When I go to sleep I’m usually “off”. It’s hard to turn over in bed. Most of the times I fall asleep, waking up every time I feel the urge to turn. By the time it’s time to rise I still feel a bit stiff. It’s usually not to easy to get out of bed, but by the time I’ve reached the bathroom I feel nicely loose and relaxed. I can take a shower and wash and pamper myself real easy. In fact I feel wonderful early in the morning. This however does not last long. In about half an hour my tremor starts his brand new day and a few moments later my muscles start to* stiffen.
Luckily I know this and I have prepared myself by taking my medication. I cannot however take my medication in time as it takes more time for the medication to break through than for my wonderfull feeling to vanish. This enables me to notice that there is a difference in the “on”-feeling I get* through my medication and the early morning feeling.
*
This makes me think that the problem might not be the level of levodopa in the brain. It’s tempting to assume that the problem is limited to the levodopa-level in the brain. Of course cells in the substantio negra that produce dopamine are damaged, leaving lewy-bodies as silent witnesses. And yes, dopamine levels in certain area’s drop dramatically. But at the same time dopamine levels in other parts of the brain even rise. And there have been numerous cases of people diagnosed with Parkinson’s Disease who, post mortally, didn’t have Lewy-bodies.
*
What are the differences in the two states as I experience them?
Early morning feeling:
Movement is smooth. Agonist muscles contract antagonist muscles release. Agonist muscles relax after movement
*
Medication feeling:
Movement is smooth antagonist muscles contract antagonist muscles release. Agonist muscles do not release immediately after movement. This gives gives dystonia and dyskinesia.
*
Off medication:
Movement is pulsatile and hard. Agonist muscles contract but antagonist muscles do not release. Muscles do not fully release after movement. Hypertonia.
*
What do you think?

Hello, Joop.
A typical morning.
I awaken 6:00 AM and arise. Immediately greeted by back pain which disappears within five to ten minutes. Slight balance problems as I shuffle to the john and then on to take the morning sinemet and head to my chair. By this time I have dystonia in the left foot but other muscles lack tone. If I sit passively I gradually come on over the next hour. If I struggle to type, muscles of upper body bunch up in rebellion but time frame is about the same. If, however, I spend time stretching and working muscles, time frame lessened by as much as half.

I suspect that this period when the circadian cycle is rather complicated is our most complex time of the day. I also think that it holds valuable clues since it is as close to a stable baseline that we get. Before the drugs kick in.

It's been my understanding, altho I know they have learned much more along the way, that our bodies continue to produce dopamine while we are sleeping. Eventually even this stops and the morning changes from reprieve to a race to beat the off or guaranteed off and trying to beat dystonia.
That something else is at play other than levodopa and dopamine is one of my hopes. The neurologix gene therapy trial i believe actually works with gaba doesn't it? Gaba also was what Dr.Levesque thought was at play with his patient and the autologous cell replacement. The patient's dopamine levels did not increase, but he maintained improvement for years.

Not suggesting that gaba is involved in the morning, just acknowledging that ldopa may not be [hope it isn't!] the end all answer.

paula

Hi Rick,

Our condition must be almost the same. I didn't describe the back pain but i do have that.
You say that the morning condition we both described is as close to a stable baseline that we get. Before the drugs kick in. I believe this too. And if it is possible to feel well for half an hour, why then is it so difficult to feel alright for a longer period. Could it be that in fact there is another neurotransmittor in short supply or some enzyme that causes among other things, levodopa levels to drop.

hello Paula,

perhaps Gaba is a candidate for that role, as well as acetylcholine and serotonine. It explains the succesfull use of amantadine or symmetrel to control dyskinesias or the effects of xtc on PD.

Joop

Granted, only 2 years into this, but the only thing that calms my spasms and tremors (which are the asbolute worst when I'm lying down), is klonopin or ativan. Both of which, I believe, act by increasing GABA. Which is why I have substantial hope that the Neurologix theory/methodology is on the right track. Didn't they also release a paper which showed that the GAAD gene, over time, not only reduced symptoms markedly, but also normalized brain circuitry in the subthalamic nucleus? I remember reading something along those lines. Anyone know why the trials on this are proceeding so slowly? I was under the impression that they had gained FDA fasttrack status.

I think they are just having trouble recruiting. No adverse effects thus far.
paula

I've never thought it was all about dopamine...I notice that when I eat fava beans, which provides a certain amount of dopamine, it feels different somehow. I can tell that there is a matrix of substances at work rather than just that edgy dopamine feel.

For a while I experimented with that half hour period of clear movement first thing in the morning, seeing how long I could extend it beyond that half hour. I got to like an hour and half, but immediately upon rising drank black coffee and take handfuls of supplements. This was going well, and I told my doctor about it and he freaked out, saying "absolutely do not miss your 6 am dose." So I felt discouraged from trying to build on what felt like my only connection for sure with my "real" dopamine process...the message was clear that the body is not to be trusted, or at least mine not....

In the past year or two, I often have dystonia first thing in the morning, if I even just get up to go to get a glass of water or whatever. It seems that the only thing that alleviates it while waiting for the meds to leisurely appear in my system is to vigorously work my body - especially my tailbone, sacrum area, which often feels very stiff. I have to do leg-ups, vigorous sit-ups, push-ups, big leg swings, circular movements of the head and neck, arms and shoulders, sometimes continually for up to 45 minutes before the intense spasms will go away. Interestingly, the few occasions I have had to just fall into a pool of water when I have dystonia - the act of moving through water that's deep enuf to swim a little instantly snuffs the spasms right out, and my limbs are fluid and relaxed again. (I wonder if I could get a prescription for an indoor pool. ) The time I wound up in the emergency room because of a severe dystonia attack which had me writhing on the ground in a parking lot - the medical staff was quite surprised when I told them, "I just have to dance!!", and started madly dancing around the emergency room cubicle doing high kicks until it went away. They didn't know what to think.

Some things that seem to characterize the mornings for us-
1) Improved function upon awakening which fades within 30 minutes or so. Activity or stretching increases period and inactivity decreases.
2) Back pain? Fades quickly.
3) Dystonia. Foot. Other? Starts about ten minutes after rising?
4) Sinemet on in an hour.
5) Coffee helps?
6) Sensory overload?

One possibility- Normally, cortisol quickly climbs to a peak just as we awaken and drops over the next hour or two. But ours doesn't go so high nor drop so low. So, at the one time of day that we need it we're low on it. And guess what one of the first things that levodopa does is - it lowers cortisol.

Hi Fiona,

It seems more people have that early morning half hour of feeling relatively well. I was also thinking about extending this period by going back to bed after half an hour. This however didn't work. What supplements do you think could work?

The only reason I can think of, why a doctor wouldn't trust a patient's observations of his own inner body, is that he cannot check what the patient is telling him. I think it's unwise to ignore what your body tells you. For myself I 've worked out a system of symptoms to guide me in taking my medication. I still use the same amount of medication as two years ago, but the disease has progressed and I use it more efficiently now. I'm convinced I would have been greatly disabled if I wouldn't have optimised my medication.

I too have dystonia. I think I'll try to make myself a program of vigorously working out. It reminds me of what Sacks called Kinesia Paradoxa. A vigorous way of moving, may involve different neurotransmittors.

Joop

Hi Rick,
I ajusted your list somewhat
1) Improved function upon awakening which fades within 30 minutes or so. Activity or stretching increases period and inactivity decreases.
2) Back pain? Fades quickly.
3) Dystonia. Foot. Other? Starts about ten minutes after rising?
4) Sinemet on in an hour. This depends on whether you eat after taking your first dose.
5) Coffee helps?
6) Sensory overload makes you off much sooner
7) if i eat after the first dose the second dose will take longer to work

Is there anyone who uses symmetrel and can describe the way this drug feels?