Sterling Marlin, Parkinson’s and Deep Brain Stimulation

Sterling Marlin, one of only three drivers to ever win the Daytona 500 two years in a row, announced his Parkinson’s Disease diagnosis in 2012. Last week, Marlin’s team announced he was undergoing surgery to implant a deep brain stimulation (DBS) device to treat his Parkinson’s.

What is Parkinson’s Disease?

Just as you can break a car down into subsystems (drivetrain, suspension, etc.), you can break the human body down into its subsystems (musculoskeletal, endocrine, exocrine, etc.). The most complex subsystem of the human body is the Central Nervous System (CNS), which includes the brain and the spinal cord. The CNS links to the peripheral nerve system, which is essentially the collection of wires that carry the brain’s commands to the rest of the body.

Some peripheral nerves, like the sciatic nerve (which runs from the lower back to the leg, foot and toes) can be over a yard long.

Neurons and Neurodegeneration

Neurons are specialized cells within the nervous system that transmit nerve impulses. We talked about how important neurons are when we discussed concussions.

The roughly 100 billion neurons in your body perform three main functions:

• receive input (touch, sight, smell, sound, taste)
• send motor commands to our muscles (turn head, lift leg, drink beer)
• relay the electrical signals at every step in between your brain and where the signal needs to go

Neurodegeneration = Neuron + Degeneration

Neurodegeneration is neuron + degeneration: neurons gradually stop working. We all experience neurodegeneration because the biggest risk factor is aging. Neurodegeneration is responsible for many of the typical ‘inevitable’ signs of aging like memory loss and slowed movement.

Neurodegenerative diseases cause neurons to degenerate more rapidly. Neurodegenerative diseases you may have heard of include ALS (Lou Gehrig’s disease), Parkinson’s disease, Alzheimer’s disease and Huntington’s disease.

There’s a difference between neurodegeneration and a neurodegenerative disease. As we get older, we may frequently forget where we put the car keys. A person with a neurodegenerative disease may forget what car keys are used for.

The difference between neurodegenerative diseases is in the specifics of how they attack neurons or which neurons they attack.

Parkinson’s Disease

Parkinson’s Disease (often abbreviated PD) affects motor neurons, which is why the early symptoms are shaking, slowness of movement, and trouble walking.

Parkinson’s arises from a combination of genetic and environmental factors. If a member of your family has Parkinson’s, you have a higher likelihood of having it, but it doesn’t mean you definitely will.

• A number of celebrities have gone public about their Parkinson’s diagnoses to raise awareness of the disease, including Linda Ronstadt, Neil Diamond and Alan Alda.
• Most people are diagnosed after age 60, but some, like Michael J. Fox, had early-onset PD. Early-onset PD accounts for about 4% of all PD cases.
• Men are more likely (3:2) to get Parkinson’s than women.
• Approximately 60,000 Americans are diagnosed with PD each year.
• The combined direct and indirect cost of PD in the U.S. is nearly $25 billion.
• In the U.S., PD affects more people than MS, Muscular dystrophy and ALS combined.
• PD is second to Alzheimer’s Disease in terms of common neurodegenerative diseases

Risk Factors

People with repeated head injuries — like boxer Muhammad Ali — have a higher risk of developing Parkinson’s. In a 2006 study of 93 pairs of twins, a twin with at least one head injury was more likely to have a later diagnosis of PD. The likelihood of PD increased with the number of head injuries and how close in time they were.

Aside from avoiding head injuries (which is a good principle in general), exercise in middle age may reduce the risk of Parkinson’s disease later in life. It also appears that people who drink a lot of caffeine have less of a chance of having PD. Smoking reduces the likelihood of Parkinson’s, but massively increases your risk of lung cancer.

History

Parkinson’s has been around for a long time. Indian Ayurvedic medicine called it Kamapavata. Galen described a ‘shaking palsy’ in 175 CE. There’s even a suggestion that Dickens was describing Parkinson’s in his characterization of Frederick Dorrit in the novel “Little Dorrit“.

The disease was named after James Parkinson, who published the first detailed description of it in 1817. World Parkinson’s Day is April 11th — Parkinson’s birthday.

A red tulip with a fringe of white is the official symbol of PD. J. W. S. Van der Wereld, a Dutch horticulturist who had Parkinson’s disease developed and named the tulip after Parkinson..

Symptoms and Diagnosis

The Mayo clinic lists the following symptoms

• Tremor or shaking, usually in a hand or fingers.
• Slowed movement (bradykinesia) may cause steps to be shorter, slow walking speed or make getting out of chairs difficult.
• Rigid muscles 
• Impaired posture and balance
• Loss of unconscious movements such as blinking, smiling or swinging your arms when you walk.
• Speech changes, such as low volume, speed changes, slurring or monotone.
• Writing changes

These symptoms are characteristic of many neurodegenerative diseases. Like Alzheimer’s, diagnosis is made via a combination of symptoms + tests that rule out other diseases. Positive confirmation requires an autopsy.

As the disease progresses, symptoms become more severe. 78% of those with PD experience dementia. Many encounter difficulties sleeping, chewing, eating and swallowing. Some have depression, anxiety, fear or loss of motivation.

Neurodegenerative diseases are incurable, largely because we don’t fully understand what causes them. The average life expectancy after diagnosis is 7 – 14 years.

Treatments

Your body (like a car) uses chemical reactions and electrical signals. We’ve talked before about how respiration, the process by which the body gets energy from food, is analogous to the chemical reaction of combustion.

Drugs

Most drugs work by changing chemical reactions in your body: providing more of something your body doesn’t produce enough of (like insulin) or eliminating something your body produces too much of (as in some antidepressants).

PD produces a drop in dopamine, a chemical that serves as hormone and a neurotransmitter. L-DOPA (aka levodopa) is a chemical that can be converted to dopamine in the brain and has been the primary treatment for PD. It doesn’t do anything to help the cells that aren’t producing dopamine anymore, but it helps the cells that are still there produce more dopamine.

The downside is that L-DOPA has some serious side effects from serious (arrhythmias, hypotension, hallucinations) to more mundane (nausea, sleep problems). Even more problematic, the longer you use it, the more likely you are to have chronic side effects, such as freezing during movement, becoming resistant to the drug so it doesn’t work anymore, and dopamine dysregulation, which can lead to compulsive behaviors like shopping, gambling and much worse.

Deep Brain Stimulation

Medication is the first line of treatment; however, after years on the drugs, many patients stop seeing improvement, have to take very high doses, or can’t tolerate the side effects.

As I mentioned, your body works on chemistry and electricity. Drugs (chemistry) are easier to get into the brain. All of us have thick skulls (literally), which are also electrically insulating. It’s not easy to introduce a current into only a very specific part of the brain.

In the 1980s, Alim Louis Benabid and others developed the idea of deep brain stimulation. As a student, Benabid could not decide whether to study medicine or physics. So he did both, and had a tremendous impact on neurosurgery.

The technique targets the parts of the brain that control movement: The thalamus, the subthalamic nucleus and the globus pallidus. These sections are located deep within the brain — hence the name deep brain stimulation or DBS.

The technique places electrodes into the brain, in contact with the specific regions that are not behaving up to spec, and uses electricity to change the cell’s behavior. The FDA approved DBS — a ‘pacemaker for the brain’ — in 1997.

A new paper published last week in Nature Reviews Neurology uses bi-directional electrodes that can both record and stimulate deep-brain signals, which may improve how DBS treats PD and open the door for using it to treat many other conditions, including depression, OCD, chronic pain and Tourette syndrome.

DBS not a panacea. It doesn’t stop the progression of disease. It is literally brain surgery, which carries inherent risks, like infection, bleeding of the brain, and seizures. And it doesn’t help everyone: If you don’t respond to medication, they won’t even try DBS.

But consider the alternative.

“Parkinson’s is a roller coaster, physically and emotionally, for both the individual and family. After considerable thought, research and consultations with numerous doctors and specialists, my dad decided to undergo Deep Brain Stimulation surgery. We ask that you send prayers for a successful final surgery and recovery.”

Sutherlin House, Sterling Marlin’s daughter

How do you Do Deep Brain Stimulation?

The DBS system has three components: the implanted pulse generator (IPG) (called a pulse stimulator in the picture above), the electrodes themselves and a wire that connects the electrode to the pulse generator.

The IPG is a battery-powered neurostimulator. The batteries last 3-7 years, although newer models have rechargeable batteries. The doctor implants the IPG beneath the collarbone.

The electrode is a thin wire, about the diameter of a piece of angel-hair pasta, as shown below. Most electrodes actually contain a bundle of even smaller wires to allow more precisely deliver current.

The area targeted in treating PD is the subthalamic nucleus, which is about the size of a black-eyed pea. The parts of the brain responsible for to vision and speech are nearby, so it’s a delicate surgery.

The wire that connects the electrode and the IPG runs down the side of the neck. If you’ve ever tried fishing wire behind drywall… it’s kinda like that.

Stimulating the right side of the brain treats symptoms on the left side of the body and vice-versa. Depending on the location and severity of your symptoms, you may need two electrodes implanted at a cost of $35,000 – $50,000 each. Insurance (if you have it) usually covers much of the cost.

The Surgery

Vanderbilt University Medical College, where Marlin is being treated, is a leader in DBS research. They have led the way in studying how DBS might be used to delay or help prevent neurodegenerative diseases like Parkinson’s from progressing.

They start by drilling four holes in your head to attach a frame that prevents you head from moving during the stereotactic surgery. Patients say that this is the most painful part of the whole process. But it’s necessary to locate the very small portions of the brain where the problem lies.

There is an option for doing the surgery while the patient is asleep, which might be necessary if the patient is incapable of cooperating, or simple can’t handle the idea of being conscious and knowing someone is sticking electrodes into your brain.

In the majority of DBS operations, the electrode(s) are placed during a 4-7 hour surgery while the patient is awake. After drilling a nickel- or quarter-sized hole in the skull, doctors insert a tiny electrode. They then apply currents while directing the person to talk or move in a specific way. The patient’s feedback helps the doctor find the best place for the electrode.

The brain doesn’t have pain receptors, so there’s no requirement for anesthetic for brain surgery.

One famous story about DBS is the surgery for the bluegrass musician Eddie Adcock, who had the surgery to address tremors that threatened his musical career. The doctors had Adcock play the banjo during surgery: When his playing improved, they knew they had the electrode in the right spot.

https://youtu.be/PjX6ErmKY14

This video, made by Vanderbilt, gives you an overview of the surgery.

Post Surgery

A doctor activates the device using a remote control a few weeks after surgery. Over the course of weeks or months, a therapist works with the patient to optimize the settings and the usage of the DBS. Some patients may benefit from having it on all the time, others for specific periods of time.

When it’s all implanted, it looks something like this:

Get Well Soon, Sterling

The press release indicated that Sterling Marlin underwent the third of four surgeries last week at Vanderbilt University Medical Center. I’m not sure why there were four surgeries: They may be doing left and right sides separately with separate controllers. The process started on March 11th.

After the final surgery, he’ll have a few weeks to heal, then he’ll spend a few months working with a therapist to ‘dial in’ his device. Everyone’s brain is different, so it’s not like they can just turn the device on and walk away. It will take some time for him to live with the effect of the device. Just like you dial in a car, Sterling is going to dial-in his DBS device.

What happens after that?

Although Marlin retired from NASCAR after the 2009 season, he didn’t stop racing. In 2011, he got involved in attempts to preserve Nashville’s Fairgrounds Speedway and has been racing in the Pro Late Model series there.

After being cleared by his doctors, Marlin will return to his Pro Late Model race car.

DBS isn’t a cure for Parkinson’s disease, but it is helping many people continue living their lives to the fullest. DBS can mitigate and maybe even delay the onset of symptoms until such time as we have an actual cure.

Get well soon, Mr. Marlin.

Note: Although private foundations do fund research, much of the research into Parkinson’s is funded by the government through the National Institutes of Health and other funding agencies. When you hear them talk on the news about cutting research budgets, research that may produce cures for Parkinson’s, Ebola, flu, and cancer is part of what they want to cut.