This project is jointly funded by Sparks and charity partner Great Ormond Street Hospital Children’s Charity through the National Research Funding Call.
Spina bifida is caused when the nerves and membranes of the spine are left exposed, due to a problem during development in the womb. Children with spina bifida can become disabled through paralysis of the lower body. However, the most life-threatening aspect of spina bifida is the Chiari II brain defect, in which the back of the brain (the ‘brainstem’) moves downwards through the hole in the base of the skull.
Nerves that control breathing are located within the brainstem. In Chiari II, the displaced brain parts can become ‘squashed’, which disturbs or prevents breathing, leading to death or severe disability. Around 90 per cent of children with spina bifida have the Chiari II brain defect, although it is not fully understood why there is this strong link.
A better understanding will help understand if future pioneering surgery while babies are still in the womb, is an effective way to help prevent Chiari II.
Professor Andrew Copp and his team at Great Ormond Street Institute of Child Health will determine why Chiari II is so commonly associated with spina bifida and how closing the exposed spinal tissue during pregnancy (by fetal surgery) could help reduce the severity of Chiari II.
His team have a theory that as fluid leaks out of the spina bifida opening, this causes a decrease in pressure, causing the brain to be smaller than it would normally be. Because the skull grows around the brain, using it as a ‘template’, a smaller brain means the base of the skull won’t grow as much.
Then, later in pregnancy, as the brain grows, the brainstem cannot be accommodated within the small skull base, and becomes ‘squeezed’ downwards, out of the skull, creating the Chiari II defect.
To test this theory, his team will analyse brain scans of children who have been treated by the neurosurgeons at GOSH, and perform brain scans on mice with spinal bifida and Chiari II during early development. In the mouse studies, they will perform an experiment to determine whether the ‘spinal fluid leakage’ theory is correct.
They will also compare the brain scans of babies undergoing spina bifida repair in the womb, a procedure currently offered by surgeon in Leuven, Belgium. This comparison should reveal whether this kind of fetal surgery reduces Chiari II brain defects. This pioneering fetal surgery will soon begin in London thanks to an ongoing collaboration between the Belgian team and surgeons at GOSH and University College London Hospitals (UCLH).
If fluid leakage from the spina bifida opening proves responsible for Chiari II, this will guide further development of fetal surgery, not only to minimise paralysis but also to avoid the life-threatening breathing problems associated with Chiari II.
A study looking to understand the causes of a common brain defect associated with spina bifida (chiari ii malformation) and determining if fetal surgery (for spina bifida) could help reduce its severity
Researcher: Professor Andrew Copp