About Parkinson’s

By Michael Jorrin, "Doc Gumshoe", April 1, 2020

The last time I wrote about Parkinson’s I had not yet become Doc Gumshoe.   It was quite a few years ago, and I was working on a continuing medical education project in support of donepezil (Aricept, from Eisai/Pfizer).   Aricept, as you may know, is one of a very few drugs approved for the treatment of Alzheimer’s.   My particular CME project had nothing to do with Alzheimer’s, but focused on the mechanism of action of donepezil/Aricept, and how it could be effective in minimizing certain of the effects of Parkinson’s.   And it was that mechanism that took me into the thicket of Parkinson’s.   We will make our way into that thicket later on.

One particular little patch of that thicket is why there are two terms attached to Parkinson’s.   Parkinson’s Disease is one term, and Parkinsonism is the other.   Why are there two terms?   Do they basically mean the same thing?   If not, how are they different?  

Here’s what my Harrison’s Principles of Internal Medicine, usually my Bible, has to say on the subject:

“Parkinsonism is a syndrome consisting of a variable combination of tremor, rigidity, bradykinesia, and a characteristic of gait and posture.   Parkinson’s disease is a chronic progressive disorder in which idiopathic Parkinsonism occurs without evidence of more widespread neurologic involvement.”

That would imply that in Parkinsonism, in contrast with Parkinson’s disease, there is evidence of a more widespread neurologic involvement.   But how is that idiopathic Parkinsonism?   

The American Parkinson’s Disease Association, in their website, just says:

“ ‘Parkinsonism’ means ‘looks like Parkinson’s disease.’ To neurologists this means that the person has a somewhat flexed posture, moves slowly, is stiff and usually walks slowly, with small steps and reduced or no arm swing.”

They go on to note that persons with Parkinsonism respond less well to levodopa, a drug that is frequently used not only to treat Parkinson’s Disease, but to confirm the diagnosis – that is, if the patient responds to levodopa, it’s likely to be Parkinson’s Disease, and if not, then not Parkinson’s Disease.

Another distinction is that if a person with the characteristic movement disorder also experiences dementia, then that person is considered to have Parkinson’s disease and not just Parkinsonism.

Unless there’s a need to distinguish one from the other, I will stay with a more general term: “Parkinson’s.” 

What are the symptoms of Parkinson’s?

Let’s start with the obvious symptoms.   These are mostly related to movement; sometimes your muscles are doing things without your telling them to, or else failing to do the things you ask them to do.   You find that your hands tremble even when you’re trying to keep them steady.   Your thumb and forefinger rub together, as though you are rolling little pills.   You may also find that when you try to move your arms or legs, you have to exert yourself to overcome a sense of rigidity.   And sometimes when you move your limbs, instead of a smooth movement, you find that you are moving in little rachety bursts, with stops in between, almost as though your muscles were controlled by an escapement mechanism, like the second hand of an old wind-up clock.   Those types of rigidity are known as “lead-pipe rigidity” and “cog-wheel rigidity.”

Persons with Parkinson’s are most commonly affected by bradykinesia, meaning slowness of movement.   Instead of walking with normal steps and a normally erect posture, swinging their arms in contrary motion with their feet, they take small steps and walk with a hunched-over posture.   Sometimes it looks as though they are running, although with tiny steps.   This is called “festination.”   My guess is that comes from the Latin phrase, festina lente, which means “make haste slowly.”    However, they may also be subject to sudden stops in their motion, as though their feet had gotten stuck to the floor.

Another common feature of Parkinson’s is muddled rotational behavior – for example, if turning from the stove to the kitchen sink requires a quarter turn to the right, people with Parkinson’s are apt to do a three-quarter turn to the left.   Similarly, Parkinsonians standing and having a conversation may appear to be doing a little dance with the person they are conversing with.

As the disease progresses, Parkinson’s tends to bring on postural instability and an impaired sense of balance.   This leads to frequent falls and, in consequence, more broken bones and reduced mobility.

Parkinsonism also affects speech, facial expression, and manual dexterity.   Persons with advanced Parkinson’s tend to speak indistinctly in a monotone and lack facial expression.   And their handwriting tends to get smaller and more cramped as the disease progresses.

Why does this happen?

The precise cause of Parkinson’s is not known, but the question of what’s going on in the brain to bring about the symptoms has at least been answered at the most general level.   When we want to do something – walk, tie our shoelaces, pick up a coffee mug – the instructions go from the motor cortex through a number of brain segments and are sent to the other parts of the body via the corticospinal tracts.   These are sometimes referred to as the pyramidal tracts because of their pyramid-like structure in the medulla oblongata.   

Parkinson’s is sometimes called an extrapyramidal disorder, because those  instructions to the muscles do not come in the normal way through the corticospinal tracts.   There is a loss of dopaminergic projection from the substantia nigra, a part of the brain central to motor control.   And also, there is a loss of dopamine receptor stimulation and an increase in dopamine receptor inhibition.   Inhibition of the thalamus is abnormally increased, and movements initiated by the cerebral cortex are not facilitated.   

(I acknowledge that the explanation above is far from crystal clear.   Perhaps it is enough to say that the transmission of instructions in the brains of people with Parkinson’s is thoroughly messed up.)

One of the mechani