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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.

Posterior fossa syndrome (PFS), or cerebellar mutism syndrome (CMS), is a collection of neurological symptoms that occur following surgical resection of a posterior fossa tumour, and is characterised by either a reduction or an absence of speech. Some authors suggest that CM is only one symptom of the CMS complex that also includes ataxia, hypotonia and irritability as well as cranial nerve deficits, neurobehavioral changes and urinary retention or incontinence. It is seen almost exclusively in children. In 1985 Rekate . published the first work describing CM as a clinical entity, occurring as a consequence of bilateral cerebellar injury. Other associated symptoms include visual impairment, altered mood, impaired swallowing and significant gross and fine motor deficits. The effects of this can have a devastating impact on both the patient and their carers, posing a significant clinical challenge to neurorehabilitation services. The reported incidence was between 8% and 31% of children undergoing surgery for posterior fossa tumour. The underlying pathologies include vasospasm, oedema, and axonal/neuronal injury. Neuroimaging has contributed to a better understanding of the anatomical location of postoperative injury. There have been a number of suggestions for treatment interventions for PFS. However, apart from some individual reports, there have been no clinical trials indicating possible benefit. Occupational therapy, speech and language therapy, as well as neurocognitive support, contribute to the recovery of these patients.

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Object Neuroendoscopists often note pulsatility or flabbiness of the floor of the third ventricle during endoscopic third ventriculostomy (ETV) and believe that either is a good indication of the procedure's success. Note, however, that this belief has never been objectively measured or proven in a prospective study. The authors report on a simple test—the hydrostatic test—to assess the mobility of the floor of the third ventricle and confirm adequate ventricular flow. They also analyzed the relationship between a mobile floor (a positive hydrostatic test) and prospective success of ETV. Methods During a period of 3 years between July 2001 and July 2004, 30 ETVs for obstructive hydrocephalus were performed in 22 male and eight female patients. Once the stoma had been created, the irrigating Ringer lactate solution was set at a 30-cm height from the external auditory meatus, and the irrigation valve was opened while the other ports on the endoscope were closed. The ventricular floor ballooned downward and stabilized. The irrigation valve was then closed and ports of the endoscope were opened. The magnitude of the upward displacement of the floor was then assessed. Funneling of the stoma was deemed to be a good indicator of floor mobility, adequate flow, and a positive hydrostatic test. All endoscopic procedures were recorded using digital video and recordings were subsequently assessed separately by two blinded experienced neuroendoscopists. Patients underwent prospective clinical follow up during a mean period of 11.2 months (range 1 month–3 years), computerized tomography and/or magnetic resonance imaging studies of the brain, and measurements of cerebrospinal fluid pressure through a ventricular reservoir when present. Failure of ETV was defined as the subsequent need for shunt implantation. The overall success rate of the ETV was 70% and varied from 86.9% in patients with a mobile stoma and a positive hydrostatic test to only 14.2% in patients with a poorly mobile floor and a negative test (p < 0.05). The positive predictive value of the hydrostatic test was 86.9%, negative predictive value 85.7%, sensitivity 95.2%, and specificity 66.6%. Conclusions The authors concluded that the hydrostatic test is an easy, brief test. A positive test result confirms a mobile ventricular floor and adequate flow through the created ventriculostomy. Mobility of the stoma is an important predictor of ETV success provided that there is no obstruction at the level of the arachnoid granulations or venous outflow. A thin, redundant, mobile third ventricle floor indicates a longstanding pressure differential between the third ventricle and the basal cisterns, which is a crucial factor for ETV success. A positive hydrostatic test may avert the need to insert a ventricular reservoir, thus avoiding associated risks of infection.

Children's brain tumours are the biggest cancer killer in children and young adults. Several techniques, such as intra-cerebrospinal fluid chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intra-arterial and intra-nasal chemotherapy, have the potential to transform the treatment of brain tumours in children. However, there have been very few clinical trials to evaluate these. In 2021, the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) and the ITCC (Innovative Therapies for Children with Cancer) brain tumour group established a Clinical Trials Working Group comprising international researchers and clinicians to address this issue. This partnership highlighted the main challenges in preclinical to clinical translation of paediatric CNS drug delivery as: (1) a lack of specific funding for prototype development and/or scale-up for clinical trials; (2) difficulties in navigating the regulatory landscape; (3) lack of accurate preclinical models; and (4) increased need for multi-centric working. In response to this, we ran a hybrid workshop in November 2021 on ‘Clinical Trial Readiness for CNS Drug Delivery’. At this workshop, around 50 delegates (comprising clinicians, researchers, trial regulatory experts, policy makers, and representatives from funding organisations, brain tumour charities and industry) came together to discuss issues around funding, preclinical models and regulatory processes. We have established speciality-specific working groups to build on the workshop discussions, with the aim of producing recommendations around the use of preclinical models and drug delivery techniques according to brain tumour type. We have also used the workshop presentations and discussions to create a ‘Roadmap’ document for preclinical to clinical translation, which will be freely shared with the neuro-oncology research community. We continue to liaise with funders and regulatory bodies to address the changes that are needed in these areas. If you would like to join our network, contact: cbtddc@nottingham.ac.uk

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.