Quote:
Originally Posted by rappleman
Two questions, pertaining mostly to the early stage PD patient.
First, is there a clear crisp answer (or even a consensus) whether to try to delay levodopa as long as possible, especially whether even first exposure (“challenge” or diagnostic dose) starts the clock toward dyskinesias? The literature seems contradictive/unclear, even argumentative. Some say “proven” benefits especially if start in early UPDRS stages, maybe even neuroprotective, dyskinesias due to disease progression (increasing amount of levodopa needed) not an effect of levodopa itself. Others say “proven” it produces both motor, mental complications eventually, even challenge dose starts the clock, eventually decreases dopamine receptor sensitivity, worsens disease, don’t start until you really need it.
Second, what about neurostimulation, both DBS and extradural motor cortex (EMCS). New articles appeared recently suggesting that EMCS is efficacious, safe, little if any downside. If so what if any reasons not to try it? Then on Valentine’s Day the NEJM article on the EARLYSTIM trial. If I read correctly, DBS improves motor symptoms and major secondary outcomes significantly better than medical therapy alone for earlier stage PD, no significant difference in serious adverse events, bottom line in favor for carefully chosen young patients. For patients with primarily motor symptoms the appeal of relief without starting the clock on levodopa is obvious, but I'm sure I'm ignorant of many things.
All thoughts/recommendations welcome, including additional references. Thank you!!
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Here's my comment on the agonist vs l-dopa choice. i was diagnosed at 47, started needing meds at 53, tried mirapex, couldn't tolerate it very well so have been on sinemet, easy decision. That was before extended release agonists and the NEUPRO patch which i assume can give more steady relief if agonists work for you.
as i alway do, i suggest you get a used copy of "THE PARKINSON'S DISEASE TREATMENT BOOK" and start from there.
http://www.amazon.com/The-Parkinsons...treatment+book
"Older guidelines for treating PD often suggest that the best drugs, especially l-dopa therapy, should be deferred until absolutely necessary. However, there is now increasing recognition that the slow progression of pd continues, regardless of whether we treat conservatively or aggressively early in the course. If we choose to suffer now, hoping to catch the best responses later, we may have done this for naught, we probably have lost an opportunity."
Keep in mind that the intestinally delivered DUODOPA l-dopa is given in slightly higher dosages than oral L-DOPA and dyskinesias are greatly reduced, so it appears that it is the fluctuation in l-dopa levels that cause the dyskinesias, not the l-dopa directly, not absolutely certain on that, have also read that short acting apomorphine can cause dyskinesias. IMPAX labs is hopefully getting the improved extended release "sinemet" approved soon which supposedly reduces dysk. and there are other improved sinemts in the pipeline.
My comment on DBS is it's a very personal decision for you and your caregivers - they'll have to take care of you if the are serious complications after the DBS, but if you qualify, have access to a center that has an excellent reputation, feel comfortable with the risk potential and can afford it, I'd say it's better than dealing with ON/OFF fluctuations and keep adding/changing drugs. Can't hurt to get a few opinions. You do have to dig into these studies and decide if the researchers were totally unbiased and was the population cherry picked. I'd at least wait until the CEREGENE and COGANE trial results are out since a DBS might preclude you from participating in a clinical trial and/or getting those treatments. Basically, if seems you have the dilemma of the risk of brain surgery complications and/or a DBS that could have some major side affects - affecting balance, voice, etc., when you could have just continued with very low risk medication. Personally, for peace of mind, knowing what I know now and now experiencing on/off if i miss a dose - but no dyskinesia - the honeymoon is over - I'd still have to have more bad than good times with sinemet before risking a DBS. but again, haven't researched DBS very much.