The Search for Answers - "Be careful what you ask for..."

In my last post, I talked about my initial diagnosis, and my reaction to a new medication. The dizziness eventually did depart, but the obvious therapeutic benefits never did arrive. After six weeks, I visited the neurologist again and reported the news. And over the next three months, so it went with Azilect, Sinemet 25/100, Sinemet CR, and Stalevo. As an added benefit, the levodopa drugs (Sinemet and Stalevo) caused violent nausea and vomiting within 20-30 minutes of every dose. Side effects were no problem – I had those by the truckload. But still no therapeutic benefit – I still had the same stiffness, slowness, unsteadiness, and lack of fine motor control that had brought me to this point to begin with.

After a very unpleasant trial period with Stalevo, I called the doctor’s office again and asked to speak to him. I needed information. The drugs don’t appear to be working; what does this mean? Is the diagnosis a mistake? Do I have a brain tumor after all, or do I just need to eat more green vegetables?

The doc called back quickly, and as I stood in the outside patio area of a Taco Cabana restaurant, he gave me his rundown.

1. I clearly had Parkinsonism. The physical symptoms were unmistakable; the cause was undetermined.
2. It didn’t appear that I was responding to medication – that was called drug-unresponsive Parkinsonism.
3. There were several things that could be the culprit. “Space-occupying defects” in my brain had been ruled out, as had several other odd possibilities such as normal pressure hydrocephalus.
4. There was something called “atypical Parkinsonism” that could be responsible. Only time would tell. We would have to wait.

New unfamiliar technical-sounding terms are almost irresistible to me, so I went to the Web again (I hardly remember anymore what it used to be like to use a library). This time, wanting to go upscale, I hit the Mayo Clinic website. I found new terms there like “corticobasal degeneration,” “multiple system atrophy,” and “progressive supranuclear palsy.” All these are atypical Parkinsonian syndromes that don’t respond to anti-Parkinson’s meds well or at all. And their common characteristic is a rapid degeneration of physical and mental function, ending in death.

I was stunned (again; you’d think I would be a little less shockable by this point). Only months ago I was happily unaware, spending time on the weekends with scuba classes, enjoying my family and my work, and living a relatively normal life. Today, I “would have to wait” to find out if I had a disease that would steal my health, my mind, my body, and then my life. I did the only thing I could think of to do – I sought another medical opinion.

I did some research to find out who I should see. There were multiple options, including road trips to the Mayo Clinic(s), Washington, Cleveland, Houston, Dallas, and many other places. There were excellent referrals right here in San Antonio, though, and I had learned enough to know I wanted to see a movement disorder specialist (a neurologist who is board-certified in movement disorders like Parkinson’s), so I made the appointment.

At my first visit with him, he listened patiently as I gave him a rundown on my life up to that point, and he asked a number of very pointed and probing questions about my previous drug challenge, my symptoms, and my history. He asked questions that I found a little strange, such as, “does your arm or hand ever do things on its own, or feel like it doesn’t belong to you?” and then administered another “hokey-pokey” exam, this one more comprehensive than any other. I walked up and down, tapped, dragged, clenched, and twisted as directed, wishing for a little music to make my timing better. He also snuck up behind me and pulled on my shoulders suddenly – I didn’t realize at the time that it was part of the exam, and just thought he had a unique way of interacting with patients.

We then sat down for a discussion. He was very clear, very straightforward, and very direct.

“Well. It’s clear to me that you have Parkinsonian symptoms, and they’re markedly asymmetric, which raises some questions. There are some possibilities we have to rule out, so here’s what we’re going to do…”

I left his office with an order for a SPECT brain imaging scan, an interesting specimen collection process to rule out Wilson’s disease (my refrigerator will never be the same), an additional blood test to eliminate several metabolic possibilities, and an extraordinarily detailed day-by-day plan for conducting a drug challenge with standard generic carbidopa-levodopa 25/100 on steadily increasing doses until I saw an effect. He was clear that, given my history, I would probably have nausea and vomiting problems from the carbidopa-levodopa, but that I should just bear it as well as I could in the interest of conducting an effective challenge.

He was absolutely right on all counts – the SPECT scan showed no brain blood flow abnormalities, the test for Wilson’s disease showed no excessive copper levels, and the other blood tests showed nothing more significant that a Vitamin D deficiency (which, according to some, is correlated with Parkinson's). All that remained was to judge my response to levodopa.

For some, levodopa is like flipping a switch – the effects are clear and obvious. For me, the effects were certainly clear and obvious, but the problem was that the only effect I saw was horrible nausea and vomiting after every dose. The doc added extra carbidopa to my daily regimen, which made a radical difference. Carbidopa keeps the levodopa from converting to dopamine prematurely in the body – when it does, it stimulates a region of the brain outside the blood-brain barrier called, unsurprisingly, the “vomiting center.” Go figure. I wasn’t getting enough carbidopa, which resulted in the predictable effects that I was experiencing.

As an interesting aside, a neurologist who came to speak at one of our support group meetings told a story about drug names. Apparently, for many of the drugs that we take, the name has significance. Since it was first used therapeutically, it’s been known that levodopa by itself causes violent nausea and vomiting. When it’s added to carbidopa, the combination has the brand name Sinemet. The doc pointed out that the name was composed of two parts–“sin,” which means “without,” and “emet,” which means, “to vomit.” Interesting, I thought; and even more interesting that it works for everyone but me.

After a long, careful increase in medication dosage until I reached 1200mg of levodopa (12 tablets of 25/100 mg carbidopa/levodopa per day), I saw my neurologist for another hokey-pokey exam.

His assessment – I was clearly much improved in motor function from the levodopa. He guessed that my previous violent reaction to the medication didn’t leave enough of it in my system to be effective. He also said that the more structured test approach to the drug challenge which gradually raised the medication to moderately high levels was much more effective for assessing my responsiveness.

The upshot of all this activity was that I apparently had “young-onset idiopathic drug-responsive Parkinson’s disease.” Nothing is ever sure in this new world I found myself in, but that probably meant I didn’t have PSP, CBD, MSA, or any of the other Parkinson’s Plus syndromes with the much more grim prognoses. Never able to leave well enough alone, though, I had to ask him, “what’s the possibility that this isn’t really even Parkinson’s? “

His response will stay with me for the rest of my life: “You need to come to terms with the fact that, if you don’t have Parkinson’s disease, the only other possibilities are much worse.” I had moved from being a normally healthy middle-aged man into a place where Parkinson’s disease was the best I could hope for. What was I supposed to do now?

Next time – family, friends, and colleagues: the ecosystem of the newly diagnosed PWP.

Additional note – On the advice of my neurologist and neurosurgeon, I’ve decided to have deep brain stimulation surgery. I’m young for it, but it makes sense, given where I am with the progression of the disease and the way I respond to medication. I’ll be writing about my journey with the DBS process over the course of the next several months, both before and after the surgery. I’d welcome your comments or observations –

So, What Happens Now?

Last time, I described the long, crooked path I walked to finally arrive at an initial diagnosis. It was a slight relief to finally have a label for the things that had been happening to me, and as I was leaving the neurologist’s office from that momentous diagnostic visit clutching my little bag of Azilect samples, I remember thinking to myself, “Well. Parkinson’s disease. Maybe that’s not so bad. Michael J. Fox has Parkinson’s, and look how cool he is. And if I only have to take one of these pills a day, I can do that. Yeah – Parkinson’s; at least it’s not a brain tumor.”

My wife was out of the country on an extended academic trip to Africa, so I had time, I told myself, to do a little research and find out how I was going to manage this thing. One little white pill a day and some minor lifestyle changes – no problem, I figured. I’d done harder things before.

My sense of relief lasted until I got home and sat down in front of the computer. I mentally flipped a coin and it came up “Wikipedia,” so off I went, typed in “Parkinson’s disease,” and started reading.

“Neurological disorder…progressive…degenerative…incurable…cardinal symptoms…tremor…bradykinesia…akinesia…cogwheel rigidity…balance disturbances…autonomic nervous system…substantia nigra…dopamine deficiency…striatum…executive function…cognition…depression…apathy…digestive disturbances…sexual function…oily skin…keratitis…levodopa…carbidopa…COM-T…MAO-B…rasagiline…selegilene…entacapone…dopamine agonist…dyskinesia…amantadine…artane…dystonia…side effects…compulsive behavior…hallucinations…vomiting…blood-brain barrier…on-off…dose failure…aspiration pneumonia…disorientation…Apokyn…freezing…Lewy bodies…dementia…deep brain stimulation…isolation…fear…loneliness…quality of life…”

I went from web site to web site for hours, scarcely believing what I was reading. I finally stepped away from that session with the computer after about 10 hours, with a myriad of new terms and concepts buzzing my head and a deep sense of unreality. How could this be? What had I done wrong? I was even surer that this must be a mistake – Parkinson’s disease was serious, and except for minor illnesses and middle age, I was healthy. This can’t be right.

I had received direction from the neurologist to “titrate up” (the first but not last time I heard that term) by taking ½ of a 1mg tablet of Azilect each day for a week, and then taking a full tablet every day for four weeks. Then I should call him back and we’d see what’s what. Simple and easy, I thought, and this certainly will show I don’t have this thing.

I didn’t have a clue what to expect, so I took my first ½ tab with a mix of trepidation and anticipation. I half-expected my left hand to just suddenly start working again, and for the whole day after that first medication, I wandered around the house, periodically sitting at the computer and typing a few lines as a test to see if things had changed. No changes; no effect.

The doctor had given me a warning about possible side effects – he said some people were susceptible to disturbances from Azilect, and I should let him know if they were too bad. With that in mind, I took the first dose on a Saturday morning, with the thought that if there were going to be side effects, I’d see them Saturday or Sunday, and would be on top of it by the time work rolled around on Monday. Reasonable, logical, and wrong.

All day Saturday, I felt fine (no changes in what I had begun to think of as “my symptoms,” though). Sunday I repeated the process – still no changes in the hand and arm, but I went to bed feeling just a little out of sorts on Sunday night.

On Monday morning, the alarm went off at the normal time, and I got up out of bed and promptly fell down as the room turned on its side. I had read that dizziness and disorientation were possible side effects, but this wasn’t dizziness – this was a carnival Tilt-a-Whirl ride missing a few bolts in strategic places. I decided to hang out on the bedroom floor for a few minutes and think this through.

I discovered that the disorientation would fade a bit if I kept my head still and moved very slowly. So, looking like Al Gore on a bad day, I made my way to the couch to rest up from the process of getting out of bed. After a few minutes, the dizziness faded somewhat and I was able to eat something. I made a couple of telephone calls – one to my office to let them know I would be working from home, and then to the neurologist to ask, “so, what is THIS nonsense all about?”

He called back later that day, and it was a short conversation:

Me: “I’m very dizzy.”

Doc: “Yes. That’s one of the potential side-effects.”

Me: “I’m sorry, I wasn’t clear. I’m VERY dizzy.”

Doc: “Yes, we discussed this. You may experience some unpleasant side effects at first. They will likely fade over time. It’s important that we determine how well you respond to medication.”

Me: “Dizzy. Very dizzy.”

Doc: “Is there anything else? No? Feel free to call anytime.”

I had started down the path that all PWPs walk at some point: the balancing act between the therapeutic benefits of various treatments and the unavoidable side-effects that, at times, can be worse than the disease. And this was just the first few days of a simple drug challenge to see how I reacted.

Next time - theres a reason it's called "Sinemet"