Moving On — Part 3: An Inside Look At Parkinson’s Effects

This is the third part in a series entitled “Moving On.” The Old Gold & Black will be publishing subsequent sections throughout the remainder of the semester, which can also be found on our website.

Two percent of respondents to the Shrag study — that is, more than 30 people — reported receiving no information at all at the time of their diagnosis. That number may feel small in the grand total, but each one is a life, with their own idea of a future and a family also affected by the disease. And in each of these cases, they faced the same situation as Lawson, a diagnosis with no prognosis. No information. No hope.

Lawson had to wait a full month until his first follow-up visit to the neurologist. In the meantime, he turned to the same resource millions of others do with their daily questions.

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“I didn’t know where to start, so I just started Googling,” Lawson said. He says he quickly learned that websites like WebMD and Mayo Clinic didn’t offer much hope. “Those places are all just doom and gloom; they tell you all the worst things about what could happen to you.” 

Next, he tried to find local Parkinson’s communities for help, but the Winston-Salem Parkinson’s support group did not have a website at the time. So he educated himself about his disease the only way he could. Those sites focused on how his symptoms might progress and offered little in terms of solutions. Lawson had found information, but it didn’t offer him any hope or agency. It wasn’t the information he needed.

In the first few weeks after diagnosis, Lawson fell into a depressive episode. “It left me in an incredibly dark place,” he said. “I didn’t know what was wrong with me. I didn’t know what to expect next.” In response, he withdrew from the world around him. His wife and children supported him as much as they knew how, but they also had their own daily lives to continue. When friends would ask what had happened to him, Lawson wouldn’t know how to explain it to them. Eventually, close friends and even some family members stopped reaching out.

Lawson doesn’t hold it against them. He imagines that they couldn’t understand what was happening to him or what they might do about it. He figures that probably made them feel uncomfortable, so instead, they stopped trying. He didn’t have the answers to his own questions about the disease; how could they know what to do?

Lawson describes that time in his life as “existing without living.” Instead of providing for others, he felt like a liability.

Unfortunately, depression and loss of community are both common themes in the story of Parkinson’s. “Do not be surprised to learn that not everyone is willing to be in your company when your symptoms worsen,” reads an article on the Parkinson’s foundation website. Another article on the website estimates that 50% of all people with Parkinson’s will experience depression at some point in their life. It is unknown if depression stems more from the physical changes in the brain caused by Parkinson’s or if it is brought about more by lifestyle changes influenced by the disease. Most likely, a crippling combination is at fault.

When Lawson finally met with his neurologist for a follow-up, communication remained stilted. Lawson believes it stems from an inability to put the science of the disease into laymen’s terms. He asked for reasons behind his thoughts and physical symptoms, but the answer he says he most commonly received was “well, that’s Parkinson’s for you.”

“It was so frustrating. That wasn’t what I wanted to hear,” Lawson said. “Maybe some people would rather not be aware of what’s wrong, but I want as much information as possible.”

First it was the wrong information, then it was too little information. What makes access to the right kind of knowledge so difficult for a patient to reach?

Communicating medicine to a general audience is an already difficult art made tougher by the fact that Parkinson’s disease is a particularly complex diagnosis to fully explain. This is partially because Parkinson’s disease is such a paradoxical disease. Recall that its two most recognizable symptoms, tremors and bradykinesia, both deal with movement. Tremors are uncontrollable movements at rest; bradykinesia, meanwhile, slows and stops movement from occurring. How can the same disease create unwanted movements and prevent goal-directed movement?

The good news for Lawson is that, compared to other neurodegenerative diseases, such as Alzheimer’s or multiple sclerosis, we know a lot about the science behind Parkinson’s disease. The answer begins with a tiny cluster of nerve cells, or neurons, located right where your spine extends upward into your skull and connects to your brain. This group of neurons is called the substantia nigra. The name, which means “dark substance” in Latin, comes from the characteristic dark stripe it forms across the brain stem. The coloration makes the substantia nigra easily distinguishable, but little was known about its function until over a century after it was first described.

In 1893, a 38-year-old tuberculosis patient wandered into the ward of famed French neurologist Jean Martin Charcot. He sought help from Charcot because he had developed a tremor on one side of his body. Charcot had no way to treat this at the time, but after the patient’s death, he performed an autopsy to try to discover what had been the cause. The autopsy revealed a small tumor in the patient’s brain. The tumor only affected one area, a small dark smear across the brain stem: the substantia nigra.

This finding remained only note of intrigue for a few years until one of Charcot’s pupils, Edouard Brissaud, finally made the connection. In 1895, Brissaud published the first paper to suggest the relationship between the destruction of the substantia nigra and the symptoms that would come to be known as Parkinson’s disease. It took another half-century and the discovery of a new chemical in the brain before anyone had a clue why.

In 1957, two scientists were independently exploring the same mysterious chemical, dopamine. First, Kathleen Montagu published a paper showing, for the first time, that dopamine was naturally present in the brain. Before this, scientists had just assumed it was an unimportant chemical byproduct found in the body. But Swedish scientist Arvin Carlsson showed the world that not only was dopamine present in the brain, it was a neurotransmitter, meaning that it functions as a chemical messenger, sending signals between nerve cells in the brain.

Through his research, Carlsson stumbled onto something unexpected. When he injected a chemical to destroy dopamine in live rabbit subjects, they turned completely immobile. No amount of prodding produced any muscle movement. When he reintroduced dopamine back into the rabbits with a drug called L-dopa though, they sprung back to action. His lab immediately connected these symptoms to those seen in Parkinson’s disease. If L-dopa could rescue the rabbits, then maybe, for the first time in history, they had hope for treating Parkinson’s disease.

Later, when they developed a technique to locate dopamine in the brain, they found a huge amount concentrated in a tiny, dark area on top of the brainstem. The substantia nigra was home to dopamine. All the evidence, gathered over decades, fit perfectly.

Today, scientists have mapped out the complicated circuit that initiates motor function and the exact relationship between the substantia nigra, dopamine and movement. We now understand that the substantia nigra is a production facility for most of the dopamine that exists in your brain. We also know that dopamine is an important neurotransmitter that can be released onto cells to activate or deactivate them. And we know that when someone starts to show the symptoms of Parkinson’s disease, they are usually already missing at least 80% of those dopamine producing cells in the substantia nigra.

The susbstantia nigra is not directly responsible for movement, though. Instead, it exerts its influence by connecting to another part of the brain called the striatum. The striatum is a major control center for movement. It receives signals which activate a complex mechanism of two competing pathways and then outputs a message to the rest of the body. One pathway promotes movement while the other prevents it, but they both end at the same point in the brain, meaning that only one message can dominate over the other at a time.

The brain is full of these mutually inhibitory circuits, evolved to make certain that processes are regulated and not allowed to run haywire. In this case, the tug-of-war dictates movement signals traveling downwards from your brain to your body.

So the striatum is essentially an on/off relay station, and, here, dopamine returns to the picture. Dopamine, released from the substantia nigra onto the striatum, is responsible for making sure that the “on” pathway has an advantage in this constant tug-of-war. With dopamine, the “on” signals easily overpower the “off” pathway so that movement is smooth and easy. Without dopamine, the two pathways start to equal out and the relay station sends sporadic and conflicting messages down to the body.

That is, in a simplified way, why the substantia nigra is critical for everyday movement. By the time Parkinon’s is diagnosed, the substantia nigra cells are almost completely wiped out. With so little dopamine left, movements become weak and difficult to initiate. Actions that require a lot of micro-adjustments like balancing a spoon as you bring it from bowl to mouth, become frustratingly difficult because the striatum no longer has the energy required to synchronize so many actions. At the same time, lack of dopamine means that the striatum switches to its “off” position much more often, leading to the slow and rigid movements in those with the disease.

Today, that drug used by Carlsson to recover movement in his rabbit subjects over 60 years ago remains the most ubiquitous treatment for those with the disease. L-dopa is known as a precursor compound — when they body synthesizes a chemical, it does so in a series of steps. L-dopa is the molecule one step before dopamine, so it can be packed into a tablet, taken orally and make its way into the brain where it is transformed into dopamine and is able to substitute for all the dopamine that is no longer created by the substantia nigra.

The only other significant advancement in treatment over the past 60 years has been the development of a technique known as deep-brain stimulation, where an electrode is implanted directly into your brain so that it can activate bunches of neurons and help keep the “on” pathway of the striatum dominating. But this can be a costly procedure which requires surgery, and it does not always result in large improvements, making it relatively rare in the community.

There is one other treatment embraced by many in the Parkinson’s community. Movement therapies of all kinds, from boxing to improvisational dance, are offered for those with the disease. Though we currently have no way to prevent Parkinson’s symptoms from progress over time, it appears that the more a patient uses their motor pathways, the longer they are generally able to hold on to them. And that alone might be the single most actionable information for anyone diagnosed with Parkinson’s disease. The act of moving may actually keep them moving for as long as possible.

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