Advanced MRI for Posterior Fossa Tumours

Study Overview
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Brief Summary
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Post-operative paediatric cerebellar mutism syndrome (pCMS) is a well-recognised complication of resective surgery for brain tumours of the cerebellum and fourth ventricle in children. Occurring in around 25% of infratentorial craniotomies, it is characterised by a delayed onset of mutism and emotional lability, and may comprise motoric and cognitive cerebellar deficits. Transient mutism gives way to prolonged, and often incomplete, recovery. Neuroimaging studies are beginning to reveal anatomical and functional aberrancies in the brain of children with pCMS. The cerebellar efferent pathways are likely to be implicated as a neuroanatomical substrate in the development of pCMS, as shown by a handful of diffusion tractography studies to date. However, the pathophysiology of this condition still remains unclear. Hypoperfusion of supratentorial cortical and subcortical structures may mediate the speech and behavioural deficits seen in pCMS, and is a candidate for a causal pathophysiological mechanism. This study aims to prospectively image children with pCMS using advanced MRI techniques including diffusion tractography and arterial spin labelling, and to correlate this with clinical descriptions of the syndrome. All children referred to Great Ormond Street Hospital for Children with a posterior fossa brain tumour will be imaged pre-operatively, post-operatively and at delayed follow-up. In tandem with this, clinical assessments will be made of children post-operatively to ascertain which patients develop pCMS. In addition, anonymised advanced MRI data on healthy controls will be used as a comparator group.

Official Title
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Advanced MRI in Surgery for Posterior Fossa Tumours - Predicting Post-operative Paediatric Cerebellar Mutism Syndrome and Surgical Guidance to Avoid it

Conditions
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Posterior Fossa Syndrome, Cerebellar Mutism

Intervention / Treatment
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* Diagnostic Test: Advanced MRI sequences


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age <18 Referred and operated upon within study period Brain tumour of cerebellum, IVth ventricle, brainstem undergoing craniotomy for resection (including re-do surgery) No restrictions as to tumour histology or grade (embryonal tumour / glioma / ependymoma) Informed consent given by parents Exclusion Criteria: Non-neoplastic infratentorial lesions Claustrophobia Contraindication to MRI Pregnant female Scans missing at >2 timepoints Tumour resection surgery at another hospital if no pre- or post-operative scans available

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| pCMS+<br>Children undergoing infratentorial craniotomy for brain tumour resection whom develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences | Diagnostic Test: Advanced MRI sequences<br>* Structural, diffusion and perfusion MRI sequences<br>|
| pCMS-<br>Children undergoing infratentorial craniotomy for brain tumour resection whom do not develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences | Diagnostic Test: Advanced MRI sequences<br>* Structural, diffusion and perfusion MRI sequences<br>|
| Controls<br>Healthy control children whom have never undergone intracranial surgery have had advanced MRI sequences acquired | Diagnostic Test: Advanced MRI sequences<br>* Structural, diffusion and perfusion MRI sequences<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diffusion MRI tractography | To compare diffusion MRI derived tractography of the fronto-cerebellar circuitry (and associated metrics of fractional anisotropy and mean diffusivity) between patients with and without pCMS. | 1 year | 
| Arterial Spin Labeling Perfusion MRI | To compare cerebral blood flow (a metric derived from perfusion MRI) in frontal lobe regions between patients with and without pCMS. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical measure of severity of pCMS | CMS Severity Score (Robertson 2006 JNS Peds 105: 444-451): Clinical diagnosis of pCMS Yes / No If yes: Time of onset immediately post op Days 1-2 Days 2-4 => Day 4 Mutism Mild (<1wk) Moderate (1-4wks) Severe (>4wks) Ataxia Mild (<1wk) Moderate (1-4wks) Severe (>4wks) Hypotonia Mild (can sit or stand by <1wk) Moderate (can sit or stand by 1-4wks) Severe (can sit or stand by >4wks) Irritability Mild (<1wk) Moderate (1-4wks) Severe (>4wks) Severe = at least 2 severe features Moderate = at least 2 moderate features or 1 moderate and 1 severe Mild = anything less than above | 1 year |