Grace Egan’s backflips for her competitive cheer team were packed with power and precision that reflected her gymnastics and ballet training. Yet, on Nov. 15, 2021, the vivacious preteen collapsed without warning at her school. The school nurse called her parents immediately.

When her father arrived, Grace had been isolated in a darkened room for observation. The commercial real estate investor who had wished his daughter a good day at school hours earlier was met with a blank stare. She had no idea who he was.

How did this star student, beaming and engaged in her classwork that morning, end up in such distress? How could she not recognize her dad?

One thing was clear: Her parents, Sara Fay and Merrick Egan, were determined to halt the downward spiral. They were single-minded about getting their daughter back.

“When we arrived at Children’s Medical Center Dallas, somebody mentioned encephalitis, but nothing was certain except her seizures and distorted thinking,” Mr. Egan said. “The doctors didn’t know at first if it was a psychological issue or a nervous system issue.”

All Grace remembered was being extremely anxious as she completed a battery of tests. Her symptoms persisted during the evaluation.

“After I met the doctor, I thought he was really cool,” said the now healthy 12-year-old, perched with her dog on the back porch of her family’s Dallas home. “I felt like I was in good hands.”

Today, she is symptom- and disease-free – thanks an established specialty team led by a UT Southwestern neuroimmunologist.

The body electric

UT Southwestern Medical Center’s Vice Chair of Clinical and Translational Research for the Department of Neurology Benjamin Greenberg, M.D., is an internationally recognized expert in treating rare autoimmune disorders of the central nervous system. When called to evaluate Grace, he discussed the possibility of a rare condition known as autoimmune encephalitis.

To Dr. Greenberg, who is also a Professor of Neurology and Pediatrics at UT Southwestern, Grace’s symptoms could have been caused by her immune system attacking itself, causing inflammation and destroying healthy brain cells, eliciting extreme behavioral changes. Specific antibody tests were negative, but there was some evidence of the condition.

Currently, there is no good estimate of how many people have autoimmune encephalitis in the United States, although the Autoimmune Encephalitis Alliance says the disorder is more common than people realize. For some people with the condition, scientists have identified specific antibodies that target the brain’s neurons. Components of the outer surface of neurons are disrupted, inhibiting the function of brain cells, which leads to the kind of neurological and psychiatric symptoms Grace was experiencing. The cause can’t always be traced. Some attacks arise spontaneously without a triggering event.

Most forms of the condition respond to immune therapies. However, in difficult cases, patients may need to undergo powerful immunosuppressive treatment for weeks or months. Patients can also relapse.

Grace stayed at Children’s Medical Center Dallas for 40 days that stretched through Christmas. During that time, Dr. Greenberg started her on immunosuppressive therapy. By temporarily keeping her natural defenses at bay in what he described as a “gut punch” to her immune system, he and his team were able to keep Grace’s body from attacking her brain cells.

The symptoms subsided. She recognized her dad again.

The enemy within

While immunosuppressive therapy has become the standard of care in difficult autoimmune encephalitis cases, the greatest challenge often lies in making an accurate diagnosis.

“One of the most important things for pattern recognition is experience,” Dr. Greenberg said. “You need clinics that see these types of rare diseases on a day-to-day basis.”

Being in Dr. Greenberg’s hands and pursuing an aggressive treatment plan was a relief to Grace’s mother.

“We consulted two other providers before deciding on UT Southwestern for care,” Mrs. Egan said. “The difference in coming to UT Southwestern is that it was clear the team had experience. Knowing exactly what you’re dealing with is a big part of the battle.”

Autoimmune encephalitis is often not diagnosed because it shares traits with psychiatric disorders. Few psychiatrists are trained to recognize autoimmune disorders that can produce symptoms that match well-known mental illnesses. Bizarre behavior and speech, delusions, and hallucinations can all be symptoms of schizophrenia but when neurological symptoms appear – like seizures or a lack of responsiveness – physicians must look deeper. Because there are currently no blood tests to detect the disease, physicians draw fluid from the spine through a lumbar puncture to test for evidence of the disease.

Kid gloves

Dr. Greenberg stops short of saying Grace’s diagnosis might have been missed had her parents gone elsewhere for her care. But he is also familiar with the advantages of being at an academic medical center known for autoimmune encephalitis expertise.

“Our ability to recognize and diagnose the disease properly is not because we are necessarily smarter than anybody else, but because we have had the privilege of practicing at UT Southwestern and seeing large numbers of patients in this category of rare disease,” he said.

With families like the Egans, the first thing Dr. Greenberg and his team do is listen and empathize. The team works closely with colleagues in psychiatry to treat children throughout the process. Controlling symptoms and keeping children safe is always a priority when trying to determine a diagnosis, and if the underlying cause is psychiatric, children and families continue to receive appropriate care, which can deliver significant improvements.

“Through testing, we first look for any identifiable antibodies that indicate a confused immune system,” Dr. Greenberg said. “Even if we don’t immediately see one of these specific antibodies, I tell families that if I find anything objective that tells me this is not a schizophrenic or a psychiatric condition, we’re going to pursue that.”

In his experience, many families prefer an autoimmune encephalitis diagnosis to a psychiatric one, because the problem can be clearly identified and treated, unlike more elusive and stubborn psychiatric illnesses that may not have as favorable a prognosis. It’s a revelation that often brings families great relief.

Meeting with Dr. Greenberg for the first time, the Egan family finally had a reason to feel hope.

“We knew it was a turning point,” Mrs. Egan said. “We were so grateful for his expertise, and his incisive mind. He gave us our daughter back.”

As part of UT Southwestern’s Collaboration on Neuroimmunology: Question, Understand, Educate, Restore (CONQUER) program, Dr. Greenberg and his colleague Nancy Monson, Ph.D., an Associate Professor of Neurology and Immunology at UT Southwestern, are working to identify unique antibodies that cause autoimmune encephalitis – all to better diagnose and treat patients like Grace. Combined with greater education about autoimmune encephalitis, designing a simple blood test that physicians could easily turn to for a rapid diagnosis is an area of active study for the team.

To support this research, the Egan family established the Grace Fund for Autoimmune Encephalopathy at the Medical Center. To date, they have raised more than $300,000 from family and friends.

“What Merrick and Sara Fay went through as parents was frightening and would have exhausted anybody’s patience,” Dr. Greenberg said. “But to their credit, they really wanted to do something that would help future families through an ordeal like this. Through their leadership in the community, they’ve encouraged generosity that will help accelerate how we diagnose cases like Grace’s.”

The Egans’ efforts have enabled researchers to collect critical patient specimens that can be used to discover new causes of autoimmune encephalitis, with the hope of providing answers and more options for people being treated for autoimmune diseases at UT Southwestern.

“We’re grateful to our friends and the community who’ve rallied to support this area of research,” Mr. Egan said. “Until meeting Dr. Greenberg, the illness was a mystery to my family. In the hands of a less experienced doctor, we might still be trying to figure out what was wrong with our Grace.

“We’re incredibly blessed and fortunate to be in a world-class city with world-class medical care.”

• Dr. Greenberg is a Cain Denius Scholar in Mobility Disorders.