The remarkable story of a Canandaigua, N.Y. woman who emerged from a more than six month long coma is now being used to educate physicians about how to recognize and treat her extremely rare condition. The elusive source of her uncontrolled seizures, which physicians at the University of Rochester Medical Center (URMC) ultimately traced to ovarian cancer, and her subsequent recovery are the subject of a paper appearing today in the journal Neurology.
In October of 2008, Donna Landrigan, a healthy, 35 year-old mother of three, began to experience nagging headaches for which over the counter pain medications provided little relief. Soon her headaches were accompanied by memory and emotional problems.
“I became very insecure and began to question myself, which was very out of character,” said Landrigan. “I doubted myself and my decisions. I was easily confused, didn’t want to drive, questioned my mothering skills, and lost my confidence. Basically, everything became an issue.”
As the headaches turned more severe, the family sought medical attention and Landrigan was hospitalized with what doctors initially believed was meningitis. After a few days, she was prescribed medications and sent home. However, her condition continued to quickly deteriorate and shortly after Thanksgiving, her husband found her collapsed and unresponsive on the floor of the family’s garage.
An ambulance was summoned and Landrigan began a journey that would take her to four hospitals and months of tests, setbacks, frustration, and ultimately a breakthrough as doctors grappled with the cause of her condition and how to treat it. She would not return to her home again until the following September.
The ambulance took Landrigan to F.F. Thompson Hospital in Canandaigua, but she was quickly transferred to Highland Hospital in Rochester. URMC neurologist Nicholas Johnson, M.D. recalled that when she arrived at Highland she was not only experiencing seizures but was also exhibiting signs of psychosis.
“She wasn’t making sense, was saying things that weren’t true, and got stuck on words,” recalled Johnson. “She was also very agitated and ultimately had to be restrained to prevent her from harming herself and others.”
She was prescribed an antipsychotic medication but after a few weeks she became unresponsive and slipped into a coma brought on by continuous epileptic seizures, a state called status epilepticus. Landrigan spent the next few weeks in the intensive care unit at Highland as physicians attempted, without success, to control her seizures with a series of drugs and determine what was causing them.
In January, she was transferred to Strong Memorial Hospital and into the care of physicians and nurses in the Strong Epilepsy Center and Medical Intensive Care Unit. Eventually she had to be placed in a drug-induced coma because there was no way to control the seizures.
“Most people with seizures don’t deteriorate the way she did,” said URMC neurologist Craig Henry, M.D. “And even the seizures of status epilepticus usually respond to one or two antiseizure medications. In Mrs. Landrigan’s case, the only way to keep her seizures from recurring was to eventually put her brain into a controlled coma.”
Epileptic seizures can be brought on by a number triggers and often are the result of encephalitis – inflammation of the brain – from a virus. In fact, to her physicians it initially looked as though Landrigan’s seizures were being caused by a viral infection. However, a battery of tests, beginning when she was still at Highland Hospital, for the more than a hundred potential viral triggers of seizures all came back negative.
As they continued their diagnostic evaluation, looming in the back of the physicians’ minds was the understanding that Landrigan’s prognosis was dire. Status epilepticus has a mortality rate of 56 percent. Added to this are the inherent health risks of a prolonged stay in an intensive care unit where additional complications can arise. The longer she stayed in a coma, the more remote her chance of recovery became.
“It is very unusual for someone to have seizure activity for that prolonged a period of time and be able to walk out of the hospital afterwards,” said James Fessler, M.D., director of the Strong Epilepsy Center. “If you can’t get the seizures under control, these cases are almost universally lethal.”
As the tests for a viral cause of the seizures were coming back negative, the physicians began to explore the idea that the seizures may be the result of a rare family of syndromes in which antibodies produced by the body’s immune system in response to certain cancers end up attacking brain cells.
The doctors sent a sample of her spinal fluid to the Mayo Clinic to be evaluated for evidence of one of these syndromes. In what looked like another potential setback, all of the tests came back negative. However, the lab did find an unidentified antibody in her system, a clue that kept alive the possibility that they could eventually find the source of the seizures. “Once that test came back positive, we knew we had to keep looking,” said Johnson.
Johnson recalled research that linked a rare form of ovarian cancer, called a teratoma, to seizures. Teratomas are tumors that can be comprised of numerous different types of tissues, including nerves. It is suspected that the antibodies produced to attack the nerve cells in this tumor – called anti-NMDA receptor antibodies – also attack nerve cells in an area of the brain that is more likely to cause seizures.
Another sample of her spinal fluid was sent to the lab of Josep Dalmau, M.D., Ph.D., a neurologist at the University of Pennsylvania who had first identified the correlation between these tumors and seizures in 2008. The tests indicated a match for the anti-NMDA receptor antibody.
From the beginning, one of the difficulties in diagnosing Landrigan’s condition was that her case was extremely rare. There have only been a couple hundred known cases of her kind worldwide and no one has described a case with seizures this severe. Even when the likely cause was finally identified, instead of becoming clearer, her case continued to confound her physicians. “We knew we where looking for a tumor, but we couldn’t find it,” said Johnson. MRIs revealed a cyst on one of her ovaries, but it was not clear that this was the source of her cancer.
After several unsuccessful efforts to get rid of the antibodies by suppressing her immune system, the medical team decided that the only remaining course of action was to remove her ovaries where they suspected – but could not confirm – the tumor resided. If this course did not stop the seizures, then it was likely she would die.
Making the decision to remove what appeared to be healthy organs was difficult. However, after careful deliberations with the gynecological surgeons and family, the decision was made to proceed. The procedure was performed in April and once removed, it was determined that the cyst in her ovaries was indeed a teratoma.
“In most situations, hearing that a loved has cancer can be devastating,” said Landrigran’s husband, Dan. “In Donna's situation, it was the best news we could have hoped for.”
The physicians then began to slowly bring Landrigan out of her coma and over a period of several weeks she awoke and became responsive. Her seizures had stopped.
Initially, Landrigan’s mind was still stuck back around the time of her collapse and she recalls thinking that it was around Christmas. “I got upset at my husband because the kids had shorts on,” she said. It was July.
Landrigan was eventually transferred to Monroe Community Hospital for rehabilitation and – determined to see her children off to school – by September she had returned home for good. Her memories of the period when her seizures first began remain spotty, but she has made close to a full recovery cognitively and emotionally. She is in a wheelchair, a circumstance that the physicians attribute primarily to her long stay in the ICU, but her physical condition continues to improve.
“It was a long journey through some pretty dark and scary moments,” said Landrigan’s husband. “But even in most dire times there was always an encouraging sign and that kept us all going. After every setback Donna’s doctors and nurses were always looking to the next step and we never gave up hope.”