Cerebellar Mutism Syndrome and Dentato-Thalamo-Cortical Tract Disruption in Diffusion Tractography Following Surgery for Medulloblastoma.

Background Cerebellar mutism syndrome (CMS), a complication following medulloblastoma surgery, has been linked to dentato-thalamo-cortical tract (DTCT) injury; the association of the degree of DTCT injury with severity of CMS-related symptoms has not been investigated. Purpose To investigate the association between severity of CMS-related symptoms and degree and patterns of DTCT injury with use of diffusion tensor imaging (DTI), and if laterality of injury influences neurologic symptoms. Materials and Methods This retrospective case-control study used prospectively collected clinical and DTI data on patients with medulloblastoma enrolled in a clinical trial (between July 2016 and February 2020) and healthy controls (between April and November 2017), matched with the age range of the participants with medulloblastoma. CMS was divided into types 1 (CMS1) and 2 (CMS2). Multivariable logistic regression was used to investigate the relationship between CMS likelihood and DTCT injury. Results Overall, 82 participants with medulloblastoma (mean age, 11.0 years ± 5.2 [SD]; 53 male) and 35 healthy controls (mean age, 18.0 years ± 3.06; 18 female) were included. In participants with medulloblastoma, DTCT was absent bilaterally (AB), absent on the right side (AR), absent on the left side (AL), or present bilaterally (PB), while it was PB in all healthy controls. Odds of having CMS were associated with higher degree of DTCT damage (AB, odds ratio = 272.7 [95% CI: 269.68, 275.75; P < .001]; AR, odds ratio = 14.40 [95% CI: 2.84, 101.48; P < .001]; and AL, odds ratio = 8.55 [95% CI: 1.15, 74.14; P < .001). Left (coefficient = -0.07, χ2 = 12.4, P < .001) and right (coefficient = -0.15, χ2 = 33.82, P < .001) DTCT volumes were negatively associated with the odds of CMS. More participants with medulloblastoma with AB showed CMS1; unilateral DTCT absence prevailed in CMS2. Lower DTCT volumes correlated with more severe ataxia. Unilateral DTCT injury caused ipsilateral dysmetria; AB caused symmetric dysmetria. PB indicated better neurologic outcome. Conclusion The severity of CMS-associated mutism, ataxia, and dysmetria was associated with DTCT damage severity. DTCT damage patterns differed between CMS1 and CMS2. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Dorigatti Soldatelli and Ertl-Wagner in this issue.

Development and validation of a nomogram and risk stratification system to predict overall survival after surgical repair for pediatric patients with medulloblastoma based on easily accessible variables.

OBJECTIVE: This study aimed to develop and validate a nomogram and risk stratification system for the overall survival of pediatric patients with medulloblastoma after surgical repair. PATIENTS AND METHODS: In this multicenter, retrospective study, consecutive patients who underwent surgery for medulloblastoma at Shanghai Children's Medical Center and the First Affiliated Hospital of Fujian Medical University from 2010 to 2022 formed the training and external validation datasets, respectively. Univariable and multivariable Cox regression analyses were performed to identify variables associated with mortality in the training dataset. A nomogram prediction model was developed based on independent variables in the multivariable Cox regression analysis to predict the 1-, 3-, and 5-year overall survival. The area under receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the nomogram. A risk stratification system based on the median risk score was also established to divide patients into two risk groups. RESULTS: In the training dataset, Cox regression analyses identified tumor size, brainstem involvement and chemotherapy as independent predictors for overall survival. The AUC of the nomogram was 0.75 at 1 year, 0. 75 at 3 years, 0.77 at 5 years in the training dataset, 0.74 at 1 year, 0.70 at 3 years, and 0.70 at 5 years in the validation dataset. The calibration curve for the probability of 1-, 3-, and 5-year survival showed good agreement between the nomogram prediction and actual observation in the training and validation datasets. The risk stratification system could perfectly classify patients into two risk groups, and the overall survival in the two groups had a good division. CONCLUSIONS: This low-cost, convenient, and noninvasive nomogram can be translated into clinical practice as a tool for risk stratification and individualized prognosis prediction for children with medulloblastoma.

National multicentered retrospective review of clinical and intraoperative factors associated with the development of cerebellar mutism after pediatric posterior fossa tumor resection.

BACKGROUND: Cerebellar mutism (CM) is characterized by a significant loss of speech in children following posterior fossa (PF) surgery. The biological origin of CM remains unclear and is the subject of ongoing debate. Significant recovery from CM is less likely than previously described despite rigorous multidisciplinary neuro-rehabilitational efforts. METHODS: A national multi-centered retrospective review of all children undergoing PF resection in four midsized Canadian academic pediatric institutions was undertaken. Patient, tumor and surgical factors associated with the post-operative development of CM were reviewed. Retrospective identification of PF surgery patients including those developing and those that did not (internal control). RESULTS: The study identified 258 patients across the 4 centers between 2010 and 2020 (mean age 6.73 years; 42.2% female). Overall, CM was experienced in 19.5% of patients (N = 50). Amongst children who developed CM histopathology included medulloblastoma (35.7%), pilocytic astrocytoma (32.6%) and ependymoma (17.1%). Intraoperative impression of adherence to the floor of the 4th ventricle was positive in 36.8%. Intraoperative abrupt changes in blood pressure and/or heart rate were identified in 19.4% and 17.8% of cases. The clinical resolution of CM was rated to be complete, significant resolution, slight improvement, no improvement and deterioration in 56.0%, 8.0%, 20.0%, 14.0% and 2.0%, respectively. In the cohort of children who experienced post-operative CM as compared to their no-CM counterpart, proportionally more tumors were felt to be adherent to the floor of the 4th ventricle (56.0% vs 49.5%), intraoperative extent of resection was a GTR (74% vs 68.8%) and changes in heart rate were noted (≥ 20% from baseline) (26.0% vs 15.9%). However, a multiple regression analysis identified only abrupt changes in HR (OR 5.97, CI (1.53, 23.1), p = 0.01) to be significantly associated with the development of post-operative CM. CONCLUSION: As a devastating surgical complication after posterior fossa tumor surgery with variable clinical course, identifying and understanding the operative cues and revising intraoperative plans that optimizes the child's neurooncological and clinical outcome are essential.

Multiparametric MRI-Based Radiomics Signature with Machine Learning for Preoperative Prediction of Prognosis Stratification in Pediatric Medulloblastoma.

RATIONALE AND OBJECTIVES: Despite advances in risk-stratified treatment strategies for children with medulloblastoma (MB), the prognosis for MB with short-term recurrence is extremely poor, and there is still a lack of evaluation of short-term recurrence risk or short-term survival. This study aimed to construct and validate a radiomics model for predicting the outcome of MB based on preoperative multiparametric magnetic resonance images (MRIs) and to provide an objective for clinical decision-making. MATERIALS AND METHODS: The clinical and imaging data of 64 patients with MB admitted to Shenzhen Children's Hospital from December 2012 to December 2021 and confirmed by pathology were retrospectively collected. According to the 18-month progression-free survival, the cases were classified into a good prognosis group and a poor prognosis group, and all cases were divided into training group (70%) and validation group (30%) randomly. Radiomics features were extracted from MRI of each child. The consistency test, t-test, and the least absolute shrinkage and selection operator were used for feature selection. The support vector machine (SVM) and receiver operator characteristic were used to evaluate the distinguishing ability of the selected features to the prognostic groups. RAD score was calculated based on the selected features. The clinical characteristics and RAD score were included in the multivariate logistic regression, and prediction models were constructed by screening out independent influences. The radiomics nomogram was constructed, and its clinical significance was evaluated. RESULTS: A total of 1930 radiomic features were extracted from the images of each patient, and 11 features were included in the construction of radiomics score after selected. The area under the curve (AUC) values of the SVM model in the training and validation groups were 0.946 and 0.797, respectively. The radiomics nomogram was constructed based on the training cohort, and the AUC values in the training group and the validation group were 0.926 and 0.835, respectively. The results of clinical decision curve analysis showed that a good net benefit could be obtained from the nomogram. CONCLUSION: The radiomics nomogram established based on MRI can be used as a noninvasive predictive tool to evaluate the prognosis of children with MB, which is expected to help neurosurgeons better conduct preoperative planning and patient follow-up management.

Application of the Rotterdam postoperative cerebellar mutism syndrome prediction model in patients undergoing surgery for medulloblastoma in a single institution.

OBJECTIVE: Postoperative cerebellar mutism syndrome (CMS) develops in up to 40% of children with medulloblastoma. The Rotterdam model (RM) has been reported to predict a 66% risk of CMS in patients with a score of ≥ 100. The aim of this study was to retrospectively apply the RM to an independent cohort of patients with newly diagnosed medulloblastoma and study the applicability of the RM in predicting postoperative CMS. METHODS: Participants had to have their first tumor resection at the authors' institution and be enrolled in the SJMB12 protocol (NCT01878617). All participants underwent structured serial neurological evaluations before and then periodically after completing radiation therapy. Imaging was reviewed by the study neurologist who was blinded to CMS status when reviewing the scans and retrospectively applied RM score to each participant. RESULTS: Forty participants were included (14 females and 26 males). Four (10%) patients had CMS. The median age at tumor resection was 11.7 years (range 3.5-17.8 years). Tumor location was midline in 30 (75%), right lateral in 6 (15%), and left lateral in 4 (10%). The median Evans index was 0.3 (range 0.2-0.4), and 34 (85%) patients had an Evans index ≥ 0.3. Five participants required a ventricular shunt. The median tumor volume was 51.97 cm3 (range 20.13-180.58 cm3). Gross-total resection was achieved in 35 (87.5%) patients, near-total resection in 4 (10%), and subtotal in 1. The median RM score was 90 (range 25-145). Eighteen participants had an RM score of ≥ 100, and of these 16.7% (n = 3) had CMS. Of the 22 patients with an RM score < 100, 1 child developed CMS (4.5%, CI 0.1%-22.8%); 3 of the 18 patients with an RM score ≥ 100 developed CMS (16.7%, CI 3.6%-41.4%). The observed rate of CMS in the cohort of children with an RM score ≥ 100 was significantly lower than the observed rate in the original RM cohort (66.7%, CI 51%-80.0%, p < 0.001). A greater risk of CMS in patients with an RM score ≥ 100 could not be confirmed (p = 0.31). CONCLUSIONS: At the authors' institution, the incidence of CMS in patients who had an RM ≥ 100 was significantly lower than the RM cohort. These findings raise questions regarding generalizability of RM; however, fewer cases of CMS and a relatively small cohort limit this conclusion.

Evolution of neurosurgical advances and nuances in medulloblastoma therapy.

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.

The Application of Sodium Fluorescein in Resection of Medulloblastoma Under YELLOW 560 Filter: Feasibility and Preliminary Results of a Monocentric Cohort and Systematic Review.

BACKGROUND: Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this tumor. Several dyes have been tested for improving tumor visualization; however, few reports with different protocols of fluorophores use are available and the results are inconsistent. Hence, we report our experience with sodium fluorescein in MB surgery, aiming to assess the role of this technique on the extent of resection. Furthermore, we performed a literature review of this topic. METHODS: Fluorescence characteristics, extent of resection, and clinical outcome were analyzed in 9 consecutively operated patients with MB. A comprehensive literature search and review for English-language articles concerning fluorescein application in MB was conducted. RESULTS: In our cohort, no side effect related to fluorescein occurred; all tumors presented with an intense or moderate yellow-green enhancement, and fluorescein was judged fundamental in distinguishing tumors from viable tissue in 7 of 9 cases. Gross total resection or near-total resection (i.e., a residual tumor volume <1.5 cm3) was achieved in 8 patients. The review explored the different techniques and surgical interpretations as well as surgical radicality; we did not find a homogenous protocol for fluorescein injection in the published articles. Fluorescence appeared moderate or intense in almost all cases, with a high percentage of usefulness and consensual achievement of a high rate of gross total resection. CONCLUSIONS: Based on these results, we can infer that fluorescein-guided surgical resection is a safe and valuable method for patients with MB.

Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study.

BACKGROUND: One of the most significant challenges in patients with medulloblastoma is reducing the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients receiving lower than standard dose of CSI therapy is important to facilitate further reduction of treatment burden. METHODS: We conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with reduced-dose CSI. RESULTS: Among the patients, 23 were classified as having a standard-risk and 15 as high-risk according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months (12.0-231.0). The median CSI dose was 18 Gy (15.0-24.0) in both groups, and 5 patients in the high-risk group received a CSI dose of 18.0 Gy. Molecular subgrouping revealed that the standard-risk cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the high-risk cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 9 of the 31 Group 3/4 cases were subclassified as subclass II, III, and V, which were known to an association with poor prognosis according to the novel subtyping among the subgroups. Patients with poor prognostic subtype showed worse prognosis than that of others (5-year progression survival rate 90.4% vs. 22.2%; p < 0.0001). The result was replicated in the multivariate analysis (hazard ratio12.77, 95% confidence interval for hazard ratio 2.38-99.21, p value 0.0026 for progression-free survival, hazard ratio 5.02, 95% confidence interval for hazard ratio 1.03-29.11, p value 0.044 for overall survival). CONCLUSION: Although these findings require validation in a larger cohort, the present findings suggest that novel subtyping of Group 3/4 medulloblastoma may be a promising prognostic biomarker even among patients treated with lower-dose CSI than standard treatment.

[Medulloblastoma].

In the 5th edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called "non-WNT/non-SHH", because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma.

A nomogram for predicting post-operative hydrocephalus in children with medulloblastoma.

Post-operative hydrocephalus is common among children with medulloblastoma after initial tumor resection. This study aimed to establish a novel model for predicting the development of post-operative hydrocephalus in children with medulloblastoma. Only pediatric patients who received initial medulloblastoma resection at Beijing Tiantan Hospital between January 2018 and May 2021 were included in this study. The potential risk factors associated with post-operative hydrocephalus were identified based on multivariate logistic regression and the nomogram. Receiver operating characteristic (ROC) curve were used to evaluate the performance of the nomogram model based on an independent cohort of medulloblastoma patients who underwent surgery from June 2021 to March 2022. A total of 105 patients were included in the primary cohort. Superior invasion (P = 0.007), caudal invasion (P = 0.025), and intraventricular blood ≥ 5 mm (P = 0.045) were significantly related to the development of post-operative hydrocephalus and thus were assembled into the nomogram model. The model accurately predicted post-operative hydrocephalus based on the calibration curve. The area under the ROC curves for the primary and validation cohorts was 0.849 and 0.855, respectively. In total, the nomogram we developed may aid clinicians in assessing the potential risk of pediatric patients with MB developing post-operative hydrocephalus, especially those who would otherwise not have received a diversionary procedure at presentation.

Predictors of postoperative complications and functional outcomes in pediatric patients with surgically treated fourth ventricle tumors.

BACKGROUND: Tumors of the fourth ventricle are frequently treated pathologies in pediatric neurosurgery. Data regarding predictors for permanent neurological deficits, long-term functional outcomes, cerebellar mutism (CM), the extent of resection (EOR), and oncological outcomes are scarce. We attempt to contribute to this topic with an analysis of our institutional cohort. METHODS: A retrospective single-center study of patients aged ≤ 19 years who underwent primary surgical resection of a fourth ventricular tumor over a 15-year period (2006-2021). Predictors analyzed included age, gender, surgical approach, anatomical pattern, tumor grade, EOR, tumor volume, and others as appropriate. RESULTS: One hundred six patients were included (64 males, mean age 7.3 years). The rate of permanent neurological deficit was 24.2%; lateral tumor extension (p = 0.036) and tumor volume greater than 38 cm3 (p = 0.020) were significant predictors. The presence of a deficit was the only significant predictor of reduced (less than 90) Lansky score (p = 0.005). CM occurred in 20.8% of patients and was influenced by medulloblastoma histology (p = 0.011), lateral tumor extension (p = 0.017), and male gender (p = 0.021). No significant difference between the transvermian and telovelar approach in the development of CM was detected (p = 0.478). No significant predictor was found for the EOR. EOR was not found to be a significant predictor of overall survival for both low-grade and high-grade tumors; however, gross total resection (GTR) was protective against tumor recurrence compared to near-total or subtotal resection (p < 0.001). In addition, survival was found to be better in older patients (≥ 7.0 years, p = 0.019). CONCLUSION: The overall rate of postoperative complications remains high due to the eloquent localization. Older patients (> 7 years) have been found to have better outcomes and prognosis. Achieving GTR whenever feasible and safe has been shown to be critical for tumor recurrence. CM was more common in patients with medulloblastoma and in patients with tumors extending through the foramen of Luschka. The telovelar approach uses a safe and anatomically sparing corridor; however, it has not been associated with a lower incidence of CM and neurological sequelae in our series, showing that each case should be assessed on an individual basis.

Efficacy of dual-task training on stability and function in children with ataxia after medulloblastoma resection: A randomized controlled trial.

BACKGROUND/OBJECTIVE: In children, medulloblastoma (MB) is the most prevalent posterior fossa tumor. The first line of treatment is maximal safe resection. Therefore, symptoms of ataxia are commonly seen. Training the brain on balance and cognitive tasks makes balance more automatic than without cognitive tasks. The goal was to assess the effectiveness of dual-task practice on balance after MB excision in children with ataxia. METHODS: Thirty children with ataxia after MB resection at Children Cancer Hospital Egypt were randomized into two equal groups. Exercises for mobility, balance, and gait training were given to both groups. The research group underwent a specific dual-task program (balance and cognitive). The program ran 3 days per week for 8 weeks. Children were evaluated before and after the treatment regimen using the Scale of Assessment and Rating of Ataxia (SARA), the HUMAC Balance System, Pediatric Balance Scale, and Functional Independent Measurement. All children's legal guardians signed an ethical agreement. RESULTS: A notable improvement in balance was found in the dual group in Pediatric Balance Scale (PBS) (p = .028) and stability test (p = .0001) in favor of the study group. No discernible difference was observed in the Functional Independent Measurement score among the two groups (p = .158), although there was a statistically significant increase in both groups after treatment. CONCLUSION: Dual-task program is more effective than traditional physical therapy alone in improving balance in children with ataxia after MB resection.

The insertion and management of an external ventricular drain in pediatric patients with hydrocephalus associated with medulloblastoma.

An external ventricular drain (EVD) is used to facilitate cerebrospinal fluid (CSF) removal in medulloblastoma patients suffering from hydrocephalus. It is essential to recognize that EVD management plays a crucial role in influencing the incidence of drain-related complications. However, the ideal method for EVD management remains undetermined. Our research sought to examine the safety of EVD placement and the impact of EVD on the incidences of intracranial infections, postresection hydrocephalus, and posterior fossa syndrome (PFS). We conducted a single-center observational study involving a cohort of 120 pediatric medulloblastoma patients who were treated from 2017 to 2020. The rates of intracranial infection, postresection hydrocephalus, and PFS were 9.2%, 18.3%, and 16.7%, respectively. EVD did not influence the occurrence of intracranial infection (p = 0.466), postresection hydrocephalus (p = 0.298), or PFS (p = 0.212). A gradual EVD weaning protocol correlated with an elevated incidence of postresection hydrocephalus (p = 0.033), whereas a rapid weaning approach resulted in 4.09 ± 0.44 fewer drainage days (p < 0.001) than the gradual weaning strategy. EVD placement (p = 0.010) and intracranial infection (p = 0.002) were linked to delayed speech return, whereas a longer duration of drainage was conducive to the recovery of language function (p = 0.010). EVD insertion was not correlated with the incidence of intracranial infection, postoperative hydrocephalus, or PFS. The optimal EVD management method should encompass a rapid EVD weaning strategy, followed by prompt drain closure. We have presented additional evidence to improve the safety of EVD insertion and management in neurosurgical patients to ultimately facilitate the establishment of standardized institutional/national implementation and management protocols.

Incidence and Risk Factors for Necessitating Cerebrospinal Fluid Diversion Following Medulloblastoma Surgery in Children.

BACKGROUND: There are insufficient data on pediatric patients with medulloblastoma who require cerebrospinal fluid (CSF) diversion following resection. Therefore, this study aimed to determine the incidence and the characteristics associated with it in this subset of patients. METHODS: We conducted a single-center, retrospective, observational cohort study of patients aged 18 years or less who underwent medulloblastoma resection at our department between 2010 and 2021. The primary outcome was the incidence of CSF diversion surgery required after resection. Participant demographics, tumor biology, and interventions were analyzed using univariate- and multivariate-adjusted models. RESULTS: Of the 183 patients admitted to our department, 131 (71.6%) participated in this study. The incidence of permanent CSF diversion was 26.0% (95% confidence interval [CI]: 18.7 to 34.3). Factors independently associated with requirement of permanent CSF diversion were medulloblastoma volume >46.4 cm3 (odds ratio [OR]: 2.919, 95% CI: 1.191 to 7.156) and CSF channel invasion (OR: 2.849, 95% CI: 1.142 to 7.102). The duration of manifestation may be a covariate of tumor volume with increased risk of requirement for permanent CSF diversion (OR: 1.006, 95% CI: 1.000 to 1.013), and tumor volume may be a predictor in patients who underwent subtotal resection (OR: 4.900, 95% CI: 0.992 to 24.208, P = 0.05). Finally, patients who required permanent CSF diversion were divided according to medulloblastoma molecular subgroups, and no significant differences were found. CONCLUSION: We report major predictive factors for permanent CSF diversion surgery in patients with medulloblastoma. Our study suggests that the presence of postresection hydrocephalus is not high enough to warrant permanent, prophylactic CSF diversion in all patients.

Cerebellar mutism is linked to midbrain volatility and desynchronization from speech cortices.

Cerebellar mutism syndrome is a disorder of speech, movement and affect that can occur after tumour removal from the posterior fossa. Projections from the fastigial nuclei to the periaqueductal grey area were recently implicated in its pathogenesis, but the functional consequences of damaging these projections remain poorly understood. Here, we examine functional MRI data from patients treated for medulloblastoma to identify functional changes in key brain areas that comprise the motor system for speech, which occur along the timeline of acute speech impairment in cerebellar mutism syndrome. One hundred and twenty-four participants, all with medulloblastoma, contributed to the study: 45 with cerebellar mutism syndrome, 11 patients with severe postoperative deficits other than mutism, and 68 without either (asymptomatic). We first performed a data-driven parcellation to spatially define functional nodes relevant to the cohort that align with brain regions critical for the motor control of speech. We then estimated functional connectivity between these nodes during the initial postoperative imaging sessions to identify functional deficits associated with the acute phase of the disorder. We further analysed how functional connectivity changed over time within a subset of participants that had suitable imaging acquired over the course of recovery. Signal dispersion was also measured in the periaqueductal grey area and red nuclei to estimate activity in midbrain regions considered key targets of the cerebellum with suspected involvement in cerebellar mutism pathogenesis. We found evidence of periaqueductal grey dysfunction in the acute phase of the disorder, with abnormal volatility and desynchronization with neocortical language nodes. Functional connectivity with periaqueductal grey was restored in imaging sessions that occurred after speech recovery and was further shown to be increased with left dorsolateral prefrontal cortex. The amygdalae were also broadly hyperconnected with neocortical nodes in the acute phase. Stable connectivity differences between groups were broadly present throughout the cerebrum, and one of the most substantial differences-between Broca's area and the supplementary motor area-was found to be inversely related to cerebellar outflow pathway damage in the mutism group. These results reveal systemic changes in the speech motor system of patients with mutism, centred on limbic areas tasked with the control of phonation. These findings provide further support for the hypothesis that periaqueductal grey dysfunction (following cerebellar surgical injury) contributes to the transient postoperative non-verbal episode commonly observed in cerebellar mutism syndrome but highlights a potential role of intact cerebellocortical projections in chronic features of the disorder.

Diagnosis of medulloblastoma in pregnant women: To continue with the pregnancy or not? A case report and literature review.

BACKGROUND: Medulloblastoma (MB) is an uncommon and challenging diagnosis in pregnant women, and especially in pregnancy after in-vitro fertilization (IVF). Clinical features are easily misinterpreted and mistaken for other more common gestation-related pathologies. We report the case of a 34-year-old patient with clinical symptoms of intracranial hypertension. MB was diagnosed and operated on during the pregnancy. OBJECTIVE: To conduct a systematic literature review of other cases of MB operated on during pregnancy, and discuss the clinical and surgical management of MB in pregnancy. METHOD: We conducted a systematic literature review according to PRISMA guidelines. RESULTS: In addition to the present case, 9 cases of MB were reported as operated on during viable pregnancy. In one case, medical abortion was decided on before surgical debulking. Pregnancy term was between 8 and 30 weeks. The most common symptoms were headache, nausea and vomiting followed by dizziness. Tumor prognosis after treatment was favorable in 6 cases out of 10 and unfavorable in 4, with 3 cases of recurrence and 3 of death. CONCLUSION: We report the first case of long-term survival after MB in a woman pregnant via IVF. In standard-risk MB, it is possible to carry the pregnancy to term. Vaginal delivery is not contraindicated a priori. Early diagnosis, close clinical and radiological surveillance and surgery are the key factors for better prognosis. Multidisciplinary collaboration is crucial to determine the best timing and treatment.

Resection cavity auto-contouring for patients with pediatric medulloblastoma using only CT information.

PURPOSE: Target delineation for radiation therapy is a time-consuming and complex task. Autocontouring gross tumor volumes (GTVs) has been shown to increase efficiency. However, there is limited literature on post-operative target delineation, particularly for CT-based studies. To this end, we trained a CT-based autocontouring model to contour the post-operative GTV of pediatric patients with medulloblastoma. METHODS: One hundred four retrospective pediatric CT scans were used to train a GTV auto-contouring model. Eighty patients were then preselected for contour visibility, continuity, and location to train an additional model. Each GTV was manually annotated with a visibility score based on the number of slices with a visible GTV (1 = < 25%, 2 = 25-50%, 3 = > 50-75%, and 4 = > 75-100%). Contrast and the contrast-to-noise ratio (CNR) were calculated for the GTV contour with respect to a cropped background image. Both models were tested on the original and pre-selected testing sets. The resulting surface and overlap metrics were calculated comparing the clinical and autocontoured GTVs and the corresponding clinical target volumes (CTVs). RESULTS: Eighty patients were pre-selected to have a continuous GTV within the posterior fossa. Of these, 7, 41, 21, and 11 were visibly scored as 4, 3, 2, and 1, respectively. The contrast and CNR removed an additional 11 and 20 patients from the dataset, respectively. The Dice similarity coefficients (DSC) were 0.61 ± 0.29 and 0.67 ± 0.22 on the models without pre-selected training data and 0.55 ± 13.01 and 0.83 ± 0.17 on the models with pre-selected data, respectively. The DSC on the CTV expansions were 0.90 ± 0.13. CONCLUSION: We successfully automatically contoured continuous GTVs within the posterior fossa on scans that had contrast > ± 10 HU. CT-Based auto-contouring algorithms have potential to positively impact centers with limited MRI access.

Placement of EVD in pediatric posterior fossa tumors: safe and efficient or old-fashioned? The Vienna experience.

PURPOSE: The perioperative treatment of hydrocephalus in pediatric posterior fossa tumors with an external ventricular drain (EVD) is the treatment of choice in our center. We analyzed our experience in using EVD concerning safety and effectivity. METHODS: This is a single-center retrospective cohort study of 100 consecutive pediatric patients who underwent resection for a newly diagnosed tumor in the posterior fossa between 2011 and 2022. RESULTS: Of the 100 patients with posterior fossa tumors, 80 patients (80%) had radiological signs of hydrocephalus at presentation, 49 patients (49%) of whom underwent placement of an EVD. In 40 patients, the EVD was inserted at a mean of 2.25 days prior to the tumor resection; 9 had the EVD inserted during tumor resection (frontal trajectory in 7 patients, occipital trajectory in 2 patients). Histology revealed pilocytic astrocytoma in 48 patients, medulloblastoma in 32, ependymoma in 11, and other histologic entities in 9 patients. Gross total/near-total resection was achieved in 46 (95.83%) of the 48 pilocytic astrocytomas, 30 (93.75%) of the 32 medulloblastomas, and 11 (100%) of the 11 ependymomas. The mean number of total days with the EVD in place was 8.61 ± 3.82 (range 2-16 days). The mean number of days with an EVD after tumor resection was 6.35 ± 3.8 (range 0-16 days). EVD-associated complications were seen in 6 patients (12.24%) including one infection. None of these resulted in a worse clinical course or any long-term sequelae. Permanent CSF diversion at 6 months after surgery was necessary in 13 patients (13%), including two VP shunt, two SD-shunt, six endoscopic third ventriculostomy (ETV), and three combined VP shunt and ETV procedures. Patients with a medulloblastoma or ependymoma had a higher rate of permanent CSF diversion needed than the group of pilocytic astrocytoma patients (27.9% versus 2.13%, p < 0.001). In patients with metastatic disease, 7 of 17 patients (41.18%) needed a permanent CSF diversion, compared to 6 of 83 patients (7.23%) in the group without metastasis (p = 0.001). CONCLUSION: The treatment of hydrocephalus in pediatric posterior fossa tumors with an EVD as a temporary measure is safe and effective, provided that a multi-professional understanding for its handling is given and there is no need for a long transport of the children.

Molecular subgroup of medulloblastoma: evaluation of contribution to CSF diversion following tumour resection.

INTRODUCTION: Medulloblastoma is the commonest malignant brain tumour in children. Pre-operative hydrocephalus is present in up to 90% of these patients at presentation. Following posterior fossa surgery, despite resolution of fourth ventricular obstruction, a proportion of these children will still require cerebrospinal fluid (CSF) diversion for management of persistent or new hydrocephalus. Various scoring systems have been developed to predict the risk for CSF diversion following posterior fossa surgery. However, no accurate tool exists regarding which pathological subset or group of medulloblastoma patients will require a shunt post-operatively. In this study we investigated the impact of molecular subgroup of medulloblastoma on shunt dependency post-operatively in paediatric patients. METHODS: We undertook a retrospective multi-centre study of children with medulloblastoma who underwent tumour resection. Those with available molecular subgroup were identified. Demographic data and clinical parameters including age, sex, presence of pre-operative hydrocephalus, extent of surgical resection, evidence of metastasis/leptomeningeal disease and need for CSF diversion post-operatively were further analysed. RESULTS: Sixty-nine children with medulloblastoma with available molecular data were identified during the study period with male to female ratio of 1.5:1 (42M:27F). Twelve patients (17.4%) belonged to SHH, 10 (14.5%) Wnt, 19 (27.5%) Group 3 and 15 (21.7%) Group 4; 13 (18.8%) were non-specified Group 3 or 4. A total of 18 (26%) patients had evidence of leptomeningeal disease at presentation (20% of Wnt, 42% of Group 3, 33% of group 4, 23% of group 3/4, and 0% of SHH). Fifteen patients (22%) underwent post-operative ventriculoperitoneal (VP) shunt insertion. No patient in the Wnt group required ventriculoperitoneal (VP) shunt post-operatively in this cohort. Need for shunt was associated with pre-operative hydrocephalus, leptomeningeal disease, with molecular group 3 or 4 demonstrating higher rate of leptomeningeal disease, and pre-operative hydrocephalus. Age, extent of resection and pre-operative EVD were not associated with need for shunt in this cohort. Regression analysis identified only pre-operative hydrocephalus and leptomeningeal disease as independent predictors of need for shunt post-resection in this cohort. CONCLUSION: All patients requiring permanent post-operative VP shunt belonged to non-Wnt groups, particularly group 3 and 4. Although medulloblastoma subgroup does not independently predict need for post-operative shunt, presence of leptomeningeal disease and pre-operative hydrocephalus, and their higher prevalence in group 3 and 4, likely account for observed higher rate of shunting in these groups.