Asleep: The Forgotten Epidemic That Remains One of Medicine's Greatest Mysteries (27 page)

T
he difficulties found by Oxford and other physicians who subscribe to the flu theory of encephalitis lethargica have given momentum to the other popular current-day theory: strep throat. A young pediatric neurologist named Russell Dale was working at the Great Ormand Street Hospital in London in 2002 when he began seeing children with remarkable and unusual symptoms. Their parents, echoing the ones in the 1920s, said that it was as if the children had changed personality overnight. Dale consulted other neurologists, physicians who had been practicing for thirty or forty years, and none had seen patients like these.

“Encephalitis lethargica wasn’t really taught in medical schools anymore because it was thought it disappeared,” explained Dale, but having read Oliver Sacks’s
Awakenings,
he developed a curiosity about the long-forgotten disease.

Today, Dale is a senior lecturer at the University of Sydney, Australia, and works with a children’s clinic, specializing in brain inflammation. Over the last several years, he has seen twenty-five pediatric cases of what he believes is encephalitis lethargica. Though it’s difficult to know if it is the same disease that circulated in the 1920s, Dale’s diagnosis is based on three classic symptoms: movement disorders, psychiatric symptoms, and sleep disorders. No other neurological condition shares that exact symptomology.

Rifling through current and historical files, Dale has found a common link among the patients: sore throats. And like the flu, sore throats are more common during the winter months, when encephalitis lethargica usually peaked. Most sore throats are caused by simple bacteria called streptococcus group A, which appear like a chain of round beads in the blood. More than sixty types of streptococcus cause a wide range of diseases, like strep throat, tonsillitis, pneumonia, infections in teeth, and even a flesh-eating disease on the surface of the skin. Harmless chains of streptococcus also are found in humans, on skin, and on surfaces.

To substantiate his theory that streptococcus is somehow linked to encephalitis lethargica, Dale went back to von Economo’s original studies in 1916 and 1917 and found that most cases had started with a sore throat. What’s more, von Economo, in his own research, tried injecting bacteria into rabbits and was successfully able to produce an encephalitis lethargica—like disease. The type of bacteria he used was called diplostreptococcus—the type of strep that causes pneumonia.

Dale’s theory expands upon the idea of autoimmunity, helping to explain
how
encephalitis lethargica happened, if not why. All bacteria have proteins along their surface that interact with the immune system. And the surface proteins of the streptococcus A bacteria look very much like the surface proteins of brain cells. In evolutionary terms, Dale explained,
all
cells are similar in their makeup. Human and ape DNA is almost 99 percent alike; we even share a close genetic relationship to rats, which makes them a popular choice in lab experiments. Like every other type of flora or fauna, bacteria also are living organisms, so our cells can closely resemble those as well. When the body comes under attack from any foreign agent like a virus or bacterium, it builds antibodies to fight the invader. But if the surface of the bacterium is similar to the surface of brain cells, the antibodies might not be able to tell the difference—a molecular case of mistaken identity. This “cross-reaction” confuses the body, which not only begins producing too many antibodies, but attacking the brain cells as well as the pathogens. And, according to Dale, the basal ganglia are particularly vulnerable to antibodies attacking the brain.

Eventually, when so many pathways going to or coming from the basal ganglia are damaged, communication to the parts of the brain that control both movement and emotion become erratic. The misfired messages might tell the body to move frantically, quickly, causing shaking and repetitive motions. Or the flood of messages might do just the opposite and neglect to tell the muscles to move at all. In much the same way, mixed messages sent to the frontal lobe might very well affect the personality of the patient.

In one study, Dale tested the blood of some twenty new cases of encephalitis lethargica. In most, there had been a preceding throat infection, and in nearly all of them, Dale found antibodies that react against the basal ganglia. Dale hopes that treatments will be able to target the problem by suppressing the immune system and essentially telling it to slow down the overproduction of antibodies.

“The idea of infection leading to a brain disorder is very old,” said Dale in one interview. After all, medical literature during the epidemic itself was peppered with references to not only the flu triggering a brain infection, but also strep bacteria. In addition to von Economo’s experiments with the strep that causes pneumonia, Rosenow, in the 1930s, was following the type of streptococcus responsible for infections of the teeth. And Science magazine reported in 1933 that a sample of streptococci had been taken from an encephalitis lethargica patient at St. Elizabeth’s Hospital for the Insane in Washington.

L
ike Oxford’s theory, Dale’s, too, leaves questions, the most obvious one of all: why did encephalitis lethargica occur in an epidemic form?

Regardless of whether or not that question is ever answered, even the few cases seen today are tragic enough in their own right to deserve the attention of modern medicine. As Dale, who has watched two dozen children succumb to encephalitis lethargica, says, “It is devastating.”

CHAPTER 25

Past or Prologue?

T
he answer to the great sleeping sickness epidemic may very well lie in a combination of today’s theories. If encephalitis lethargica is, in fact, an immune response, the human immune system provides the most clues. One consistent characteristic of the encephalitis lethargica epidemic was that it struck concentrated populations, often those where other diseases were already circulating, like army camps, field hospitals, and crowded metropolitan areas. Where people are concentrated, so are germs. Perhaps, then, it wasn’t one single pathogen that was to blame, but many.

For encephalitis lethargica to occur as an epidemic, it had to be shadowing one or more infectious diseases during the 1920s. The flu pandemic was certainly the largest of the time, but even if there is a connection to influenza, it may only be a
relationship,
not a cause and effect.

As it turns out, the immune system is also to blame for the high mortality in the influenza pandemic in one of two ways—either by working too hard or not working hard enough. The 1918 flu pandemic was set apart from other, less deadly outbreaks of flu by the shift in pattern. Instead of killing the very young or the very old, it homed in on the healthiest portion of the population. And, often, it was those healthiest men and women who died within hours. The reason for this may have been their strong immune systems. If the standard response to an invading virus is fever and fluid secretions in the lungs, healthier victims with a good immune system might overreact—what scientists today broadly refer to as “cytokine storm.” If so, the healthiest and strongest immune systems would produce so much fluid, so fast, that the patient could literally drown.

It is more likely, however, that the 1918 flu pandemic was so deadly because of weaker immune systems, not stronger ones—and there we may find some answers to the encephalitis lethargica epidemic. Most people with a case of pandemic flu—without complications—survived. Those who died fell victim to a secondary infection, the most common being pneumonia. That would also explain the unusual W-shaped mortality pattern of the flu victims—high deaths among infants, high deaths among twenty-five- to forty-year-olds, and high deaths among the very old. It was the spike among young adults that was out of the norm, and the reason was probably their lifestyle. After a case of the flu, their immune systems were weakened, but most young adults, like soldiers, parents, or workers, went right back to work and were frequently and consistently exposed to contagious germs, which took hold like burrs in their weakened immune systems. What’s more, the flu virus had already destroyed cells throughout the respiratory tract, making it an ideal place for bacteria to flourish.

In 2008, a study aimed at protecting public health during the next flu pandemic showed that pneumonia was the leading cause of death during the Great Flu and went so far as to use archived brain samples from 1918. All had evidence of damage from bacteria. And one of the leading bacteria to cause pneumonia: streptococcus A.

So far, only the strep that causes a sore throat has been linked to encephalitis lethargica, but different forms of strep appeared prolifically during the epidemic. In World War I, strep, as well as staph bacteria, were rampant in battlefield wounds, as well as in the lungs of flu patients. And the 1920s saw an epidemic of scarlet fever, caused by yet another type of strep A, which killed thousands of people in New York. In 1921 alone, there were over thirteen thousand deaths from scarlet fever, more than double the number of deaths from the year before. Bacterial meningitis was also occurring in epidemic form.

What’s more, strep was only one of the many deadly pathogens of the 1920s. Health reports are peppered with cases of polio, measles, diphtheria, septic sore throat (not the same as strep), typhoid, and tuberculosis. Troop movements helped spread epidemics faster and more efficiently. This was also the height of the vaccine age. For the first time, vaccines and antitoxins were being used widely in the population—not only for viral diseases, but for infections like diphtheria and meningitis that would be treatable with antibiotics decades later. These vaccines may have exhausted the immune system. The environment in which people lived also changed, with cleaner water and food in most major cities. Sanitation had improved. As polio proved, the cleaner the world became, the less immune and more vulnerable people became.

In the complex world of epidemiology, it could have been the overwhelming number of diseases—what one physician called satellite infections—circulating at the time, from a highly virulent flu to strep throat, from scarlet fever to pneumonia. Perhaps people’s immune systems were just overtaxed, making them more sensitive to infection and making a defeated immune system more likely to confuse the flood of foreign cells with the body’s own cells. Somewhere on the evolutionary ladder of disease resistance, we may have stepped back a rung or two, and as a result, encephalitis lethargica a got a foothold.

W
hen and if this mystery is solved, it will certainly be one of medicine’s longest and greatest examples of epidemiological prowess. The medical investigators who studied the disease during the epidemic are long since gone. Nearly a century later, a new set of medical investigators is building upon those old case studies, circling the same theories, trying to find a pattern in a disease with no clear archetype.

With the benefit of hindsight, we now know the epidemic of encephalitis affected as many as five million people worldwide, but scientists also speculate the number may be lower. We also know the epidemic probably started earlier than 1916, with sporadic cases as early as 1903 and an outbreak in Bucharest in 1915. The major epidemic came in two waves—the first began in 1916 and peaked in 1920. After that, the epidemic waned to just a few thousand cases worldwide. The second wave hit suddenly in 1924, and the number of cases rose dramatically, especially in the United States. And then chronic symptoms left a cruel legacy for several decades.

The hope is that many of the remaining questions will be answered before encephalitis lethargica returns in any type of widespread form. If, indeed, the flu and bacterial infections were tandem culprits in the pandemic of an autoimmune disease called encephalitis lethargica, answers are needed before the next major flu pandemic. Antivirals, antibiotics, and steroids could all help a patient recover
before
encephalitis has a chance to cause damage. Scientists are committed to that work today.

But the interplay between living organisms—both the ones causing a disease and the ones trying to survive it—has always been tenuous. Pathogens change and grow stronger, and the antibiotics and antivirals used against them lose their advantage. That fact will always make epidemics a frightening and real possibility.

The original epidemic, and the lesson learned from it, was too easily dismissed, too easily forgotten, and in the words of Oliver Sacks, “such forgettings are as dangerous as they are mysterious.”

EPILOGUE

Virginia and the Forgotten Epidemic

There is nothing to save, now all is lost, but a tiny core of stillness in the heart like the eye of a violet.

—W. H. AUDEN, SON OF DR. GEORGE AUDEN

W
ith the epidemic of encephalitis lethargica so widely forgotten in the United States, it is a wonder that the subject ever came to my attention. Sleeping sickness may have been “the forgotten epidemic” to most, but for me it was always present in my grandmother Virginia. The prologue touched on her story. The year was 1929, and she was sixteen years old, living in Dallas, Texas. She had an infection of some type and was feverish the day she fell down the staircase of her parents’ home.

Her parents put her to bed, and she fell asleep—the long, frightening sleep so many patients in this book experienced. She did not open her eyes for 180 days, missing most of her school year. In the days before modern diagnostic tools, her pulse grew so shallow that she was declared dead three different times by her doctors.

And then, miraculously, she awoke. A third of all sleeping sickness patients
did
recover. Physically, she remained weak and was never able to return to school. Thankful to have her awake again and recovering well, her family did not immediately notice the changes in her personality.