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Around 1917, an unknown illness dubbed "sleeping sickness" caused people to suffer severe sleepiness and delirium. Some even became paralyzed for decades until a temporary cure was discovered in the 1960s. The story of this illness is tragic but offered new insight into how our brains function.

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Imagine you woke up tomorrow to discover that forty years had passed, Rip Van Winkle style.

After the brief moment of excitement to see the future, you realize half your life is gone and you have to make peace with it. For many of those with an unusual disease called encephalitis lethargica, or EL, that was basically what happened. In the late 1960s and early 70s, after years in almost a complete stupor, they suddenly woke up.

While some had trouble understanding that time had passed, others revealed were they were mostly aware of every passing day, they just hadn't been able to move. Pretty soon, though, the same medication that had allowed them to wake up caused such debilitating side effects that almost every patient had to return to the way they were before.

The story of EL is a tragic one. But it also says a lot about the brain chemistry that translates will into action, what happens when disease interferes, and how even the most promising drugs can unexpectedly backfire.

It all began around 1917, when people began to suffer severe sleepiness, delirium, problems moving their eyes, and paralysis. Over the next several years there were about a million cases worldwide. Autopsies revealed that the disease, which people started calling "sleeping sickness," caused inflammation in your part of the brain we now know is involved in keeping you conscious.

But doctors couldn't find an effective treatment and the disease, which we now know think it was a virus, killed about a third of the people it infected. When the flu epidemic started killing tens of millions of people in 1918, people kind of stopped talking about EL as much.

But unfortunately, even among those who survived EL, the story didn't stop there. After their initial recovery, sometimes years or even decades later, many developed symptoms similar to Parkinson's disease. In Parkinson's some nerve tissues start to break down, causing things like tremors, stiffness, and slow movement.

But it generally develops in order people, and the patients who'd had EL weren't necessarily old. In some ways, these patients' symptoms were also more extreme. For example, they'd sometimes slow down and completely stop moving, holding whatever awkward positions they found themselves in, even if someone else moved their body.

Eventually, a lot of them became catatonic or immobile. Later on, some would describe the experience as a resistance that would stop them from moving the way they wanted to. Even weirder, they'd occasionally move in response to some stimulus - like by catching a ball if you threw it to them.

Researchers knew that Parkinson's came from deterioration in the "substantia nigra," a part of the brainstem involved in motivation and movement. So, doctors figured that EL patients' symptoms were connected to that part of the brain too.

But without any useful treatments, patients in this state were mostly just left to live in hospitals and mental institutions for decades. At least until the late 1960s, in the Bronx hospital where the now-famous neurologist Oliver Sacks, who was just starting his career, decided to try a newly-invented drug called L-dopa. That's when some of the patients suddenly woke up.

See, those deteriorating neurons in the brainstem were the ones responsible for transmitting dopamine, a neurotransmitter involved in reward and motivation. In other areas of the brain, dopamine is associated with feelings of reward and pleasure, but in the substantia nigra it seems to be associated with the motivation to move at all. You can't just fix the problem by taking straight-up dopamine because it can't cross the blood-brain barrier.

But L-dopa was a form of dopamine that could get into the brain and stimulate the dopamine receptors there. In 1967, this drug was found to help people with Parkinson's disease, so Sacks thought it might help those EL patients too. And it worked!

Almost every patient experienced some kind of miraculous awakening and returned to health... at least at first. One patient, identified only as Rose R., began telling stories of celebrities like George Gershwin, all in perfect detail, even though they'd happened more than 40 years earlier. She also knew the dates of big events that happened while she was catatonic, like Pearl Harbor or the Kennedy assassination, but said none of it felt real.

Others, like a patient named Leonard L., were eager just to leave the hospital, which he called a "human zoo," to experience the outside world. But within weeks, or in some cases just days, almost everyone began to suffer severe problems with the drug. Some had hallucinations, explosive and aggressive behavior, or sexual side effects.

On top of that, the drug seemed to lose its effectiveness over time. Sacks tried to find doses that would work without such extreme side effects, but for almost every patient, there was just no middle ground. Very few were able to continue treatment beyond a couple of months, and afterward, they went right back to they way they were or got even worse.

And, although some of the patients who could talk said they were grateful to have another taste of "full experience" again, others said they felt newly-robbed of the life they almost got back. The fact that the worked at all supported what doctors thought was happening in those patients' brains. L-dopa stimulated the substantia nigra, compensating for the degraded neurons.

For the patients, it suddenly felt like the "resistance" was gone; when they wanted to do something, they actually could. But doctors didn't expect the drug to backfire so badly. They hadn't seen that response in people with Parkinson's disease, although it did start to happen later on, it just took longer.

There are probably several reasons for the severe side effects in EL patients. For one thing, these people had been suffering for decades, so their neurons had degraded more than in Parkinson's patients, who are usually diagnosed late in life. Another problem was that L-dopa couldn't be targeted to just the substantia nigra.

Eventually it overstimulated their reward system too, leading to side effects like aggression impulse control and hyper-sexuality. It's also possible that by-products of dopamine are neurotoxic in high doses and can cause hallucinations, which would explain why these side effects also happened in late-stage Parkinson's patients. There is a lot we still don't know about all of this.

The cause of the original EL outbreak is a mystery: it infected tons of people and then almost completely disappeared. And even though there have been only a handful of cases since, there's no reason to think the epidemic couldn't happen again. Still, if nothing else, what happened with L-dopa taught us a lot about how our brains translate desires into actions.

When the process works, we don't even have to think about it, but when it starts to break down, fixing it takes a lot more than just replacing what's missing. L-dopa might have seemed like a miracle drug at first, but its effects on the brain were a double-edged sword, and in the end it hurt more than it helped.

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