Levodopa Induced Dyskinesia

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This thread is extracted from another thread which was large and cumbersome to use,

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John Pepper wrote:

Hi Grey. I have pondered this one but I am unable to come up with an answer.

I have not come across anybody who has dyskinesia who is not taking levodopa medication! Someone, I thought it was you Grey, said that dyskinesia is caused by levodopa!

That makes sense, bu then we come to the person who took an MAO-b inhibitor and sinemet and gave up the MAO-b inhibitor in order to overcome the dyskinesia. I think I can explain that! The MAO-b inhibitor helps the brain retain more of the dopamine that is already in the brain, but now we have a problem, is the dyskinesia caused by too much dopamine or too much levodopa?

Hence the quandary! I know what I would have given up! It would not have been the MAO-b inhibitor.

John

[grey in reply to grey]

Grey wrote:

Yes, John, I did say in a post above here Levadopa is the culprit. That was a one word answer to a rather complex scenario. Reading the literature available to me, it suggests that the actual mechanism causing the movements we are familiar with are not fully understood. It has a name - Levadopa Induced Dyskinesia (LID).

The problem is thought to result from the way levadopa is administered, which is intermittent doses. This results in damage to an area of the brain called the striatum. I should add that dopamine agonists are believed to cause same problem.

The striatum is in the basil ganglia (BG). It is the primary input to the BG. It also co-ordinates motivation with body movement.

It is believed that the damaged striatum produces “abnormal motor outputs” which result in the involuntary movements associated with dyskinesia.

Still awake?

LID has been known about for a long time and was first reported Cotzias who led the team credited with the first successful use of levadopa in PD treatment.

It is interesting to note that areas of the striatum are sites for some of DBS operations and the current GDNF trials at Bristol.

[grey in reply to grey]

Continued....

So we have a damaged striatum, which emits abnormal signals causing the dyskinetic movement. What triggers this?

Concentration of levadopa in blood!

It normally occurs at peak concentration (PDD - peak dose dyskinesia). As the disease progresses, it changes to when there is rise and fall in concentration (DD - dysphasic dyskinesia).

Your final question, John, I think I can answer with simple logic.

The patient doesn't have enough dopamine to function.

MAO-b saves some of dopamine from the garbage can.

Some of not enough is less than not enough

Therefore patient needs more.

And that's why she takes the God dammed awful shit which damages her striatum which sends out signals to move and she moves when her concentration of levacrap is at a level depending on what stage she's at, whether she likes it or not, and a point that seems to be missed is that she wouldn't be able to walk because, like me, she can only shuffle if she doesn't have enough l-dopa to form dopamine to transmit a signal across a synaptic gap or two million.

[movinngroovin]

MY TWO CENTS IS THIS--DYSKINESIA IS CAUSED BY TOO MUCH DOPAMINE PERIOD-THAT BECAME CLEAR TO ME ONCE I HAD DBS ON MY ONE SIDE (NEXT SIDE IS COMINING IN FEB), ANYHOW, WHEN THE INITIAL SIDE WAS TURNED UP TOO HIGH I HAD SO MUCH DYSKENSIA ON THAT SIDE MY ARM FLAILED AROUND EVERYWHERE --IT HAD TO BE CUT IN HALF--THAT SAID, NOW I CAN EASILY TELL WHICH SIDE IS TREMOR AND WHICH SIDE IS DYSKINESIAS AND ADJUST MY SINAMET ACCORDINGLY. CAN HARDLY WAIT FOR THE OTHER SIDE TO BE DONE! MY NEURO SAYS THAT THE LEVADOPA IS TOCONTROL THE GASTOINTESTINAL DISTRESS FROM THE CARBIDOPA (DOPAMINE ESSENTIALLY. JUST WATCH MICHAEL J. FOX SOMETIME--FLAILI NG & WRITHING IS CAUSED BY TOO MUCH DOPMINE--THAT'S MY POINT IN REAL TIME!...

[grey in reply to movinngroovin]

Hold on there, MnG. Turn your caps lock off a mo and quit shouting! You produce not one shred of evidence to back up your claim that dopamine is the culprit.

In my researched version, the striatum, damaged by the intermittent doses of levodopa, emits motor outputs which cause the involuntary movement. The trigger is concentration of levodopa in bloodstream (presumably linked to the intermittent doses of levodopa).

I’ve already noted that areas of the striatum are potential sites for DBS (as it turns out, a stroke of genius I think you are forced to agree!)

“the device [DBS] will be switched on and the electrodes will deliver high-frequency stimulation to the area of the brain that is targeted. This stimulation will change some of the electrical signals in the brain ...” The signals being those transmitted by the faulty striatum.

Ta da

Explain how Dopamine causes voluntary muscles to contract?

[grey]

Well MnG, your unequivocal answer leaves no room for debate!

John, that's three answers to your question; my interpretation of the texts, my soul exposed and the bionical groover with a dollop of soul.

John, your verdict? Who leaves the Dysfunctional House this week? or do the public get to vote......

[Balderdash]

What progress have we really made,The answer is as far way as ever,Srip it back and start again, or go backwards to go forward on a bad PD day going backwards works for me.Pomegranite juice and coconut oil rub it in or drink it,Whatever works for YOU is what matters.Keep asking keep looking keep trying keep talking ,I just hope santa doesn't bring me a pair of killer slippers again.

[grey in reply to Balderdash]

Try this balderdash,

Levodopa better than newer drugs for long-term treatment of Parkinson's, largest ever trial shows

sciencedaily.com/releases/2...

It's a useful report. Para 3 is shocking, samples too small . But back to day 1 but now with guidance.

[etterus]

As dismal as it still seems, I recall the pre c-l dopa days of pd management that almost all the victims were in longterm care within 2 years and usually dead within another year or so due to recurring urinary or pulmonary infections.

I am curious. does anyone have stats on the incidence of dyskinesia related to dosage, duration, or age of onset?

[grey in reply to etterus]

You're right, it is rather dismal. So they fix the infections and deny us the right to drift off - a sort of cure I guess. Who gave them permission to do that, it wasn't on my copy of life's T's & C's. Do the ethics people think that's correct?

Talking of ethics, well you weren't really, you were just being dismal which, when you think about it, for most of us, ethics and dismal sit rather neatly side by side so you may forgive me for being so presumptuous, but anyway, do you think it ethical to have the same ethics rules for people who suffer from a chronic progressive condition as the rules applying to those without chronic and progressive labels? Indeed, would you agree to a third set for people suffering from a terminal condition?

Stats, I wonder how do you get those? Most stats I guess would be held with researchers or their employers rather than held centrally. I've pondered in the past over fate of data. It should freely available to all once the research paper is produced for the benefit of mankind.

[etterus in reply to grey]

I live in Oregon and there is a mechanism to terminate your life. It has to pass a board review that I don't know much about. You also have to be able to administer the lethal dose by yourself. Not much good news fo the C4 quad.

[grey in reply to etterus]

Termination of life is an important topic, but I was thinking more of risk taking, for example should we be allowed to take bigger risks than normal in a drugs trial or testing a surgical procedure.

For example.

Fast track is an ethical alternative clinical testing procedure for use on chronic progressive diseases. It allows for clinical testing to be accelerated and if successful, drugs to come to market as soon as tests are completed.

Say it shaves 5 years off time to market. Shouldn't I be allowed to use fast track, given that I'm informed of the extra risks and suffer from a chronic progressive disease.

Indeed, isn't denial of this a breech of my rights?

[Sedona in reply to grey]

As people living with chronic, progressive disease, we should all have this right! They are not protecting us, they are denying us hope.

[michaela13 in reply to grey]

Yes!

[Hidden in reply to etterus]

I hope I am not a 'dope'. I take no levodopa or any other Park meds. I recently "celebrated" my second anniversary since dx and I am still alive. I am looking forward to more years... (...usually -not- dead).

[grey in reply to Hidden]

Hi Roy Prop,

I'll add my stats

Grey

Dx jan 2005 -

Month O to 18 - no medication

Month 19 to 33 - started meds ropinerole and selegeline

Month 34 to 45 - no medication

Month 46 on. - neupro patch add Sinemet add selegeline

Mix up, shake up, f*** up

Not quite the normal curve, but 10 years of my life. There's a story under there, was it worth it? Can the story be teased out of the data? I doubt. Looking backward, alive to zombie and back again, never dead, well not that I remember. Rebel who never found the cause.

And you Roy, no levodopa or any Park Meds, why?

[Hidden in reply to grey]

no levodopa or any Park Meds (neupro patch the doc gave me at the time I was diagnosed but only for less than one week)

I do not know why the doc would want me on med right away unless it was part of the diagnosis.(if patch reduced the tremors, bingo, Parkinsons)

When the doc told me it was PD, I was not emotional. The doc instructed me not to read about the disease on the internet.

I read and researched and continue to read. Mostly now on HU. Soon after I was diagnosed and I discovered what P can do to one, I cried.

Some Neuros recommend starting meds as soon as one is diagnosed. Some say it will not hurt to delay. The effectiveness of drugs last a few years, maybe five, then you need more or different drugs. Neupro costs one hundred dollars a week.

Drugs have serious side effects. I have chosen to refuse meds until it is absolutely necessary due to severity of symptoms.

I have not been back to the Neuro since dx. His dx simply said, typical P.

My "homework" suggests tremor dominant P. My prayer is that I am right and it does not turn out to be (PIGD) posture instability gait disorder form of P.

I told my GP that I want him to manage my P and Meds as necessary. when necessary. He said he would and that he would learn about P treatment with me.

(learning curve)

[grey in reply to Hidden]

Roy, do yourself a big favour and read this report. Start with the last three lines: ".... ts that the fears that have served as the groundwork in establishing levodopa phobia -- that often results in patients experiencing unnecessary and easily managed disability and reduction in quality of life in the early years of their disease -- are unfounded."

sciencedaily.com/releases/2...

I wish this had been available a decade ago.

[Hidden in reply to grey]

I am still playing with CO, on and off again. I stopped CO over one week ago. Over that time, my tremors became more pronounced. I consumed some CO and then stopped for observation of affect. Not conclusive.

Taking CO again and seems to have helped. I question this as my tremors may fluctuate from day to day normally, w/ or w/o CO

[mistydog1]

My 2 cents I was having sever painful dyskinesis on my left side. My neuro thought maybe due to my PD may not have progressed to the point I needed the full 25/100 Carbidopa tablet. Today I take 1/2 tablet of the Carbidopa/Levo and 0.5Mg of Azilect and things are fine walking fairly normal and best of all no more pain ! Carbidopa acts only as a transport to mask the Levodopa across the blood brain barrier where it can get utilized. In my case the dyskinesis was due to too much Levodopa !!

[movinngroovin]

no shouting here, just easier to type one way or the other..sigh..My only evidence is from my own experience and conjecturing about it with my neurosurgeon and DVS programmer..that's all--which is good enough for ME!!

over and out..

[grey in reply to movinngroovin]

Good enough, even if it's wrong? You deserve better cos you're worth it.

[Balderdash]

Its all interesting,this is a snippet from a really old article 70s will post it in full if anyone wants it.

The most important factors in obtaining significantly favourable results and in avoiding major side effects from L-dopa treatment appear to be the gradual upward titration of the oral dose as well as a program of mobilization. If these two principles are closely adhered to, as outlined many times by Cotzias, it is possible in almost all patients reach a "plateau" dose level without complications.

By slowly modifying the dose upward or downward, it is possible to maintain improvement without a recurrence of the initial annoying side effects of nausea, vomiting, loss of appetite or postural hypotension. In our experience there has been at least partial improvement in most all symptoms of Parkinson's disease in the majority (90%) of patients.Even if the improvement can be considered sustained, there is often a marked variation in individual performance from day to day or within the same day. Occasional short-lasting refractory periods varying from a few minutes to three or four hours will occur in patients who otherwise are perfectly control led. During these episodes there is often increased restlessness, a feeling of tension or of body warmth, and excessive nasal discharge with hyperhydrosis and even pupillary dilatation. These refractory periods occur usually one to two hours after an oral dose of L-dopa and are worse after a heavy protein meal. Similarly there may be episodes of longer duration, lasting up to a few weeks, with suboptimal performance despite maintenance of the same dosage schedule. At such times there is a marked increase in freezing and the re-emergence of tremor.

A most striking, and important, side effect is the production of abnormal involuntary movements in more than 50% of patients. This phenomenon appears to be dose related and occurs approximately at the time of optimal performance. An important observation is that when these dyskinesias appear, tendon reflexes are weak and there now is hypotonia. Very often patients can predict the onset of these movements through a strange feelling of warmth or tingling in the part of the body eventually affected. The types of movements observed are almost as variable as the number of patients

At this time, suffice it to say that they occurred in 50% of our parkinsonian patients, but could certainly be found in almost 100% if the level of L-dopa was pushed sufficiently high. To date they have been reversible upon reducing the dose of the drug, but in some cases after a few months they have tended to recur at progressively lower doses.

This is from a 1970’S review by BARBEAU

I still think observation are classical still much is applicable

[grey in reply to Balderdash]

It's all worth it - balderdash Balderdash! Haven't you noticed, people talking here apparently discussing same thing but take a closer look, they're talking to themselves! Is this pushing any thing any any where? The boundaries of knowledge fear not pollution from this "forum" white noise only!

Over and out, what does that mean? Impossible. Listening out.

[JohnPepper]

Hi everybody. You all seem to have done very well without my lecturing you! Damn! I really need to be needed, (joking).

I tend to put my pennyworth on the levodopa, but I really think it should be tested! For many years patients have been told that dyskinesia is a Pd symptom! It is definitely not!

If it is levodopa and the patient takes both an MAO-b inhibitor and levodopa medication, then he/she should cut down the levodopa and not the MAO-b. However, the MAO-b does nothing specifically for any of the symptoms, excepting for the fact that the patient has more use of the dopamine already in the brain than would otherwise have been the case.

Now I come to the walking and GDNF!

If the patient is enabled to walk, as a result of medication, either MAO-b inhibitors and levodopa, and he/she builds up her/his strength very slowly, the GDNF should start to repair the damaged brain cells and the brain will produce more dopamine and the patient can cut down slowly on the levodopa. Here endeth the lesson for today girls and boys!

Merry Christmas to all of you!

Kindest regards

John

[grey in reply to JohnPepper]

John, thanks for not responding to my reply to your question. It was, however, worthwhile, I learnt something. So thanks for asking the question.

And merry Christmas to you!

And in answer to a previous question, yes you are a nuisance and well you know it! Keep up the good work. G.

[JohnPepper]

Hi Grey. Someone has to stir the pot, otherwise we would be drowning in a sea of boredom.

Have a wonderful Christmas, hopefully with your family and loved-ones.

Kindest regards to everybody this festive season!

John

[arthur84]

I really enjoy this website{makes my day} I have now another question? Have never asked if anyone has severe burning mouth, throat, even esophagus, some days. Drs. have told me I'll probably never know the cause, sometimes all over, can't take gabapentin. This occursnow after I eat, along with the shortness of b reath, pain in diaphram,then I get rapid heart beat. Have to stay in bed. The BP gets high. So miserable.. do have other health issues. RA, blood cancer,I take Carbidopa Levo25/100,one every 3 or 4 hrs., 2 50/ /200. Usually feel normal when I awaken. I also take 20mg. paxil," boom", after eating, things go down hill. I'm 88, 8 years with PD. Any discussion with this problem. Tried azilect, gave me vertigo. Will see a new neuro dr. soon to see if she can help me. Never can plan to go any place.

Thanks,

arthur84