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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| pCMS+ | Children undergoing infratentorial craniotomy for brain tumour resection whom develop pCMS will undergo pre-, post-operative and delayed follow-up advanced 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 |
| |
| Controls | Healthy control children whom have never undergone intracranial surgery have had advanced MRI sequences acquired |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Advanced MRI sequences | Diagnostic Test | Structural, diffusion and perfusion MRI sequences |
|
| 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 |
| 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
Mutism
Ataxia
Hypotonia
Irritability
Severe = at least 2 severe features Moderate = at least 2 moderate features or 1 moderate and 1 severe Mild = anything less than above |
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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
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All children referred to our institution with a brain tumour of the posterior fossa
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Great Ormond Street Hospital for Children | London | WC1N 3JH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36137658 | Derived | 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 Oct;43(10):1508-1515. doi: 10.3174/ajnr.A7637. Epub 2022 Sep 22. |
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| 1 year |