From Patient to Progress: New insights into preventing shunt blockages

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By: Maggie A. Khuu and Dr. Jenna Koschnitzky, Director of Research Programs

While shunt implantation is a typical treatment option for people with hydrocephalus, there have been surprisingly few advances to decrease shunt failure rates since the 1950s. For patients that receive permanent shunts, the initial feeling of relief after a successful surgery can quickly turn to worry and anxiety about shunt failure. Shunts often fail due to buildup of organic materials (tissue and cells) that block the cerebrospinal fluid (CSF) catheter intake holes and prevent the proper drainage of CSF. Shunt obstruction attributed to physical blockage by cells or tissue accounts for more than half of the shunt failures in children with hydrocephalus.

Dr. Brian Hanak, Seattle Children’s Research Institute, and Dr. Carolyn Harris, now running her own lab at Wayne State University, are working to change that.

In the study, published in the Journal of Neurosurgery: Pediatrics, researchers from Seattle Children’s Research Institute collected failed shunt hardware from pediatric patients ages 7-13 to identify which cellular substrates (e.g., cells floating in CSF) could be responsible for these obstructions. It was reported in earlier studies that the choroid plexus, a bundle of cells that produces CSF in the brain, and ependymal cells, cells that line the CSF filled spaces in the brain, were often found blocking the intake holes of these failed shunts.

The team hypothesizes that astrocytes and microglia first stick to the catheter and then act as a “bridge” for the choroid plexus and ependymal cells to attach to the shunt catheter. Together, these cells all contribute to shunt obstruction.

However, the team found that many shunts which, with the naked eye, seemed to have no cells attached to the shunt catheter, had microglia and astrocytes attached to the CSF intake holes when viewed under a microscope. Microglia and astrocytes are cells that support neurons by holding them in place, supplying them with nutrients and oxygen, and destroying harmful bacteria and viruses, among other duties. What was unknown prior to this study was that the choroid plexus and ependymal cells did not appear to attach directly to the catheter but attached instead to the microglia and astrocytes.

Essentially, the team hypothesizes that astrocytes and microglia first stick to the catheter and then act as a “bridge” for the choroid plexus and ependymal cells to attach to the shunt catheter. Together, these cells all contribute to shunt obstruction. Based on the data from this study, it appears that astrocytes and microglia are the primary cell types responsible for ventricular catheter obstruction.

Above are images of two holes from an explanted shunt catheter. The green and red show the astrocytes and microglia attached to and blocking the holes. The black surround is the surface of the catheter that has no cells attached. Image courtesy of Dr. William Shain & Dr. Carolyn Harris (2014).

While further studies are needed to include a broader panel of cell markers, these new findings may lead to better and more targeted ways to prevent shunt catheter obstruction. Understanding exactly why the catheter holes become blocked will allow the development of new coatings and catheter materials that specifically prevent these cells from sticking and blockages from occurring, leading to less shunt failure.

In 2015, Dr. Hanak received the Hydrocephalus Association Resident’s Prize which is an annual award given to the most promising hydrocephalus-related research paper presented by a neurosurgical resident at the Pediatric Section meeting of the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS).

Dr. Carolyn Harris began working on hydrocephalus as a graduate student with Dr. Pat McAllister and brought this project to the lab of Dr. William Shain as a postdoctoral fellow. She is now running her own independent lab at Wayne State University, College of Engineering, where she is an Assistant Professor.

In 2016, Dr. Harris received the annual Gift of Knowledge Award honoring the pediatric neurosurgeon Norman Guthkelch from the Society for Research into Hydrocephalus and Spina Bifida with her presentation, ‘Investigating the mechanisms of shunt obstruction in hydrocephalus using human shunt explants’. Also in 2016, Dr. Harris received a National Institutes of Health (NIH) grant worth almost $2,000,000 to continue this line of research. The project is entitled, ‘Investigating the cellular mechanisms leading to repetitive shunt failure in the treatment of pediatric hydrocephalus’.  Dr. Harris is continuing to build her lab, which now includes 11 students. Many in our community know Dr. Harris through both the Seattle and Detroit WALKS and the Detroit Community Network meetings. Dr. Harris is also a staple at the biennial National Conferences on Hydrocephalus and has dedicated her career to understanding and preventing shunt occlusion.

 

Additional information on shunts can be found here:

http://www.hydroassoc.org/shunt-systems/

http://www.hydroassoc.org/complications-of-shunt-systems/

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