Friday, 8 June 2018

Field Notes from a Medicare Disaster: Seven

Whatever-it-is finally had a name--Parkinsonian syndrome. We kept asking about the difference between Parkinson's Disease and Parkinsonian syndrome: the answers we got described differences so insignificant as to be no difference at all. "A difference, to be a difference, must make a difference" is a rubric I learned long ago when I was studying political theory: medical practitioners might reflect on that when naming q syndromes with the same title as a disease. Parkinsonian syndrome seemed in most respects similar to Parkinson's Disease. Certainly the front line treatment was the same--Sinemet--followed by a few other dubious sounding concoctions, also offered by Big Pharma, if Sinemet proved ineffective. (How could it prove ineffective, therefore leading to these other options, when a positive response to it is the way the clinical diagnosis is confirmed, you ask?  Sorry: no answer.) It was disturbing to learn that none of the drugs on offer were said to alter or even slow the course of Parkinson's, or its same-name syndrome. In addition, these drugs' side effects were known to cause problems, serious problems. Not that anyone spelled those problems out to us, as you will see, other than to offer a prescription for constipation. Was constipation a byproduct of Sinemet or of the disease itself? No one explained.

Here is what we--he, Daughter Number One and Daughter Number Two and I--knew going in. We knew a person who has Parkinson's Disease: a man named Bill. Bill is the father of one of Daughter Number One's public school classmates. He was diagnosed at around age 50. We knew of others who had it too, such as Andy Barrie, formerly the morning voice on CBC Toronto's Metro Morning radio show. Barrie had been forced to retire early due to Parkinson's. We knew he had endured a surgical treatment called Deep Brain Stimulation which is done at Toronto's Western Hospital and is said to alleviate symptoms: heard him discussing it one morning on Metro Morning. (Later I would wonder how he got into that program so quickly: more than two years after my guy was referred to Western's movement disorder clinic, where Deep Brain Stimulation and other methods of coping with the disease and its syndrome are practiced, we still await acknowledgement, let alone information about, where he resides on their waiting list. They don't return phone calls of inquiry. )In addition, my sister- in- law's father had been diagnosed with Parkinson's Disease. However, my sister-in-law's father, an internist, soon realized that this diagnosis was incorrect and properly re-diagnosed himself with another neurodegenerative disease significantly different from Parkinson's. Nevertheless, he too took Sinemet, large doses of Sinemet, which caused numerous problems and yet did not prevent him from becoming so immobilized that he required helpers plus a lift to get in and out of bed. We also knew that Canadian actor, Michael J. Fox had been diagnosed with Parkinson's Disease very young though it is considered to be a disease of aging. We knew he'd set up the Michael J. Fox Foundation to raise money for research. The Foundation maintains a website where things may be learned. On this site I learned that Parkinson's Disease afflicts men more than women, though recent studies of prevalence and incidence are few and far between. Allegedly, the median age of onset is about 60. The incidence is said to be 1 in 100,000, therefore relatively rare. Yet over the next 12 months, two of our female acquaintances, plus one much older male relative, would also be diagnosed with Parkinson's Disease.  In that same period no one we knew was diagnosed with heart disease, which is much more common. Parkinson's may be less rare than we suppose, or its incidence is changing. Regardless, if it is a disease of ageing, as the Baby Boomers enter their final laps around this good Earth, the actual number of sufferers is going to explode.

My guy's symptoms were not like theirs, which is why, we were told, the diagnosis of Parkinsonian syndrome applied to him. It means that his symptoms are atypical. Yet those with the Disease also had symptoms unlike each others'. According to the websites we visited, atypical is typical of Parkinson's. For example, our friend Bill had serious tremors of the hands and arms, could not stand erect, had an immobile face and speech so profoundly altered he was often difficult to understand. Yet he walked quite well. Andy Barrie had voice issues but his speech was perfectly understandable though his voice timbre changed. Michael J. Fox displayed jerky, spasmodic movements of the head and neck, arms and legs. Our older relative, formerly an avid golfer, moved very slowly and developed the facial mask. The two women friends have hand tremors. Essentially, my guy is atypical among the other atypicals. His voice remains essentially normal, although sometimes it is too soft, and his face is as mobile as ever. He displays no jerky movements, no tremor of the hands, no pill rolling movement of the fingers, another symptom that appears on the symptom lists posted on various websites, along with difficulty swallowing. He swallows just fine. He had trouble maintaining his balance, which seemed to get worse with the Sinemet, not better. He had trouble walking, which also got worse with the Sinemet. Soon he had freezing moments too. Also, instead of a slow onset of symptoms, my guy went from not quite right to quite wrong in no time flat, especially after that second fall.

As I read through various websites, I was fascinated to note significant differences between those based in the US and those based in Canada. On a Canadian Parkinson's website it clearly states that no specific cause is known, no genetic component is known either, though interesting genes have been identified in association with it, and there might be a higher risk for children if a parent has it. On a US Parkinson's website, considerable space was devoted to possible causes, including traumatic brain injury and poison by pesticides, not mentioned on the Canadian sites. What are we to conclude from these differences? 

Wikipedia explains that both Parkinson's and various Parkinsonian syndromes are problems derived from the death of dopamine-producing neurons in an area of the brain known as the substantia nigra (translation from the Latin: black substance) which itself is part of an area called the basal ganglia, which processes movements, automatic and otherwise. The substantia nigra is divided into two parts which have different functions and employ different chemical signal systems, one involving dopamine (which, when released, gives pleasure as well as transferring signals and so has a role in addictions as well as movement) and GABA which inhibits/disinhibits -- in other words, stops/starts motions that would otherwise be continuous. The dominant theory is that it takes a long time for a person to be affected by the loss of dopamine producing neurons in the substantia nigra, that by the time symptoms appear, 80% of these cells have died. How do we know this? Apparently from the study of animal models -- rodents in which the symptoms of Parksinson's have been induced by injecting them with certain chemicals that destroy these cells. They are "sacrificed," meaning killed, and dissected, and neuron loss estimated. Human studies of the brain are only done after death on those diagnosed with Parkinson's who donated their brains to science. But the human studies, like the rodent studies, are problematic: dead donors tend to be older, and the brain shrinks with age so it is possible the loss of these neurons attributed to the disease is actually simply a product of  the aging process.

In other words: the more we read, the more it became clear that Parkinson's and Parkinsonian syndrome are names for a grab bag of symptoms which overlap. Some symptoms don't appear to fit the substantia nigra neuron theory. What does the death of dopamine-producing neurons have to do with the disturbed sleep and hallucinations which afflict some who have Parksinson's? Or are these symptoms the product of the drugs, such as Sinemet, which contains levodopa, a molecule that supposedly is a dopamine precursor. In other words, does Sinemet cause this symptom? The loss of the ability to smell is also listed as an early symptom of Parkinson's. But what does loss of information from the olfactory bulb have to do with the dying cells in the substantia nigra? Other symptoms listed on the Mayo Clinic's website include a stooped stance. One one site I found an image of a man with shoulders slumped forward which is exactly the way my guy stood before his second fall. It was this posture which first aroused my concern. But he doesn't stand like that anymore. Why?

As I read some of the symptom lists I found myself raging at my computer: why in hell had that first neurologist ruled out Parkinson's when my guy clearly displayed some of those symptoms? If he hadn't ruled it out, and if my guy had been started on treatment early, might he have avoided those terrible falls and concussions? On the other hand, one symptom that appeared on everybody's list excessive sweating? Yet my guy no longer sweats at all, which causes him to overheat and droop like a flower on a hot July day.

Eventually I gave up on websites and went after recent scientific papers. I found that there was interesting work going on at the University of Saskatchewan, in association with Harvard, which proposed introducing stem cells into the brain to replace those dying dopamine producing neurons. There were other trials going on elsewhere. We thought we should try to join a stem cell clinical trial.

The Canadian guidelines on treatment showed that the drugs on offer have dire side effects. All pointed out that when taking Sinemet one must be careful to leave about an hour between ingestion of the drug and ingestion of proteins or iron because both interfere with its absorption. Some sites suggested that those who suffer from Parkinson's should avoid dairy altogether and load up on carbs until the last meal of the day. They also mentioned that unexplained weight loss was a symptom of Parkinson's. So we became religious about the timing of drugs versus protein and vitamins.

Soon these websites prescribing diet changes led me down a series of rabbit holes suggesting other causes for Parkinson's, causes not shown on Parkinson's Society websites. I found papers by an Australian physician who thought he could show that Parkinson's may be caused by a massive die off of certain bacterial colonies in the gut (which interact with neurons in the brain), due to an infection by H.pylori. When my father was still practicing medicine, H. pylori was discovered to be the major cause of stomach ulcers. Instead of surgery,  the treatment became an antibiotic. The Australian physician determined that many of his Parkinson's patients had had major gastric problems before their Parkinson's symptoms appeared. He found that many had had H. pylori. There is an easy test which shows whether a patient has been exposed to it.  After treatment with a complex round of antibiotics, his patients showed marked improvement in their Parkinson's symptoms as the bacterial colonies in their guts became more diverse.

I soon found papers showing that the bacterial species in the guts of people suffering from Parkinson's are less diverse than the bacterial colonies in the guts of healthy people.

Bob's your Uncle, I said to my guy. We need to get you tested to see if you ever had an H.pylori infection, like back when your gut was going nuts a few years ago. If so, there's an antibiotic regimen to try.

I then got in touch with an expert on the behavior of bacterial colonies, a man I had interviewed for a book called SMARTS, one of the leading geneticists of his generation. He had argued that bacterial colonies, as opposed to single bacteria, display intelligent behavior and communicate with each other. I explained that I wanted to know what a normal distribution of bacterial colonies in the human gut might be. I explained why I was interested, asked for papers to read. He responded by saying he had just been diagnosed with Parkinson's himself.

By then, we had found a new family physician associated with St. Mike's. Luckily for us, she had been a student of neuroscience before she went into medicine. We explained at his first appointment that we wanted to explore several alternatives to standard Parkinsonian syndrome treatment. We explained about the stem cell trials. If the dopamine-producing neuron death theory is correct, we said, it seemed to us that stem cell replacement therapy might be really effective.  She said she knew the man leading the stem cell work at University of Saskatchewan and would write him to ask if my guy could join a clinical trial. When we explained the H. pylori thesis, she also ordered an H.pylori test. It came back negative.

It was about then that we finally got our first appointment with the neurologist assigned to his case at St. Mike's that February. The appointment was early in the summer. By then, we had read that we needed to be careful to leave an hour between eating proteins and iron and taking Sinemet. By then, he had gone off dairy. By then, we had followed the H.pylori trail to a dead end but were pursuing the stem cell ideas. By then, we had also heard that the right exercise guided by a physiotherapist knowledgeable about Parkinson's could help recruit stem cells to the substantia nigra to replace dopamine producing cells that had died off. We were also interested in Dancing With Parkinson's and Boxing With Parkinson's. We hoped for better guidance from the neurologist.

The neurologist came into the waiting area and called his name, then turned and walked down the long twisting hallway to his examination room. My guy was exhausted by the time he got there. He asked if I could sit in. Sure, the neurologist said, but there was no chair for me so I leaned against the wall.

The neurologist is a silver haired man of about 60 who wouldn't get a second look on a golf course. He dressed like a golfer. That kind of shirt. Those kinds of pants. But he was as sociable as a prison guard. I was shocked by how far he deviated from my father's methods of greeting patients to make them feel comfortable. There were no jokes, no friendly questions. I expected him to offer his hand to shake. Nope. Finally, after my guy made it into a chair, he had him get up again, and show him how smoothly he could do it. He seemed very pleased with his speed. He felt his arms, looking for rigidity, asked him to move his fingers in that pinwheel fashion.When he was done, I shot a look at my guy who had given me permission to ask the questions. He gave me the high sign to begin.

So we have a few questions, I said.

Such as, he said.

Well, we've been told that he will do better without eating any dairy and so we've been doing that.

Don't ask me questions like that, he said. I'm no nutritionist.

But we read that it's a problem to take Sinemet with protein, it inhibits absorption of the drug.

Oh, he said. First I've heard of that.

Well that was surprising as most of the websites went on and on about it.

So we are going to do physiotherapy if you think it will help. Can you make recommendations about that? And can you refer us to a movement disorder clinic? The one at Western? Or how about Baycrest?

I've heard exercise is good, he said.

That response seemed very vague to me. As vague as his answer on dairy. Yet I charged on. So the other thing we're very interested in is stem cell therapy, I said. We know there is a clinical trial that's going to happen soon in Saskatoon.

Where's that? he said.

At first I thought he was joking. Then I realized he wasn't, he didn't know that Saskatoon is the location of the University of Saskatchewan which he appeared to be unfamiliar with as well.

My guy and I exchanged looks. His eyes said, don't bite. Be nice. We might need this guy.

So I explained where Saskatoon is, and that it is the location of the University of Saskatchewan where a senior neurosurgeon/neuroscientist was working up a clinical stem cell trial in association with a group from Harvard. He seemed to have heard of Harvard.

So have you been following the papers suggesting that stem cells might replace dead dopamine-producing cells? I asked.

No, he said.

If you're interested, I could send you the links.

Not really interested, he said.

By that point, I was having trouble locking down my temper. He seemed to find my questions faintly amusing but not worth considering.

I decided to switch direction and ask him something he could easily answer.

Can you please tell us something about the narrative arc of this disease?

He looked blank. You know, I added, what we can expect. Like can we travel?  Can he get on a plane for business if he has to?

Oh I wouldn't cross any time zones, he said.

Why not?

Confusion, he said. But you could go to Florida if that's what you're asking.

I wasn't asking about Florida. I had Europe and the Middle East in mind. So I asked him again what we could expect as the disease took its course. I was thinking he would say something like, you can expect a gradual decline, a gradual worsening of symptoms over the course of several years...

Here's what he said: "Worse."

And with that, the appointment was over.

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