OBJECTIVESThe goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors.METHODSAll patients referred to the authors’ institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications.RESULTSThree hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment.Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach.CONCLUSIONSSurgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population.

Background Diffuse Intrinsic pontine gliomas (DIPGs) are lethal pediatric brain tumors. Presently, MRI is the mainstay of disease diagnosis and surveillance. We identify clinically significant computational features from MRI and create a prognostic machine learning model. Methods We isolated tumor volumes of T1-post contrast (T1) and T2-weighted (T2) MRIs from 177 treatment-naïve DIPG patients from an international cohort for model training and testing. The Quantitative Image Feature Pipeline and PyRadiomics was used for feature extraction. Ten-fold cross-validation of LASSO Cox regression selected optimal features to predict overall survival (OS) in the training dataset and tested in the independent testing dataset. We analyzed model performance using clinical variables (age at diagnosis and sex) only, radiomics only, and radiomics plus clinical variables. Results All selected features were intensity and texture-based on the wavelet filtered images (three T1 grey-level co-occurrence matrix (GLCM) texture features, T2 GLCM texture feature, and T2 first order-mean). This multivariable Cox model demonstrated a concordance of 0.68 [95% CI: 0.61-0.74] in the training dataset, significantly outperforming the clinical-only model (C=0.57 [95% CI: 0.49-0.64]). Adding clinical features to radiomics slightly improved performance (C=0.70 [95% CI: 0.64-0.77]). The combined radiomics and clinical model was validated in the independent testing dataset (C=0.59 [95% CI: 0.51-0.67], Noether’s test p=0.02). Conclusion In this international study, we demonstrate the use of radiomic signatures to create a machine learning model for DIPG prognostication. Standardized, quantitative approaches that objectively measure DIPG changes, including computational MRI evaluation, could offer new approaches to assessing tumor phenotype and serve a future role for optimizing clinical trial eligibility and tumor surveillance.

BACKGROUND Clinicians and machine classifiers reliably diagnose pilocytic astrocytoma (PA) on magnetic resonance imaging (MRI) but less accurately distinguish medulloblastoma (MB) from ependymoma (EP). One strategy is to first rule out the most identifiable diagnosis. OBJECTIVE To hypothesize a sequential machine-learning classifier could improve diagnostic performance by mimicking a clinician's strategy of excluding PA before distinguishing MB from EP. METHODS We extracted 1800 total Image Biomarker Standardization Initiative (IBSI)-based features from T2- and gadolinium-enhanced T1-weighted images in a multinational cohort of 274 MB, 156 PA, and 97 EP. We designed a 2-step sequential classifier – first ruling out PA, and next distinguishing MB from EP. For each step, we selected the best performing model from 6-candidate classifier using a reduced feature set, and measured performance on a holdout test set with the microaveraged F1 score. RESULTS Optimal diagnostic performance was achieved using 2 decision steps, each with its own distinct imaging features and classifier method. A 3-way logistic regression classifier first distinguished PA from non-PA, with T2 uniformity and T1 contrast as the most relevant IBSI features (F1 score 0.8809). A 2-way neural net classifier next distinguished MB from EP, with T2 sphericity and T1 flatness as most relevant (F1 score 0.9189). The combined, sequential classifier was with F1 score 0.9179. CONCLUSION An MRI-based sequential machine-learning classifiers offer high-performance prediction of pediatric posterior fossa tumors across a large, multinational cohort. Optimization of this model with demographic, clinical, imaging, and molecular predictors could provide significant advantages for family counseling and surgical planning.

PurposeTo determine the value of structural magnetic resonance imaging (MRI) in predicting post-operative paediatric cerebellar mutism syndrome (pCMS) in children undergoing surgical treatment for medulloblastoma.MethodsRetrospective cohort study design. Electronic/paper case note review of all children with medulloblastoma presenting to Great Ormond Street Hospital between 2003 and 2013. The diagnosis of pCMS was established through a scoring system incorporating mutism, ataxia, behavioural disturbance and cranial nerve deficits. MRI scans performed at three time points were assessed by neuroradiologists blinded to the diagnosis of pCMS.ResultsOf 56 children included, 12 (21.4%) developed pCMS as judged by a core symptom of mutism. pCMS was more common in those aged 5 or younger. There was no statistically significant difference in pre-operative distortion or signal change of the dentate or red nuclei or superior cerebellar peduncles (SCPs) between those who did and did not develop pCMS. In both early (median 5 days) and late (median 31 months) post-operative scans, T2-weighted signal change in SCPs was more common in the pCMS group (p = 0.040 and 0.046 respectively). Late scans also showed statistically significant signal change in the dentate nuclei (p = 0.024).ConclusionsThe development of pCMS could not be linked to any observable changes on pre-operative structural MRI scans. Post-operative T2-weighted signal change in the SCPs and dentate nuclei underlines the role of cerebellar efferent injury in pCMS. Further research using advanced quantitative MRI sequences is warranted given the inability of conventional pre-surgical MRI to predict pCMS.

Post-operative paediatric cerebellar mutism syndrome (pCMS) occurs in around 25% of children undergoing surgery for cerebellar and fourth ventricular tumours. Reversible mutism is the hallmark of a syndrome which comprises severe motor, cognitive and linguistic deficits. Recent evidence from advanced neuroimaging studies has led to the current theoretical understanding of the condition as a form of diaschisis contingent on damage to efferent cerebellar circuitry. Tractography data derived from diffusion MRI studies have shown disruption of the dentato-rubrothalamo-cortical tract in patients with pCMS, and perfusion studies have indicated widespread supratentorial regions which may give rise to the florid signs and symptoms of pCMS. Given the difficulties in predicting pCMS from standard structural MRI, this review discusses findings from quantitative MRI modalities which have contributed to our understanding of this debilitating syndrome, and considers the goals and challenges which lie ahead in the field.

Background Cerebellar mutism syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need for subgroup-specific analysis. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of CMS. Methods We assembled a cohort of 370 molecularly characterized medulloblastoma subjects with available neuroimaging from 5 sites globally, including Great Ormond Street Hospital, Christian Medical College and Hospital, the Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children’s Hospital. Age at diagnosis, sex, tumor volume, and CMS development were assessed in addition to molecular subgroup. Results Overall, 23.8% of patients developed CMS. CMS patients were younger (mean difference −2.05 years ± 0.50, P = 0.0218) and had larger tumors (mean difference 10.25 cm3 ± 4.60, P = 0.0010) that were more often midline (odds ratio [OR] = 5.72, P < 0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumor volume, Wingless (adjusted OR = 4.91, P = 0.0063), Group 3 (adjusted OR = 5.56, P = 0.0022), and Group 4 (adjusted OR = 8.57 P = 9.1 × 10−5) tumors were found to be independently associated with higher risk of CMS compared with sonic hedgehog tumors. Conclusions Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumor volume and midline location. These findings have significant implications for management of both the tumor and CMS.

ObjectiveTo examine patient knowledge about sudden unexpected death in epilepsy (SUDEP) compared to other risks in epilepsy. To explore patients’ experiences surrounding SUDEP disclosure and opinions on how information should be delivered.DesignA cross-sectional questionnaire.SettingRoyal Free Hospital, London outpatient epilepsy clinics.ParticipantsNew and follow-up patients attending epilepsy clinics at a London teaching hospital over six months. Patients identified as being at risk of suffering negative emotional or psychological consequences of SUDEP discussions were excluded.Main outcome measuresPatient knowledge about epilepsy risks; patient opinion regarding source, timing and delivery of SUDEP information; impact on health seeking behaviour.ResultsNinety-eight per cent of patients were aware of medication adherence, 84% of factors influencing seizure frequency, 78% of driving regulations, 50% of SUDEP and 38% of status epilepticus; 72% of patients felt that SUDEP information should be given to all patients. Preferences for timing of SUDEP discussions varied between those wanting information at diagnosis (40%) and those preferring to receive it after three clinic appointments (18%) to avoid information overload at the first consultation. Emotional responses (48% positive, 38% negative) predominated over measurable behavioural change following SUDEP discussions.ConclusionsLess than half the patients knew about SUDEP and status epilepticus. Although the majority of patients with epilepsy wish to be informed about SUDEP early on in their diagnosis, information must be delivered in a way that promotes patient knowledge and empowerment.

Purpose of review: This review discusses the evidence base behind current and emerging strategies of management of intracranial and spinal ependymoma in children, with a particular focus on aspects of surgical techniques, challenges and complications. Recent findings: The cornerstone of management remains maximal safe resective surgery, which has repeatedly been shown to correlate with improved survival. This is followed by focal conformal radiotherapy, although good results using proton beam therapy, with the potential for diminished side effects, are emerging. The role of chemotherapy remains largely unproven for paediatric ependymoma. Despite optimal management strategies, many children with ependymoma suffer from tumour recurrence.