Advanced MRI for Posterior Fossa Tumours

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

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.

Study Overview

• Status: Completed
• Conditions: Cerebellar Mutism; Posterior Fossa Syndrome
• Intervention / Treatment: Diagnostic test: Advanced MRI sequences

• Study Type: Observational
• Enrollment (Actual): 82

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All children referred to our institution with a brain tumour of the posterior fossa

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
pCMS+; 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; Structural, diffusion and perfusion MRI sequences
pCMS-; 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; Structural, diffusion and perfusion MRI sequences
Controls; Healthy control children whom have never undergone intracranial surgery have had advanced MRI sequences acquired	Diagnostic test: Advanced MRI sequences; Structural, diffusion and perfusion MRI sequences

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
• Investigators: Principal Investigator: Chris Clark, PhD, University College London Institute of Child Health; Principal Investigator: Kristian Aquilina, MD, FRCS, Great Ormond Street Hospital; Principal Investigator: Sebastian M Toescu, MBChB (Hons), University College London Institute of Child Health

Publications and helpful links

General Publications

• Toescu SM, Hales PW, Cooper J, Dyson EW, Mankad K, Clayden JD, Aquilina K, Clark CA. Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery. AJNR Am J Neuroradiol. 2022 Sep 22;43(10):1508-15. doi: 10.3174/ajnr.A7637. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): September 9, 2020
• Study Completion (Actual): April 7, 2021

Study Registration Dates

• First Submitted: February 23, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 20, 2018

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neurodevelopmental Disorders; Language Disorders; Communication Disorders; Speech Disorders; Syndrome; Mutism; Infratentorial Neoplasms
• Other Study ID Numbers: 17NI17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No