT), graphomotor training (GT), and cognitive-motor training (CMT). Statistical analysis was performed using the Friedman test for repeated measures and post-hoc Durbin-Conover test. The results indicated significant improvements in visuospatial working memory, visual attention, eye-hand coordination, semantic verbal fluency, auditory-motor synchronization, reaction time, and a decrease in the rate of ataxia. These improvements remained stable even in the absence of direct intervention. The findings demonstrate positive effects and feasibility of the intervention and suggest the need for further research in this area including randomized controlled feasibility studies with a larger sample.

Symptomatic infratentorial ependymal cyst arising from the medulla: a case report with review of literature.

BACKGROUND: Ependymal cysts (EC) typically present supra-tentorially near the lateral ventricle, juxta ventricular, or temporoparietal regions. Previous cases have also identified infratentorial EC of the brainstem, cerebellum, and subarachnoid spaces. They are mostly asymptomatic. In this paper, we present the first-ever case of a symptomatic medullary ependymal cyst treated with surgery, along with a comprehensive review of the literature on EC of other parts of the brain stem. CASE DESCRIPTION: This 51-year-old female presented with hearing loss, dizziness, diplopia, and ataxia. Radiographic imaging indicated the presence of a non-enhancing lesion in the medulla with a mass effect on the brainstem. Pathological examination confirmed its characterization as an ependymal cyst. The patient underwent a suboccipital craniotomy for the fenestration of the medullary ependymal cyst under neuro-navigation, Intra-op ultrasound and intra-operative neuro-monitoring. Histopathological examination confirmed the diagnosis of an ependymal cyst. At one month follow-up, her KPS is 90, ECOG PS 1, and her ataxia has improved with complete resolution of diplopia. CONCLUSION: Due to their rarity and potential similarity to other cystic structures, EC may be overlooked or incorrectly diagnosed resulting in mismanagement and surgical disaster. Therefore, a comprehensive understanding and awareness of their distinct characteristics are essential for accurate diagnosis and appropriate management.

Evaluation of safety of fluoxetine for cerebellar mutism syndrome in children after posterior fossa surgery.

BACKGROUND: Cerebellar mutism syndrome (CMS) occurs in 8-29 % of children undergoing posterior fossa tumor surgery. Its main symptoms are mutism and emotional lability. Although it is always transient, recovery time can be lengthy with long-term cognitive sequelae. There is no approved drug treatment for CMS, but some drugs are used in everyday medical practice. One of these is fluoxetine, which has been used for many years in our institution. The main objective of this study was to establish the safety profile of fluoxetine in this condition. MATERIALS AND METHODS: The records of patients admitted to the pediatric intensive care unit after brain surgery at Angers University Hospital from 2010 to 2020 were reviewed. Children aged 2 years and older who underwent a posterior fossa tumor surgery and were diagnosed with CMS were included. Data on patient characteristics, prescription of fluoxetine treatment, side effects if any, and complete mutism duration were collected. RESULTS: Among 246 patients admitted to the pediatric intensive care unit for brain surgery during the study period, 23 had CMS and eight were prescribed fluoxetine. No serious adverse event related to fluoxetine was reported. Complete mutism duration did not differ significantly between the fluoxetine group and the non-fluoxetine group(p = 0.22). However, the treatment was initiated after recovery from complete mutism in half of the treated patients. CONCLUSION: This study suggests a positive safety profile of fluoxetine used in postoperative CMS. It does not answer the question of whether the treatment is effective for this indication. A randomized controlled trial based on a syndrome severity scale should be conducted to provide a more reliable assessment of the efficacy and safety of fluoxetine.

Implications of DNA Methylation Classification in Diagnosing Ependymoma.

BACKGROUND: Ependymoma is a central nervous system (CNS) tumor that arises from the ependymal cells of the brain's ventricles and spinal cord. The histopathology of ependymomas is indistinguishable regardless of the site of origin, and the prognosis varies. Recent studies have revealed that the development site and prognosis reflect the genetic background. In this study, we used genome-wide DNA methylation array analysis to investigate the epigenetic background of ependymomas from different locations treated at our hospital. METHODS: Four cases of posterior fossa ependymomas and 11 cases of spinal ependymomas were analyzed. RESULTS: DNA methylation profiling using the DKFZ methylation classifier showed that the methylation diagnoses of the 2 cases differed from the histopathological diagnoses, and 2 cases could not be classified. Tumor that spread from the brain to the spinal cord was molecularly distinguishable from other primary spinal tumors. CONCLUSIONS: Although adding DNA methylation classification to conventional diagnostic methods may be helpful, the diagnosis in some cases remains undetermined. This may affect decision-making regarding treatment strategies and follow-up. Further investigations are required to improve the diagnostic accuracy of these tumors.