Doctor's diagnosis drew laughs, but it saved woman's life
Monday, December 6, 2010; 4:46 PM
As the all-too-familiar number flashed on his cellphone shortly before 9 p.m., Dan Landri-gan reflexively braced himself for bad news. The caller was one of the doctors treating his wife, Donna, who had been in a coma for four months. "She sounded pretty choked up," Landrigan recalled.
"I think we've found out what's making your wife sick," the specialist at the University of Rochester's Strong Memorial Hospital told him, as a wave of relief flooded his body. "I was completely shocked," said the telecommunications executive, now 37. "My hope for so long was that this was the phone call I was going to get."
Doctors at three Upstate New York hospitals had been stymied by Donna Landrigan, whose case was unlike any they had seen. The previously healthy 35-year-old mother of three had initially become so psychotic she had to be tied to her hospital bed to keep her from hurting herself or attacking others. A few weeks later she had been placed in a medically induced coma to protect her from the continuous seizures wracking her brain, spasms that could have killed her.
Every promising lead had seemed to turn into a dead end, and the dangers of prolonged coma, including severe brain damage, were mounting. Things looked so hopeless that doctors had begun discussing whether to suggest terminating life support.
That phone call on April 29, 2009, was the first good news in months. It represented both a turning point for the Landrigans and vindication for the second-year neurology resident who had closely followed Donna's case since December 2008, when she was initially hospitalized. The startling diagnosis that Nicholas Johnson proposed, he recalled with understatement, had been met with "a little bit of laughter" by senior physicians, amused by the exotic and sometimes outlandish diagnoses made by residents.
This time Johnson's spot-on deduction, and his persistence, not only solved the mystery but also saved Donna's life. Her case, which made medical history, was recently described in the journal Neurology.
"For someone to beat this is amazing," said neurologist James Fessler, director of the Strong Epilepsy Center, who also was involved in treating her.
The first sign of Donna's illness occurred shortly before Halloween 2008, when she complained of severe headaches, then a stiff neck. A spinal tap revealed viral meningitis, and she spent three days in the hospital; once home, she got progressively worse. Most noticeable was her increasingly strange, often paranoid, behavior, which involved the couple's twin sons, then 11, and their daughter, who was 4 at the time.
A stay-at-home mother whose life revolved around her children, Donna recalled what happened the day she forgot to bring a snack for her daughter's preschool class. "You would have thought someone had died, I was that emotional," she said recently, summoning one of the memories she retains from that time; the next seven months are a blank.
Doctors counseled patience and warned that recovery might be bumpy. "We would chalk up any weird symptom to her just getting better," Dan recalled.
The night of Dec. 4, while talking on the phone, he realized that Donna had not returned from the garage. He found her face down on the concrete floor beside her minivan; she was unresponsive and her mouth bore foam from an apparent epileptic seizure.
Donna regained consciousness in the ambulance but was incoherent and combative. After a day or two of tests at a hospital, a psychiatrist was summoned. He told Dan that Donna was a secret alcoholic in the throes of withdrawal. Dan said the psychiatrist flatly dismissed his protests that Donna was strictly a social drinker.
A few days later, after it was clear alcohol wasn't Donna's problem - the seizures and psychosis had lasted too long - she was transferred to a larger hospital affiliated with the University of Rochester. Johnson was one of the doctors who crowded into her room that first day. "I remember he was the quiet guy in the back of the room," Dan said.
By then Donna was so violent that she would pull out her IVs, scratch herself uncontrollably and thrash wildly, insisting that people were trying to kill her. Massive doses of antipsychotic drugs had little effect; she required a round-the-clock nurse and virtually stopped eating.
At home Dan had his hands full: The couple's young daughter cried for her mother every night, and the boys, though stoic, were clearly scared. "I was terrified," Dan recalled. "I had this vision of my entire life unraveling in front of me."
Three days after her transfer, the news grew more ominous: An EEG showed that Donna's brain was being ravaged by continuous seizures, a condition known as nonconvulsive status epilepticus. Unless doctors controlled the seizures, she would die.
Running out of time
Because of her age and sex, and the fact that the usual causes of her symptoms - meningitis, HIV, substance abuse and several forms of encephalitis - had been ruled out, Johnson early on thought she might be suffering from an extremely rare, newly identified illness he had heard about two years earlier, while interviewing for a residency at the University of Pennsylvania.
Josep Dalmau, a neuro-oncologist at Penn, and his colleagues had published studies describing anti-NMDA receptor encephalitis, a rare reaction seen in young women to a common ovarian tumor called a teratoma, which is typically harmless. In some patients, antibodies produced to fight the tumor, which contains nerve cells, also attack nerve cells in the area of the brain that can trigger seizures. Removing the tumor stops the seizures and can lead to a full recovery, particularly if treatment is initiated within three months of the development of symptoms. Fewer than 200 cases of the illness have been reported worldwide, none with seizures as severe as Donna's.
When Johnson, then 28 years old, proposed the diagnosis shortly after Donna's arrival, "there was some incredulity" among senior physicians, he said. That faded as doctors pursued, then discarded, other diagnoses.
"They were willing to let me order the tests I thought were needed," Johnson said of his skeptical supervisors. In late December, a sample of Donna's spinal fluid was sent to the Mayo Clinic, home of one of the world's preeminent pathology labs.
In the meantime, doctors tried various drugs, which failed to improve her condition. In late January, after she had been transferred to the intensive care unit at Strong hospital, her results came back. Tests for 100 viruses and other seizure triggers were negative, but doctors had found one unknown antibody. The only way to determine whether it was related to the newly identified illness was to send it to Dalmau, who had developed a test for it. Within days, the results from Penn were in: The sample matched.
Meanwhile, doctors had begun searching for a tumor that might be responsible for generating the antibodies. But several scans, including an MRI, revealed only an apparently harmless cyst on Donna's left ovary.
"They thought for sure they were going to find a tumor," Dan recalled. "I said, 'Just take her ovaries,' but it's not that simple. I kept telling myself that I needed to be as patient as possible for Donna's sake, the kids' sake and her parents' sake. There was just a lot of waiting to see if various treatments worked - and none of them did."
Doctors tried to suppress her immune system using a series of drugs, but those had no effect. Some specialists agreed with Dan, figuring there was nothing to lose by removing the ovaries of a gravely ill woman who had completed her family. But the gynecologic surgeons balked, questioning the ethics of removing apparently healthy organs without evidence of disease. It took several weeks of convincing, including consultations with Penn gynecologists, and a ruling by the hospital's ethics committee before surgeons agreed to operate.
"It was basically the point of no return," Johnson recalled. Days after the April 24 surgery, doctors discovered that the cyst spotted months earlier was actually a benign teratoma.
The next question was whether the seizures would stop. Dan was warned that after so many months in a coma, his wife might have suffered irreversible neurological damage. Prolonged status epilepticus has a mortality rate of 56 percent, and no patient with NMDA encephalitis and seizures as long as hers had ever been reported, Johnson said.
Two weeks after surgery, the seizures disappeared. "I was thinking, 'This is incredible,' " Johnson recalled. "It was very gratifying. We had come to the correct diagnosis, and we could see she was getting better."
In late May, Donna briefly awoke, smiling at the nurses who had taken such terrific care of her that she never developed a bedsore. The first family visit she clearly remembers occurred in late June, when Donna scolded her husband for letting their children wear shorts; she thought it was December. "I was just very confused for a long time," she said.
She spent two months in a rehabilitation hospital, returning to her Canandaigua, N.Y., home in September 2009, in time to see her children off to their first day of school.
Although Donna's cognitive function is undamaged, she cannot walk. Doctors suspect this is a consequence of her coma and hope it is not permanent. "It's another part of the mystery, but nobody really has any answers," she said. "That's the hardest part: the unknown. I'm so thankful to be back with my family, but I miss my old life."
Johnson, now a chief resident, is sympathetic. "It's 20/20 hindsight, but if we had been faster, we might have spared her some of the weakness and leg issues," he said. Studies have found that the rate of disability increases significantly in patients whose tumor is identified more than three months after symptoms occur; at the time of her surgery, Donna had been ill for six months.
Because of her case, several Rochester patients have undergone testing for NMDA antibodies; all were negative. "We'd think about it more readily now that we've seen a case," Johnson said.
Dan, who sees slow progress, is convinced his wife will walk again. He does not allow himself to contemplate the what-ifs. Johnson, he said, "single-handedly saved Donna's life. We were blessed he just happened to be in the room that day."
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