Comprehensive testing leads to targeted treatment for rare autoimmune encephalitis antibody: Spencer Lodin

Patient Spotlight

What started as a persistent headache for Spencer Lodin soon devolved into slowed speech, seizures, and hallucinations, symptoms which stumped ER doctors into thinking he had meningitis or was suffering from psychosis. Finally, specialized testing at Mayo Clinic identified Spencer's condition as GFAP-IgG associated autoimmune encephalitis, which allowed for targeted treatment and a full recovery.  

It was April 2020, the COVID-19 pandemic in full swing, when Spencer Lodin, 37, a mail carrier from the Twin Cities, experienced a persistent headache, which soon devolved into numbness on his left side, slowed speech, seizures, and hallucinations. After a series of ER visits and subsequent hospitalizations, Spencer's doctors began to suspect encephalitis — inflammation of the brain for which there can be various causes. Specialized testing at Mayo Clinic revealed he had GFAP-IgG associated autoimmune encephalitis. Once this rarer antibody was identified, Spencer could begin more targeted treatment, and the long road to healing.

Spencer with two cats he adopted in March 2023.

When Spencer first complained about his headache to his primary care physician, the doctor told him to switch from ibuprofen to Tylenol. It didn't help. Then he started losing sensation on one side of his body.

"My brother-in-law, a doctor, was concerned I wasn't getting better and suggested I go to the ER," says Spencer, who is the youngest of five. "I went to the ER at the University of Minnesota Health Center. They gave me a CAT scan that came back with nothing abnormal. So, they discharged me and said I was fine."                                  

But Spencer wasn't fine. Two days later he was back in the ER. The numbness on his left side had gotten worse, and his headache was still raging. An MRI found inflammation in his brain. Spencer then underwent a spinal tap. His initial diagnosis was meningitis, and he was checked into the hospital. "They put a PICC line in me and then released me after three days with a schedule of drugs," Spencer recalls. "My sister said that when I got home that day, my speech had really slowed down and I wasn't sounding like myself."

Spencer's initial misdiagnosis of meningitis isn't uncommon, according to Andrew McKeon, M.B., B.Ch., M.D., a neurologist and director of the Neuroimmunology Laboratory at Mayo Clinic. "Once the inflammation gets into the brain you can get signs of conditions like viral or bacterial meningitis, because the initial presentation is not very specific," says Dr. McKeon, who treated Spencer once he came to Mayo.  

Walking in circles

At its worst, Spencer's condition required a prolonged hospital stay while doctors worked to identity the cause, and solution, to his symptoms.

A couple of days later, Spencer was at home on a Friday night hanging out with a friend when, at one point, his friend noticed him walking around in circles. "And they were like, 'Are you OK?'" Spencer says. "I apparently told them I was trying to walk off the pain of the headache." An ambulance was called, and Spencer was taken back to the ER. But he ended up at a psychiatric hospital. He was examined more for psychosis rather than for his other symptoms.

"When Spencer was seen in that state of mental agitation, one might think of an early psychosis," Dr. McKeon says. "But when you add the headache, and numbness down one side, and slowed speech, it begins to indicate encephalitis."

Spencer was discharged that same night. He tried to call for a ride but was too disoriented to complete a simple phone call. He somehow made it home, barefoot, after an hour's walk. Spencer continues, "When I woke up in the morning the left side of my body had gone numb again," he says. "So, I went downstairs to the person who lives below me and asked them to call an ambulance. The ambulance brought me to the hospital. And that is the last thing I remember for a month."

After a host of additional tests, doctors at the University of Minnesota suspected Spencer had encephalitis. But they needed to confirm the particular antibody causing the inflammation of his brain. A sample of Spencer's cerebral spinal fluid was sent to Mayo Clinic Laboratories for testing. The results would take two weeks because such testing is extensive.

"Our approach is, if the patient has encephalitis, we should include in our test evaluation every antibody that's pertinent to that disease state," Dr. McKeon says. "The GFAP antibody was discovered at Mayo, and as soon as we validated it clinically, we included it in our evaluation for autoimmune encephalitis. And that's what came back as positive in Spencer's case."

Mayo Clinic is the only hospital in the country that offers testing for GFAP-IgG. Shannon Hinson, Ph.D., principal developer in Mayo's Neuroimmunology Laboratory, developed and validated the test.

"GFAP-IgG was first identified by its unique staining pattern of mouse brain tissue," Dr. Hinson says. "Once we realized it was a unique staining pattern, and a group of patients all had similar clinical symptoms, we worked on discovering what the pattern was. After we identified it as GFAP, we developed a test for it." The test takes time because, as Dr. Hinson adds, "It's homegrown within the lab, meaning we don't buy the test. We grow the cells and plate the cells here." There are different types of encephalitis, which can be caused by a viral infection, an insect bite, or an autoimmune reaction as in Spencer's case.

"That's why this test is so valuable, because it helps narrow down the type of encephalitis," Dr. Hinson says. "And it helps guide the doctors on how to treat the patient. Plus it gives the patient an answer. It provides comfort to the patient to know, ‘This is what I have.'"

Losing hold of reality

While waiting for his test results in the hospital, Spencer's condition deteriorated into an agitated, incoherent state. "I think what was happening is that my brain wasn't able to see reality, and I was having visions in my head. I was physically reacting to what was happening inside my head," he says.

Spencer had to be strapped to his bed, and decisions about his care were left to his oldest sister, Kari. His doctors by now strongly suspected autoimmune encephalitis and discussed a treatment option called plasma exchange. This would mean putting an IV line into Spencer's jugular vein. "Plasma exchange is typically done to remove autoantibodies," Dr. Hinson says. "It's an immune treatment, in which they take out the immunoglobulin and then put your plasma back in again."

But doctors worried that, even though strapped down, Spencer might still find a way to rip the IV from his jugular, which could kill him. So they held off and instead gave him calming meds. Days later, when Spencer's test came back positive for GFAP-IgG, he was calm enough to begin the plasma exchange.

"It was a 10-day treatment — five treatments every other day," Spencer says. "I'd say after the second treatment is when the lights came back on. I was becoming more myself again and was able to have complete conversations."

Spencer spent six weeks in the hospital and lost 30 pounds. Before being released, he needed a few weeks of rehab. The encephalitis left him in a similar state as a stroke victim. He had to learn how to use his left side again, how to walk normally, tie his shoes, and zip up a sweater. Once he was discharged and back home, Mayo Clinic took over his aftercare.

"The University of Minnesota recommended I take steroids for a while, orally," Spencer says. "But Dr. McKeon wanted to change that up. To really nip the encephalitis in the bud, he thought it'd be better if I did steroids intravenously, once a week for a month. He ordered an MRI and a spinal tap to check on the inflammation. He wanted to do some EEGs to check on how my seizures were doing. I'd say by this point, I really wasn't having any seizures. So he was just doing a lot of testing right off the bat."

Dr. McKeon adds: "The initial care is pretty intense, but then it doesn't require a huge amount of follow-up — once every six months."

Spencer did have one slight relapse, which manifested as another persistent headache in January of 2022 and sent him back to an ER in the Twin Cities. An MRI detected inflammation in his brain again, so Spencer was admitted to the hospital. But this time, because his records indicated his positivity for GFAP-IgG, he was put on steroids right away, which nixed further complications. He was released after a few days. "When I was able to talk to Dr. McKeon about it, that's when he put me on a longer treatment plan, an IV dose of steroids then oral steroids, which I tapered off of, and he has me on an immunosuppressant," Spencer says.

Thanks to the diagnostic testing and treatment he received at Mayo Clinic, Spencer has made a complete recovery and is now back on his mail route.

Spencer's immunosuppressant is currently mycophenolate. "We have to be careful about figuring out a maintenance steroid plan and gradually de-escalating the dose over time," Dr. McKeon says. "Timing for treatment is important, and with a maintenance treatment, people should generally do well."

Today, Spencer has made a complete recovery and is back on his mail route. Being unable to work for a few months was not fun for him. "Driving is one of my favorite things to do," he says. "I just really take pride in it, and I love being behind the wheel. So I was very anxious to get back in the car. Once I got the clear to do that, and after not being able to do much, I was ready to get back into full-time work and be like myself again." 

Chris Bahnsen

Chris J. Bahnsen covers emerging research and discovery for Mayo Clinic Laboratories. His writing has also appeared in The New York Times, Los Angeles Times, and Smithsonian Air & Space. He divides his time between Southern California and Northwest Ohio.