Male Predisposition in Cerebellar Mutism Syndrome: a Cohort Study.

The aim of this study was to explore the association between sex and cerebellar mutism syndrome and to examine other potential risk factors. This ambispective cohort study examined 218 pediatric patients (132 boys) with a posterior fossa tumor who underwent tumor resection from July 2013 to March 2021. The patients' demographics and tumor characteristics were examined and statistically analyzed to explore the associations among the variables. Multivariable and subgroup analyses were conducted to validate the independent risk factors for cerebellar mutism syndrome (CMS). The male and female patients did not differ significantly in terms of age, tumor size, tumor location, tumor consistency, VP shunt placement before resection, extent of resection, or surgeon, as well as with respect to the presence of hydrocephalus or paraventricular edema. The overall incidence of CMS was 32.6%. The incidence of CMS was significantly higher in male patients than that in female patients (41.7% vs. 18.6%; P = 0.001). In the multivariable analysis, male sex (adjusted odds ratio [OR], 3.27; P = 0.001), solid tumor consistency (adjusted OR, 5.61; P = 0.001), midline location (adjusted OR, 3.78; P = 0.004), and hydrocephalus (adjusted OR, 2.56; P = 0.047) were independent risk factors for the CMS. Chi-square analysis revealed that solid tumor consistency and midline location were associated with medulloblastoma (P < 0.001). Male patients had a higher risk of developing CMS after a posterior fossa tumor resection. Midline location, solid tumor consistency, and hydrocephalus were independent risk factors for CMS.

Older age is a protective factor for academic achievements irrespective of treatment modalities for posterior fossa brain tumours in children.

The treatment of children with posterior fossa brain tumours (PFBT) impacts their long term functional and imaging outcomes. This study aimed to evaluate academic achievement correlated with long-term sequelae after different PFBT treatment modalities. The study cohort consisted of 110 survivors (median age at diagnosis 10.1 years and median time of follow up 13.2 years) who completed hearing questionnaires, neurological assessment and MRI of the brain ≥5 years after the end of treatment. There were three treatment groups. A cisplatin group which underwent cisplatin chemotherapy, radiotherapy and surgery (medulloblastoma N = 40), a radiotherapy group which underwent radiotherapy and surgery (astrocytoma/ependymoma N = 30), and a surgery group (astrocytoma N = 40). Academic achievement was correlated to the age at diagnosis, ototoxicity, Karnofsky score (KS), and MRI findings (Fazekas Score (FS)- treatment related parenchymal changes). For a modelled age at diagnosis of five years, the cisplatin group had lower academic achievements compared to the radiotherapy (p = 0.028) and surgery (p = 0.014) groups. Academic achievements evaluated at a modelled age of 10 years at diagnosis did not significantly differ among the treatment groups. The cisplatin group exhibited a higher occurrence of ototoxicity than the radiotherapy (p<0.019) and surgery groups (p<0.001); however, there was no correlation between ototoxicity and academic achievements (p = 0.722) in older age at diagnosis. The radiotherapy group exhibited lower KS than the surgery group (p<0.001). KS significantly influenced academic achievements in all groups (p<0.000). The cisplatin group exhibited higher FS than the surgery group (p<0.001) while FS did not correlate with academic achievement (p = 0.399). Older age is a protective factor for academic achievements irrespective of a treatment modality.

Genetic predisposition to longer telomere length and risk of childhood, adolescent and adult-onset ependymoma.

Ependymoma is the third most common brain tumor in children, with well-described molecular characterization but poorly understood underlying germline risk factors. To investigate whether genetic predisposition to longer telomere length influences ependymoma risk, we utilized case-control data from three studies: a population-based pediatric and adolescent ependymoma case-control sample from California (153 cases, 696 controls), a hospital-based pediatric posterior fossa type A (EPN-PF-A) ependymoma case-control study from Toronto's Hospital for Sick Children and the Children's Hospital of Philadelphia (83 cases, 332 controls), and a multicenter adult-onset ependymoma case-control dataset nested within the Glioma International Case-Control Consortium (GICC) (103 cases, 3287 controls). In the California case-control sample, a polygenic score for longer telomere length was significantly associated with increased risk of ependymoma diagnosed at ages 12-19 (P = 4.0 × 10-3), but not with ependymoma in children under 12 years of age (P = 0.94). Mendelian randomization supported this observation, identifying a significant association between genetic predisposition to longer telomere length and increased risk of adolescent-onset ependymoma (ORPRS = 1.67; 95% CI 1.18-2.37; P = 3.97 × 10-3) and adult-onset ependymoma (PMR-Egger = 0.042), but not with risk of ependymoma diagnosed before age 12 (OR = 1.12; 95% CI 0.94-1.34; P = 0.21), nor with EPN-PF-A (PMR-Egger = 0.59). These findings complement emerging literature suggesting that augmented telomere maintenance is important in ependymoma pathogenesis and progression, and that longer telomere length is a risk factor for diverse nervous system malignancies.

Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features - a retrospective analysis of the HIT ependymoma trial cohort.

INTRODUCTION: Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols. METHODS: Tumor samples of 134 patients aged 0.2-15.9 years treated between 1999 and 2010 according to HIT protocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and genomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier method with log rank test and multivariate Cox regression analysis. RESULTS: Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as predictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features including vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox regression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS and OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that separates patients with standard, intermediate and high risk, and which outperforms current stratification procedures. CONCLUSION: The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification model for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide the basis for risk-adapted treatment of children with ependymomas of the posterior fossa.

Outcome after surgery in supratentorial and infratentorial solitary brain metastasis.

BACKGROUND: The aim of this retrospective study was to investigate and compare the outcome after surgery in patients with a supratentorial solitary metastasis (SSM) and an infratentorial solitary metastasis (ISM). A worse prognosis has been reported in ISM. METHODS: Fifty-two patients with a newly diagnosed solitary brain metastasis on MRI were included to identify risk factors affecting the outcome. Key variables included tumor size, staging of the primary tumor, time span of presurgical work-up, and surgical technique. Outcome variables included postoperative complications, tumor recurrence, and mortality. Kaplan-Meier survival analysis was applied. RESULTS: Thirty patients with a SSM and 22 patients with an ISM underwent gross total resection. The tumor size did not have a statistical significant effect on survival. Presurgical work-up time was similar in SSM and ISM. Postoperative complications were more frequently encountered in ISM. Recurrence rate was comparable in SSM and ISM. Carcinomatous meningitis (CM) was more frequently seen in ISM, and CM was seen more often with the piecemeal resection technique. There was no statistical difference in overall survival between SSM and ISM. CONCLUSIONS: This study identified factors that play a role in the outcome after surgery in patients with ISM and SSM on MRI. Postoperative complications seemed to be higher in ISM and CM was more often seen in ISM, but the worse prognosis in patients with ISM compared with SSM could not be confirmed.

Visual Complications of Pediatric Posterior Fossa Tumors: Analysis of Outcomes.

OBJECTIVE: Visual abnormalities are common among children with posterior fossa tumors, resulting from disruption of ocular afferent and efferent systems due to the tumor or surgery. This study describes the visual complications and outcomes associated with these tumors. METHODS: Clinical and radiographic data of patients who underwent index surgery for resection of posterior fossa tumor from 2007 to 2016 were reviewed. Descriptive statistics, univariate, and multivariate regression were performed to assess factors contributing to visual acuity and postoperative strabismus. RESULTS: There were 182 patients who underwent posterior fossa craniotomy for neoplasm were included. Ophthalmologic symptoms were the fourth most common presenting complaint; initial ophthalmologic examination was abnormal in 40% of patients. Evaluation of visual acuity demonstrated a good outcome in 88% of patients following treatment. The most common postoperative oculomotor finding was esotropia (29%) which resolved spontaneously in more than half of patients. A good outcome was obtained in all patients who underwent surgery for esotropia. Hypertropia was noted in 14% of the cohort and less than half resolved spontaneously; less than half undergoing strabismus surgery for hypertropia had a good outcome. Multivariate analysis confirmed the association between cerebellar mutism and postoperative esotropia and hypertropia. Clinically significant pathological nystagmus was seen in 8% of the cohort. CONCLUSIONS: Our results indicate a good visual outcome in the majority of pediatric patients undergoing resection of posterior fossa tumors. Ophthalmologic complications should be appropriately evaluated and addressed to allow for the best possible vision to survivors of posterior fossa tumors.

Suboccipital Craniotomy Versus Craniectomy: A Survey of Practice Patterns.

OBJECTIVE: Open surgical access to the posterior fossa traditionally has been achieved by permanent bone removal and remains the mainstay of posterior fossa surgery, although craniotomy is an alternative. Considerable variation exists at both the national and international levels within a variety of neurologic and neurosurgical disciplines. In this study, we surveyed current practice patterns regarding preference of suboccipital craniotomy or craniectomy. METHODS: The membership directory of the American Academy of Neurological Surgeons was reviewed. SurveyMonkey was used to distribute the survey to members of the American Academy of Neurological Surgeons via a modified Dillman method for e-mail correspondence. Comparisons of frequency distributions, means, and medians, as well as multiple logistic regression were used to determine surgical preferences for craniotomy versus craniectomy. RESULTS: We received 1102 responses (19.6%). Overall, 542 (49.7%) respondents prefer craniotomy and 548 (50.3%) prefer craniectomy. Respondents who prefer craniotomy had completed a residency more recently than respondents who preferred craniectomy (15.9 vs. 21.1 years, P < 0.0001) and were more likely to practice outside of North America (P < 0.01). Some 81.4% of pediatric neurosurgeons prefer craniotomy compared with 43.6% of adult neurosurgeons (P < 0.0001). Craniotomy was most highly preferred for tumor resection and vascular malformation. Within the United States, there was significant variation in preference for craniotomy based on geographic region, with New England most commonly preferring craniotomy and the Mid-Atlantic region most commonly preferring craniectomy. CONCLUSIONS: Our results show that preference for suboccipital craniotomy or craniectomy varies according to geographic location of practice, time since completing residency, and age of patient population.

[Brain tumors in children: about 136 cases]. / Tumeurs cérébrales de l'enfant: à propos de 136 cas.

Brain tumors are the most diagnosed solid tumors in children under the age of 15 years worldwide. However, the epidemiological and anatomopathological profile of these tumors has been poorly described in African and, particularly, in Moroccan literature. This study highlights the epidemiological and anatomopathological peculiarities of primary brain tumors in children living in the region of Marrakech (south Morocco). We conducted a retrospective study in the Division of Anatomic Pathology at the Mohammed VI University Hospital, Marrakech from 2004 to 2016. One hundred and thirty-six patients were diagnosed with primary brain tumor, a mean of 11.33 cases per year. The average age of patients was 8.28 years. Sex-ratio (M/F) was 1.6 with a slight male predominance. Infratentorial tumors were found in 61,53% of cases while supratentorial tumors were found in 38.47% of cases. Infratentorial tumors mainly occurred in the cerebellar hemisphere (61.4%). Eighteen histological types were diagnosed. Astrocytoma and medulloblastoma accounted for 46,32% (29.41% and 16.91%, respectively). In our context, the majority of brain tumors in children was predominant in both age groups: 5-9 years and 10-15 years. The epidemiological data of these tumors from south Morocco are mostly consistent with those already published in North Country's literature and in other non-african countries' literature.

A Review of Visual and Oculomotor Outcomes in Children With Posterior Fossa Tumors.

Tumors of the posterior fossa represent the most common solid malignancy of childhood and can affect the visual system in several ways. This article outlines the relevant visual anatomy affected by these tumors and reviews the visual and oculomotor outcomes associated with the following 3 most common tumor types-medulloblastoma, juvenile pilocytic astrocytoma, and ependymoma. The available data suggest that the rate of permanent vision loss is low (5.9%-8.3%), with patients having juvenile pilocytic astrocytoma demonstrating the best outcomes. The rate of long-term strabismus (25%-29.1%) and nystagmus (12.5%-18%) is higher and associated with significant morbidity.

Cerebellar mutism syndrome in children with brain tumours of the posterior fossa.

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.