Reclaiming her joy: Joy Carol
Joy Carol lives with a passion born out of deep convictions. Raised to believe quitting is not an option and gratitude is a daily practice, Joy recognizes life as a precious gift — a point reinforced several years ago when she suffered a near fatal attack by a severe autoimmune disorder.
It was August 2013 when, at 75, Joy’s body suddenly betrayed her. “I was in Greece when I started having problems with not walking well,” says Joy, who at the time lived in Manhattan. “When I got back to New York, I started falling all over the place, and I went to my general practitioner who said I must have pinched a nerve.”
Her doctor recommended an MRI, but Joy’s insurance delayed approving the advanced imaging.
“In the meantime, I was falling everywhere; I was black and blue,” she says. Shortly after Joy’s legs stopped working correctly, her shoulder froze. Next, her mouth began to lock. She started shedding weight.
Joy Carol at the River Liffey in Ireland
“Finally, my general practitioner said, ‘Joy, meet me at the emergency room because they need to admit you to the hospital and test you, and that will force the insurance to pay the bill.’ That was the beginning of weeks spent trying to find out what was wrong.”
Eventually, Joy learned through antibody testing (Test ID: MDS2, MDC2) — ordered by her New York neurologist and performed at Mayo Clinic’s Autoimmune Neurology Laboratory — that her immune system had mounted an assault on cells in her brain and spinal cord. She had a disorder known as paraneoplastic encephalomyelitis, a rare, autoimmune neurological condition that occurs when the immune system, in response to cancer, is activated to attack healthy nervous system cells.
In Joy’s case, undiagnosed breast cancer propelled the misguided autoimmune response. 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.
At the end of August, the news came back that Joy had a paraneoplastic syndrome associated with the amphiphysin autoantibody found in her blood.
“Mayo Clinic Labs had said it was very difficult to diagnose and very difficult to cure. That it was often fatal and always dangerous,” Joy says.
“I remember very clearly saying, ‘I’m going to go on living a full life because that’s who I am. My dad told me that I should never ever give up and to live my life as though every day counts.’”
Despite Joy’s diminished condition — in just a few months she lost all ability to care for herself and required 24/7 assistance — she held on, believing a way back existed.
“I was almost dying. I’d lost 30 pounds. I was just a bag of bones sitting in a wheelchair, not able to get out of bed to care for myself,” Joy says. “What a joyful moment that was for me to know what was wrong with me and how to approach this problem.”
The approach first involved identifying the cancer triggering Joy’s autoimmune response. Shortly after learning from Mayo Clinic Labs’ neuroimmunology team that her illness was associated with either breast or lung cancer, she underwent a PET scan, which revealed stage 2 disease.
“In about 80% of cases, a cancer is identified,” says Vanda Lennon, M.D., Ph.D., who founded Mayo Clinic’s Autoimmune Neurology Laboratory. Dr. Lennon participated in pioneering research in 2005 that confirmed autoantibodies against the synaptic vesicle protein amphiphysin, or amphiphysin IgG, was one of several key biomarkers for paraneoplastic syndromes.
“The associated cancer is usually small and unsuspected. The patient doesn’t know they have a cancer, and the doctors certainly don’t know,” Dr. Lennon says. “The immune response to the cancer is so good that it often suppresses the advance of the cancer.”
Indeed, Joy had received a normal mammogram about a month prior to developing symptoms.
The theory behind the misguided immune response is that particular proteins, or antigens, present in certain cancers activate the body’s immune response, explains Mayo Clinic neurologist Kurt Jaeckle, M.D. “Unfortunately, those proteins or antigens in the tumor resemble proteins found in some nerve cells. So there’s a connection, and the immune system’s killer T-cells that accompany the antibodies detected in Joy’s case attacked the cancer, but also attacked the nervous system, thinking it’s foreign.”
Joy Carol in San Antonio, Texas
While Mayo Clinic did not discover amphiphysin IgG, Mayo Clinic Laboratories was the first lab in the country to introduce testing for that antibody and has discovered many other nervous system-reactive autoantibodies that aid in the diagnosis of paraneoplastic autoimmune syndromes.
“The antibodies against amphiphysin don’t necessarily stand alone,” Dr. Lennon says. “They’re often accompanied by other antibodies directed against the same cancer and different parts of the nervous system. So that’s one reason patients might have a mixture of symptoms and signs.”
That confusing mixture also is one of the reasons the diagnosis can be elusive. However, the longer diagnosis and treatment are delayed, the more devastating the damage, Dr. Lennon says.
For as much damage as can be caused by the illness, it is treatable, Dr. Jaeckle says. “In cases where the antibodies can bind to the surface of nerve cells, they appear to be functional. In other words, they interrupt function of the nervous system. So, if you can block the antibodies, the person can improve.”
In Joy’s case, amphiphysin-specific killer T-cells accompanying the autoantibodies are thought to have been responsible for her neurological symptoms.
Joy’s first treatment was surgery to remove the tumor, which had spread to adjacent lymph nodes. Following surgery, Joy received an MRI to evaluate whether the cancer had been completely removed. The imaging showed lingering cancer cells, so nine days after her first surgery, Joy underwent a second operation to remove more breast tissue and additional lymph nodes. A few weeks later, Joy started chemotherapy and also underwent radiation therapy.
“But I still wasn’t getting better, so that’s when they tried plasmapheresis,” Joy says. But cleaning her blood by spinning it through a centrifuge to remove the harmful antibodies also failed to improve her symptoms. “I was on my way out, literally.”
As a last resort, her New York team started Joy on Rituxan, a biologic drug with proven ability to interfere with the body’s immune response. The aggressive therapy was delivered slowly via infusion over the course of many hours to prevent side effects that could be fatal to Joy given her diminished state.
“It took hours and hours. After a couple of weeks, for the first time as I was laying on my back, I moved myself a little to the right, and I didn’t scream out in pain. A couple weeks later, I could turn on my side, and I hadn’t done that for a long time,” Joy says.
“I got a little bit better in New York, but I knew that I would get really better if I could get to the doctors who understand paraneoplastic syndromes.”
One of those doctors was Dr. Jaeckle, who had trained with one of Joy’s New York neuroimmunologists and was on staff at Mayo Clinic in Jacksonville, Florida.
“So, I moved to Florida,” says Joy of her 2014 relocation to the Sunshine State. “I just brought my easy chair, a handful of books, some clothes and a few knick-knack things that mean something. I sold my apartment in Manhattan, my beach house, and I’ve never regretted it.”
As Dr. Jaeckle’s patient, Joy was started on immunosuppression. “One of our other treatment tools to subdue the immune response — and there are several choices — is to use steroid medicine,” Dr. Jaeckle says. “To prevent against the side effect we dislike from steroids, we do it in a pulse fashion. Right now, she’s getting that every two months. And we’ve been able to suppress the antibody marker of the autoimmune response quite well.”
From a high measure of amphiphysin antibody detection in Joy’s blood in a 15,000-fold diluted specimen, the antibody is no longer detected in minimally diluted blood.
“Once in a while my count spikes and everyone panics, and I go back in for a PET scan to make sure the cancer hasn’t come back, which would set off the paraneoplastic syndrome,” says Joy, who’s been in remission for several years. “But I’m now on my ninth year — talk about gratitude. I’m one grateful girl. And the lab at Mayo Clinic is the secret to my coming through everything.”