Advanced MRI for Posterior Fossa Tumours

Completed

• Conditions: Cerebellar Mutism; Posterior Fossa Syndrome
• Interventions: Diagnostic Test: Advanced MRI sequences

• Registration Number: NCT03471026
• Lead Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-23
• Study First Submitted QC: 2018-03-13
• Study First Posted: 2018-03-20
• Study Start: 2018-04-09
• Primary Completion: 2020-09-09
• Status Verified: 2020-12
• Study Completion: 2021-04-07
• Last Update Submitted: 2021-07-05
• Last Update Posted: 2021-07-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
pCMS+	Advanced MRI sequences	Children undergoing infratentorial craniotomy for brain tumour resection whom develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences
pCMS-	Advanced MRI sequences	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
Controls	Advanced MRI sequences	Healthy control children whom have never undergone intracranial surgery have had advanced MRI sequences acquired

Primary Outcome Measures

Name	Time	Method
Arterial Spin Labeling Perfusion MRI	1 year	To compare cerebral blood flow (a metric derived from perfusion MRI) in frontal lobe regions between patients with and without pCMS.
Diffusion MRI tractography	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Clinical measure of severity of pCMS	1 year	CMS Severity Score (Robertson 2006 JNS Peds 105: 444-451): Clinical diagnosis of pCMS Yes / No; If yes: Time of onset; 1. immediately post op; 2. Days 1-2; 3. Days 2-4; 4. =\> Day 4; Mutism; 1. Mild (\<1wk); 2. Moderate (1-4wks); 3. Severe (\>4wks); Ataxia; 1. Mild (\<1wk); 2. Moderate (1-4wks); 3. Severe (\>4wks); Hypotonia; 1. Mild (can sit or stand by \<1wk); 2. Moderate (can sit or stand by 1-4wks); 3. Severe (can sit or stand by \>4wks); Irritability; 1. Mild (\<1wk); 2. Moderate (1-4wks); 3. 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

Trial Locations

Locations (1)

Great Ormond Street Hospital for Children; 🇬🇧 London, United Kingdom