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Research Update: Aneurysm and Stroke Care

Complications can be life-threatening for patients who experience the rupture of an intracranial aneurysm. When an aneurysm ruptures, it bleeds into the space between the skull and the brain or into the brain tissue, causing symptoms ranging from headache to brain damage and even death.

Karol Budohoski, MD, is a cerebrovascular, endovascular, and skull base neurosurgeon researching intracranial aneurysms and 

Dr. Budohoski and Sarah in the lab

the complications that arise from their rupture. He is also involved in global health work, researching access to stroke care in settings with limited resources and medical infrastructure.

Dr. Budohoski is developing methods of determining whether or not a patient is at risk of developing serious complications after an intracranial aneurysm rupture.

“We’re trying to get a close look at what the exact genes are that get activated within the aneurysm when it ruptures. This information will help us understand what drives the very serious complications we see in our patients,” Dr. Budohoski shared. The causes of complications seen after intracranial aneurysm ruptures are, unfortunately,

Sarah Dabb in Dr. Budohoski's lab

very complicated, which is why Dr. Budohoski and lab technician Sarah Dabb are in the process of building a full gene expression profile using cells taken directly from inside and outside of an aneurysm.

Aneurysmal subarachnoid hemorrhage is associated with a 30–40% fatality rate and significant morbidity. Advancements in treatment protocols have improved patient outcomes, but there can still be major complications—for which there are no treatment options in place—that are likely caused or at least mediated by endothelial cells, the cells that line the inside of vessels. Minimally invasive procedures allow the team to sample those cells and identify how genes are activated and which patterns may be responsible for the complications that occur after aneurysm rupture. 

“We obtain endothelial cells directly from ruptured intracranial aneurysms and peripheral arteries that we access during neurosurgical interventions,” Dr. Budohoski said. “We then perform single-cell RNA sequencing and compare endothelial cell gene expression from the aneurysm with control 

Dr. Budohoski displaying endothelial cells

endothelial cells from the same patient to identify novel targets to prevent and treat these complications.” 

At this time, Dr. Budohoski and his team are gathering preliminary data but plan to expand the study to more patients in the future. When the gene expression profile is completed, the team should be able to tell patients whether they’re at risk of developing complications after aneurysm rupture before it ever happens.

Sarah Dabb working with enothelial cells

Dr. Budohoski is also working with resident Sarah Nguyen, MD, to improve stroke care on a global scale. Dr. Nguyen will be undertaking a Masters of Education in Health Professions structured around the development of mechanical thrombectomy programs during her research year.

Mechanical thrombectomy is a highly beneficial and cost-effective treatment for stroke, but only 30% of Americans who are eligible for thrombectomy receive it. Fewer than 3% of those who need thrombectomy receive it globally, and fewer than 1% of eligible patients receive this life-saving treatment in low-income countries. 

Stroke is the second-leading cause of death worldwide and has been designated a priority by the World Health Organization. A recent survey of 17 African countries demonstrated that there were only 5 stroke units and 2 designated stroke centers across the region and that access to thrombolysis and thrombectomy is highly limited. Many of the recommendations and guidelines that have been developed cannot be applied in settings with limited medical infrastructure.

Graphic of Africa showing availability of stroke care

Dr. Budohoski is the founder of the Tanzania Stroke Project, an initiative dedicated to increasing access to stroke care in Tanzania and East Africa. The team includes dedicated physicians from various geographical regions that have adopted a three-pronged approach.

First, they are working to determine the true incidence of patients experiencing severe stroke in those underserved areas. This information will allow the team to calculate the real needs and possible costs of developing new stroke programs. “Without knowing how many patients currently suffer severe stroke in Tanzania, it is impossible to engage stakeholders and develop real needs assessments,” Dr. Budohoski said. Secondly, Dr. Budohoski is leading a study that will establish the essential requirements for developing programs that offer mechanical thrombectomy, which could be used in countries like Tanzania. “It is very difficult to start these programs from scratch,” Dr. 

Budohoski noted. “A blueprint describing the necessities for creating a thrombectomy program can help countries without this treatment to direct resources more efficiently.” Last is the hands-on training of physicians in Tanzania that will allow them to provide endovascular treatment. Dr. Budohoski has partnered with neurologists, neurosurgeons, and interventional radiologists from Muhimbili National Hospital in Dar es Salaam, Tanzania. “We’ve been lucky; our partnership with the physicians at Muhimbili National Hospital has come at a time when many providers are discussing stroke care and there is a visible drive to improve and develop these programs," Dr. Budohoski said. He provides training in Dar es Salaam at least twice a year. “It is difficult to provide in-person training so far from home, so we are working to find more international teams to join this project. The idea is to have training teams present as frequently as possible to provide an immersive environment similar to a fellowship.”

Dr. Budohoski is conducting this work in partnership with Mission Thrombectomy (a global alliance of physicians working to improve access to stroke treatment worldwide) with the long-term goal of expanding access to mechanical thrombectomy to the East African region. “It’s an immense pleasure for me to be part of these developments,” Dr. Budohoski shared. “Although it can be difficult to improve access to a particular treatment in a place where it’s not 

Dr. Budohoski with Dr. Godlove Mfuko (Chief Medical Officer at Mloganzila National Hospital)

available, the dedication of my colleagues from Muhimbili National Hospital makes this work the most rewarding of anything I do.”