Can I just say how much I LOVE these old papers! Today I present to you one of the best historical papers neuroscience has to offer, and a real classic in the field.
Parkinson, J. “An Essay on the Shaking Palsy”. Published in Neuropsychiatry classics, Journal of Neuropsychiatry and Clinical Neuroscience, 14 (2), 2002. Originally published as a monograph in 1817. (I cannot for the life of me find the DOI.)
I’m sure that everyone has at least heard of Parkinson’s, otherwise known as Parkinson Disease or PD. It affects about 120-180 out of everyone 100,000 people worldwide, though in some populations it is more prevalent than in others. Though that doesn’t seem like too many, when I go into children’s classrooms to talk about neuroscience, it seems like every child knows someone or is related to someone with PD.
Now obviously, Parkinson didn’t call it Parkinson’s disease, though it would have been a magnificent feat of ego to say “I would like to characterize a disease that I shall name after Myself, and it shall be called ‘Parkinson’s’ disease, because ‘James’s disease’ just didn’t sound as good”. No, Parkinsons’s has been diagnosed since the time of Galen, but James Parkinson was the first to document the symptoms and to clearly distinguish them from any other disease. Parkinson would have known the disease as “paralysis agitans”, or the shaking palsy. The neurochemical changes behind Parkinson’s weren’t identified until 1950, by Dr. Carlsson, the discoverer of dopamine as a neurotransmitter in it’s own right (not just the precursor to norepinephrine), who got the Nobel Prize in 2000 for the finding.
The Shaking Palsy
“Shaking Palsy: involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the turnk forwards, and to pass from a walking to a running pace: the senses and intellects being un-injured.”
Of course, Parkinson wasn’t entirely right in his diagnosis, where he thought the disease originated in the nervous system, and how it was caused, but he described several case studies in his monograph, and many of them clearly highlight classic PD symptoms. He was also the first to give a clear description of the progression of Parkinson’s.
At first, the disease is “slight and imperceptible” and the patients usually didn’t go a doctor with the problem, and so what Parkinson most often saw were the advanced cases. The first symptoms he saw were weakness and trembling in one limb. Usually the symptoms started in the arms, but every once in a while he would see tremor start in the head. After a year or two, the symptoms will spread to the other hand or arm. Parkinson classified this as the first stage of the disease.
After a while the patient starts to notice that their posture isn’t as great as it once was. Usually a patient wouldn’t go to the doctor about it, because they had experienced “but little inconvenience”. But the patients usually begin to see a doctor after they start to have problems writing, and also when they begin to have severe problems walking, taking on the shuffling walk that is characteristic of PD. They also begin to have problems with motor coordination, becoming unable to successfully feed themselves, because they cannot raise and fork to their mouth without it shaking too much.
We don’t see severely advanced PD as often now, because of the medications and treatments that are now available (patients can hide their symptoms with the medication for a significant amount of time), but Parkinson got to see the full continuation of the disease. When Parkinson’s becomes more advanced, the patient starts to have major difficulty sitting still, because each time they sit still one, part of their body is going to start to shake. It gets worse and worse, until the patient jerks into another position, and then the shaking will begin somewhere else. This makes patients with PD want to walk, which relieves the tremor a little, and will distract them because it takes so much effort.
Unfortunately, after a while walking won’t even help the symptoms. Their posture gets worse, and soon they are unable to stand up straight, and have to walk on the balls of their feet, and are thrown continuously off balance. Because they are thrown so far forward, the patients have to shuffle faster and faster to retain their balance, and end up in a shuffling run, which of course makes it even harder avoid tripping and falling. Parkinson found several patients as case studies after he found them literally running down the street, with footmen running backward in front of them to keep them from falling.
In the advanced cases that Parkinson saw, sleep started to be affected. They shake so much, even in their sleep, that some of the patients shook the whole room, and woke up constantly in fear. The patients described horrible constipation, with “the expulsion of faeces from the rectum sometimes requiring mechanical aid”, until they lose control over that, as well, and can’t control either urinating or defecating. After a long time with the disease, patients could no longer swallow, suffered weight loss, drooled constantly, and were completely unable to sleep. When they finally died, Parkinson believed that it was the result of starvation, delirium, and insomnia that finally killed them.
None of the patients that Parkinson saw were less than 50 years old, and so he diagnosed it as a disease of old age, thought now we know that the first symptoms can show up as early as age 35.
Parkinson’s is classified as a Central Nervous System motor disorder, though it has lots of symptoms that are “extra-motor” or outside of the motor system. There is still a great deal of controversy as to what exactly happens to cause the symptoms known as Parkinson’s. It’s a pretty big list of symptoms, but the big ones are below:
The set of symptoms that doctors will look for in diagnosing Parkinson’s goes under the mnemonic TRAP:
Tremor: This is the symptom that everyone thinks of when they think of PD. The tremor (shaking), usually is the first symptom to be described, and usually starts on one side of the body (usually a hand), though it can also start as a shaking of the head. Because PD is a progressive disorder, it will then spread to the other side of the body, and then to other body parts. It’s worst at rest.
Rigidity: This refers to stiffness of the limbs, and when someone else moves the arm or leg while it is at rest, you’ll see kind of a ratchety movement, with the limb moving up and down in stages.
Akinesia/bradykinesia: bradykinesia refers to slowness of movement, while akinesa refers to absence of movement. The problem here is difficulty instigating a movement, but once they have successfully begun a movement, they often are forced to speed up to correct for balance problems until they are nearly at a shuffling run. This is called “festination” which, though it’s a terrible symptoms, is a pretty cool word.
Postural Instability: In PD, the postural reflexes fail, and the patient takes on a hunched posture, leaning forward, which has a negative effect on balance and can lead to falls.
Other major symptoms include:
Shuffling: In PD, patient’s feet barely leave the ground, and door lintels and other things close to the ground will cause them to trip and fall.
Drooling: This symptom happens in the more advanced stages of PD, and is usually a byproduct of stooping and having problems swallowing.
Dysphagia: Problems swallowing.
Impaired coordination: in severe untreated cases, the patient will not even be able to pick up a pen and write without major effort.
Even more symptoms include: speech problems with slowed speech, slowed reaction time, insomnia, dementia, dizziness, urinary incontinence, and constipation.
Obviously this is a pretty rough group of symptoms, and since it’s progressive, a patient must suffer more and more of them as time passes, and the disease can progress for 20 years or more. Right now, we don’t think the disease is terminal in and of itself. And now of course there are several treatments available (including Levodopa, deep brain stimulation, and dopamine agonists).
Where Dr. Parkinson went wrong, however, was in searching for the cause of the symptoms, though he was right that it was clearly a nervous system disorder, rather than a muscle problem. He was correct to infer that, since the tremor was widespread to all the limbs, it was not caused by neural problems to a specific hand or arm, but had to originate in the central nervous system.
However, he incorrectly placed the seat of the disorder in the medulla oblongata, after he observed that several patients with head trauma to the medulla developed Parkinson-like symptoms. Now we know that PD involves the destruction of dopamine neurons in the substantia nigra, which is an area of the midbrain above the pons. The dopamine neurons of the substantia nigra supply dopamine to the striatum and influence movement via a direct pathway. During PD, dopamine neurons are destroyed, and the direct movement pathway is unable to function, resulting in predominance of the indirect movement pathway. Right now there is controversy as to whether the symptoms are a result of indirect pathway predominace or the direct lack of dopamine neurons.
Unfortunately, Parkinson didn’t have any idea as to how the shaking palsy was to be cured. He said that, if caught early enough, he could cure PD with “leeches, stimulating fomentations, and a blister”. Basically, he leeched them, cleared the bowels as much as possible, and then applied a hot cup to the back to the neck to create a large blister, and then released the pus. Obviously, this had no real effect on the disorder, and if the patients noticed any lessening of symptoms, it was probably a placebo effect. Now we know that dopamine replacement alleviates the symptoms of Parkinson’s, and can allow patients to exist with the condition for a very long time with relatively few problems. When the dopamine cells are depleted past the point of dopamine replacement therapy, techniques such as deep brain stimulation can also be used to help patients.
Unfortunately, there is still no cure, and few causes have been found. Parkinson had several patients propose causes. One said that he had been forced to sleep on hard damp ground for some time, and this gave him his disease. Another said that it was his “indulgence of spiritous liquors”, though most seemed to look at the problems as one of those things you get when you’re old.
Recently, many different things have been implicated in the causes of PD. There appears to be a genetic component to the disease in some cases, and some researchers have found symptoms following direct chronic exposure to pesticides. There have also been cases of Parkinson’s found after drug abusers ingested contaminated meth. The drug turned out to be MPTP, a chemical which facilitated the first model of Parkinson’s Disease and has led to a lot of new insights. That case was documents in The Case of the Frozen Addicts, a book which I am DYING to get my hands on.
I definitely recommend Parkinson’s monograph, partially because it’s always interesting to read the old lit, and also because his case descriptions are incredibly vivid and empathetic. Although his methods of treatment probably brought little real cure, he was a compassionate physician and a brilliant man of his time, who put together all the dots to define what we now call Parkinson’s Disease.
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