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Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (

Objective Encephaloceles are considered to result from defects in the developing skull through which meninges, and potentially brain tissue, herniate. The pathological mechanism underlying this process is incompletely understood. We aimed to describe the location of encephaloceles through the generation of a group atlas to determine whether they occur at random sites or clusters within distinct anatomical regions. Methods Patients diagnosed with cranial encephaloceles or meningoceles were identified from a prospectively maintained database between 1984 and 2021. Images were transformed to atlas space using non-linear registration. The bone defect, encephalocele and herniated brain contents were manually segmented allowing for a 3-dimensional heat map of encephalocele locations to be generated. The centroids of the bone defects were clustered utilising a K-mean clustering machine learning algorithm in which the elbow method was used to identify the optimal number of clusters. Results Of the 124 patients identified, 55 had volumetric imaging in the form of MRI (48/55) or CT (7/55) that could be used for atlas generation. Median encephalocele volume was 14704 [IQR 3655–86746] mm3 and the median surface area of the skull defect was 679 [IQR 374–765] mm2. Brain herniation into the encephalocele was found in 45% (25/55) with a median volume of 7433 [IQR 3123–14237] mm3. Application of the elbow method revealed 3 discrete clusters: 1) Anterior skull base (22%; 12/55), 2) Parieto-occipital junction (45%; 25/55) and 3) Peri-torcular (33%; 18/55). Cluster analysis revealed no correlation between the location of the encephalocele with gender [χ2 (2, n = 91) = 3.86, p = 0.15]. Compared to expected population frequencies, encephaloceles were relatively more common in Black, Asian and Other compared to White ethnicities. A falcine sinus was identified in 51% (28/55) of cases. Falcine sinuses were more common [χ2 (2, n = 55) = 6.09, p = 0.05] whilst brain herniation was less common [χ2 (2, n = 55) = .16.24, p

Background and ObjectivesApproximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar outflow pathway is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort.MethodsWe evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated ‘lesion-symptom map’ of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/).ResultsWe found supporting evidence for both hypotheses. Compared with CMS-patients, CMS+ patients (n=10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen’s d=.73, p=.05), and the CMS lesion-symptom map (Cohen’s d=1.1, p=.004).DiscussionThese results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.

Background The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB. Methods We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers. Results For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86. Conclusions We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.

INTRODUCTION Hydrocephalus persists in 10-40% of children with posterior fossa tumours (PFT). A delay in commencement of adjuvant therapy (AT) can negatively influence survival. The objective of this study was to determine whether postoperative cerebrospinal fluid (CSF) diversion procedures caused potentially preventable delays in AT. METHODS A retrospective study of children diagnosed with PFT requiring AT from 2004 to 2018 from two large centres was conducted. Data on histology, timing of ventriculo-peritoneal shunt (VPS) insertion, and AT was collected. The modified Canadian Preoperative Prediction Rule for Hydrocephalus (mCPPRH) score was calculated. The primary outcome was delay in AT beyond 40 days post-resection. Progression-free and overall survival were assessed. RESULTS Out of 196 primary PFT resections, 144 fitted the inclusion criteria. Mean age was 6.57 ± 4.62. Histology was medulloblastoma (104), ependymoma (27), and others (13). Forty patients had a VPS inserted; 17 of these experienced a delay in AT. A total of 104 patients were not shunted; 15 of these had delayed AT (p = 0.0007). Patients who had a VPS insertion had longer intervals from surgery to commencement of AT (34.5 vs 30.8, p = 0.05). There was no significant difference in mCPPRH score between those who had a VPS (4.03) and those who did not (3.61; p = 0.252). Multivariable linear regression modelling did not show a significant effect of VPS or mCPPRH on progression-free survival or OS. CONCLUSION CSF diversion procedures may cause a preventable delay in the initiation of adjuvant therapy. Early post-operative VP shunt insertion, rather than a 'wait and see policy' should be considered in order to reduce this delay.

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.

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.

The dentato-rubro-thalamo-cortical tract (DRTC) is the main outflow pathway of the cerebellum, contributing to a finely balanced corticocerebellar loop involved in cognitive and sensorimotor functions. Damage to the DRTC has been implicated in cerebellar mutism syndrome seen in up to 25% of children after cerebellar tumor resection. Multi-shell diffusion MRI (dMRI) combined with quantitative constrained spherical deconvolution tractography and multi-compartment spherical mean technique modeling was used to explore the frontocerebellar connections and microstructural signature of the DRTC in 30 healthy children. The highest density of DRTC connections were to the precentral (M1) and superior frontal gyri (F1), and from cerebellar lobules I–IV and IX. The first evidence of a topographic organization of anterograde projections to the frontal cortex at the level of the superior cerebellar peduncle (SCP) is demonstrated, with streamlines terminating in F1 lying dorsomedially in the SCP compared to those terminating in M1. The orientation dispersion entropy of DRTC regions appears to exhibit greater contrast than that shown by fractional anisotropy. Analysis of a separate reproducibility cohort demonstrates good consistency in the dMRI metrics described. These novel anatomical insights into this well-studied pathway may prove to be of clinical relevance in the surgical resection of cerebellar tumors.

Cerebellar mutism syndrome (CMS) is a severe neurological complication of posterior fossa tumour surgery in children, and postoperative speech impairment (POSI) is the main component. Left-handedness was previously suggested as a strong risk factor for POSI. The aim of this study was to investigate the relationship between handedness and the risk of POSI.We prospectively included children (aged 18 years) undergoing surgery for posterior fossa tumours in 26 European centres. Handedness was assessed pre-operatively and postoperative speech status was categorised as either POSI (mutism or reduced speech) or habitual speech, based on the postoperative clinical assessment. Logistic regression was used in the risk factor analysis of POSI as a dichotomous outcome.Of the 500 children included, 37 (7%) were excluded from the present analysis due to enrolment at a reoperation; another 213 (43%) due to missing data about surgery (n = 37) and/or handedness (n = 146) and/or postoperative speech status (n = 53). Out of the remaining 250 (50%) patients, 20 (8%) were left-handed and 230 (92%) were right-handed. POSI was observed equally frequently regardless of handedness (5/20 [25%] in left-handed, 61/230 [27%] in right-handed, OR: 1.08 [95% CI: 0.40-3.44], p = 0.882), also when adjusted for tumour histology, location and age.We found no difference in the risk of POSI associated with handedness. Our data do not support the hypothesis that handedness should be of clinical relevance in the risk assessment of CMS.

BACKGROUND: Postoperative paediatric cerebellar mutism syndrome (pCMS) is a common but severe complication which may arise following the resection of posterior fossa tumours in children. Two previous studies have aimed to preoperatively predict pCMS, with varying results. In this work, we examine the generalisation of these models and determine if pCMS can be predicted more accurately using an artificial neural network (ANN). METHODS: An overview of reviews was performed to identify risk factors for pCMS, and a retrospective dataset collected as per these defined risk factors from children undergoing resection of primary posterior fossa tumours. The ANN was trained on this dataset and its performance evaluated in comparison to logistic regression and other predictive indices via analysis of receiver operator characteristic curves. Area under the curve (AUC) and accuracy were calculated and compared using a Wilcoxon signed rank test, with p

Aims Cerebellar mutism syndrome occurs in 25% of children following resection of posterior fossa tumours. Characterised by mutism, emotional lability and cerebellar motor signs, the syndrome is usually reversible over weeks to months. Its pathophysiology remains unclear, but evidence from diffusion MRI studies has implicated damage to the superior cerebellar peduncles in the development of this condition. The objective of this study was to describe the application of automated tractography of the cerebellar peduncles to provide a high-resolution spatiotemporal profile of diffusion MRI changes in cerebellar mutism syndrome. Method A retrospective case-control study was performed at Lucille Packard Children’s Hospital, Stanford University. Thirty children with midline medulloblastoma (mean age ± standard deviation 8.8 ± 3.8 years) underwent volumetric T1-weighted and diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, were included as age- and sex-matched controls. Cerebellar mutism syndrome status was determined by contemporaneous casenote review. Automated Fibre Quantification was used to segment each subject’s cerebellar peduncles (Figure 1), and fractional anisotropy was computed at 30 nodes along each tract. A non-parametric permutation-based method was used to generate a critical cluster size and p-value for by-node ANOVA group comparisons. Z-scores for patients’ fractional anisotropy at each node were calculated based on values from controls’ corresponding nodes; these were analysed using mixed ANOVA with post-hoc false discovery rate-corrected pairwise t-tests. Results 13 patients developed cerebellar mutism syndrome. Automated fibre segmentation successfully identified the cerebellar peduncles in the majority of participants, but was more robust at follow-up timepoints (78.7% vs. 44.7% pre-operatively). Fractional anisotropy was significantly lower in the distal regions of the left superior cerebellar peduncle pre-operatively (p=0.0137) in patients compared to controls, although patients could not be distinguished pre-operatively with respect to cerebellar mutism syndrome status (Figure 2). Post-operative reductions in fractional anisotropy in children with cerebellar mutism syndrome were highly specific to the distal left superior cerebellar peduncle, and were most pronounced at follow-up timepoints (p=0.006; Figure 3). There were no significant differences in other cerebellar peduncles, either in along-tract fractional anisotropy or Z-scores, with respect to cerebellar mutism syndrome status. Conclusion A novel application of an automated tool to extract diffusion MRI data along the length of the cerebellar peduncles is described in a longitudinal retrospective cohort of paediatric medulloblastoma. Changes in fractional anisotropy in the cerebellar peduncles following tumour resection are described in a heretofore unprecedented level of spatiotemporal detail. In particular, children with post-operative cerebellar mutism syndrome show changes in the distal regions of the left superior cerebellar peduncle, and these changes persist up to a year post-operatively. These findings will have direct clinical implications for neurosurgeons performing resection of midline paediatric posterior fossa tumours.

BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged

Made available in DSpace on 2021-06-25T15:20:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-04 BACKGROUND AND PURPOSE: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children. MATERIALS AND METHODS: A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children?s Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen ?, and each diagnosis was analyzed for accuracy. RESULTS: A total of 148 cases were included, with a median age of 3.4?years (interquartile range, 2.1?6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%?79%; specificity = 92%?99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors. CONCLUSIONS: The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice. Childrens Hosp Philadelphia, Div Neuroradiol, Dept Radiol, 3401 Civ Ctr Blvd, Philadelphia, PA 19104 USA UCL, Great Ormond St Hosp Children, Dept Radiol, London, England UCL, Great Ormond St Hosp Children, Dept Neurosurg, London, England Sao Paulo State Univ, Dept Biostat, Inst Biociencias, Sao Paulo, Brazil UCL, Great Ormond St Inst Child Hlth, Dev Biol & Canc Programme, London, England Hosp Clin Sao Paulo, Fac Med Sao Paulo, Dept Radiol, Sao Paulo, Brazil Sao Paulo State Univ, Dept Biostat, Inst Biociencias, Sao Paulo, Brazil

Background: Brain tumours are the most common childhood tumours. Half of them are in the posterior fossa, where surgical removal is complicated by postoperative speech impairment (POSI) in up to 25% of patients. POSI manifests within days of surgery, while improvement takes weeks or months. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We investigated the risk of developing POSI, the time course of its resolution and its association with surgical approach and other clinical factors. Methods: 426 children aged 0–17·9 years undergoing primary surgery for a posterior fossa tumour at 26 centres in nine European countries were prospectively included. Speech was classified as either mutism, reduced or habitual at two weeks, two months, and one year after surgery. Findings: POSI developed in 30% of patients: Mutism in 15% (56/378) a median 1 day after surgery (IQR, 0–2; max 10) and reduced speech in 15% (58/378). In multivariate analysis, POSI was associated with using a telovelar approach (odds ratio (OR), 1·7; 95% CI, 1·03–2·9, p

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 least absolute shrinkage and selection operator Cox regression selected optimal features to predict overall survival 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 (3 T1 gray-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 = .02). Conclusions 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.

Introduction Tractography derived from diffusion MRI can provide important insights into human brain microstructure in vivo. Neurosurgeons were quick to adopt the technique at the turn of the century, but it remains plagued by technical fallibilities. This study aims to describe how tractography is deployed clinically in a modern-day, public healthcare system, serving as a snapshot from the 'shop floor' of British neurosurgical practice. Methods An 11-question survey was circulated to the mailing lists of the Society of British Neurological Surgeons and British Neurosurgical Trainees' Association, including questions on frequency, indication, tracts reconstructed, specific details of techniques used and personnel by whom it was performed, and a free-text section on the limitations of tractography. Results 58 survey responses were received, covering all 40 neurosurgical units in the UK and Ireland. Overall, responses were received from neurosurgeons at 36 units (90.0%) stating tractography was in use at that unit. 74.1% of the responses were from Consultants. The most common indication for tractography was in tumour resection. It was most commonly performed by neuroradiologists or imaging scientists. 75.9% of respondents stated that the model used to process tractography was the diffusion tensor (DTI). Many respondents were unaware of which algorithm (74.1%) or software tools (65.6%) were used by the operator to produce tractography visualisations. The corticospinal tract was the most commonly reconstructed tract. The most commonly cited limitations of the technique were perceived inaccuracy and brain shift. Conclusions In this UK-based survey of practising neurosurgeons, we show that 90% of neurosurgical units in the UK and Ireland use tractography regularly; that predominantly DTI-based reconstructions are used; that tumour resection remains the most frequent use of the technique; and that large tracts such as the corticospinal tract are most frequently identified. Many neurosurgeons remain unfamiliar with the underlying methods used to produce tractography visualisations.

Purpose The optimum strategy for the surveillance of low-grade gliomas in children has not been established, and there is concern about the use of gadolinium-based contrast agents (GBCAs), particularly in children, due to their deposition in the brain. The number of surveillance scans and the use of GBCAs in surveillance of low-risk tumours should ideally be limited. We aimed to investigate the consistency and utility of our surveillance imaging and also determine to what extent the use of GBCAs contributed to decisions to escalate treatment in children with grade 1 astrocytomas. Methods This was a retrospective single-centre study at a tertiary paediatric hospital. All children with a new diagnosis of a non-syndromic World Health Organization (WHO) grade 1 astrocytoma between 2007 and 2013 were included, with surveillance imaging up to December 2018 included in analysis. The intervals of surveillance imaging were recorded, and imaging and electronic health records were examined for decisions related to treatment escalation. Results Eighty-eight patients had 690 surveillance scans in the study period. Thirty-one patients had recurrence or progression leading to treatment escalation, 30 of whom were identified on surveillance imaging. The use of GBCAs did not appear to contribute to multidisciplinary team (MDT) decisions in the majority of cases. Conclusion Surveillance imaging could be reduced in number and duration for completely resected cerebellar tumours. MDT decisions were rarely made on the basis of post-contrast imaging, and GBCA administration could therefore potentially be restricted in the setting of surveillance of grade 1 astrocytomas in children.

Cerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome. In this retrospective study, twenty-eight children with medulloblastoma (mean age 8.8 ± 3.8 years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy (FA) at 30 nodes along each tract. Thirteen patients developed cerebellar mutism syndrome. FA was significantly lower in the distal third of the left superior cerebellar peduncle pre-operatively in all patients compared to controls (FA in proximal third 0.228, middle and distal thirds 0.270, p = 0.01, Cohen's d = 0.927). Pre-operative differences in FA did not predict cerebellar mutism syndrome. However, post-operative reductions in FA were highly specific to the distal left superior cerebellar peduncle, and were most pronounced in children with cerebellar mutism syndrome compared to those without at the 1-4 month follow up (0.325 vs 0.512, p = 0.042, d = 1.36) and at the 1-year follow up (0.342, vs 0.484, p = 0.038, d = 1.12). High spatial resolution cerebellar profilometry indicated a site-specific alteration of the distal segment of the superior cerebellar peduncle seen in cerebellar mutism syndrome which may have important surgical implications in the treatment of these devastating tumours of childhood.

Purpose To 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. Methods Retrospective 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. Results Of 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). Conclusions The 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.

BACKGROUND: Brain tumors in the first year of life are rare and their management remains challenging. OBJECTIVE: To report on the contemporary management of brain tumors in infants with reference to previous series from our institution. METHODS: Retrospective cohort study design. Electronic/paper case note review of all brain tumors diagnosed at our institution in children aged

BackgroundCerebellar 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.MethodsWe 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.ResultsOverall, 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.ConclusionsMedulloblastoma 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.

This review discusses the evidence base behind current and emerging strategies of management of intracranial and spinal ependymomas in children, with a particular focus on aspects of surgical techniques, challenges and complications. 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. The standard of care for paediatric ependymoma comprises surgery and radiotherapy. Results of ongoing clinical trials will help shape its management in order to leverage our increasingly sophisticated understanding of the genetic drivers behind these tumours into survival benefit for this challenging group of patients.

OBJECTIVE Cerebellar mutism syndrome (CMS) is a severe neurological complication of tumour surgery in the posterior fossa in childhood. The incidence is reported between 8 and 39%, where CMS sets in within days of surgery and resolves within months, yet long-term sequelae are seen in most patients. This prospective cohort study investigates the course of CMS and the surgical cause of the syndrome. POPULATION AND METHODS We included 500 children with a tumour in the posterior fossa with planned surgery or open biopsy. Enrolment was conducted between 2014 and 2020 in 26 centres in ten European countries. Speech, neurological symptoms and surgical procedure were registered in predefined standardized forms pre-operatively and at three post-operative follow-ups within one year. PRELIMINARY RESULTS A total of 426 children underwent primary surgery and were eligible for analyses. CMS occurred in 56 patients (13.1%) one day (median; IQR: 0–2 days) after surgery and resolved within 38 days (median; IQR: 4–52 days). Another 58 patients (13.6%) had less severe speech impairment. Mutism was associated with lower age (OR: 0.91 [95%CI: 0.85;0.98, p=0.014]), medulloblastoma (OR: 2.5 [95%CI: 1.4;4.7, p=0.0036]) and ATRT (OR: 12.9 [95%CI: 3.4;51.9, p=0.00018]) and tumour location in the fourth ventricle (OR: 4.0 [95%CI: 2.3;7.2, p CONCLUSION CMS is a common complication predominantly seen in younger children after tumour surgery for a medulloblastoma or ATRT in the fourth ventricle. The incidence is not related to the surgical access in this study population.

We report the case of a large osteoblastoma arising in the frontal bone of a 20-year-old female. The lesion was first noted after a fall, and grew steadily in size following further head injury during pregnancy. Initial plain radiography demonstrated an area of radiolucency, with subsequent cross-sectional imaging revealing the extent of the lesion. Following successful surgical resection, histological features were suggestive of an aggressive osteoblastoma with aneurysmal bone cyst-like changes. We consider the influence of pregnancy and trauma on osteoblastoma behavior.

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-rubro-thalamo-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.

Brown tumours affecting the cervical spine are a rare but recognised complication of renal failure-related secondary hyperparathyroidism. We present a case of a 26 year-old female with radiculopathy who was managed successfully with 360° cervical spine fixation and parathyroidectomy.

A 49-year-old female underwent multiple craniotomies for resection of recurrent malignant meningiomata (WHO grade III). She re-presented with sepsis due to a ventricular empyema. The craniotomy wound was urgently debrided, and isolates of the gram-negative rod, Weeksella virosa, were identified on 16S PCR. This species is most commonly found as a genitourinary commensal. We present the first documented intracranial infection by Weeksella virosa and its successful treatment with oral β-lactam antibiotics.

ObjectivesTo characterise the surgical management of paediatric 4th ventricular tumours and their attendant neurological complications.DesignRetrospective cohort study.SubjectsChildren referred to our institution with tumours of the 4th ventricle between 2008–2017 inclusive.MethodsClinical notes and imaging review. Two-tailed Fisher’s test used to determine differences between proportions.Results95 patients were seen (53 males, mean 5.81y). The commonest presenting symptom was vomiting (63.3%). The commonest tumour type was medulloblastoma (54 cases)>pilocytic astrocytoma (20)>anaplastic ependymoma (12)>ATRT(4)>Teratoma (2), with 3 miscellaneous lesions. 55 pts presented with hydrocephalus. 27.4% of patients had an EVD (30.8% of these prior to tumour surgery), and 23.3% a VP shunt sited. The surgical approach was either via telovelar (50%) or transvermian (50%) routes; 29.5% were done in the sitting position. In the first 5y of the series, 7/31 cases used the telovelar approach, whilst in the latter 5y, this proportion was 30/51 (p=0.0015). New post-operative deficit was evident in 68% of cases (42.4% gait abnormality, 23.9% cranial neuropathy, 16.3% diplopia). There was no significant difference in the rates of cerebellar mutism syndrome between telovelar or transvermian approaches (p=0.62). There was 1 mortality within 30d of operation.ConclusionsResection of paediatric 4th ventricular tumours is increasingly performed by the telovelar route, and carries significant morbidity, although surgical mortality remains low.

Objective To 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. Design A cross-sectional questionnaire. Setting Royal Free Hospital, London outpatient epilepsy clinics. Participants New 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 measures Patient knowledge about epilepsy risks; patient opinion regarding source, timing and delivery of SUDEP information; impact on health seeking behaviour. Results Ninety-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. Conclusions Less 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.

Mephedrone is a stimulant drug of abuse whose public profile rose dramatically in 2009. At that time, it was designated as ‘legal high’ and was predominantly sold over the Internet for as little as £10 a gram, meaning it quickly became the UK's sixth most popular recreational drug. Media furore over mephedrone came on the back of several reports of teenage deaths attributed to the drug, and the government was pressed into action, banning the substance despite lacking the scientific evidence necessary to do so. So, it seems that the politics and science of drugs were at odds in the curious case of mephedrone. This article represents a synthesis of the heretofore limited evidence base on mephedrone into a risk assessment, with a closing discussion which looks at issues raised by the mephedrone saga with respect to present and future drug legislation in the UK.

Disparity exists between clinical practice and guidelines on discussion of Sudden death in epilepsy (SUDEP) with patients. This study examined how patients were informed about SUDEP; the impact of such discussion, and their views on the discussion.MethodsA quantitative/qualitative questionnaire was given to 50 consenting patients attending epilepsy clinics. Exclusions were patients with intellectual disability, and/or those deemed at risk of negative consequences on completing the study.Results98% of patients were aware of the importance of medication adherence, 78% of driving regulations in epilepsy, and 84% of factors influencing seizure frequency. Only 50% of patients were aware of SUDEP and 38% of status epilepticus.42% of patients preferred SUDEP information at diagnosis and 36% only after three clinic appointments.Negative emotional responses (in 38%), and not behavioural changes, resulted from SUDEP discussions.ConclusionsIn this small in-depth study, only half the patients recalled information about SUDEP. More than one-third of patients reported adverse consequences. There was no improvement in self-management.We suggest a paradigm shift: embedding SUDEP discussion with all potential complications of epilepsy; and emphasising optimal healthcare and self-management. This model has been successfully applied in other areas to empower patients and improve outcome.

Scleroderma renal crisis (SRC) is a major complication of systemic sclerosis (SSc). We present a case of a patient who died of complications attributable to SRC in the context of recently diagnosed SSc. We review the typical clinical and laboratory features of SSc present in our patient and highlight those that identify greater risk of progression to SRC. Particular risk factors for SRC include cutaneous involvement, positive anti-RNA polymerase III antibodies and use of corticosteroids (CS). The authors emphasise the importance of risk evaluation when choosing to use CS in patients with SSc.

Background Patients with Parkinson9s disease (PD) are at risk of complications related to incorrect prescribing when admitted to hospital. The ‘Get It On Time’ campaign by Parkinson9s UK aims to raise awareness of inpatient prescribing issues. This prospective audit was undertaken to establish current practice in dopaminergic medication prescribing in a district general hospital (DGH). Methods All patients with a Parkinsonian syndrome admitted over two months were included. Case notes and drug charts were reviewed at admission and while an inpatient. Correct medication regimes were identified from clinic letters and faxed primary care documents. Results 34 patients were identified (mean age 79y). 25 patients had idiopathic PD. The majority (28 patients) were taking co-careldopa or co-beneldopa. 56% of patients had medications incorrectly prescribed at admission; 26% received doses at incorrect times. 26% of patients self-administered their medication. Although 17 patients were nil per oram, only 2 patients received medications by alternative routes. 4 patients received anti-dopaminergic medication. Conclusions Our study highlights that greater accuracy is required in inpatient prescribing for PD. These findings are comparable to other studies. Following this audit, a talk was delivered to incoming junior doctors at the DGH regarding Parkinson9s medication prescribing. We are currently re-auditing.

Background As a chronic disorder Parkinson9s disease (PD) is mostly managed in outpatient clinics and primary care. Admission of PD patients is often the result of complications or associated comorbid disease. A wealth of literature identifies the problems associated with inpatient PD care, in particular inadequate and untimely delivery of dopaminergic agents after admission is a recurrent problem. This was specifically noted within a recent National Patient Safety Alert and spurred the ‘Get It On Time’ campaign run by the Parkinson9s Disease Society. Aim To assess the inpatient management of PD across Barnet and Chase Farm NHS Trust with a view to highlighting areas of strength and areas for service improvement. Methods We completed a retrospective case note, drug chart and electronic patient record review for all patients admitted with a coded diagnosis of “Parkinson9s Disease” (ICD10 code: G20). Only patients with idiopathic PD were included. Correct medication regimes were identified from previous clinic letters and GP faxed documents. Results Our search identified 24 patients with idiopathic PD. Their length of stay varied from 3 to 120 days (average 25). 4 patient9s charts were missing from their notes. 50% had correct prescriptions of medication and timing of doses, 35% had the correct medication prescribed but incorrect timing, and 15% had incorrectly prescribed drugs and regimes. A delay in receiving the first dose of dopaminergic agent was experienced by 70%, ranging from 3 to 72 hours (average 13.6). Antidopaminergic agents were administered for aggression in one case and the patient experienced increased rigidity as a result. Laxatives were prescribed in 75% of cases. 10% of patients administered their own medications. We are now presenting our findings locally and producing an inpatient PD guideline. We plan to re–audit after these interventions. Conclusion Similar to previous studies, we have found that PD drugs are often incorrectly prescribed following hospital admission. Lack of awareness of the importance of prompt dopaminergic agent administration in this vulnerable group can lead to poorer outcomes such as increased length of stay and PD associated complications. Levodopa is often not available in A&E and non–neurology wards, which is a frequent reason given for delayed and missed doses.

A 64-year-old man presented with a 12-month history of angina. Following coronary angiography he underwent percutaneous coronary intervention with deployment of drug-eluting stents to the left anterior descending and main diagonal branch. He was discharged on diltiazem 200 mg daily as an antianginal and antihypertensive drug, aspirin, clopidogrel and atorvastatin; as well as his regular medications omeprazole and fluoxetine. When reviewed 2 weeks later he was free of angina but had developed skin shedding …