Mayo Clinic Laboratories’ “Life of a Specimen” video series delves into the journey specimens take through advanced laboratory testing. Whether arriving for testing in Rochester, Minnesota; Jacksonville, Florida; or Scottsdale, Arizona, specimens are treated with the same level of care and respect provided to Mayo Clinic patients. We’re rooted in Mayo Clinic’s primary value that the needs of the patient come first, and it is those patients who drive our commitment to testing excellence.

The fourth episode in our series provides a more detailed picture of Joy Carol’s diagnosis and the mechanics of a rare autoimmune neurological condition. Sudden, severe, and difficult to diagnose, the illness nearly claimed her life. But evaluation of her blood and cerebrospinal cord fluid through antibody testing revealed insights that highlighted a treatment path.

A surprising revelation

When Joy Carol was at her lowest — confined to a New York City hospital bed, unable to move, and completely dependent on others to survive — she could feel herself slipping away.

“I was this close to going over the edge,” Joy says.

Before the illness struck, she was in constant motion. Her work as a teacher, social worker, preacher, and coordinator of international relief work required robust physicality. But within weeks of experiencing her first symptoms while on holiday in Greece, her life had come to a standstill. Her body would not cooperate, and she lost all ability to care for herself.

“I was a bag of bones that they lifted up in a wheelchair and rolled around places,” says Joy. “But I was still here.”

Joy’s care team tested her for a slate of neurodegenerative conditions, including Parkinson's disease and amyotrophic lateral sclerosis (ALS). But none of the tests run locally came back positive. As a last resort, a member of her local care team sent samples of Joy’s blood and cerebrospinal fluid (CSF) to Mayo Clinic Laboratories.

“Then Mayo Clinic came up with the diagnosis,” Joy says. “They said I had a very difficult to treat, impossible to cure, and perhaps fatal illness.”

Joy had developed paraneoplastic encephalomyelitis, a rare autoimmune neurological condition.

“The term paraneoplastic encephalomyelitis is actually kind of an umbrella term that's used to cover several different disorders that have been recognized based on the clinical syndrome,” says Kurt Jaeckle, M.D., emeritus professor of neurology at Mayo Clinic and Joy’s physician. “They’ve been put into different categories and some of them have been associated with specific antibodies that you can measure in the blood. And these are specific antibodies. In other words, they're different for each (condition).”

“Paraneoplastic neurologic disorders really speak to the remote effects of cancer,” says Andrew McKeon, M.B., B.Ch., M.D., co-director of the Clinical Neuroimmunology Laboratory. “This means that the immune response against the cancer, which is appropriate and desired, somehow develops an aberrancy and patients get self-reactive immunity, what we call autoimmunity against the nervous system. Typically, patients actually present with neurological problems, not with cancer.”  

The outward presentation of autoimmune neurologic disease can be diverse, and one of the manifestations is a phenomenon known as stiff person syndrome.

“Patients will present with stiffness in the lower extremities, with superimposed spasms often triggered by startle that can lead to falls with injury,” Dr. McKeon says.

Test results of patients suspected of having a paraneoplastic autoimmune disorder often clarify not only the specific autoimmune disease but also the cancer type.

In Joy’s case, an undiagnosed breast cancer propelled the misguided autoimmune response.

“We would've never looked for the cancer in her if it hadn't been for that antibody test that was done at Mayo Clinic,” Dr. Jaeckle says.

Joy was surprised to learn that breast cancer was the cause of the life-threatening neurological symptoms.

“Just a few months before I had paraneoplastic syndrome, I had my mammogram and an ultrasound,” Joy says. “They were normal, and my doctors said to come back in a year.”

The impact of antibodies

Some tumors, like that which affected Joy, contain certain proteins that resemble other proteins found in nerve cells, Dr. Jaeckle says.

“And the immune system’s killer T-cells that accompany the antibodies attacked the cancer, but also attacked the nervous system thinking it’s foreign,” Dr. Jaeckle adds.

As a result of the assault on her central nervous system, Joy developed stiff-person phenomena, a disorder resembling the stiff-man syndrome initially identified by Mayo Clinic neurologists in 1956.

“Mayo has over many years, since the mid-70s or so, developed a series of antibody panels that are directed at this kind of thing and pretty much canvas the waterfront in terms of the common antibodies that might be associated with nervous system conditions,” Dr. Jaeckle says.

The stiff-person and movement disorder evaluation that evaluated Joy’s blood and CSF identified two specific antibodies. The first was synaptic vesicle protein amphiphysin, or amphiphysin IgG. Amphiphysin was identified as one of several key biomarkers for paraneoplastic syndromes through pioneering Mayo Clinic-led research in 2005. In individuals with amphiphysin antibodies, cancer is identified in up to 80% of cases.

The second antibody identified in Joy’s sample was glutamic acid decarboxylase, or GAD, which is associated with stiff-person syndrome.

“GAD is present in 80% of people with this condition and rarely present, less than 5% of people, in the normal population,” Dr. Jaeckle says.

As scientific discovery about the association between antibodies and autoimmune disease continues to advance, more healthcare physicians and professionals understand their utility in diagnosing illness.

“What’s really given this momentum to this area is biomarkers and antibody tests,” Dr. McKeon says. “We know this and have been able to document this through epidemiology studies.”

For example, a recent epidemiology study conducted in Olmsted County, which is the home to Mayo Clinic in Rochester, Minnesota, compared the frequency of autoimmune encephalitis with the frequency of infectious encephalitis by looking at two separate time points.

“What was noticed with the more recent measurement was that autoimmune encephalitis had increased in incidents so much that it was now comparable to infectious encephalitis,” Dr. McKeon says. “In fact, it looked to be a little more common than infectious encephalitis. That’s purely down to recognition, purely down to the fact that doctors are now recognizing these diseases, know to test for them, and they’re getting back antibody test results. That is all through scientific discovery — that is all through science.”

Casting a light on the road ahead

The weight that lifted when Joy received an accurate diagnosis was a sharp contrast to the fear that permeated living in the unknown.

“I remember I just said ‘Hallelujah!’” Joy says. “I was so glad because we’d just been batting around with nothing on our plates — you can’t play a baseball game without the right equipment.”

Even in cases where the prognosis is poor, patients find incredible meaning in their diagnosis, Dr. McKeon says. “Patients will sometimes say, ‘Well, at least I now know what is going on. The diagnostic odyssey is over, and I can move onto the next stage of things.’”

For individuals who falsely believed themselves to have incurable neurogenerative conditions, the news that the disorder can be treated is sometimes overwhelming, Dr. McKeon adds. 

“There’s a lot of joy, a lot of hope, and we always have to temper that a little in terms of expectations because with the nervous system, particularly the central nervous system, nonprogression is the achievable goal. And we have to differentiate that from cure or complete cure, which we can accomplish in some patients. But for a lot of patients, the disease is something we treat, and they won’t progress further.”

The timing of diagnosis is also important for individuals with certain neuroimmunologic conditions.

“The earlier you can find it, the better. For most conditions, if you start treatment earlier, it is better,” Dr. Jaeckle says.

Understanding the reason for Joy’s physical decline and identification of the two antibodies that were causing her nervous system to malfunction helped Joy’s team develop a treatment strategy for her condition.

“It was a relief for me to know I had something that they could try to treat, even though there wasn’t really a cure to this,” Joy says. “You don’t live very long with paraneoplastic syndrome if something isn’t happening with you, and without the diagnosis, there was no way of knowing how to treat me.

“I would say to everyone, if you don’t know what is wrong with you, don’t stop there. Ask your doctor to go to another doctor or get another opinion. Or ask them to go to the research labs or best of all go to Mayo Clinic.”

Check out the final episode of “Life of a Specimen” to learn how laboratory testing on Joy Carol’s blood and spinal cord fluid enabled treatment that changed her life.