not sure if I'll have a top 10 of WED questions soon, but I seem to be well underway
One thing that has always bothered me is the relationship between "augmentation" and "natural disease progression". I can't explain exactly why, but I feel uneasy about the distinction between natural progression and augmentation. After all, both have exactly the same manifestation - but augmentation is assumed if the symptoms get better after a few weeks being off the dopamine agonist medication. However, there are natural fluctuations in the symptom intensity, and most of us do have triggers that will significantly exacarbate symptom intensity. Is augmentation really different from a long-acting trigger? What if dopamine agonists and L-Dopa induce chemicals/neurotransmitters that cause WED symtoms, or deplete natural reservoirs of stuff our body needs to calm the legs? In other words - what if dopamine agonists and L-Dopa combine two actions on WED, one that calms the legs (possibly the dopamine) and something different that provokes WED? It wouldn't surprise me if this was the case, and that it takes days to weeks to recover from the WED-provoking stuff after stopping L-Dopa or dopamine agonists. These substances would have to be somewhat longer acting than the dopamine, which would explain why symptoms flare up as the L-Dopa or dopamine agonist dosage in the body is reduced.
Clearly dopamine agonists work different than natural dopamine, manifested by the large number of side effects that are not associated with dopamine. On the other hand, the highest augmentation rates come from L-Dopa, which is assumed to basically increase the natural dopamine level. But opioids, which are supposed to do exactly the same, are not associated with augmentation. What's the difference between these three substance classes?
- L-Dopa is processed into dopamine, noradrenaline and adrenaline.
- Dopamine agonists are supposed to activate some dopamine receptors.
- Opioids increase the natural dopamine level and reduce the amount of GABA released.
Of course, the question "why does augmentation occur" is only one side of the medal. The other side is "why does the disease progress [assumed naturally]"? Is it really a genetic/age thing that we can't influence, or is it possible that the remedies that we use somehow cause the disease to get progressively worse? I know about a few people who experienced a rapid progression of their symptons while being on dopamine agonists (me included), and symptoms did not rescind (much) after coming off dopamine agonists. Is is quite frequent that our body reacts more strongly to a substance after a prolonged time of exposure.
Let't compare WED to an allergy to a substance X. (Follow me here, after thinking about it for some time it seems to be a good analogy.) If I understood it correctly, what happens there is that the body starts production of antibodies to X, and this production gets more efficient over time. Therefore large quantities of X are required at first to set of an reaction, but with prolonged exposure or over the years it takes less and less of X to provoke a reaction - the body develops a higher sensibility to X ("sensitization"). We can calm down the reaction by stopping the exposure to X, or with medication that treats the symptoms (but does not prevent the antibody production).
Now, back to WED. Assume that a similar process is at work here: Something (whatever - let's call it X again, possibly synonymous for a lot of different quantities) offsets WED, and the body responds with pain or the urge to move, which relieves the urge. After some time, the body "learns" that movement is an efficient measure, and gets more sensitive - thus it will respond easier and easier to X. At the end, even small amounts of X cause severe WED symptoms. (Remember the speculation that WED sympotoms may not be a sensory thing, but kind of a safety valve for our body? What if we do not simply have an urge to move, but movement causes our body to produce substances that should help against the originating condition? This theory meshes well with what I'm developing here.)
Now it get's interesting. It would appear that all WED medication does not interact with the underlying problem (the body being sensitive to X), but simply adresses the symptoms - similar to antiallergic medication not stopping the antibody production, but calming the symptoms instead. If it is true what I suspected above (that dopamine agonists and L-Dopa trigger WED), then patients taking this stuff would be pretty much screwed. Why? The dopamine agonists we're taking contain/produce both something provoking WED (X2) and a substance calming WED (say Y, possibly dopamine). By taking it daily we increase the sensibility to X and X2 over time (worsening WED). After some time, more dopamine agonists are required - either due to tolerance (Y does not work as well as before) or because the body reacts more strongly to the environmental X (we started the process, so there must have been something that caused WED that was not in the dopamine agonist). All right, we increase the dosage, and become even more sensible. What happens if we stop taking the dopamine agonist? After some time X2 leaves the body, giving us a bit of relief. Still, the increased sensibility to X remains for good, and our WED became permanently more severe.
There are some more similarities between WED and allergies: Like WED, allergies have a LOT of different triggers and a wide range of symptoms. Like WED, we do not always know why we react allergic to something. Like WED, allergies usually get progressively worse with age, but may get better on their own (by avoiding the substance causing the reaction).
Does this make sense to you? Note that some weird effects are explained here - why some people are more susceptible to augmentation than others (they react to X2 in the dopamine agonist, while other people don't), why some people augment and others don't, and why people augment much faster if they take up the drug a second time (they are already sensitizised to X2). What are the treatment options for WED, where is the glimmer of hope? With allergies, there is the possibility of desensitization. Is there something similar for WED? I guess we would need to find out why exactly we have the urge to move (see http://bb.rls.org/viewtopic.php?f=5&t=8928), and stop that.
In any case, if WED is really similar to allergies then we should consider the consequences:
(1) Avoid everything else that triggers your WED, as it may worsen your condition (sensitization).
(2) Avoid L-Dopa, dopamine agonists and everything else that may cause augmentation (sensitization again).
(3) All drugs used to calm WED symptoms will contribute to the progression, because with efficient treatment we do no longer realize what causes the WED symptoms. Throughout treatment we get gradually more sensitive, until our medication is no longer sufficient to control the symptoms - we need a higher dose or a different drug. The only "good" option we have is to find out what we're reacting to, and avoid it.
A closing remark: I am aware of the fact that I may be way off target with my musings. I simply tried to develop a theory, think it through and see where it leads me. Don't be surprised if I come up with a completely different (and contradictory) theory in my next post...