A Shock to the System

To slow the progress of Parkinson’s disease, doctors planted electrodes deep in my brain. Then they turned on the juice.

Wired.com
Issue 15.03 - March 2007
By Steven Gulie
http://www.wired.com/wired/archive/1...insurgery.html

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I'm lying in an operating room at the Stanford University hospital, head shaved, waiting for my brain surgery to begin. Sure, I feel anxious, but mostly I feel crowded. There are 10 people milling about, tinkering with instruments and examining me. It’s an impressive crew, including a neurosurgeon and his fellow, a neurologist and her fellow, an anesthesiologist, an experimental physicist, and a graduate student in electrical engineering. That’s right, a physicist and an electrical engineer. Directly behind me, out of my sight, is the star of the show, chief neurosurgeon Jaimie Henderson: 44 years old, tall, erudite, and handsome. On my right, flexing my hands, is neurologist Helen Bronte-Stewart: brisk, smart, and beautiful. In fact, nearly everyone is not only brilliant but also pretty enough to play themselves in the movie version of this story. I call them Team Hubris.
Today I’m an honorary member. I’ll be kept awake for the entire procedure. During the surgery I will talk and move my limbs on command, which helps Team Hubris know which part of my brain is being poked.

Unfortunately, this also means I’m conscious when Henderson produces what looks like a hand drill and uses it to burr two dime-sized holes into the top of my skull. It doesn’t hurt, but it’s loud.

Team Hubris is installing a deep brain stimulator, essentially a neurological pacemaker, in my head. This involves threading two sets of stiff wires in through my scalp, through my cerebrum — most of my brain — and into my subthalamic nucleus, a target the size of a lima bean, located near the brain stem. Each wire is a little thinner than a small, unfolded paper clip, with four electrodes at one end. The electrodes will eventually deliver small shocks to my STN. How did I get into this mess? Well, I have Parkinson’s disease. If the surgery works, these wires will continually stimulate my brain in an attempt to relieve my symptoms.

The first half of the operation goes smoothly. Through amplifiers connected to the probes, the team can listen to my neurons fire as the wires move through my cortex. This helps pinpoint the location of the probes. When I move a limb, for example, my subthalamic nucleus ignites, resulting in a loud burst of static. The doctors and the physicist practically sing along: “That’s driving it!” “Yes!” “Listen to that!” “Dorsiflexion!” “Perfect!” The fellows’ eyes are shining. Everyone looks happy and expectant — proud. Following instructions from the neurologist, I tap my fingers, open and close my mouth, stick out my tongue. She is pleased.

After positioning the first electrode, which takes about three hours, we stop for 10 minutes to prep for the second electrode. I listen to my iPod; several doctors step out to stretch. For some reason, when we’re ready to start again, the neurologist, Bronte-Stewart, isn’t there. They page her. They wait. They page her again. (She later says she never got the first page.) Eventually, they proceed without her. The neurology fellow steps in, flexing my hands and asking me to stick out my tongue. She doesn’t seem too happy.

She’s not the only one. Team Hubris is struggling with the second electrode. “That sounds like it, but it’s dorsal, too dorsal.” “I don’t like this electrode.” “I don’t think it’s the electrode.” “I think maybe it’s a software problem.” “Try another cable.” “Another audio cable?” “Well … yes.”

Bronte-Stewart returns at last. She relieves the fellow and begins flapping my wrist and flexing my legs. She seems upset. Meanwhile, the physicist and the engineer continue working on the errant electrode. This is not good.

The tremors started in 1999. I remember pouring a glass of wine and my hand starting to shake. “What’s that?” my wife at the time asked. “Parkinson’s,” I joked. We laughed. I was only 43. It seemed funny.

The shaking went away, but over the next few weeks I started using the computer mouse and eating with my left hand. I didn’t know it, but the Parkinson’s was affecting the fine motor control on my right side. It was subtle, but enough to make me more comfortable as a southpaw. “That’s odd,” I thought. “When did I become left-handed?”

Then I quit surfing. As a Santa Cruz, California, local, I had gone out on the water at Sewer Peak or Steamer Lane almost every day for years. Suddenly I wasn’t catching any waves. I just couldn’t get the nose of my board down, couldn’t coordinate the movements to shift my weight forward and transfer the swell’s momentum to my board. “I’m getting old,” I thought. “Old and fat. And weak.”

But I was getting old too fast. I felt like I was 70. Finally, in 2000. I went to the doctor and got the official diagnosis: Parkinson’s disease. It affects about one person in 100, usually people in their seventies. I was in my forties. That made me more like one in 4,000. That’s like winning the lottery. Whoops, wrong lottery.

Parkinson’s causes brain cells in the substantia nigra (Latin for “black stuff”) to die off. This area is where the neurotransmitter dopamine gets manufactured, and without dopamine, the brain’s circuits start misbehaving. When the substantia nigra is 50 to 80 percent gone, you begin to experience Parkinson’s symptoms: usually tremors but also constipation, stiffness, and depression. You slowly lose smooth motion of all kinds, as well as the ability to feel pleasure. It’s a darkness that covers you.

Doctors can’t give you replacement dopamine to fix the problem, because dopamine can’t cross the blood-brain barrier — the fine mesh that keeps coarse intruders like bacteria out of the brain. Instead they give you levodopa (L-dopa), a dopamine precursor with molecules small enough to slip through the barrier. It’s like flooding an assembly line with partly manufactured goods; if one of the workers is in the mood to make a little dopamine, it’s easy to finish the product. But many of the workers on this particular assembly line are already dead, and the rest aren’t feeling so good. Consequently, production is spotty. And there are side effects. Most of the uncontrolled movements we associate with Parkinson’s aren’t actually symptoms of the disease; they’re caused by L-dopa.

As time goes on and you need more L-dopa to produce any dopamine at all, the side effects become worse. It gets so you can’t walk, your movements are so out of control. But it’s still better than the alternative: no dopamine, leading to paralysis, the inability to swallow, and death.