Subtypes...further proof and intrigue
 

Hi,

This topic was broached under the Stalevo thread, but I think there has been sufficient interest to merit its own headline.

We discussed that Jankovic et al. at Baylor U had noted the clinical observation of two distinct subtypes of PD: Tremor-Dominant and Postural-Instability-Gait-Dominant.

Debi Brooks added that MJFF had funded research on subtypes and the potential impact they might have on clinical trials and treatments.

Based on additional questions and comments by Girija and Rick, I began to wonder whether there were any proof beyond clinical and PWP observation to the existence of PD subtypes, and I stumbled upon this research gem originally posted by Ann in Lyon:


At last, other works have largely confirm Braak's staging of LB-pathology in PD and added other considerations to the initial pattern with different morphological lesion patterns for the clinical subtypes of PD (Jellinger K.A).

a) The akinetic-rigid type shows more severe cell loss in the ventrolateral part of substantia nigra zona compacta (SNZC) that projects to the dorsal putamen than the medial part projecting to caudate nucleus and anterior putamen, with negative correlation between SNZC cell counts, severity of akinesia-rigidity, and dopamine loss in the posterior putamen. Reduced dopaminergic input causes overactivity of the GABA ergic inhibitory striatal neurons projecting via the "indirect loop" to SN zona reticulata (SNZR) and medial pallidum (GPI) leading to inhibition of the glutamatergic thalamo-cortical motor loop and reduced cortical activation.

b) The tremor-dominant type shows more severe neuron loss in medial than in lateral SNZC and damage to the retrorubral field A8 containing only few tyrosine hydroxylase and dopamine transporter immunoreactive (IR) neurons but mainly calretinin-IR cells. A8 that is rather preserved in rigid-akinetic PD (protective role of calcium-binding protein?) projects to the matrix of dorsolateral striatum and ventromedial thalamus. Together with area A10 it influences the strial efflux via SNZR to thalamus and from there to prefrontal cortex ".

This difference is noted in post-mortem analysis. Fascinating too is the research conducted by Mito, Yoshida, et al. (2005) Journal of the Neurological Sciences. Researchers scanned both PWP subtypes by SPECT and found that the PIGD dominant participants registered reduced blood flow in the anterior cortex, with no significant blood flow reduction in those who were Tremor dominant compared to the norm group. This, in turn, indicates there are different pathologies and neurochemical processes at work in each type.

This in part may explain why and how we experience PD so differently and hopefully leads to progress for much more effective treatments than what we now have. Girija had asked if these subtypes are now a first order of classification? I don't know if neurologists routinely classify newly diagnosed patients; I received a verbal reassurance from my MDS that because I presented with a tremor and that remained my main symptom that I had a "milder" form of PD. lol. as if this somehow lessens the blow. I do think that this research has exciting implications for refining diagnoses and helping us better understand what we're experiencing and to better chart a course of long term treatment. My neuros have done neither but here's' hoping that things will change; I'm left wondering where does the neurologist fit into all of this? Do any of them advocate on the need for change? PAN pressures lawmakers, we press for change with pharma and the research community, but who challenges the neurologist? I think I now need to respectfully start asking my doctors some of these questions.

Laura

calling all researchers
 

Because i have been catching up there this morning Laura, and you may have seen this too, but MJFF is waiting and ready and putting out an all call about PD subtype research.

http://www.pdonlineresearch.org/news...-subtypes-look

paula

moving over to here
 

<<Rick,

I'm a bit mixed up. Where do the tremor-dominant and Postural-gait-dominant subtypes fit in here? Do you think that age and pathogenesis correlate with a certain subtype? I don't disagree just in need of a little clarification. I started a new thread on this with some further research findings that go beyond clinical observation. I'd love to see how your theory complements these findings.

Laur«>

I don't see a direct connection to the subtypes noted thus far although there may be. What I am saying is that the St. Jude's research confirms the work of others and that, taken together, they show that, in some cases but not all, an aggressive virus does indeed lead to an immune response involving the microglia and leading to PD That is probably what appened in 1918.

The above can occur at any age and time to symptoms would vary with the individual but the effects of aging would probably be a factor. Thus a variety of presentations.

However, Carvey et al have demonstrated an identical immune response involving the same microglia but originating in the womb from exposure to the bacterial endotoxin LPS. Like the viral insult, the bacterial one activates the same immune response although it seems not to manifest until puberty.

This versionis much more complex due to the recurring interaction with LPS over the years, the wide variance in sensitivities to LPS, the synergies between LPS and environmental factors such as pesticides, stress sensitivity, in short all the usual suspects. Since this one begins at puberty it would result in the complexities of young onset.

Finally, a third form exists with a similar cascade resulting from exposure to LPS without prenatal priming. This is what happened to Ilse Niehaus (google that), a young lab tech exposed by a wound to LPS from a salmonella lab culture. This presumably would account for origins in nocardia exposure as well.

Logically, those three subgroups should exist from what we know. There may be another teir of subtypes a an overlay on these. Heck if I know.

PD subtypes: Thanks Laura!
 

Laura,
THANK YOU SO MUCH. This information you posted in here seems to be extremely important to the classification of PD subtypes. I still have to sit with a "map of the brain" to understand these differences, If I manage to a get a picto version of the information you sent (thats one way these circuits stay in MY BRAIN and help me understand PD!!!) , I will certainly post it here
MJFF is asking for input on PD subtypes (Deb mentioned it in the other thread), can you please post your information on PDresearchonline? I think there is way non-members can do this. If you have difficulty, please let me know, I will post it on your behalf.
Once again, thanks a lot!

Girija

There is also Mixed Type! Plus, I think we may need to establish genomic types. The following study tests people with idiopathic PD with SPECT scans. Would those with known mutations like LRRK2 respond differently??

Striatal FP-CIT uptake differs in the subtypes of early Parkinson’s disease

In idiopathic Parkinson’s disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished.

http://www.springerlink.com/content/p401815x11517j79/

these subtypes are not new
 

pdonline research shows research thus far reported by mjff's todd sharer as showing 3 subtypes altho more research needed. as we thought, and this isn't that new, i heard about the two subtypes years ago and that rigidity/bradykinesia is worse on cognition and dementia. and the third type listed by sharer is a "worse prognosis". i saw somewhere in this thread that there is a mixed type. i personally could name people of each subtype after ten years in the community. For example, stitcher doesn't look like she has progressed since i met her. now that she has ceregene, hopefully she will remain stable. but all of my rigid friends are looking bad now [the ones my age who have had it awhile] they are falling with postural and gait involvment, which DBS doesn't help yet altho they are working on one for these symptoms.

there is only one drug that several participants declared a cure, and it seems like the UK had more of them but maybe that's because they were on it for 3 years, - gdnf. they had a different pump catheter that was not approved in the US .so a medtronic was used. ok so maybe they are finding better neurotrophic factors than gdnf. but Amgen also didn't hold to their word on follow up. Shouldn't these people have been followed up for subtypes? Was anything handled correctly in that trial? Now some have died, but their medical records and physicians should be able to group them in those three rather broad areas to see if there is a pattern to the ones that claimed recovery. isn't this just logical? we tried as patients and succeeded in getting follow up conditions of several of the patients on Grassroots Connection. But we weren't familiar with subtypes at the time and didn't ask them that.

with gdnf being pump infused, it was a continuous monthly treatment, not gene therapy. they didn't give it enough time. what a screw up sorry but i still get upset over it..

it's not too late to try to establish whether the gdnf participants who did not have dislodged catheters and found it successful were of a particular subtype. what other treatment has done as well? why not do this before doing another trial? and perhaps they are. but i have yet to hear a cere 120 patient claim to be cured. if i am wrong i'd be happy to be corrected and it sounds like dosing is going to be varied; they were able thru autopsy to do discover delivery problems. i applaud them for sticking with it and seeing the 18 mos [?] improvement...follow up is imperative....Amgen just totally abandoned them.

now apparently no one wants to try the gdnf with the pump infusion because gene therapy is now all the rage. i don't know of anyone claiming anything spectacular with gene therapy trials so far but realize that the field is young. But the gdnf gene therapy trial is now the only human delivery gdnf trial i know of coming up in the US. By the NIH - and including people who have believed in it since before Amgen owned it. Delivery? not sure some new device and gene therapy. This means they don't know what dose, and they can't turn it off.

It just seems logical to study the people in the Amgen trials first. we found many of them all by ourselves.

The subtypes are not cut and dry. i remember the days when my neuro said mine was as slow progressing as he has ever seen. but he drew a horizontal line and then plunged it down a fast moving vertical slant. that drop does come. question is - how much is meds and how much the illness?

everyone is a word wizard.....when the online community is a goldmine.

and they wonder why we think they have no urgency, just a career. prove me wrong, please. i have to issue these challenges - we deserve thoroughness. if we are just going to be abandoned to die, then why should we go thru the torture of a clinical trial with sham surgery first?

we want to trust, why wouldn't we want to trust? but first we need to understand. i'm grateful for pdonline research. as you can see, we are paying attention. hopefully, these are understandable logical questions.

paula

correction: actually we did know about the subtypes mentioned in this thread then, but they were not the issue or receiving the attention that they are today.

launch in 20 min. jets guarding air space are circling and too loud to sleep anyway.

well as i type in my email
 

http://www.eurekalert.org/pub_releas...-usc082809.php

it's a start. love this community.

paula

Thanks for this Conductor ...
 

I argued some time ago in another thread that there is only one PD, that we all end up with the same prognosis, however with time I think I could have been wrong.

I agree that the Neuros need to be engaged in this process. My Neuro has seen enough PD to know that there are major differences between PWP, "everyone's Cancer is not the same" was a quote I remember from him.

He often talks to me of the differences in disease progression between different types of patients, however the main thrust of his sub types is age, young onset versus "older age" onset. I have never asked him if he agrees with different sub types of PD based on disease presentation.

I find this whole field fascinating, many thanks for the pdonlineresearch link, I was unaware of it.

Paula, I still believe Steven Gill at Frenchay in Bristol has developed a more effective GDNF delivery unit and got rights from Amgen, but I don't know the timescale of a trial.

Neil.

Current work to validate hunches is not yet conclusive
 

While many neurologists and patients have been able to plainly see that PD (symptom constellation and disease progression) vary within the patient population, we have yet to scientifically validate clear subtypes. And, that still remains the case. The "three groups" are loosely defined and there are experts in the field that still disagree with the observations and specific descriptions of such subtypes. That is why it is said that further work is needed. It’s not clear additional subtypes will be described and it’s not clear that these early classes will be completely validated. But, everyone agrees that if we can validate the subtypes it will be extremely useful.

Debi

Neil,

I heard that too and we even wondered at first if it was going to be used in the NIH gene therapy trial, but we don't know the answer; don't know if it was ever FDA approved. I'm confused about devices getting approval as well as the treatment.

paula

We need designer treatments.
 

Paula,

I certainly don't place much on the whole disease prognosis that supposedly goes along with the subtype territory. I'm already a sub, sub, sub set by having a pregnancy. Have those hormones adversely and permanently affected my symptoms? You bet. I hear the same from other women who have become moms after diagnosis; interestingly too, that most of us (me included) note an increase in stiffness and rigidity. Just when I think I have that settled, I hear from a 31 year old that pregnancy eased her symptoms and she remained that way post partum. Do researchers have something to learn here? Of course they do, at this point; however, I am weary of adding yet another piece to the puzzle.

Always there are exceptions. If anything, I learn that the more we know, paradoxically, the more we don't know.

In the deep, gaping void that is a cure, we need to rally around what can be done. Really the identification of subtypes is not new stuff; Jankovic's research on clinical observations was published in 1985. I think looking at it in terms of classifying/diagnosing and targeting treatments is a rather novel approach. Hence, the interest by MJFF in the last few years. While I still hope for a cure, I agree with Carey's (Indigogo) recent post that the best we can do right now is focus on better treatments- maybe a cure will spring from this. I think it is much more realistic to establish subtypes on a biochemical level and then streamline treatments. How can we throw Filene's bargain basement treatments at a designer disease and expect everyone to benefit?

Laura

Amgen...
 

Wanted to address Amgen...

I'm not sure what can ever be done about Amgen? They serve as a poster child for everything that is wrong about the research milieu. We often express anger and sadness here or in our blogs over what went wrong, but frankly I wonder if that's entirely wasted energy. Why aren't we, instead, carrying posters outside their headquarters in protest? If a tree falls in the forest and no one is around to hear does it make a sound?

Has a Parkie group ever organized and protested anywhere? While I don't think this is necessarily the best or only way to affect change; the publicity would surely be welcome. I'm thinking that orchestrating a protest around on/off times might elevate the whole thing to performance art. A dopamine dependent Cirque de Soleil, so to speak. It sure would be nice to see something in the news beyond the usual scientific trivial pursuit.

Laura

laura,
i love your images: " might elevate the whole thing to performance art. A dopamine dependent Cirque de Soleil, so to speak. It sure would be nice to see something in the news beyond the usual scientific trivial pursuit." It's all so visually wonderful! And we could have a whispering chorus singing protest songs like Holly Near's "We are gentle, angry people and we are singing for our lives", a current favorite of mine.

katherine

GDNF from amgen is over
 

Laura,

We didn't protest in the tradtional sense but did, through the help of PDF, actually sit down at the table with the research investigators. MJFF also hosted us for a discussion about it. There was much more and i would recommend that you read Monkeys... There i sn't anything that can be done at this point.

It keeps coming up because newly diagnosed haven't heard the story, pwps offline know nothing about it, many neuros don't know about it and because it opened our eyes to the realization that our generation had lost the treatment that we had been waiting for.

When you do the math, 14 or more yrs for a treatment - there you have it....they can't stop it in time for some of us. SPIT is a message to sergey really and others with markers,who have the capability [money] to try to stop it for future pwp,as well as pwp who can help by participating in the genetic analysis. it will always be about time.

When a child goes missing, the probability clock starts ticking. If they don't find the child within a certain time period the probability of success drops and continues to drop as time goes by. URGENCY is everything.

That sense of urgency is not present in much of the pd community and you can't really grasp it unless you are a patient.

That's why we "go off" , sound like complainers, criticize, etc.. things which some would call "negative". The whole process is bogged down in red tape, hiring more employees to do the red tape.....well you get the idea.

If we were missing children we'd be lost forever...............quite likely dead.

But there's a part of me that knows we are too complicated for anyone to ever figure it out. i would like to see symptom relief tho, as quality of life becomes quite poor.

paula

"Issue these challenges"
 

Paula W. wrote….with gdnf being pump infused, it was a continuous monthly treatment, not gene therapy. they didn't give it enough time. what a screw up sorry but i still get upset over it…
it's not too late to try to establish whether the gdnf participants who did not have dislodged catheters and found it successful were of a particular subtype. what other treatment has done as well? why not do this before doing another trial?... follow up is imperative....Amgen just totally abandoned them.
It just seems logical to study the people in the Amgen trials first. we found many of them all by ourselves…
…and they wonder why we think they have no urgency, just a career. prove me wrong, please. i have to issue these challenges - we deserve thoroughness. if we are just going to be abandoned to die, then why should we go thru the torture of a clinical trial with sham surgery first?
we want to trust, why wouldn't we want to trust?...” - Paula W.

Bob Dawson says: Paula W., you are entirely right again. Unbelievable that they apparently have not followed up on the 48 volunteers; incredible abuse and shattering of trust; it’s outrageous that Amgen abondoned them – and thus abandoned all of us. It should have just been handed over for criminal prosecution. What you and those around you went through, Paula, makes me furious every time I think about it. I was diagnosed in 2004 but did not even hear about the Amgen misconduct until very recently. All I can think of doing is spreading the story, telling more people about it. Your calls for action are much more to the point… the silence from Amgen is deafening. And they did not have then, and do not have now, the moral or ethical right to do what they did… and what they continue to do… Amgen violated the laws of man and God and nature and common sense.
But it’s not over. It’s not over. Amgen thinks it’s over. They are wrong. Again.

I was recruited by a PWP
 

I was recruited by a 70 year old woman. My website was about dancing; in Chapters 8 and 8.5 I praised the pharma companies. She discussed it with other PWP and they decided to send her to conk me on the head with the Amgen story. She had photocopies and web addresses for me and told the story in front fo 30 PWP in the waiting room. There is a powerful train coming smoking down the tracks. And the granny who recruited me made me pass the Litmus Test. What's your opinion about the Amgen controversy? Correct answer: There is no controversy. It was WRONG. And anybody who does not think it was WRONG should not be treating PWP.

conspiracy!
 

And she never did tell me how she knew i would be in the waiting room that day!

Hey Bob ...
 

I share your righteous anger re. Amgen and GDNF and don't get me started about Spheramine.

However ...

what waiting room were you in and what exactly have you been recruited into ?

Neil.
p.s. nice blog buddy.

<In my best Rod Serling "Twilight Zone" voice-

"For your consideration. Bob Dawson, simple dancing PWP, enters a waiting room. A waiting room at the edge of ...the Twilight Zone."

They don't make themlike that anymore. I still get the heebie-jeebies over the one where the kid fell through the rip in space-time :D

Oh, it was the waiting room of the neurology department in Montreal - waiting for my regular appointment with neuro.
I already had the blog and praised and joked about pharma in chapters 8 and 8.5 The rest is dancing and joy and good stuff. She recruited me to this awareness and anger about Amgen. That was her only mission. SHe brought photocopies, web addresses and told the story of the amgen experiences.
In posts above, people ask what we could do. That;s one example - recruit targeted people; and also supply info in waiting rooms and elsewhere -- and moreso - impose the Litmus Test. What DOES your doctor believe about the Amgen story? Not just doctor, but anybody. Give them the litmus test and if they flunk tell them they are in the wrong line of work or to stay away from PWP

yes, very twilight zone... you go see the doc; this granny shows up and leads you to this hidden community of PWP rebels up in the hills, and they are preparing to counter-attack the Amgen tribe of murderers, and you have been recruited to join something you did not know existed - the rest of the world does not know about it.... you are entering the ZONE

that's amazing
 

bob,

how old would you estimate her to be? now i'm intrigued and could even know her. that's how the internet works and nothing surprises me anymore. what was in the pictures, do you recall?

paula

Is the dithering worthwhile?
 

Debi, you said:

This is why I am not a scientist. Can you explain their reluctance? It worries me that those who are more conservative in their approach are standing in the way of those who might want more innovation. There hasn't been a PD treatment breakthrough in decades. We're waiting and wasting while they dither. At least that is how it feels.

Carey,
That statement "The "three groups" are loosely defined and there are experts in the field that still disagree with the observations and specific descriptions of such subtypes." is troubling for me too.

I am interpreting it as experts in the field are looking for subtype classification at the molecular level not just by the physical characteristics of a PWP> They believe that some features are innate to PD, and some are drug induced and hence, the classfication needs to be done at the molecular level.

It is clear to me that there are several sub groups among PWPS whether the experts agree or not. This in fact, reminds me of how cancer research was before we knew benign, malignant and metastatic cancers. Each stage comes with its own dysregulation of genes and cascades of complex regulation. THey are all cancers, but the severity and manifestations are different.

Laura's post about differences in the brain in autopsy of PD patients is telling something about the diff. Tremor dominant vs rigidity dominant forms of PD and a mix of both are the basic classification. at present we can only go by physical symptoms and may be some scans to identify subsets. A good place to start and go onto much more specific parameters. Very basic questions come to my mind as I dont have a good grip on the literature on PD out there yet (I am trying!),
hence these questions; if answers are known I apologize and please do let me know!

What is basic diff in the genetic profile of rigidity dominant Vs tremor dominant patients?
Are any of the known mutations associated wiht one form or the other?
Among those who exhibit both subtype features, what is the progression rate?
Are there any biomarkers or even physical markers that can predict whihc way PD would go?
(Frozen shoulder seems be so common among PWPS, is this a tentative marker along wiht others)
Way too many questions to ponder as usual..

In my opinion, just going back to the data generated from the clinical trials that "failed" and reclassifying patients into these three groups will be the simplest thing to do to get an idea of whats going on.. Is anyone re-evaluating data based on subtypes?
Girija

70+
 

I checked out the granny later, and she was over 70 years old at that time, which was only a few months ago, or maybe a year, when JimmyBear was complaining about the warnings on Seligilene and I was praising Mirapex. The granny gave me photocopies - like about Andy Grove and the 1,000 turning to ten billion because Andy knows how to run a shop; and interviews with Andy - but I don't remember which were from newspapers and which from websites - probably a lot of it came from this site. And then, and then, the article by the professor about Andy being wrong. Andy - the one who is wrong. Says this researcher.
Well.
And more quotes about Andy, all negative, all from the Parkinson's Research Industry.
Well.
By this time I am steaming and the whole waiting room is watching. I figure that's the story, but no - that was just the introduction.
THEN she tells me about Amgen. And then she tells me about the 48 volunteers. And then she tells me about the before and the after. And then she tells me how they fought for their lives. And then she tells me how they were treated. And then she tells me that I had better watch my step in the PD Industry, and this message is being handed down to the newbies by those who are closer to death, but it used to be whispered if mentioned at all - a kind of urban legend whispered in the hospital waiting room: "Is it true what they say?" "What? What do they say?" "About drilling holes in people, into their heads, and then just letting their suffer." "Jimmy, Jimmy, now who tells your those stories? Don't be afraid, it's just your regular check-up." "They won't do that to me, will they?" Whispering. Taboo subject.
Well, Granny was not whispering. She was talking real loud.
And she was telling it like it is; she saw exactly what happened and it was told in her voice, she showed us what she saw with her eyes, what she heard, she used words that showed what she felt - it was all just the truth, and she knew exactly what she was talking about - and in those few years when these events transpired, she had lived about 5 lifetimes of some of the most intense things a person can live through; Some professor could go on lecturing for hours; she could say a lot more in one sentence. Because she was the one who was there. The professor was not there. Neither was I. The people who were there need to know that's it's okay to come out of hiding; write the story as you saw it; sing songs and dance away from it. Y'all sure got one heck of a story goin' on there. I mean, in my days, I've have seen some things that happened.
But you folks! Good Lord! What you have lived through! It involves everything. Everything and then some more.

Is it just me?
 

Is there not a clear difference between Young Onset and Senior? I'm not saying that I can define it but it seems to be there.

Just reading forums leads me to think that YOPD are far more vulnerable to acute stress than SOPD. And YOPD seem to have more of a "driven" personality. They also seem to report more life trauma. It might take some work to decide where to draw the line, but it sure looks like two different disorders. Heck, they even tell you that YOPD progresses more slowly.

Who's on First?
 

Carey and Girija,

Your questions leave me wondering not only when things will happen, but how? We already know the painstakingly slow research process for new treatments, but what is the time line for how research informs clinical practice? In other words, how much more research or validation at the molecular level is needed before the AAN begins to redefine guidelines for diagnosis and treatment of Parkinson's? There seems to me a huge disconnect between research and practice.

As Girija stresses, we already seem to have some hard evidence that there are molecular differences between subtypes with different pathologies and chemicals at play. Is there anyone out there trying to connect these dots? In looking over the MJFF funded research results on subtypes (found at PDOnline), I was at first surprised that researchers could not agree on the results. Then, I wondered it's not so surprising if no scientific model or standard exists for each to apply when trying to validate subtypes? If each researcher is using their own set of measurements, how can they ever reach some sort of consensus? Maybe I'm way off base here in my understanding of research at this level and scientists would not want or need to first define common measurements in establishing subtypes at the molecular level. We have morphologies, PET scans, just what more is needed to bring the clinical observation together with the hard proof? Biomarkers and genetics, as Girija has mentioned, may be another way to help bridge the divide.

So, what is with the dithering? Charcot described two variants of Parkinsonism in the 19th century. The research of K.A. Jellinger linking clinical observation of subtypes to distinct biochemical areas of the brain dates back to 1991. Everyone involved; scientists, clinicians, patients, we all realize that time is of the essence, so what does it take for theory to more quickly evolve into practice? This isn't Vaudeville, though after a talk with a neurologist, it sometimes seems that way; why should we have to ask "Who's on First?" The problem seems to be that we don't have a team in the first place...scientists generate a lot of information, neurologists plod along with substandard diagnostic "tools" and treatment approaches, and we endure. Ultimately, this research seems futile when there is little connection to clinical practice and no real progress in treatment.

Laura

Girija mentioned that it might be helpful to have a visual model of the chemical pathologies in brain regions identified by Jellinger as unique to subtypes...ran across one at Google Books: Diagnosis and Treatment of PD-State of the Art

Yep, my neuro ...
 

is convinced there is a difference between yopd and sopd. I believe this is accepted by the broader pd world. yopd have slower progression, more dyskinesia, and no increased risk of dementia/cognitive troubles. sopd have more chance of dementia, less dyskinesia.

There are other differences but these are the ones he mentioned.

As I said earlier, never asked him his opinion re. sub types.

Neil.

article relevant to this by jankovic here:

http://jnnp.bmj.com/cgi/reprint/79/4/368

lindy

Dear All,
Thanks for all the info and articles.
As you know PDonline research has asked for suggestions on subtype classification so that funding can be channeled in the right direction. THank you MJFF!

Laura, I have a suggestion. If its OK with everyone, may be we can summarize our questions and suggestions (from an informed patient's perspective) and post them PDonline along with your info. It would be good to hear experts opinion. I dont mind doing that, but unclear of the legalities of this process as I work for a company..... Deb, if you are reading this, could you please advise us.

girija

Th

Clarification
 

I wrote above:
"....whispered if mentioned at all - a kind of urban legend whispered in the hospital waiting room: "Is it true what they say?" "What? What do they say?" "About drilling holes in people, into their heads, and then just letting them suffer." "Jimmy, Jimmy, now who tells your those stories? Don't be afraid, it's just your regular check-up." "They won't do that to me, will they?" Whispering. Taboo subject...."

Clarification: It was not the general hospital waiting room, it was the waiting room at a neurological department specialized in PD. I doubt that the story would be told in a general hospital. The "Jimmy" in question is JimmyBear, who read out loud the warnings on a Seligiline container in my Chapter 8 - they took away his driver's licence so sometimes I drive him to his medical appointments. He is very intelligent but is very nervous about medical procedures. The story of Amgen circulates from patient to patient - by the time it gets up here to Quebec, the name "Amgen" is forgotten and it is a strange incomplete story that goes around in small groups of PWP. JimmyBear did not know, and still does not really believe, that they were volunteers. He was genuinely afraid when he asked, "They won't do that to me, will they?" He thought they just might grab him and do it to him. Or eventually they do it to everyone. He is often not sure if has choices.
That is why it would be much better if the Parkinson's People had complete information about what was done. As it is now, it is a whispered taboo subject that is genuinely frightening to some PWP who are not at all sure who is in charge of their fate - JimmyBear, for example, was afraid that they were trying to starve him to death when he read the list of forbidden food in the Selegilene warning- "do not eat meat, fish, chicken, most vegetables, etc. etc." He kept asking, for weeks, "What can I eat?" I told him he could eat insects, hay, and the bark of trees. Sounds cruel of me, but it works with JimmyBear when I take him a bit further into the absurdity of the situation and make him laugh. He complained that he was told not to eat chocolate so I bought him one of those huge Toblerone chocolate bars and double-dared him to share it with me.
Bits and pieces of information about the Amgen horror are worse for people than knowing the whole dreadful story.. and all the JimmyBears (and there are thousands) will know that they don't have to whisper any more. We can all ask right out loud: "They aren't going to do that to me, are they?" Followed by an explanation of the Litmus Test. And JimmyBear can not only ask that question out loud in the waiting room, he can also ask the doctor, the nurse, other PWP - or the "general population" for that matter.
We are not the ones who have to whisper.

4 years ago, Paula taught the band to play
 

Bumping up.
As Reverette 123 points out here: http://neurotalk.psychcentral.com/sh...883#post977883
the researchers are slowly getting to where the citizen scientists were years ago


It was four years ago today,
Paula taught the band to play
They've been going in and out of style
But they're guaranteed to raise a smile
So may I introduce to you
The act you've known for all these years
The Parkinson’s Lonely Hearts Club Band

For a recent review see:

"Parkinson's disease subtypes: lost in translation"
Marras C., Lang A.
J Neurol Neurosurg Psychiatry2013;84:409-415 doi:10.1136/jnnp-2012-303455
http://jnnp.bmj.com/content/84/4/409.full

John

what about the other 80-90 percent
 

Ugh, lost my post.

In a nutshell, I now find this research ludicrous. Here is why. In a 2009 MJFF funded grant update, researchers report that of roughly 500 participants resulted in 10 being tremor dominant and 50 PIGD with 3/4 of them (that is over 300 peeps) being "mixed type". Am I missing the point? It is not like we have vastly different treatment options.

https://www.michaeljfox.org/foundati...p?grant_id=299

IMO, we should be looking at more symptoms and seeing if any clusters closely conform to genetic variant (18 and counting)phenotypes of PD. Oh no, this won't happen because it would likely result in finding that many more younger onset patients have a clear genetic link. Nothing can be perturbed in the myths of PD. That would mean they can no longer hide behind the claim that there is an idiopathic PD with one common cause. It is handy for them to tell us that only 3-5% of PD is inherited form. My contention is if they do not routinely test young onset people for at least a battery of 3-7 of the most common variants, of course that number will fallaciously continue to be low. Not to mention skew the research pool by mixing genetic PD with idiopathic. This could totally sway outcomes.

Laura