Controlling Coordination after Childhood Cerebellar Cancer – Pilot

• Research type

  Research Study

• Full title

  Controlling Coordination after Childhood Cerebellar Cancer – Pilot Study

• IRAS ID

  278249

• Contact name

  Caroline C V Blanchard

• Contact email

  caroline.blanchard@nottingham.ac.uk

• Sponsor organisation

  University Of Nottingham

• Clinicaltrials.gov Identifier

  NCT04501731

• Duration of Study in the UK

  1 years, 6 months, 0 days

• Research summary

  Posterior fossa tumours (PFT) frequently affect the cerebellum, which is the part of the brain at the back of the head responsible for coordinating movement, balance, emotional control, and more. PFT survivors can present variable motor difficulties resulting from changes in the brain tissue structure due to the tumour itself and its treatment.

  State-of-the-art magnetic resonance imaging (MRI) scans can allow us to measure a variety of different biological processes in the brain, and we believe that some of these MRI measures (called MRI biomarkers) can be useful indicators and potential predictors of the difficulties experienced by children and young people with history of PFT during motor skills recovery. Indeed, biomarkers are very important for the development of intervention because 1) they help us understand the recuperation process and 2) they allow us to effectively assess whether or not a treatment or intervention works.

  Transcranial magnetic stimulation (TMS) is a powerful research tool that can help to evaluate the nerve fibres from the brain that control the hand. It is a procedure that applies magnetic pulses on the surface of the scalp to reach underlying brain tissue. TMS can also be used as therapeutic tool in clinics.

  The 5C-pilot study is therefore an important first step towards understanding how potential MRI biomarkers and brain responses to TMS relate to motor symptoms in PFT young survivors. Once completed, this study will allow us to select the most promising stimulation protocols to take forward into future treatment trials. We aim to use them to stimulate the recovery of motor skills, help the development of targeted therapies, and consequently improve long-term quality of life in children and young people with history of brain tumour.

  The proposed research intends to prove the feasibility of such brain stimulation and brain imaging and collect some preliminary measures.

  Summary of results
  Recruitment We aimed to recruit 4 young PFT survivors (16-22 years, not currently under oncological treatment, and able to undergo MRI scanning without sedation) and 6 age-matching controls. After a delayed start due to the COVID pandemic, we recruited 3 out of the 4 planned PFT young adults and 6 out of the 6 planned healthy controls (i.e. 9 out of 10 of our original recruitment aim).

  MRI
  9 out of 9 participants recruited had a brain MRI Thanks to goggles, we offered them to watch/listen to something on YouTube ( or similar) during most of the time of the scanning session. They reported that the video made them more comfortable lying in the scanner tube for 40 minutes. They also played a homemade alien theme-based game to assess their visual-motor coordination. They found it “fun”.
  All brain images were usable with standard image quality (not too much movement, etc.). They have been pre-processed and further analyses are ongoing

  Motor performance
  9 out of 9 participants recruited had a motor assessment We assessed motor performance thanks to 3 different set-ups: (1) a grooved pegboard for measuring dexterity, (2) a homemade reaching and grasping task for measuring visual-motor coordination and online movement correction and (3) an isometric dynamometer to measure grip force

  TMS
  8 out of the 9 participants recruited had a TMS session.
  On the day of their visit only, one participant mentioned having a mini-seizure after their brain surgery. According to our ethics and exclusion criteria, we could not run the TMS session for this participant even though they were very keen to have it anyway. participants enjoyed it, especially as we displayed muscle activity recordings and response maps on screens in front of them.

  Conclusion
  Thanks to the 5C-pilot study, we established the feasibility and tolerability of having a brain MRI and TMS for either group (Satisfaction questionnaires and feedback from participants and families about their MRI/TMS experience. Images, electromyograms and other recordings displayed a satisfying quality As expected, we observed differences between PFT and control young adults in terms of brain anatomy, brain functioning, muscle force (illustrated below), variability and latency of motor responses, etc. The small sample will only allow us to describe single cases but will not allow further statistical analyses.

  The main difficulty was recruiting young adults with PFT with no history of seizures; most experienced mini-seizures immediately after their surgery. History of seizure was an exclusion criterion for the described pilot study. After discussing this with a paediatric oncologist, we conclude that it might be possible to include participants who experienced only seizure post-surgery and no other seizure episodes. That is something that needs to be discussed with a larger number of clinical care members including neurologists before further study.
  On a side note, having an MRI and then the TMS session on the same day was the option chosen by all the participants. This option was more convenient than planning visits on two different days, shorter in terms of time commitment and travel duration but definitively represented a long day for the participants.
  We need to run further analyses on MRI metrics (like cerebellar volume and parcellation, brain activation maps during the hand motor task, and anatomical and functional brain connectivity) and motor performance (kinaesthetic parameters of hand movement during home-made reaching and grasping task; measures of max grip force, and score (timing/error) during grooved pegboard task) and TMS metrics (Parameters of Muscle Evoked Potentials (MEPs) - thresholds, amplitude, latency, etc.)

• REC name

  South Central - Hampshire A Research Ethics Committee

• REC reference

  20/SC/0368

• Date of REC Opinion

  1 Dec 2020

• REC opinion

  Further Information Favourable Opinion