My Basic "Understanding" of PD Has Been Wrong

[jimcaster]

We all know that the causes of Parkinson's Disease are complicated, varied, and not completely known. Yet, I have always understood that, at its core, PD is the gradual and unpreventable death of dopinergic neurons caused by the misfolding of a protein and the accumulation and aggregation of alpha synuclein. The longer one lives with PD, the greater the death of dopinergic neurons and the worse their symptoms become. Medication only relieves symptoms, but does nothing to prevent the inevitable progression of the disease.

Isn't that what we have all been told? That's why I have been so excited about stem cell therapy. Even though it's not a cure, it's been described as a refilling of the dopamine tank. Based upon my simplistic understanding, "refilling the tank" seemed like an exciting, cutting edge solution to PD.

Then, along comes Dr. Daniel Jeanmonod and his success with PTT treating lenamm, and M B Anderson, Trixiedee, and Markbit and I am now excitedly, but confusingly, second guessing everything I thought I knew.

Pallidothalamic Tractotomy (PTT) and other forms of Focused Ultrasound have been performed on our friends who have had PD for over a decade (20 years for Trixiedee). No dopamine is replaced. No alpha synuclein is somehow cleaned out. Yet, each of them reports amazing results, significant symptom reductions, and maybe even the elimination of medication.

Everything I thought I "understood" about PD has been turned on its head. Maybe everything our doctors have "understood" is similarly misguided. Maybe that's why the "gold standard" for treatment (Levodopa Carbidopa) has not changed for fifty years. Maybe we have all been barking up the wrong tree.

[KERRINGTON]

That crossed my mind once, you just renewed my curiosity.

[park_bear]

The PTT results are undeniable, and, it is also possible that the understanding that you set forth is still correct.

[jimcaster in reply to park_bear]

I suppose that's possible,, but if the whole game is lost dopamine and/or the aggregation of alpha synuclein and PTT neither restores dopamine nor cleans out alpha synuclein, but stops progression and virtually eliminates symptoms 20 years after diagnosis, something doesn’t make sense to me -- even acknowledging that the causes of Parkinson's are multifaceted. At a minimum, it seems that my obsession with dopamine and alpha synuclein is too simplistic.

[lenamm]

Dr. J calls the dopamine loss the match that starts the reaction. When I asked him if I would still have PD after both my PTT were gone he said yes as there will still be the loss of dopamine cells in my brain but we have cut the reaction that happens from the match the PTT overfiring . Yes IMHO stem cell will not work in anyone past stage 1 - match - of the disease i.e anyone who meds no longer help.

[Parkie- in reply to lenamm]

I didnt ask Dr Jeanmonod but from my reading of his papers and from papers on ablations even before they were made with ultrasounds, I also think I'll still have pd, alpha synuclean misfolding etc, but ptt will interrupt the *dysrhythmia that is causing my major motor symptoms.

*The term thalamocortical dysrhythmia (TCD) was coined by Prof. Rodolfo Llinas and describes the basic physiological mechanism of functional brain disorders.

(copied from Sonimodul Website)

[MBAnderson in reply to Parkie-]

good explanation.

[Despe in reply to Parkie-]

PTT reminds me of an older person's face lift. The face lift improves dramatically physical appearance, but that doesn't mean that the person will stop aging. Only that the person will always look younger than her/his real age.

[Parkie- in reply to Despe]

Well, I would'nt say it's like plastic surgery. The benefits of symptom relief are drastically improving quality of life for some, who like me, are med résistant.

[Gioc in reply to lenamm]

Hi Lenamm

I was wondering if Dr. Jeanmonod has a theory of why the FUS PTT works. It too is simply supposed. A appears to be a rebalancing of brain networks and the consequent rebalancing of neurotransmitters. Just a weak opinion of mine.

[lenamm in reply to Gioc]

Yes indeedsonimodul.ch/parkinson/

and

sonimodul.ch/wp-content/upl...

[Gioc in reply to lenamm]

Thank you very much.

[MarionP]

Imagine stopping a car without brakes (maybe not enough fluid, or a leak in the system, or an electric failure, or a programming failure, or brake fluid that has water, or dirty fluid, or code that won't let the engine slow, or someone pushing or pulling your vehicle, or a stuck accellerator, and on and on. You can stop the car still, just using various bypassing strategies...gearing, finding sources of friction, hitting something, using the manual parking break, driving uphill, cutting out the motor, ruining the transmission by shifting into reverse or such (one of the we could call "PTT") , but that doesn't fix, or even necessarily change, the particular specific mechanism that caused the brakes to fail in the first place. Complex systems and phenomena composed of billions of working parts can be, well, complex; as can some solutions. Take law, for instance...in fact, take anything modern. Take computers. Take weather. You know, we still can't explain fully why water contracts as its temperature drops to near freezing, but then after that, as its temperature drops further, expands. And we also don't know what cats think.

[Grumpy77 in reply to MarionP]

??? ☹️

[MarionP in reply to Grumpy77]

We also don't know why some people like iguanas and chameleons. Anyway the more you know the more you know you don't know.

[Tacitus1953]

Interesting view!Could the Swiss doctor shine a light on the question?

[jimcaster in reply to Tacitus1953]

I believe he describes the death of dopinergic neurons as the first event in a chain of events which is Parkinson’s Disease. Neuronal death is the match which starts the fire -- but it is not the fire. That analogy helps me a little bit, although I guess I am less concerned with figuring out why PTT "stops the car" as Marion says than I am with being confident that PTT does, in fact, stop the car -- or at least slowing it to a level better than any other treatment.

[Despe in reply to jimcaster]

Jim,

I have written before: There are doctors who believe that neurons don't die, they hibernate. If they become necrotic, do they stay in the brain, what happens to them?

[Parkinsonjisung]

Does it work on rigidity and bradykenesia also?

[delboy381 in reply to Parkinsonjisung]

It works for rigidity, bradykinesia, tremor, dystonia and dyskinesia.

[Husbandsupporter]

No, your information was/ is correct. And your understanding is also what has been taught and lived by until more up to date and successful therapy is proven. The focused ultra sound and ultra laser therapy targets specific "neurons and channels" in the brain to hit ones most affected. Another way to help that's less invasive then DBS (deep brain simulation). Also what may help some by these may not be ones that DBS can address successfully.

Are you or have you asked to be involved in any clinical trial? Doing that, if it's something you'd entertain doing, is the best way for scientists and Drs to try new therapy and treatments to further the research to find a cure.

[PNIAuthor60]

I'm too confused right now to be hopeful, but grateful to be among others who struggle with Parkinson's in the hopes of learning anything that would help my 40 year old son who only through his medical record did we discover that the severity of his Parkinson's was more severe than we were ever told.

Also curious as to whether or not there are other Care-Partners or family members in this group?

[Cashewpup in reply to PNIAuthor60]

I am a care partner, my husband has had Parkinson’s for going on 5 years now. I’m always on the lookout for hopeful information.

[Farooqji]

I had read in one of Dr. Daniel Jeanmonod's paper that FUS stops the progression. If this is the case, why is he not offering the procedure to everyone who has PD? Why he picks and chooses patients after detailed evaluation?

[jimcaster in reply to Farooqji]

I don't know many of the criteria, but some people with Parkinson’s are not able to undergo PTT. For example, as someone mentioned awhile back, your skull has to have a certain thickness, etc. Also, medication must no longer be working well for you. Finally, Dr. Jeanmonod and Dr. Gallay are just two people. They can't possibly treat everyone with Parkinson’s Disease -- which is why I hope we can bring greater awareness of this procedure to other neurosurgeons, neurologists, and movement disorders specialists.

[Despe in reply to Farooqji]

Very good question, and asking myself, too!

[Parkie- in reply to Farooqji]

DBS is also picking and choosing than: I was turned down for DBS but very thankful I was accepted for PTT. Being med resistant and pd progressing fast, sure glad I fall into some category for treatment somewhere in this world!

[billybobAK]

Does anyone have some links to articles about PTT?

[laglag in reply to billybobAK]

I subscribe to this site that talks about FUS, but I haven't had the time to read it too much, but it appears to have alot of information.

us8.campaign-archive.com/ho...

[billybobAK in reply to laglag]

Thanks

[jimcaster in reply to billybobAK]

Google "SoniModul Clinic" and look at all the info on their website. Also search for YouTube videos by Dr. Daniel Jeanmonod of SoniModul Clinic. He has a series of informative videos.

[billybobAK in reply to jimcaster]

Thanks

[1rocketman]

Wow. You are an example of why forums like these are important. I never heard of PTT, but looking into it, it looks promising. If nothing else, we need to continue the hope for some resolution beyond current medications. I feel my role as future caregiver to my spouse is to exhaust every avenue within reason. Thanks for calling attention to something I did not know existed.

[Redginger]

Yes, indeed, I second everything that 1rocketman just expressed! Thanks to you Jim!

[jimcaster in reply to Redginger]

Thank you, but it was lenamm, M B Anderson, and Trixiedee who brought this to everyone's attention and had the courage to have the procedure done. Lena started a wonderful, informative Facebook page called "Focused Ultrasound for Parkinson's Disease" which is a great resource, too.

[Sapeye2020 in reply to jimcaster]

First off I would like to thank all the pwp-people that have had this new treatment and now are on a new adventure that, I assume, we all would like to take after it has been accepted by the ''main stream'' Drs. and closer to home.

I was sitting reading and I had a flashback to 2013 when I was sent to about 5 locations for the bits and pieces needed by different Drs. for my Open Heart Surgery. The flashback item was the Ultra Sound done on my neck arteries , not a long diagnostic, 10 min per side(?), but when it was over my NECK was SO RELAXED I wondered if I should buy one for personal treatments since I already had a Dx of Parkinson's, no massage or Acupuncture to attempt relaxation .. no, I did not get one..

The link/ issue I see is the relaxing benefits of the warming of the area(s) focused on ... To my knowledge the brain does not feel very much so, other than PD head aches it , and maybe an adolescent night out. Can the Brain suffer from aches and pains which are muscular based.?..

Now for the far out part of this idea, when the pioneers that took FUS, PTT (and other treatments to come), be autopsied by the 'experts' who did the procedure, so we all get to learn from you brave pioneers!

My questions would be: What happened to the a-Syn? broken up?

Was there a new build up of New Tangles?

[Cashewpup in reply to Redginger]

Me too!

[Canddy]

I totally think that we/they have been barking up the wrong tree!

[AaronS]

I do like the way your thinking, my belief is somewhere around the Korean study i think where they hypothesise that the dopeamenic cells become dormant but not die. Reawakening them is the issue ....

[Kia17]

The problem is that we have been given a jigsaw puzzle with a million pieces and each of us has made a tiny shape out of few of them and think we have completed the jigsaw. No we haven’t. It’s a continuous process and it goes on and on endlessly. We are traped by our limitations.

There will be no cure for chronic diseases unless they (scientists) look at the whole picture. Just name a chronic disease that has been cured.

[Canddy in reply to Kia17]

I agree that PD is extremely complex - however I think it is time to support newer potentially disease modifying therapies and procedures. FUS doesn't appear to halt PD and thus is not a disease modifying agent but it seems to show promise with significantly better symptom control than drugs alone - I will take that type of relief any time. If FUS does pan out to be an effective therapy for symptoms it buys time for researchers to get to the root(s) of PD while giving PWP blessed symptom relief. Perhaps by focusing more research on FUS it will open doors to PD pathways and abnormalities yet to be discovered. We need to go in a different direction and provide more effective therapies than the decades old DBS procedure (Deep brain stimulation (DBS) surgery was first approved in 1997 to treat Parkinson's disease (PD) tremor, then in 2002 for the treatment of advanced Parkinson's symptoms) and the almost half century old drug (the first levodopa combination, carbidopa/levodopa, became commercially available in 1975).

[sharoncrayn]

360 interventions since 2011 with 16 interventions failing or worsening for a 4.44% failure rate.

"The long term efficiency of the treatment stands at 60 – 70% mean relief of all Parkinson symptoms, with a stability documented over 5 years in one of our studies."

"Long term results of the focused ultrasound treatments are not yet available."

"The small group (15) of bilateral PTTs at 1 year follow-up shows similar results as compared to unilateral PTTs but does not allow to draw firm conclusions at this point."

"At 1 year, 26 total UPDRS scores were collected" from 47 patients in the study or only 55% of the potential 47 UPDRS scores were actually tabulated in determining the results.

[Kia17]

It is a story of a group of blind men who have never come across an elephant before and who learn and conceptualize what the elephant is like by touching it. Each blind man feels a different part of the elephant's body, but only one part, such as the side or the tusk. They then describe the elephant based on their limited experience and their descriptions of the elephant are different from each other. In some versions, they come to suspect that the other person is dishonest and they come to blows. The moral of the parable is that humans have a tendency to claim absolute truth based on their limited, subjective experience as they ignore other people's limited, subjective experiences which may be equally true.