Safety and effectiveness of evicel® fibrin sealant as an adjunct to sutured dural repair in children undergoing cranial neurosurgery.

PURPOSE: Cerebrospinal fluid (CSF) leakage is a challenging complication of intradural cranial surgery, and children are particularly at risk. The use of dural sealants confers protection in adults, but pediatric studies are scarce. We evaluated the safety and efficacy of Evicel® fibrin sealant as an adjunct to primary dural suturing in children undergoing cranial surgery. METHODS: A multicenter trial prospectively enrolled pediatric subjects (< 18 years) undergoing cranial neurosurgery who, upon completion of primary sutured dural repair, experienced CSF leakage. As agreed by the EMA Evicel® Pediatric Investigation Plan, 40 subjects were intra-operatively randomized 2:1 to Evicel® or additional sutures ('Sutures'). Data analysis was descriptive. The efficacy endpoint was treatment success rate, with success defined as intra-operative watertight closure after provocative Valsalva maneuver (primary endpoint). Safety endpoints were postoperative CSF leakage (incisional CSF leakage, pseudomeningocele or both) and surgical site complications (secondary endpoints). RESULTS: Forty subjects (0.6-17 years) were randomized to Evicel® (N = 25) or Sutures (N = 15) (intention-to-treat). Intracranial tumor was the most common indication and procedures were mostly supratentorial craniotomies. Success rates were 92.0% for Evicel® and 33.3% for Sutures, with a 2.76 estimated ratio of success rates (Farrington-Manning 95% CI [1.53, 6.16]). Sensitivity analyses in per-protocol and safety sets showed similar results. Despite a higher rescue treatment rate, the frequencies of postoperative CSF leakage and wound complications were higher for Sutures than for Evicel®. CONCLUSION: This small-scale prospective study shows Evicel® treatment to be safe and effective as an adjunct to primary sutured dura mater closure in a pediatric population. Compared to additional sutures, Evicel® was associated with reduced postoperative CSF leakage and surgical site complications. (Trial registration: The trial was registered as NCT02309645 and EudraCT 2013-003558-26).

Pediatric Congenital Anterior Skull Base Encephaloceles and Surgical Management: A Comparative Review of 22 Patients Treated With Transnasally, Transcranially, or Combined Approach With a Review of the Literature.

BACKGROUND AND OBJECTIVES: Anterior basal encephaloceles are considered a rare entity and are often associated with midline cerebral abnormalities. Those with a large skull base defect and herniation of brain parenchyma in the neonate or young infant present unique challenges for surgical management. METHODS: We analyzed the neurosurgical administrative and operative databases between 1986 and 2022 to determine clinical presentation, operative approach, and outcome of basal encephaloceles. RESULTS: Over the 36-year period, 27 pediatric anterior basal encephaloceles were managed, of which 22 had full documentation and images allowing comprehensive review. Mean age at presentation was 5 years (SD 4.94). The majority were transethmoidal encephaloceles (59%), followed by the transsphenoidal-sphenoethmoidal type (32%). Overall, 91% were managed surgically by a transcranial, endoscopic, or combined approach. Four children required subsequent procedures, predominantly for persistent cerebrospinal fluid leak. No significant differences in proportion of patients requiring interval/revision surgery after initial conservative, endoscopic endonasal, or transcranial surgery was identified. Neither age at surgery nor size of the defect on computed tomography scan was associated with the need for revision surgery. Size of cranial defect was significantly smaller in the endoscopic group (P = .01). There was a historic tendency for younger children with larger defects to have a transcranial approach. With the addition of endoscopic skull base expertise, smaller defects in older children were more recently treated endoscopically. CONCLUSION: Basal encephaloceles are rare and complex lesions and are optimally managed within a skull base multidisciplinary team able to provide multiple approaches. Large skull base defects with brain parenchymal involvement often require a transcranial or combined transcranial-endoscopic approach.

MRI-Guided Focused Ultrasound for the Treatment of Dystonia: A Narrative Review.

Contemporary surgical management of dystonia includes neuromodulation via deep brain stimulation (DBS) or ablative techniques such as radiofrequency (RF) ablation. MRI-guided focused ultrasound (MRgFUS) is an emerging modality that uses high-intensity ultrasound to precisely ablate targets in the brain; this is incisionless, potentially avoiding the surgical risks of a burr hole and transcortical tract to reach the anatomical target. There is some evidence of efficacy in essential tremor and Parkinson's disease (PD), but, to date, there is no study aggregating the evidence of MRgFUS in dystonia. In this narrative review, we searched Medline, Embase, CINAHL, EBSCO, and ClinicalTrials.gov for primary studies and clinical trials on MRgFUS in the treatment of dystonia. Data were analyzed concerning dystonia phenotype, reported outcomes, and complications. PD-related dystonia was also included within the scope of the review. Using our search criteria, six articles on the use of MRgFUS in adult dystonia and three articles on the use of FUS in dystonia in PD were included. Four trials on the use of FUS in dystonia were also found on ClinicalTrials.gov, one of which was completed in December 2013. All included studies showed evidence of symptomatic improvement, mostly in focal hand dystonia; improvements were also found in dystonia-associated tremor, cervicobrachial dystonia, and dystonia-associated chronic neuropathic pain as well as PD-related dystonia. Reported complications included transient neurological deficits and persistent arm pain in one study. However, the evidence is limited to level-4 case series at present. MRgFUS is an emerging modality that appears to be safe and effective, particularly in focal hand dystonia, without major adverse effects. However, the quality of evidence is low at present, and long-term outcomes are unknown. High-quality prospective studies comparing MRgFUS to other surgical techniques will be useful in determining its role in the management of dystonia.

Fibre orientation atlas guided rapid segmentation of white matter tracts.

Fibre tract delineation from diffusion magnetic resonance imaging (MRI) is a valuable clinical tool for neurosurgical planning and navigation, as well as in research neuroimaging pipelines. Several popular methods are used for this task, each with different strengths and weaknesses making them more or less suited to different contexts. For neurosurgical imaging, priorities include ease of use, computational efficiency, robustness to pathology and ability to generalise to new tracts of interest. Many existing methods use streamline tractography, which may require expert neuroimaging operators for setting parameters and delineating anatomical regions of interest, or suffer from as a lack of generalisability to clinical scans involving deforming tumours and other pathologies. More recently, data-driven approaches including deep-learning segmentation models and streamline clustering methods have improved reproducibility and automation, although they can require large amounts of training data and/or computationally intensive image processing at the point of application. We describe an atlas-based direct tract mapping technique called 'tractfinder', utilising tract-specific location and orientation priors. Our aim was to develop a clinically practical method avoiding streamline tractography at the point of application while utilising prior anatomical knowledge derived from only 10-20 training samples. Requiring few training samples allows emphasis to be placed on producing high quality, neuro-anatomically accurate training data, and enables rapid adaptation to new tracts of interest. Avoiding streamline tractography at the point of application reduces computational time, false positives and vulnerabilities to pathology such as tumour deformations or oedema. Carefully filtered training streamlines and track orientation distribution mapping are used to construct tract specific orientation and spatial probability atlases in standard space. Atlases are then transformed to target subject space using affine registration and compared with the subject's voxel-wise fibre orientation distribution data using a mathematical measure of distribution overlap, resulting in a map of the tract's likely spatial distribution. This work includes extensive performance evaluation and comparison with benchmark techniques, including streamline tractography and the deep-learning method TractSeg, in two publicly available healthy diffusion MRI datasets (from TractoInferno and the Human Connectome Project) in addition to a clinical dataset comprising paediatric and adult brain tumour scans. Tract segmentation results display high agreement with established techniques while requiring less than 3 min on average when applied to a new subject. Results also display higher robustness than compared methods when faced with clinical scans featuring brain tumours and resections. As well as describing and evaluating a novel proposed tract delineation technique, this work continues the discussion on the challenges surrounding the white matter segmentation task, including issues of anatomical definitions and the use of quantitative segmentation comparison metrics.

Transcallosal approach and post-operative subdural collections: 12-year paediatric neurosurgery tertiary centre experience.

INTRODUCTION: Following transcallosal surgery for tumour resection, the formation of convexity or interhemispheric subdural cerebrospinal fluid collections may lead to clinical deterioration and may influence decision-making with regards to additional interventions. The aim of this study was to determine the incidence, risk factors, and management of subdural collections following the transcallosal approach in a paediatric cohort. METHODS: A retrospective case note and radiological review of all children who underwent transcallosal surgery for intraventricular and thalamic tumours was carried out covering a 12-year period (2012-2023) in a single-centre tertiary paediatric neurosurgery unit. Parameters including demographics and clinical information including lesion location, pathology, extent of resection, need for and type of shunt required, as well as depth, laterality, and location of the collection were analysed prior to shunting, and at approximately 3 weeks, 3 months, and latest follow-up available post-operatively in order to further elucidate the natural history of these subdural collections and their clinical significance. RESULTS: Sixty-four cases satisfied the inclusion criteria of transcallosal surgery for tumour resection; 13 did not have adequate post-operative imaging and were excluded. Of the remaining 51 cases, there were 32 children (63%) with post-operative CSF subdural collections, of which 59% were ipsilateral, with the remainder showing bilateral distribution. The overall shunt insertion rate was 25.5% (12 ventriculoperitoneal and 1 subdural-peritoneal shunt) at 3 months, with a mean time to shunting of 19 days post-operatively. Children who developed post-operative subdural collections had a higher rate of shunting, at 37.5%, compared to 5.2% in those who did not. Pre- and post-operative hydrocephalus and subtotal resection were identified as risk factors for development of subdural collections post-operatively. Subdural collections showed a natural course of reduction and regression over follow-up, with the exception of 3 children where they persisted or increased over time; although none of these required shunting. Those children who underwent shunt insertion showed greater regression in the size of the subdural collection over time compared to the non-shunted group. CONCLUSION: In this paediatric cohort, 25.5 % of children required insertion of a shunt by 3 months following transcallosal surgery. Pre- and post-operative hydrocephalus and subtotal tumour resection were risk factors for development of subdural collections post-operatively.

Selective dorsal rhizotomy in non-ambulant children with cerebral palsy: a multi-center prospective study.

PURPOSE: Assess the effects of selective dorsal rhizotomy (SDR) on motor function and quality of life in children with a Gross Motor Function Classification System (GMFCS) level of IV or V (non-ambulatory). METHODS: This is a prospective, observational study in three tertiary neurosurgery units in England, UK, performing SDR on children aged 3-18 with spastic diplegic cerebral palsy, and a GMFCS level of IV or V, between 2012 and 2019. The primary outcome measure was the change in the 66-item Gross Motor Function Measure (GMFM-66) from baseline to 24 months after SDR, using a linear mixed effects model. Secondary outcomes included spasticity, bladder function, quality of life, and pain scores. RESULTS: Between 2012 and 2019, 144 children who satisfied these inclusion criteria underwent SDR. The mean age was 8.2 years. Fifty-two percent were female. Mean GMFM-66 score was available in 77 patients (53.5%) and in 39 patients (27.1%) at 24 months after SDR. The mean increase between baseline and 24 months post-SDR was 2.4 units (95% CI 1.7-3.1, p < 0.001, annual change 1.2 units). Of the 67 patients with a GMFM-66 measurement available, a documented increase in gross motor function was seen in 77.6% (n = 52). Of 101 patients with spasticity data available, mean Ashworth scale decreased after surgery (2.74 to 0.30). Of patients' pain scores, 60.7% (n = 34) improved, and 96.4% (n = 56) of patients' pain scores remained the same or improved. Bladder function improved in 30.9% of patients. CONCLUSIONS: SDR improved gross motor function and reduced pain in most patients at 24 months after surgery, although the improvement is less pronounced than in children with GMFCS levels II and III. SDR should be considered in non-ambulant patients.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

Intracranial invasive group A streptococcus: a neurosurgical emergency in children.

OBJECTIVE: Invasive group A streptococcus (iGAS) infections are associated with a high rate of morbidity and mortality. CNS involvement is rare, with iGAS accounting for only 0.2%-1% of all childhood bacterial meningitis. In 2022, a significant increase in scarlet fever and iGAS was reported globally with a displacement of serotype, causing a predominance of the emm1.0 subtype. Here, the authors report on iGAS-related suppurative intracranial complications requiring neurosurgical intervention and prolonged antibiotic therapy. METHODS: The authors performed a retrospective chart review of consecutive cases of confirmed GAS in pediatric neurosurgical patients. RESULTS: Five children with a median age of 9 years were treated for intracranial complications of GAS infection over a 2-month period between November 2022 and December 2022. All patients had preceding illnesses, including chicken pox and upper respiratory tract infections. Infections included subdural empyema with associated encephalitis (n = 2), extradural empyema (n = 1), intracranial abscess (n = 1), and diffuse global meningoencephalitis (n = 1). Streptococcus pyogenes was cultured from 4 children, and 2 were of the emm1.0 subtype. Antimicrobial therapy in all patients included a third-generation cephalosporin but varied in adjunctive therapy, often including a toxin synthesis inhibitor antibiotic such as clindamycin. Neurological outcomes varied; 3 patients returned to near neurological baseline, 1 had significant residual neurological deficits, and 1 patient died. CONCLUSIONS: Despite the worldwide increased incidence, intracranial complications remain rarely reported resulting in a lack of awareness of iGAS-related intracranial disease. Awareness of intracranial complications of iGAS and prompt referral to a pediatric neurology/neurosurgical center is crucial to optimize neurological outcomes.

Neuroanatomy of Cerebellar Mutism Syndrome: The Role of Lesion Location.

Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. We 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/). We 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). These 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.

Comparison of endoscopic sinus sampling versus intracranial sampling for microbiological diagnosis of intracranial infection in children: a case series and literature review.

INTRODUCTION: Intracranial infection is often associated with contiguous sinus infection, with Streptococcus intermedius being the most common pathogen. Microbiological assessment is possible via sinus or intracranial sampling. While a sinus approach is minimally invasive, it is not clear whether this yields definitive microbiological diagnosis leading to optimized antimicrobial therapy and avoidance of intracranial surgery. METHODS: A retrospective review of a prospectively collected electronic departmental database identified patients between 2019 and 2022. Further demographic and microbiological information was obtained from electronic patient records and laboratory management systems. RESULTS: Thirty-one patients were identified with intracranial subdural and/or epidural empyema and concurrent sinus involvement during the 3-year study period. The median age of onset was 10 years with a slight male predominance (55%). All patients had intracranial sampling with 15 patients undergoing sinus sampling in addition. Only 1 patient (7%) demonstrated identical organism(s) grown from both samples. Streptococcus intermedius was the most common pathogen in intracranial samples. Thirteen patients (42%) had mixed organisms from their intracranial cultures and 57% of samples undergoing bacterial PCR identified additional organisms, predominantly anaerobes. Sinus samples had a significant addition of nasal flora and Staphylococcus aureus which was rarely grown from intracranial samples. Of concern, 7/14 (50%) of sinus samples did not identify the main intracranial pathogen diagnosed on intracranial culture and additional PCR. Literature review identified 21 studies where sinus drainage was used to treat intracranial empyemas, with only 6 authors reporting concurrent microbiology results. This confirmed our cohort to be the largest comparative study in the current literature. No center has observed a greater than 50% concordance in microbiological diagnoses. CONCLUSION: Endoscopic sinus surgery may have therapeutic benefit, but it is not an appropriate approach for microbiological diagnosis in pediatric subdural empyemas. High rates of contaminating nasal flora can lead to misdiagnosis and inappropriate treatment. Routine addition of 16S rRNA PCR to intracranial samples is recommended.

A new era for optic pathway glioma: A developmental brain tumor with life-long health consequences.

Optic pathway and hypothalamic glioma (OPHG) are low-grade brain tumors that arise from any part of the visual pathways frequently involving the hypothalamus. The tumors grow slowly and present with features driven by their precise anatomical site, their age at presentation and the stage of growth and development of the host neural and orbital bony tissues. Up to 50% of optic pathway glioma arise in association with Neurofibromatosis type 1 (NF1), which affects 1 in 3,000 births and is a cancer predisposition syndrome. As low-grade tumors, they almost never transform to malignant glioma yet they can threaten life when they present under two years of age. The main risks are to threaten vision loss by progressive tumor damage to optic pathways; furthermore, invasion of the hypothalamus can lead to diencephalic syndrome in infancy and hypopituitarism later in life. Progressive cognitive and behavioural dysfunction can occur, as part of NF1 syndromic features and in sporadic cases where large bulky tumors compress adjacent structures and disrupt neuro-hypothalamic pathways. Persistently progressive tumors require repeated treatments to attempt to control vision loss, other focal brain injury or endocrine dysfunction. In contrast tumors presenting later in childhood can be seen to spontaneously arrest in growth and subsequently progress after periods of stability. These patterns are influenced by NF status as well as stages of growth and development of host tissues. The past two decades has seen an expansion in our understanding and knowledge of the clinical and scientific features of these tumors, their modes of presentation, the need for careful visual and endocrine assessment. This influences the decision-making surrounding clinical management with surgery, radiotherapy, chemotherapy and most recently, the potential benefit of molecularly targeted drug therapy. This article, based upon the authors' clinical and research experience and the published literature will highlight advances in approach to diagnosis, the established role of vision loss as justification of treatments and the emerging evidence of endocrine and neurological consequences that need to be incorporated into judgements for case selection for therapy or observation. Consideration is given to the current state of biological evidence justifying current trials of new therapies, the genetic studies of the NF1 gene and the potential for new approaches to OPHG detection and treatment. The outstanding health system priorities from the perspective of children, their parents and health system commissioners or insurers are discussed.

Endoscopic third ventriculostomy for shunt malfunction in the pediatric population: a systematic review, meta-analysis, and meta-regression analysis.

OBJECTIVE: Despite growing published evidence of the merits of endoscopic third ventriculostomy (ETV) instead of shunt revision at the time of shunt malfunction (secondary ETV), concerns about its efficacy and complications remain and ETV is still not used widely in this context. This study aimed to carry out a comprehensive meta-analysis and reports on the success and safety of secondary ETV in the pediatric age group. METHODS: In accordance with the PRISMA guidelines, systematic searches of Medline, Embase, and Cochrane Central were undertaken from database inception to September 7, 2022. ETV success was defined as the lack of need for a shunt and was the primary outcome measure. Secondary outcome measures were the rates of complications and mortality. A random-effects model was used. Summary-level meta-regression was performed to identify predictors for success in accordance with the ETV Success Score (ETVSS). RESULTS: Sixteen studies reporting on 584 patients who underwent secondary ETV for shunt malfunction were included in the meta-analysis. The overall pooled mean (95% CI) age was 6.1 (3-9) years, and 57.0% of patients were male. The pooled prevalence rates of the hydrocephalus etiologies were as follows: aqueduct stenosis (39.3%); myelomeningocele (27.6%); postinfectious (17.1%); posthemorrhagic (13.0%); neoplasm (13.0%); and malformation (11.3%). The overall pooled success rates of ETV for shunt malfunction at 3 months, 6 months, and 12 months were 65.69% (95% CI 52%-77%, prediction interval 47%-81%, I2 = 0, p = 0.775); 63.25% (95% CI 54%-72%, prediction interval 38%-83%, I2 = 65, p < 0.001); and 53.37% (95% CI 24%-81%, prediction interval 1%-99%, I2 = 47, p = 0.154). The overall pooled prevalence of intraoperative bleeding was 4.96% (95% CI 0%-64%, prediction interval 0%-99%, I2 = 85, p < 0.001). The overall rates of complications were low, with new neurological deficit (transient or permanent) having the highest rate at 1.61% (95% CI 0.68%-3.72%, prediction interval 0.67%-3.78%, I2 = 0, p > 0.999). On meta-regression, age (p = 0.138), proportion of patients with postinfectious hydrocephalus (p = 0.8736), and number of shunt revisions (p = 0.1775) were not statistically significant predictors of secondary ETV success at 6 months. CONCLUSIONS: This meta-analysis demonstrates that secondary ETV after shunt malfunction in pediatric patients is a feasible option with acceptable success rates and low complication rates. Clinical trial registration no.: CRD42022359573 (PROSPERO).

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.

Investigating lesion location in relation to cerebellar mutism following pediatric tumor resection.

Background and Objectives: Approximately 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. Methods: We 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/). Results: We 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). Discussion: These 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.

Left-handedness should not be overrated as a risk factor for postoperative speech impairment in children after posterior fossa tumour surgery: a prospective European multicentre study.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.

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 (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.

Fibre tract segmentation for intraoperative diffusion MRI in neurosurgical patients using tract-specific orientation atlas and tumour deformation modelling.

PURPOSE: Intraoperative diffusion MRI could provide a means of visualising brain fibre tracts near a neurosurgical target after preoperative images have been invalidated by brain shift. We propose an atlas-based intraoperative tract segmentation method, as the standard preoperative method, streamline tractography, is unsuitable for intraoperative implementation. METHODS: A tract-specific voxel-wise fibre orientation atlas is constructed from healthy training data. After registration with a target image, a radial tumour deformation model is applied to the orientation atlas to account for displacement caused by lesions. The final tract map is obtained from the inner product of the atlas and target image fibre orientation data derived from intraoperative diffusion MRI. RESULTS: The simple tumour model takes only seconds to effectively deform the atlas into alignment with the target image. With minimal processing time and operator effort, maps of surgically relevant tracts can be achieved that are visually and qualitatively comparable with results obtained from streamline tractography. CONCLUSION: Preliminary results demonstrate feasibility of intraoperative streamline-free tract segmentation in challenging neurosurgical cases. Demonstrated results in a small number of representative sample subjects are realistic despite the simplicity of the tumour deformation model employed. Following this proof of concept, future studies will focus on achieving robustness in a wide range of tumour types and clinical scenarios, as well as quantitative validation of segmentations.

Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome.

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.