While working as a clinician at Children’s Hospital Colorado, Krista Eschbach, MD, an associate professor of pediatric neurology at the University of Colorado Anschutz School of Medicine and investigator at the Adult and Child Center for Outcomes Research and Delivery Science (ACCORDS), found herself with more questions than answers as she treated patients with new-onset refractory status epilepticus (NORSE).
NORSE is a rare but severe condition in which a child or adult who is previously healthy — without an underlying active neurological illness nor traumatic brain injury — goes into prolonged seizure activity that doesn’t respond to initial treatments. Febrile infection-related epilepsy syndrome (FIRES) is a subtype of NORSE in which there is a preceding febrile illness starting at least one day before seizure onset.
While rare, NORSE can be life-changing, with up to 20-30% mortality acutely and a wide range of outcomes for a patient, from ongoing drug-resistant epilepsy with persistent chronic seizures to neurocognitive symptoms, like a change in thinking, memory, communication, and even mood and behavior.
Simple questions about which treatment options can best help these patients went unanswered, spurring Eschbach to change her career from predominantly treating patients to conducting health services research.
“I switched my career to include a focus on finding the answers that I wanted to be able to provide to patients and their families,” said Eschbach.
In collaboration with lead investigator Lawrence Hirsch, MD, professor of neurology at Yale School of Medicine; Margaret Gopaul, PhD, MSCP, assistant professor of neurology at the Yale School of Medicine; and Nora Wong, PhD, executive director of the NORSE Institute, Eschbach is co-leading the first large-scale randomized study of its kind focused on NORSE. With the support of funding from the Patient-Centered Outcomes Research Institute, a nonprofit research funding organization, the study team is comparing two immune therapy medications used in the treatment of NORSE: tocilizumab and anakinra.
While both treatments are currently in use by clinicians as part of the NORSE treatment recommendations, the choice between the two can be unclear due to a lack of data. That’s something Eschbach is looking to change. “This study will hopefully answer that question: which one is more effective, or if they are similarly effective. If we can identify whether one treatment is more effective, it can lead to improved patient outcomes,” she said.
Eschbach noted this study is unique because it is a collaboration with NORSE patients, their families, and their caregivers on how to measure the study’s outcomes, especially for long-term outcomes.
“Some of the feedback I’ve received from patients and families contributed to our thinking about what’s important for them when we’re measuring outcomes. Yes, survival is certainly important, as well as how long someone is in the intensive care unit and how long they’re in the hospital. But there’s other important long-term outcomes that we’ve heard from patients and families that needs to be examined,” she said.
As a result of centering the patients and families feedback, this study will examine longer-term results as a primary outcome. While data on rare diseases like NORSE has grown over the years, there’s still a gap in information that would help support patients and their families – a gap Eschbach’s study will hopefully begin to close.
“Ultimately, my long-term goal is for us to have better interventions, both in the acute treatment of NORSE and in the post-acute phase so we know the best ways to treat patients and improve outcomes,” said Eschbach.
Making a career shift from a primary clinical role to also being a health services researcher can be challenging for some, and Eschbach credits ACCORDS as a factor in her success. From 2022 to 2024, Eschbach participated as a Scholars in Clinical Outcomes Research (SCORE) fellow at ACCORDS, prior to becoming an investigator for the center.
“Certainly, my shift from a clinical one to research has been facilitated by my participation as a SCORE fellow," she said. "Having my own section support and then the addition of benefits of SCORE fellowship has been really helpful.”
Those benefits include a strong career development curriculum, one-on-one mentorship, as well as access to additional SCORE mentors and a grant writing course, all of which provided additional support to Eschbach as she pivoted to research in her quest for answers.