Asleep: The Forgotten Epidemic That Remains One of Medicine's Greatest Mysteries (26 page)

It was an idyllic childhood in Crosby, England, a residential neighborhood outside of Liverpool, where Philip’s father was a silversmith. On sunny days, Philip and his sister played in the garden and stole loganberries to eat. And on winter days, Philip wrote his stories, the otherworldly tales of Magton, tinged with magic, draped in the tapestry of childhood imagination.

Then, something inside Philip’s mind shattered.

The year was 1931, and for Philip time stopped; the world seemed to cease moving, imploding. Philip’s parents and his sister appeared by his bedside, and in between fits of sleep, he could comprehend some of what they said: fever. Flu. Not recovering. Lethargy. Sleepy. A disturbing lilt in their voices could be perceived—it was the way they asked. The fear they gave off. The feeling that this mysterious disease was out of their control.

In nightmares, Philip was trapped inside his own body. It was worse than death; it was purgatory. Though his body would not respond, his mind was always awake, filled with nothing. An overwhelming, deafening, suffocating nothing.

For his parents, the transition was terrifying. Philip would not wake, even when shouted at, even when shaken. When he did open his eyes, they stared, frozen, at something no one else could see. The day that his illness finally broke, and Philip began to recover, the whole family felt enormous relief. But the Philip who awakened from that deep sleep was not the same.

At first, the differences were small. Philip’s demeanor could become clouded with a darker sense of mischief and unruly behavior. Teachers complained. Then he began walking with an unusual gait, his shoulders hunched forward. His physical appearance began to change, and he would repeat the same movements over and over again, obsessively. Finally, one night, when playing a favorite game of hiding beneath his bedsheets, he refused to come out. He stayed there for three days.

Philip’s parents took him to see a leading neurologist—Dr. George Auden, poet W. H. Auden’s father. He told Philip’s parents the sober news: Philip suffered from the effects of encephalitis lethargica. He was admitted to the only place available at the time, a mental institution in a ward with senile, elderly men. Philip would live there for the next seven decades, enduring mind-altering medications and shock treatments. By the year 2002, much too far in the future for any of the doctors or their patients to imagine at that point in time, Philip would be the world’s last known survivor of the encephalitis lethargica epidemic. Surely the doctors during the epidemic believed that a cure or a vaccine would arrive in the following decades. With so many medical advancements ahead of them, including electron microscopes, CT scans, MRIs, and mapping of the human genome, surely the answers to this epidemic would be found.

That would not be the case. And so when Philip died later in 2002, his sister gave to medicine the only thing science could never fix—his brain.

CHAPTER 24

Gray Matter

S
liced and cross-sectioned, a human brain looks more like a sea creature from the lightless depths of the ocean than the complex organ that it is. It is flat, putty-colored, and shaped like an inkblot test.

Dr. John Oxford, who describes himself as a virus hunter, was in London the day Philip died, so he took a train to the institute and was unceremoniously handed Philip’s brain in a box. At Oxford’s lab, the brain was sliced and fanned out on a metal sheet. Oxford has long believed there to be a connection between the 1918 flu pandemic and encephalitis lethargica. Oxford has more than a passing interest in the flu. As a young medical student, he studied under one of England’s famed virologists, Sir Charles Stuart-Harris, a researcher who served on the team that isolated the first flu virus. Oxford continued his investigations of the flu in the decades to come, even conducting research on a vaccine for the 1968 flu outbreak. Oxford’s theory that encephalitis lethargica is somehow related to the 1918 flu is a strong one.

Josephine Neal, in her writings about the disease, noted that a majority of children’s cases of epidemic encephalitis were preceded by flu. In the United States, encephalitis lethargica cases were highest in the cities where pandemic flu had hit hardest, primarily Philadelphia and New York.

Another compelling connection between the 1918 flu and encephalitis lethargica is the story of American Samoa. Roughly one hundred miles away, neighboring Western Samoa was devastated by the flu pandemic and encephalitis lethargica, losing 22 percent of its population. American Samoa therefore quarantined itself, avoiding the influenza pandemic entirely and suffering only two cases of encephalitis lethargica.

And, after all, there seems to be a logical connection when history’s most devastating flu pandemic struck at the same time as history’s largest pandemic of sleeping sickness.

Many doctors at the time of the epidemic also believed the two were linked—that the virus left a smoldering infection that later flamed up into encephalitis. “This is a major, unsolved mystery,” Oxford told the BBC. “My personal interest in this project is in hopefully discovering, hopefully identifying, the cause of that mega-outbreak in the ’20s, so we can help prevent such a thing happening in the future.”

T
oday, cases of encephalitis lethargica still happen sporadically throughout the world. The disease has never disappeared entirely, but it has not again occurred in epidemic form. There has even been a fund established in England and named for Sophie Cameron, a promising young student who planned to be a doctor, but instead fell into a deep sleep from which she never recovered. The Sophie Cameron Trust raises money for further research on encephalitis lethargica. In Britain especially, physicians have been focusing on these outbreaks.

The BBC’s 2004 documentary on encephalitis lethargica, “Medical Mysteries: The Forgotten Plague,” shows what it’s like to watch a normal, healthy person go quickly insane or quietly immobile. In one modern segment, a young woman’s case was frighteningly like those of the 1920s when she flew into a sudden rage, threw furniture, and became truly unrecognizable to her parents. In her hospital bed, her body tensed, she panted, her hands clawed, and even her toes curled tightly. The hospital staff had never seen anything like it, and her physician worried that the brain swelling would soon cause brain damage—what patients in the 1920s would have experienced as chronic symptoms. The young woman eventually recovered after receiving large doses of steroids, and after her recovery, her doctor showed her video footage of herself during the illness.

“This doesn’t feel like me,” the young woman said. “It just doesn’t feel like I’m watching myself... it’s amazing.”

Though steroids do not work in every encephalitis lethargica a case, they do work in some, and that offers new clues to the disease. It is very likely that the disease is actually an autoimmune response. That means that some pathogen enters the body, and the human immune system makes a mistake, attacking the body along with the intruder. Most often, the body responds by growing inflamed—in this case, swelling in the brain. Encephalitis has often been culpable in immune responses to infections caused by viruses or even the vaccines intended to control them. Viruses like measles, syphilis, herpes, HIV, Epstein-Barr, and several arthropod-spread ones like West Nile cause swelling and neurological complications. An autoimmune response might also explain why the severity of the infection had little correlation to the encephalitis—a mild case of the flu could cause encephalitis the same way a severe case would because it was the immune response, not the pathogen, that was to blame. And autoimmunity would explain why some patients have responded well to steroids, which decrease swelling and slow the immune response.

It’s possible then that had patients in the 1920s had the benefit of steroids during the acute stage of their disease, their brains might have been spared the damage that eventually caused so many chronic disabilities. Steroids may even have helped the patients who died while still in a deep sleep.

Like those during the epidemic, however, today’s cases are erratic and difficult to predict. In 2006, a healthy high school football player was admitted to a hospital in Houston, Texas. He had experienced some sort of seizure at school, his body growing tense and his eyes rolling into the back of his head, before he finally lost consciousness. Eventually he regained consciousness, but he could only say that he had felt numbness and tingling on one side of his body earlier that week. He showed no other symptoms.

The hospital ran tests, including a CT scan, but the doctors failed to find anything out of the ordinary. Later that afternoon, the boy told his mother his food didn’t taste right. He felt tired and lethargic, and his mother noticed that he had started making an unusual sound—a hissing noise. His body soon twisted left and grew stiff. His doctors struggled to find out what was causing these unusual symptoms and how to control them. Physicians suspected some type of encephalitis, but his MRI scans continued to come back normal.

Over the next several weeks, the high-schooler lost thirty pounds and grew more lethargic and childlike. At times he experienced psychotic episodes; at other times he had outbursts of obscenities. His mother barely recognized him, describing the situation as similar to some sort of demonic possession.

One of the physicians at the hospital had an interest in medical history and had happened upon an article about Constantin von Economo and encephalitis lethargica. The physician ran through the list of symptoms, most of which he had seen in this case. The boy could fall asleep for days at a time, and it was difficult to wake him, even for food. With no treatment options available, the hospital tried both steroids and levodopa. The steroids and L-dopa had no immediate effect on him as the physicians had hoped they would, and so they put him in a protective environment and waited to see what happened. Slowly, over the next few weeks, the patient did recover. To the boy’s bewildered parents, the physician explained how rare encephalitis lethargica is and added, “We’ve just scratched the surface in understanding this form of encephalitis.”

T
he question nettling Oxford and other neurologists today is the same one that confronted the neurologists in the 1920s: what is encephalitis lethargica’s relationship to the flu? The question is not just a matter of history; it has a direct effect on our future. If most sleeping sickness epidemics have coincided with flu epidemics, as many scientists have found, the next major flu pandemic could again produce these tragic encephalitis patients.

There seems little doubt that an avian or swine flu will strike once again. Either an entirely new flu strain will overwhelm human populations or one of the strains already identified will mutate into a more deadly form. At that point, influenza will spread around the world like a flame chasing oil. In 1918, that was accomplished through troop movements during World War I; today, it would be spread by mass transportation. In 2009, we saw just how quickly the H1N1 flu spread through airplane travel, and in spite of quarantines, how far it stretched.

O
xford’s modern hunt for the virus began with an amazing discovery from the past. In the basement of his hospital, Queen Mary’s in London, he found shelves stacked with wooden boxes marked
Post-mortem.
The hospital had taken samples from fatal disease cases dating as far back as the turn of the century. He pulled the crate labeled
P.M.
—
1918.
In it, he found eight brain samples of patients who died of encephalitis lethargica during the epidemic. Physicians during that time were unable to solve the mystery, and now in the twenty-first century, Oxford had found this brain tissue, preserved in formalin and sealed in wax as though the scientists of the 1920s were keeping a time capsule for scientists of the future. The pea-sized samples were sliced paper-thin and tested for genetic evidence of influenza using today’s advanced technology. The tests came back negative. Likewise, tests showed that Philip’s brain did not have any traces of the flu. And in the United States, a 2001 study conducted at the Armed Forces Institute of Pathology also studied archived brain tissue for the flu virus. Those results also came back negative.

This disappointing outcome left Oxford in the same position so many physicians found themselves in during the 1920s—with far more questions about this disease than answers.

There are other problems with the flu theory as well. Without a test to identify flu viral strains in the 1920s, how many cases were actually flu and not some other type of pathogen? It is also impossible to track with certainty how many flu cases actually sparked a case of epidemic encephalitis, or how many were mild enough to go unnoticed. In her book
Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It,
Gina Kolata pointed out the statistical conundrum: “Most people alive in 1918 got the flu. Even if encephalitis lethargica had nothing to do with the flu, by chance alone most people who got encephalitis lethargica would also have had the flu.” And as American encephalitis lethargica a researcher Dr. Joel Vilensky recently noted, “it is extremely difficult scientifically to prove a negative, in this case, to prove that influenza did not cause EL [encephalitis lethargica].” He wrote an article in response to a recent book published in Britain that unequivocally links influenza and epidemic encephalitis. Vilensky, however, has his doubts.

Vilensky, a professor of anatomy and cell biology at Indiana University School of Medicine, Fort Wayne, is working with other researchers on a database system, funded in part by the Sophie Cameron Trust, recording key symptoms of historical and contemporary cases of encephalitis lethargica. He hopes the database will not only give a more accurate estimate of the number of cases during the 1920s, but also help physicians identify modern-day cases as they arise. In the event that encephalitis lethargica
does
return with the next flu epidemic, Vilensky believes, “Difficulty in the diagnosis could again become a problem, and possibly a serious public health issue.”