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!!

I'm in the same boat. On Azilect 1MG daily since Oct last year when I was diagnosed. I can already tell I will need to make a move to new medication soon. Would rather not start the levodopa route. If anyone has had DBS, EMCS early in the Disease please chime in and give us the scoop.

My hope is the Ceregene project pans out and this becomes a viable alternative soon.

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.

Hi to our newbs!

Definitely keep your eye on Ceregene. Neurotrophics are closest we may come to a cure, imho. The NIH and Genzyme are also conducting similar trials.

Okay here is my lengthy reply to you both. I am sure you will get other opinions but I just set forth the facts and the important things to consider. Hope it helps! BTW, I can provide research to back everything I post, so just ask if you want it...

Unfortunately, I was started on drugs day one of diagnosis after five years of being treated for Essential Tremor, so I never even questioned the meds, at that point I just wanted relief and normalcy. I was far too trusting. Looking back I wish I had started with amino acid replacement (levodopa precursors), mucuna pruriens (plant source of dopamine), and intense exercise. However it may not have been enough symptom control while still working, so who knows? You will find it is all largely trial and error.

Whatever you choose you need to think first about how symptomatic you can tolerate being. If you don't have to hide your condition, you have more options. Likely the doctor will want to start you on agonists, but although they alone do not cause the dreaded "D" word, they do cause personality changes akin to Obsessive Compulsive and Bi-polar like disorders.

There are things neurologists do not readily share about Mirapex or Sinemet. Agonists do not provide as good a symptom control as Levodopa, so most likely you will be on a high dose sooner than later. That commonly causes hallucinations. For me, starting Sinemet early was an easy decision because it totally alleviates my symptoms and on just that I felt most normal and my best. I also feel like Sinemet is the devil I know whereas the adverse effects of agonists are just now starting to reveal themselves.

Lastly, the dyskinesia fear mongering is really over the top and the common belief that levodopa only works for five years is just false. Many people do fine with it long term. Dyskinesia is a temporary effect of having taken too much levodopa; it is not a constant state. In my PD circles, I have enountered maybe 5 people who had out of control dyskinesia and that is over a period of 7 years.

However, I have met too many people who are worse after DBS. In my book 1 botched DBS wipes out like 20 successes. If it were a matter of improving vs. baseline then bring on the wires! It is far too risky. It is, in my opinion, a highly invasive way to make up for the addictive effects of Sinemet. It was also not even necessary in that an intestinal pump delivery system for levodopa already existed and Medtronic could easily have developed it, so right off the bat, I question the whole concept of DBS. Keep in mind there is a Duodopa pump system that we hope/think will be approve by the FDA this year. It seems a far superior treatment and has been available in Europe for like 15 years.

After two years of trying at least 10 different PD meds in varying combos, my doctor is pushing DBS. I am in my 40's and have a child at home. I am applying to clinical trials either neurotrophic factors, or Pico Tesla Magnetic fields. DBS is a last resort; I will go on a drug holiday before I got that route.
Be wary of the DBS promotion early on; there is a trend in promoting it in younger patients and many are doing it. It is scary; there is conflicting research on its neuroprotective potential; they cannot even figure out how it works let alone determine it slows progression. Plus, the few studies I have seen were totally biased with authors disclosing ties to Medtronic. I will leave you with this article:


Management of Referred Deep Brain Stimulation Failures
A Retrospective Analysis From 2 Movement Disorders Centers

Laura

laura,
i had a different experience, didn't have kids to raise, was self-employed, worked at home, not much of a social life so held off on drugs as long as i could. i tried a lot of alternative medicine including chelation, IV glutathione, 1200mg coq10 daily, b-12 injections, every supplement mentioned in research papers, LOW DOSE NALTREXONE, vigorous exercise mainly because i enjoyed it which involved playing 2-3 men's soccer games a week, running or swimming on the non-soccer days for 5 years, much more vigorous exercise than the forced exercise they are doing on the bikes. this was before exercise became such a hot topic. and here i am, 11 years after diagnosis, taking 800mg of sinemet daily and acting like a 90 year old man when off. now maybe i should have continued some of those alternative therapies longer but the day i took my first sinemet was a very happy day and i have no regrets. i have tried mucana, makes me naseous and doesn't help my parkinson's, i am planning on trying it again but toasting it first to inactivate enzymes - 225 F for 30minutes. as far as AA therapy, just haven't met anyone that has tried it. so i guess i'm saying i tried a lot of stuff and i still have advanced pd. of course everyone is different but i'm not regretting starting sinemet at all.

Laura and soccertese;
I very much appreciate and applaud your thorough and frank replies to these new forum posters. You both do a great job of laying out the options without biasing their decisions about the way forward for someone recently diagnosed. Keyboard work never has been a strong talent for me, so I allow myself to be somewhat lazy with responses.
Robert

You already received two thorough exceptional answers from two of the most knowledgeable people on this list. If I might add another couple of thoughts. First is a request to consider being part of the Michael J Fox PPMI research study. They are looking for people who are diagnosed with Parkinson's but have not started any medication. This does not mean that you don't get to start medication, just that when they are doing their baseline reports you have not had any yet. The person who is taking Azilect will not qualify for the Michael J Fox program. Second, it's important to understand, as the others have emphasized, that every person has their own personal journey with Parkinson's. My onset was later, after I was 62 years old, and has followed a different course than the others. A year after my diagnosis I began cycling and by doing that was able to decrease my dose of dopamine agonist and eliminate Azilect. You can read more about that on the Pedaling for Parkinson's thread. I have needed to try three different types of dopamine agonists and then I'm constantly monitoring myself to see where I am and what more I might need or what less I might need. The one constant is my ability to cycle and I need to keep on cycling. it will not work for everyone, but it is worth giving it a try.

One thing to consider when trying to decide whether to start medication or not is if you allow yourself to become too symptomatic, it will be tough to follow a good exercise program. There has been some research done that demonstrates what a good effect exercise can have on PD, and my own personal experience really supports that. My first symptoms appeared about 13 years ago, but I still work six or seven hours a day at a demanding job, and enjoy walking and stretching daily and frequently swimming, cross-country skiing, snow-shoeing and biking. I'm trying to convince myself that weight training would be a good thing, but am not quite there yet! I also believe that a good diet, friends, and enough sleep are super important.

I've taken Mirapex for nearly nine years now - the only side effect is a tiny bit of ankle swelling. I'm very aware of the possibility of OCD, and my husband is on the alert for it. I've also taken Sinemet for eight years, and have never had any side effects. The thought of being seriously dyskinetic scares me, but so far so good. I'm always trying something to improve the situation, and my latest is eating a ton of vegetables a la Terry Wahls.

Good luck with sorting out your life with PD. I guess you could say it's an interesting journey.

I'm adding to rappleman's and laura's comments on DBS use in the early stages of Parkinson's, and comparing DBS to duodopa.

Check out the duodopa vs. DBS discussion starting at 60:12 in the video "2011 – Research Update: Part 1" located at: http://www.theparkinsonsgroup.com/pastwebcasts.asp

The consensus among the four MDS specialists/researchers seems to suggest that if they personally had to choose between duodopa and DBS, they would choose duodopa. According to them, both treatments have their complications, but the therapeutic benefits of the two options are comparable and yet the risk of complications, in their opinion, is less in duodopa (in the stomach - peritonitis, etc.) compared to DBS risks (in the brain - stroke, brain infections, etc.).

Based on what I've read and seen (and my opinion I'm sure will evolve and change dozens of times in the years to come as my PD worsens), I too would exhaust all non-invasive options (exercise, supplements, etc.), all pill options AND try duodopa (once FDA approved, or go to Canada!) before I would try DBS.

---------
rappleman: “...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.”

conductor71: “DBS is a last resort; I will go on a drug holiday before I got that route. Be wary of the DBS promotion early on; there is a trend in promoting it in younger patients and many are doing it. It is scary; there is conflicting research on its neuroprotective potential; they cannot even figure out how it works let alone determine it slows progression. Plus, the few studies I have seen were totally biased with authors disclosing ties to Medtronic.”
---------

Greetings and welcome! Sorry to see you here but glad to help. You have already gotten valuable advice, particularly from Laura and Soccertese and I echo most of it. In order to save space, however, I will try to address my contribution to expand on theirs rather than to duplicate it.

On your "virginal" state vis-a-vis medication- You are very fortunate to have some important decisions to make. As Laura pointed out, most of us had them made by others who had their own biases. There are a number of areas that are open for you to explore. You cannot cover them all so take some time to think about it and share your experience here.

On DBS, Ldopa, etc.- Something about DBS doesn't feel right to me. Too much of little boys playing with toys. It seems to replace some of the lost manufacturing ability where Ldopa is concerned but it does not claim to reverse damage nor does it claim to improve function. It also does not seem to alter the future course of the disease and degradation continues unabated. The bottom line is that it seems to be an expensive and very risky replacement for sinemet. It brings to mind the old adage of, "Just because we can do it does not mean that we SHOULD do it."

On dyskinesia- My own opinion is that it is the result of hypersensitization of receptors (presumably those for dopamine. I base this entirely on observation of my own problems with it and may be totally wrong. But certain things set me off twitching and twisting. Bright light does it, especially if it is brighter in one visual field than the other. Environmental stressors such as loud sound will do it as will social stressors such as confrontation. Talking on the phone (especially to my mother) will set me off. It comes and goes with ingestion of sinemet.

On how to start out- I would give some thought on experimenting with advanced alternatives at first. Things that depend upon your "virginal" status and that you can never have the opportunity again. For example, I have wondered what would be he outcome if I used mucuna like a condiment at the dinner table and thereby maintained a steady state condition that I would monitor for new symptom "breakouts".

Finally, on the matter of just when to start Ldopa. I vote that it is best to keep the system at as low a stress level as possible. Stress is the enemy and nothing is quite as stressful as being frozen in place in a busy parking lot as cars whip by.

Good luck - Rick