Genomic Research May Help Identify Best Candidates for Anti-Seizure Surgery
By Heide Aungst
Hansel Greiner, MD
When neurologist Hansel Greiner, MD, meets with families of children who are about to undergo brain surgery for epilepsy, they usually have one important question for him: “Why?”
As Co-Director of the Epilepsy Surgery Program at Cincinnati Children’s, that crucial question also haunts Greiner’s research: Why do some children develop seizure-causing focal cortical dysplasia (FCD)? Why can some children be treated successfully with medication, while others need surgery? Why does surgery work best for children with one kind of FCD, but not the other?
While wrestling with these questions, Greiner knew he wanted to go beyond understanding only why some children develop FCDs. He also wanted to develop a minimally invasive diagnostic tool that could help him determine — before surgery — if a child had FCD, and, if so, if it was the type that could be helped most by surgery. To do all that, he knew, would take a different kind of research than he had ever done before.
MR imaging findings of cortical dysplasia in three patients. Top row: Two adjacent coronal T2 FLAIR images demonstrating focal signal along the bottom of a frontal lobe sulcus (left) and adjacent tapering signal abnormality extending into the white matter (right). Bottom row: Coronal T2 FLAIR image (left) demonstrating an abnormally deep sulcus with associated abnormal cortical signal and cortical thickening. A Coronal T1 image (right) demonstrating an abnormally deep sulcus, with associated cortical thickening and adjacent heterotopic gray matter. While findings of cortical dysplasia may be diagnostic, imaging findings are often subtle. In many children with pathologically proven cortical dysplasia, MRI may be normal. Images are courtesy of James Leach, MD, Cincinnati Children’s.
EXPERT IN EPILEPSY, NEW TO GENOMICS
“I noticed some of my colleagues really get some good information on rare diseases using high-powered genomic sequencing, and I thought, ‘Why can’t we do that?’” Greiner says.
About four years ago, Greiner began collecting brain tissue and blood samples from patients, ages newborn to 30, who were undergoing FCD surgery performed by neurosurgeon Francesco Mangano, DO, at Cincinnati Children’s. Once he had samples from about 20 patients, he wanted to move forward with exome sequencing, but he wasn’t exactly sure how to take the next steps.
That’s when he applied for and received a pilot project award from the Center for Pediatric Genomics (CpG). In addition to providing funding to sequence his samples, CpG connected Greiner with other collaborators within Cincinnati Children’s to help him find the best solutions for processing and storing his data.
CENTRAL DATA COMMONS ADDS VALUE
In fact, one of CpG’s key objectives is to create a central data commons — ¡VIVA! — a one-stop place where researchers can process, store and access genomic data for their studies. Ultimately, ¡VIVA! also will allow for collaboration outside of Cincinnati Children’s, promoting powerful genomic research.
“This convenient access to data will allow us to raise genomic literacy, foster collaboration, and build multidisciplinary teams to tackle complex genomic disorders,” says Peter White, PhD, Director of the Division of Biomedical Informatics and Co-Director of CpG, who is working with a steering committee to develop the data repository.
Although Greiner is still gathering initial data, he’s excited about using genomics to answer those tough questions about FCD, which he hopes will lead to new diagnostic tools and therapies.
“One of the biggest challenges for me has been to learn how to design an experiment using genomics that can yield results,” Greiner says. “There are so many things we can learn with genomics. And the most important is ‘How can we improve a patient’s life?‘"