Every summer, hundreds of farm families from across northern China begin appearing at regional pediatric wards, bringing children so sick that they can't walk, can't swallow and can't even breathe.
In provincial hospitals, lines form quickly for available respirators.
While parents wait for a free machine, they must spend 24 hours a day, seven days a week by their children's beds, pumping on a bag-shaped device that keeps them alive by forcing air into their lungs.
Since this annual polio-like epidemic began about 20 years ago, physicians in China and abroad have blamed it on Guillain-Barre syndrome, a brief but devastating illness that shares many of the same clinical features.
But after two years of study, a team of Chinese and U.S. doctors led by a Johns Hopkins physician has concluded that the illness isn't Guillain-Barre and isn't polio -- in fact, it doesn't resemble any known disease.
"This is different from anything we've seen before; it doesn't add up to anything we know," said Dr. Guy M. McKhann, the leader of the team and head of Hopkins' Mind-Brain Institute.
Undiagnosed illnesses are not uncommon in cases involving a few patients. But doctors say that it is rare to stumble on and document an unnamed ailment of epidemic scope.
"It happens once in a lifetime," said Dr. McKhann.
Chinese doctors have been remarkably successful in coping with the annual onslaught of young patients, their U.S. colleagues say. Over the past two decades, they have cut the death rate from the mysterious paralysis from about one in five to one in 20 or 30.
"It's amazing how well they do with these kids with not nearly as sophisticated equipment as we have," Dr. McKhann said. "They're dedicated to their care."
But the disease puts a severe strain on the country's medical system and the families of its victims. Several months' treatment, one physician said, can cost a patient's family about $500, while the average monthly wage in China is about $40.
Dr. McKhann and his team, who returned to the United States several weeks ago, are trying to track down the cause of what they're calling the Chinese Paralytic Syndrome, or CPS. So far, the cause has eluded them.
The discovery of CPS came almost by accident, beginning with the visit to Baltimore six years ago of a top-ranking Chinese general who came to Dr. McKhann for treatment of a neurological disorder.
The grateful Chinese government, in turn, invited the neurologist to visit China. He eagerly accepted.
Although Dr. McKhann had never been to China, his father, a professor of pediatrics and co-inventor of the iron lung, had spent several years working in Beijing in the late 1930s. A student of the elder Dr. McKhann's, in fact, became China's leading pediatrician.
BTC In 1986, Dr. McKhann visited the mammoth, 900-bed Beijing Children's Hospital to lecture on Guillain-Barre, which obviously was of special interest to the Chinese. Afterward, he was invited to see some patients.
"I went up to the ward, and it was like the old polio days," he recalled. "There were two wards full of these kids flat out, on respirators."
Guillain-Barre, which causes nerve damage and temporary paralysis, strikes only about 4,000 people a year in the United States. Even large hospitals seldom have more than a few cases.
Beijing Children's Hospital, he recognized, could provide researchers with a rare opportunity to study the illness.
In 1990, he returned, leading a team of Americans that included Tony Ho, then a Hopkins medical student, Dr. David R. Cornblath and Dr. John Griffin of the Hopkins medical school, and Dr. Arthur K. Asbury of the University of Pennsylvania.
Dr. Griffin said the researchers knew that they were on to something peculiar by the third day of the visit, when they sat down to dinner in their hotel and reviewed the first results of tests on patients' nerve tissue.
Studies have shown that Guillain-Barre breaks down myelin, the fatty protective sheath around the nerve axons, which act as wires between nerve cells. The disease weakens the signals sent to muscles.
But the team's tests showed no such deterioration. "It was clear the diagnosis didn't make sense," said Dr. Griffin.
With the enthusiastic support of Dr. Jiang Zaifang, the chief of research at the hospital, the team reviewed records, took patient histories and analyzed samples.
They also visited a hospital in Shijiazhuang, a regional capital about 3 1/2 hours southwest of Beijing by rail.
Dr. Ho, now a resident at Massachusetts General Hospital, speaks Chinese and talked to the families of CPS victims.
The disease, which can cripple a healthy child overnight and paralyze him within two or three days, left families "very surprised and shocked and nervous."
Often they would have to carry their sick children 200 or 300 miles by bus, train or truck to the nearest hospital, he said.
After returning to the United States last year, Dr. McKhann and his team studied a limited number of tissue and blood samples from Chinese subjects. (For cultural reasons, the Chinese conduct few autopsies.)
They published articles about their 1990 work in Lancet, a British medical journal, in September, and in Science magazine last month.
And they talked with experts in paralytic diseases -- including the world's two authorities on polio, Dr. Albert B. Sabin and his longtime rival, Dr. Jonas Salk.
L Dr. Salk saw the Science article and telephoned Dr. McKhann.
"Are you sure this isn't polio?" he asked. "Or are you sure this isn't a form of the disease coming from polio vaccine, recently vaccinated kids?"
Dr. Sabin wondered whether the disease weren't some unidentified form of polio.
But the evidence gathered during the U.S. team's second visit in September rules out any polio link, Dr. McKhann said.
"There's very little evidence of an inflammatory process, which you would expect to see with a primary infection like polio or a similar-type virus," he said.
Doctors say the new disease follows no known pattern.
Polio, for example, usually occurs in clusters of unvaccinated children living in urban areas. Guillain-Barre usually affects adults, and there is no particular geographic or seasonal distribution.
The Chinese syndrome typically hits children, ages 5 to 8, living in rural areas in the summer months -- usually after a period of heavy rains. Most of its victims are widely scattered around the countryside.
"It is unheard of to see two kids from the same family, or two kids from the same school or two kids from the same village," Dr. McKhann said.
While the mystery hasn't been solved, the investigators have some suspects.
One possibility, Dr. McKhann said, is that CPS is triggered by a poison produced by a bacterial organism, "a toxin that is very selective in what it does."
Or a particular kind of bacteria could be "setting up some kind of immune response" in which antibodies in the blood attack the body's own nerve tissue.
If it is a bacterial disease, Dr. McKhann said, it may be Campylobacter jejuni, a diarrhea-causing bug found worldwide. Recent medical evidence suggests that Campylobacter infections lead to some cases of Guillain-Barre and hint that it may also play a role in CPS.
On the other hand, he said, "maybe we're not dealing with an infection at all but with some kind of toxin" in the environment.
Children might be exposed to poisonous insecticides, fertilizers or plants.
Buckthorn disease, for example, paralyzes children in Texas and Mexico who eat berries from the buckthorn shrub.
Whatever the cause, CPS may not be limited to China.
Dr. Sabin reported on a polio-like ailment in Mexico in 1969 that sounds suspiciously like CPS.
And the World Health Organization has reported that large numbers of children in Brazil and other South American countries have been hit in recent years with a mysterious paralysis that shows some similarities.
Meanwhile, the U.S. doctors are continuing their laboratory work and planning another trip to Beijing next year. Dr. Ho plans to take a year off to study CPS in China.
D8 "We're not giving up on this one," Dr. McKhann said.