You Never Miss the Dopamine Until the Brain Runs Dry

What a piece of work is a man, how noble in reason, how infinite in faculties, in form and moving how express and admirable, in action how like an angel, in apprehension how like a god! the beauty of the world, the paragon of animals—and yet, to me, what is this quintessence of dust?

Hamlet , Act II, Scene II, Page 3

William Shakespeare

I know the Bard wasn’t writing about, and Hamlet wasn’t speaking about Parkinson’s disease here.  But this verse came to my mind after today’s round of physical therapy .

What an ASTOUNDING piece of machinery we are.  Whether created by a benevolent God or formed by chance through one cosmic accident after another, what a WONDERFUL thing the human brain is.  Wonderful, mystifying, marvelous and terrifying all at once.

I think of all the people on the planet, going about their daily business.  Going here and there without giving the slightest thought to the tenuous nature of the delicate, silky spider web that keeps their brain functioning properly.  So many things that can go wrong, so many things that DO go wrong on a daily basis to millions of people, whether through their own actions or by no fault of their own.

Riding with my wife to the mall today, I saw people walking, holding hands with their children, taking long, striding steps.  Do they realize what’s INVOLVED in that?  Of course they don’t.  I never considered it before being diagnosed with Parkinson’s.  Neither did you.

Think about it now.  Think of the various balance of chemicals your brain is supposed to produce on a moment-by-moment basis.  Something gets a little out of kilter, not enough serotonin, perhaps, and you get depressed.  You can’t sleep.  Or you sleep too much.  You either see a doctor to replace the lost chemical, to enhance the receptors in the brain to fool it into thinking it’s getting MORE of the lost chemical than it actually is.  Or you ignore it, the depression gets worse, you sink into a dark melancholy, and in the worst case, you end your own life.

Dopamine is one of those tenuous, delicate spider webs upon which the smooth movement of the body depends.  When you consider it pragmatically, what is the body if not solely for the purpose of getting the brain from place to place?  To keep the heart beating so that oxygenated blood can keep your brain alive, so that the nutrients you absorb keep all the working parts of the machine working so they can follow the orders your brain gives to them.  Your eyes and ears and nose and tongue and skin transfer vital information to your brain which will then decide how the body should react to whatever stimulus it is you are feeling so you’ll know whether or not to flee from the stimulus or to embrace and seek more of it.

Dopamine is what makes that part of the body work so smoothly.  By the time you start to notice “something ain’t right” in Parkinson’s disease, around 80 percent of the cells in your brain that make this vital chemical have already died, no longer able to create this all-important neurotransmitter, this “lube oil” that allows impulses created by your brain to jump from nerve ending to nerve ending from the point of origination in your brain (“Move left foot!”) to the muscles the brain is attempting to command, (muscles in leg contract causing foot to move in accordance to the orders it receives), back to the brain (Message received, foot has moved.)

When you walk, do you THINK about it?  Of course you don’t!  Who does?  Other than making the conscious decision to walk faster or to run or to stop because the “Don’t Walk” sign is lighted, the act of taking normal step after normal step is something that doesn’t cross your mind.  And why should it?  Your BRAIN is controlling it.  That part of your mid-brain that regulates everything, it sends out the dopamine that is absorbed by the dopamine receptors on the neurons in your brain and the signal transmits smoothly, without conscious effort.

When the dopamine is gone, so is that fluidity of movement.

In advanced Parkinson’s disease, speaking for myself, I still do not think about every step I take.  Because my brain is no longer producing sufficient amounts of that “lube oil” to ensure smooth transfer of brain impulses from neuron to neuron, the muscles that control the motion of my legs do not get the correct instructions.  Imagine sitting at the microphone at a radio base station.  You send an order to a squadron of attack jets.

“DROP YOUR BOMBS ON THE MUNITIONS DUMP, BUT BE CAREFUL BECAUSE THERE IS A SCHOOL HOUSE AND A HOSPITAL WITHIN THE IMMEDIATE AREA.”

Because the message you sent is garbled in transmission, what the jet pilots hear is…

“DROP… BOMBS ON… SCHOOL… AND… HOSPITAL… AREA.”

Tragedy ensues.

In Parkinson’s disease, for whatever reason, different parts of the brain react in different ways to this lack of dopamine.  You can take a dopamine substitute, like a levodopa/carbidopa combination, that synthesizes into dopamine when it crosses the blood/brain barrier.  But that only lasts for so long and after years of this treatment, your brain betrays you by accepting the dopamine replacement and causing you to twist and writhe uncontrollably with dyskinesia.

You can electrically stimulate a part of the brain called the subthalamic nucleus to jam the erratic signal it gives out when it doesn’t get the dopamine it wants.  That smooths out your movement to a degree, relaxes the rigid muscles somewhat.  But it’s not a cure.

And then, there are the parts of your brain that do not react to the dopamine replacement.  Why?  Nobody knows yet.  Balance.  Gait.  Speech.  Swallowing.  For some reason, they are resistant to dopaminergic treatment.  Take all the levodopa your doctor prescribes, get yourself some deep brain stimulation.  It does a lot of good in the areas where it can help.  It does nothing in the areas it can’t help.

I think back to this morning’s physical therapy.  I was on the treadmill.  We had it going 2mph.  While holding on to the hand rails, I am able to take long, striding steps.  Why?  Because the mid-brain is receiving the signal from my hands that we are holding on to something secure and are not likely to fall.  The mid-brain sends out a signal that all is well and normal stepping is possible.  I let go of the hand rail.  The mid-brain loses that “safety signal” and orders the legs to take smaller steps to maintain my balance.  Gone is the “heel/toe” step of a normal person.  I am taking shorter, flat-footed steps.

The therapist slows the machine down to 1mph.  I grab the bar.  Without any conscious effort, I am now able to take long, graceful striding steps.  It feels wonderful.  I’m stretching muscles in the back of my thighs that don’t get used regularly.  He tells me to let go with one hand.  There’s not a whole lot of difference, except I can no longer take the longer, exaggerated, striding steps.  The mid-brain feels confident that we’re still holding on to something, but we’re not as secure as we were.

The therapist tells me to let go of the rail one finger at a time.

Four fingers, not much change.

Three fingers, the steps get shorter, but we’re still going heel/toe.

Two fingers, one finger…

The steps are shorter and shorter.  I’m walking flat-footed.

Let go entirely.

The mid-brain believes we are unstable.  Therefore, we must take short, Frankenstein-like halting steps.  Flat-footed.  And, at the slower speed, the difficulty is compounded by having to spend more time on each foot than we did at the higher speed.

Clomp!  Clomp!  Clomp!  Clomp!

I focus.  I concentrate.  I try my level best to extend my stride and return to some semblance of the proper heel/toe step.  My mid-brain acquiesces, but only a little.  The stride increases, but it is a struggle.  My thighs are tight.  My muscles just will not stretch to allow it, because my mid-brain is still sending the signal that we are in danger of falling…

Until I grab the rail again.  Then all is well.  With no conscious effort at all, the stride lengthens, we return to the normal heel/toe stepping pattern.

Why does the mid-brain do this?  Nobody knows.  Why does my brain not send orders to my muscles to stop me from falling if I tip too far forward, backward, left or right?  It probably does.  But the muscles just don’t receive the messages.  Instead, they bomb the school and hospital.

Why does the lack of dopamine cause the frontal lobes of the brain to malfunction, leading to something called executive dysfunction and for up to 80 percent of us with Parkinson’s, outright Parkinson’s disease dementia?  I’m a smart person.  I’m as smart as I ever was, probably even smarter.  So why, after taking ibuprofen for ankle pain last night, did I try to put the bottle cap onto the glass I drank the water from?  “Cap no go THERE,” my brain said.  “Cap go on BOTTLE!  Not GLASS!”  Why have I, more than once, found myself looking in the mirror with my toothbrush in my left hand and a tube of Preparation H or some sort of antibiotic ointment or anti-itch cream in my right hand instead of toothpaste?  Why did I take a pill, drink half the glass of water, dump the water on the counter before putting the glass into the sink?  Why did I recently pull some labels (those long, sticky “size” labels you get on new sweat pants) and try to flush them in the toilet?  Why did I try to flush an empty toilet paper roll?  Why did I pour freshly ground coffee beans into my wife’s cup instead of into the coffee machine’s filter?  Why did I think that a group of little ornaments dangling from our car’s rear view mirror was a kid my wife was about to run over?  Why did I once see a guy standing near the off ramp on the express way, only to have him vanish like a mirage when we got closer?  Why do I depend on an audio alarm to remind me to take my pills?  Why did I lay awake the other night because I couldn’t remember the opening segment of “The William Tell Overture” — a piece of music I know as well as my own name — and had to get up, find a copy on iTunes and listen to it before I could get any rest, which it turned out I couldn’t get anyway because I forgot to take my nightly sleep pills?

There’s a lot of “why’s” in the alphabet of Parkinson’s disease.  Does anyone have the answer key to this persistent quiz?

I share this info, not with a sense of sadness, not with a sense of regret, without the slightest hint of depression.  I share it because it confirms something I learned too late in life.  That is, what a wonderful machine we are, and how dependent we are on the tiniest things.

As the Bard of Avon wrote a page earlier in Scene II, Act II of Hamlet…

…for there is nothing either good or bad but thinking makes it so.

Or, to put it in the 21st Century vernacular…

It is what it is.

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