After mysterious neurological symptoms began in 2010, Brad Karon, M.D., Ph.D., was diagnosed with paraneoplastic syndrome, a rare condition that led to groundbreaking research and test development at Mayo Clinic. Years later, pulmonary fibrosis and a double lung transplant would test him once again — and redefine his resilience.
It started with a buzzing sound followed by the loss of hearing in his right ear. Symptoms that would mark the beginning of a nearly 15-year health odyssey for Brad Karon, M.D., Ph.D., division chair of Mayo Clinic’s Clinical Core Laboratory Services. It was January of 2010. “Over the next six months, I developed dizziness, walking problems, ataxia, and double vision,” he says. “And I couldn't read and track things with my eyes.”
Dr. Karon’s condition turned out to be a rare form of neurological paraneoplastic syndrome, which had not been previously described. That situation changed in 2019 when Mayo Clinic developed the first assay of its kind (Mayo IDs: K11CS and K11CC) that detects kelch-like protein 11 (KLHL11), the antigen associated with this syndrome.
Back to 2010: as his symptoms worsened, Dr. Karon became a Mayo Clinic patient himself after seeking help from his colleagues. One of them was Sean Pittock, M.D., director of Mayo's Center for Multiple Sclerosis and Autoimmune Neurology. Because Dr. Karon’s symptoms were suggestive of an inflammatory disorder of the brain, Dr. Pittock ordered an autoimmune encephalitis evaluation from blood (Mayo ID: ENS2) and spinal fluid (Mayo ID: ENC2). The testing is performed in Mayo Clinic’s Neuroimmunology Laboratory, which Dr. Pittock codirects. Founded in the early 1970s, the lab now tests about 300,000 patients a year for inflammatory brain diseases.
"For this test, we take the person's blood or spinal fluid, and we look for antibodies that bind to mouse tissue,” Dr. Pittock says. This particular test uses a special fluorescent dye, and when antibodies bind to the mouse tissue, they are visible under the microscope. Different antibodies show up as different patterns under the microscope. “In Dr. Karon’s sample, we didn’t see any of the usual antibodies we were testing at the time. However, we noticed a very unusual pattern that we called the ‘sparkles pattern.’ We had seen this same pattern in a few other patients and so we knew this was important. Even though we knew very little about the target and the test was not yet validated, we knew how to help Dr. Karon.”
So what did the “sparkles pattern” mean?
“The other men who had that pattern under the microscope all had testicular cancer. They developed very serious, progressive inflammation of the back of the brain, brainstem, or cerebellum, called rhombencephalitis,” Dr. Pittock says. “Most patients had progressed to the point of being wheelchair bound. We recommended a prompt evaluation for testicular cancer.”
Strangely, on investigating Dr. Karon for seminomas (testicular tumors), the team did not find any. They did, however, find a lesion in his chest via a PET scan. “And when we went and biopsied that chest lesion, what do you think we found? A testicular cancer,” Dr. Pittock says. “It had already metastasized to the chest, initiating an immune attack of the brain”.
“In Dr. Karon’s sample, we didn’t see any of the usual antibodies we were testing at the time. However, we noticed a very unusual pattern that we called the ‘sparkles pattern'."
— Sean Pittock, M.D.
A more drastic treatment for a unique case
To treat Dr. Karon’s rare disease (which affects about two people per 100,000), surgeons successfully resected the seminoma cancer from Dr. Karon’s chest. But even after the tumor was resected, the immune attack on the nerve cells continued. So, Dr. Karon was immediately treated with steroid and immunoglobulin therapies.
Unfortunately, Dr. Karon’s body didn’t respond to these therapies, so Dr. Pittock’s team had to do something more drastic.
“We made the decision, in 2010, to treat him aggressively with chemotherapy, a drug called cyclophosphamide,” Dr. Pittock says. “This treatment was aimed not at the cancer, which had been cured, but at his immune system to stop his cytotoxic T cells from attacking his neurons. The treatment lasts for one year.”
This time, the treatment worked. “Dr. Pittock treated me aggressively with immunosuppression for paraneoplastic syndrome,” says Dr. Karon, who is also dean of Mayo’s School of Health and Sciences. “By the end of 2012, I felt much improved. I had moderate neurologic damage, but the brain has redundant systems for balance and movement, so I was able to recover function thanks to early intervention and lots of rehab and physical therapy.”
Persistent investigation
Identification of a new pattern under the microscope is the first step in the development of a new test. The neuroimmunology team persisted in their work on this antibody pattern and, in 2019, Mayo Clinic, in collaboration with the University of California, San Francisco, identified KELCH 11 as the antigen targeted by the “sparkles pattern” antibody.
KELCH 11 antigen is found in both testicular tissue and in neurons. The body’s appropriate immune response to the tumor also causes an attack of the KELCH 11, expressing neurons in some patients. A seminal paper in The New England Journal of Medicine introduced this rare inflammatory brain disorder to the world. And now, testing for KELCH 11 antibodies, via a validated Mayo Clinic test, is the standard of care in the evaluation of patients, especially men, with new-onset ataxia.
A remarkable recovery, then a downturn
Dr. Karon’s profound recovery was almost as rare as his disease. The key was early intervention. “We got in really quickly with treatment,” says Dr. Pittock. “By the time most patients get to Mayo, years have passed since disease-onset and they're in a wheelchair. But we actually got access to Dr. Karon within months of his onset. So, we were able to stop his neurological disease progression.”
Unfortunately, Dr. Karon’s health odyssey wasn’t over. In 2013, he began experiencing shortness of breath. He again turned to Mayo Clinic, this time seeing a pulmonary specialist.
“I was diagnosed with a rare form of pulmonary fibrosis, a disease where your lungs basically start to turn to scar tissue,” he says.
The cause? An idiosyncratic drug reaction to one of the therapies used to treat him for the paraneoplastic syndrome. Dr. Karon continues: “The disease was progressive, but slowly progressive. I was under treatment from Pulmonary here, and I did fairly well until September of 2023.”
Dr. Karon’s disease jumped from a slow to a rapid progression. That September, he went into respiratory failure and was hospitalized at Mayo Clinic’s Saint Marys Hospital for two weeks. “I went from feeling normal, walking around healthy, to needing oxygen almost all the time to do any exercise, and for sleeping,” he says.
After being discharged from the hospital, Dr. Karon regained some strength. However, his oxygen needs did not change. By January of 2024, Dr. Karon’s disease had progressed so much that he was put on the waitlist for a double lung transplant. Four months later, on May 13, he received two new lungs.
Another enigmatic disease
The reason for Dr. Karon’s sudden downturn remains unexplained. Very little about his case, it seems, has been seen before.
“It's difficult to determine what exactly caused such a severe disease requiring transplantation in Dr. Karon's lung,” says Joanne Yi, M.D., a consultant and professor in Mayo Clinic’s Division of Anatomic Pathology, who is part of Dr. Karon’s pathology team. She acknowledges that the development of this severe pulmonary fibrosis is somewhat unusual for a simple cyclophosphamide toxicity. And this may be associated with multiple underlying causes.
“Given the predominant localization within air spaces for peculiar giant cell reaction associated with cholesterol cleft, one can consider a possibility of chronic aspiration as a contributing factor,” Dr. Yi says. Dr. Karon’s difficult clinical journey could still inspire some future research and investigation that could benefit the medical community at large. It turned out that the decision made by Dr. Karon and his clinical team to proceed to lung transplantation was literally vital to his survival and ensuing quality of life.
Autoimmune Neurology testing
The Neuroimmunology Laboratory at Mayo Clinic was the pioneer in offering comprehensive blood tests to diagnose paraneoplastic neurologic autoimmune disorders – conditions where unusual neurological symptoms are the first signs of an underlying cancer. The lab continues to lead advancements in autoimmune neurology by identifying and clinically validating new autoantibody patterns. These discoveries enhance neurological diagnostics and help direct the search for hidden cancers.
Visiting his explanted lungs
Not long after his double lung transplant, Dr. Karon took part in a program called On My Path. The program, conducted within Mayo Clinic’s Department of Laboratory Medicine and Pathology, offers heart and lung transplant patients the chance to view their explanted organ(s) and learn about their particular disease from a pathologist.
When Dr. Karon visited his explanted lungs, he was hosted by his longtime colleague, Dr. Yi. “You can not only see but also touch your old, explanted organs that have been fixed in formalin and sliced into multiple slabs,” Dr. Karon says. “And to actually see my lungs and see how damaged they were, wow, these were really scarred lungs. There wasn't a lot of good lung tissue left. So the experience was meaningful and impactful, even though I’m a pathologist who understands my disease more than the average patient.”
Dr. Yi offers her perspective: “The patient and accompanying family members get to see and touch the organs. This provides an invaluable experience to them. Everyone gets to appreciate the difficulty the patient has endured and the fortune of receiving new, normal lungs. Then, at the end, we give them a 3D model of the specimen (representative slices from the right and left lungs). And the patients love it because of the educational benefit. It’s a rare opportunity to talk to their pathologist, who they normally would never get to meet.”
Exceptional integration and communication
Today, Dr. Karon is doing well. He’s back to working “80%” of his pathology role and leads a fairly normal life. And now that he’s been a patient at Mayo, he’s come away with a new perspective.
“I always knew our labs offer amazing, innovative tests and a rapid turnaround time, and all that has proved true in my case.”
— Brad Karon, M.D., PH.D.
“I always knew our labs offer amazing, innovative tests and a rapid turnaround time, and all that has proved true in my case,” he says. “I've been practicing here at Mayo for 20 years, and what impressed me the most is how integrated the whole lung transplant team is. The relationship between the pulmonologists and the ICU in the hospital, where you're very sick, and the various lab areas that are supporting transplant — Toxicology, Microbiology, Anatomic Pathology — the level of integration and communication and understanding of the needs of lung transplant patients, it’s really amazing.”
Learn more about autoimmune neurology testing at Mayo Clinic Laboratories.
Related Content
For many, the path to a correct diagnosis can be long and filled with uncertainty. This story highlights the resilience and determination of one patient who navigated a complex medical journey to find answers and hope at Mayo Clinic. The patient asked to remain anonymous for personal privacy reasons.
After years of misdiagnosis, Tyler Hart found answers at Mayo Clinic, discovering he had NF155-IgG4 autoimmune nodopathy instead of CIDP
Justin Fugelsang and Zach Pedowitz have never met. Yet both young men were diagnosed with a rare form of Charcot-Marie-Tooth disease, called sorbitol dehydrogenase (SORD) deficiency, and both found clarity through Mayo Clinic Laboratories' innovative SORD testing. Their journeys inspire resilience, as Justin has channeled his emotions into guitar playing, and Zach has embraced educational leadership.