[olsen]

Vol. 67 No. 7, July 2010

http://archneur.ama-assn.org/cgi/con...ct/67/7/798?ct


Neurological Review

When Does Parkinson Disease Start?
Rodolfo Savica, MD, MSc; Walter A. Rocca, MD, MPH; J. Eric Ahlskog, PhD, MD


Arch Neurol. 2010;67(7):798-801. doi:10.1001/archneurol.2010.135

...evidence that the Parkinson disease neurodegenerative process begins many years before the onset of motor manifestations. Initial estimates based on nigral neuropathological findings or striatal dopamine imaging suggested a 5- to 6-year preclinical period. However, more recent evidence of Lewy body pathology in other neuronal [structures]...suggests that the preclinical phase may be much longer... manifestations, such as constipation, anxiety disorders, rapid eye movement sleep behavior disorder (RBD), and anemia, suggest that the preclinical period extends at least 20 years before the motor manifestations. Olfactory impairment and depression may also precede the onset of motor manifestations; however, the lag time may be shorter. Recognition of a nonmotor preclinical phase spanning 20 or more years should guide the search for predictive biomarkers and the identification of risk or protective factors for Parkinson disease.

[Conductor71]

20 years earlier? Wow...this puts me at around 12 years old. In other words something must have happened between then and my first motor sign at age 30 to really set in motion

Interesting...especially in light of field of neurometabolic disorders that begin in childhood and untreated take on the look of Dystonia, Ataxia, Parkinsonism, etc.

Laura

[lurkingforacure]

While I appreciate the post here, I do wonder why they keep recycling things as if they are new discoveries. ALL of this information was previously published years, yes years, ago, in an article by a mayo clinic doc (can't remember his name and don't have the article) called "Beating a Dead Horse".

The article was basically saying that dopamine is NOT all there is to PD, and researchers need to recognize that and start looking at the other things that manifest years, often decades, before motor symptoms appear. It was a fabulous article and the only one our neuro has ever given to us (I guess we're on about a 50:1 ratio, for every 50 or so articles we give him, we get one!). But it was good, and said all the things this article says.

Sorry to poo-poo this, it's just that the article our neuro gave us was written in 2007, three years ago....now here's the same information and what has been done with this information/"discovery" during those three years? No wonder things take so doggone long, it's so frustrating.

[Conductor71]

Originally Posted by lurkingforacure

While I appreciate the post here, I do wonder why they keep recycling things as if they are new discoveries. ALL of this information was previously published years, yes years, ago, in an article by a mayo clinic doc (can't remember his name and don't have the article) called "Beating a Dead Horse".

The article was basically saying that dopamine is NOT all there is to PD, and researchers need to recognize that and start looking at the other things that manifest years, often decades, before motor symptoms appear. It was a fabulous article and the only one our neuro has ever given to us (I guess we're on about a 50:1 ratio, for every 50 or so articles we give him, we get one!). But it was good, and said all the things this article says.

Sorry to poo-poo this, it's just that the article our neuro gave us was written in 2007, three years ago....now here's the same information and what has been done with this information/"discovery" during those three years? No wonder things take so doggone long, it's so frustrating.

Lurking,

No need to apologize! This is one of my criticisms of the PD "machine" that we end up in. I hate to say it, but clearly research and the field of neurology seems rather to be running in place; they do not want to move forward. Only they don't lose time, like we do.

Glad you brought this up, as I have noted a few popular "scientific" site recycle old clinical articles as "news". Unfortunately, when they do this they shape public perception that "so much research is being done surely there will be a cure". Though in end that has opposite effect, people think all will be cured if only enough money is thrown at it. Truth is it only takes one real, outside the box find to make a difference and it could even be just a thought that causes a major shift that sets us on the right course.

As for a few of us out here, we are experiencing some very bizarre and troubling issues with what I think is thyroid based, so of course, now I wonder if a major part is our endocrine system?

Laura

[reverett123]

Asking when is like asking when a river becomes the sea. Thus the graphic (duh!).

The work with rats exposed to bacterial toxins in the womb found that the priming of the immune system showed up at puberty. Since so much body chemistry gets turned on its head, there may be several relevant changes at that time. Add 20 years and you are in the neighborhood.

Originally Posted by Conductor71

20 years earlier? Wow...this puts me at around 12 years old. In other words something must have happened between then and my first motor sign at age 30 to really set in motion

Interesting...especially in light of field of neurometabolic disorders that begin in childhood and untreated take on the look of Dystonia, Ataxia, Parkinsonism, etc.

Laura

[reverett123]

1. Neurology. 2007 Oct 23;69(17):1701-11.

Beating a dead horse: dopamine and Parkinson disease.

Ahlskog JE.

Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905,
USA. eahlskog@mayo.edu

Comment in:
Neurology. 2008 May 27;70(22):2087.
Neurology. 2008 Nov 11;71(20):1651; author reply 1651-2.

Our collective thinking about Parkinson disease (PD) has been heavily influenced
by the dramatic response to dopamine replacement therapy. For progress to
continue, however, we need to take a broad view of this disorder, which includes
recognition of the following. First, substantial evidence now indicates that
dopamine oxidation is unlikely to substantially contribute to the pathogenesis of
PD. Second, levodopa therapy is not associated with neurotoxicity. Third, the
first neurons affected in PD are nondopaminergic; the substantia nigra and other
dopaminergic nuclei are affected only later in the course. Thus, PD is much more
than degeneration of the dopaminergic nigrostriatal system. Fourth, in the
current era, most of the disability of advancing PD is from involvement of
nondopaminergic systems, including levodopa-refractory motor symptoms, dementia,
and dysautonomia. Motor complications associated with levodopa therapy can be
problematic, but they can be controlled in most, using available medications and
deep brain stimulation surgery. We have reached the point of diminishing
therapeutic returns with drugs acting on dopamine systems; more dopaminergic
medications will provide only modest incremental benefit over current therapies.
Finally, the benefits from transplantation surgeries aimed at restoring
dopaminergic neurotransmission will be limited because later-stage PD disability
comes from nondopaminergic substrates. Scale.

PMID: 17954785 [PubMed - indexed for MEDLINE]

[olsen]

Rick, the author of the article you posted is the last author of the article I posted.

The article I posted is a "review"--not new information. Just summation of available literature reports. Researchers prominent in a specific field or sub category of a field are often asked to write "reviews", I think for slow news months. both the postings I made today are "reviews"--nothing really new, nor were these meant to be.
madelyn

[lurkingforacure]

to know it's the same author. Thanks, Rick, for finding the abstract. The full article, which our neuro gave us, was fascinating for me. It highlighted the many things that commonly occur prior to the typical PD signs: REM sleep disorder (with a pretty good explanation of it, to boot), constipation, and olfactory dysfunction, among others.

What I especially liked was, if I remember correctly, his discussion of the various types of neurons involved, not all of which are dopaminergic, so if PD were just about dopamine, then all of those symptoms would be improved when one began taking dopamine....but we all know they are not. In fact, sinemet has next to no effect on my husband's sleep (or lack of same), constipation, or sense of smell. Oddly, we found that when we were still using the nicotine patch, it would pretty much fix any constipation we were grappling with...that's not dopamine.

I wonder what this author has done since October of 2007 when he published the article I referred to...when I get a chance I may give him a ring. I have found researchers are very generous with their time and knowledge when you call them...maybe I can learn something and if I do, I'll certainly share with everyone here.

[alongcamejones]

Representing healthy sceptics: Medical Science research in the past has been inherently flawed, not robust, or vigorous and plagued by Massive Egos, has been shallow and narrow and has led to the prescription of vast amounts of unnecessary, expensive and dangerous drugs and has been easily manipulated by Big Pharm to research this and not that to prescribe this and not that. Most worringly, as a previous thread about MS proves, many neuros and medicos are unable to see the flaws in current treatments based on faulty diagnosis. They live in silos and will not consider they may be wrong.

Apart from that everything is fine, except I dont believe them about well.... lots of things, and I think thats reasonable based on the vast amount of info the internet has made available.

Jak

Originally Posted by olsen

Vol. 67 No. 7, July 2010

http://archneur.ama-assn.org/cgi/con...ct/67/7/798?ct


Neurological Review

When Does Parkinson Disease Start?
Rodolfo Savica, MD, MSc; Walter A. Rocca, MD, MPH; J. Eric Ahlskog, PhD, MD


Arch Neurol. 2010;67(7):798-801. doi:10.1001/archneurol.2010.135

...evidence that the Parkinson disease neurodegenerative process begins many years before the onset of motor manifestations. Initial estimates based on nigral neuropathological findings or striatal dopamine imaging suggested a 5- to 6-year preclinical period. However, more recent evidence of Lewy body pathology in other neuronal [structures]...suggests that the preclinical phase may be much longer... manifestations, such as constipation, anxiety disorders, rapid eye movement sleep behavior disorder (RBD), and anemia, suggest that the preclinical period extends at least 20 years before the motor manifestations. Olfactory impairment and depression may also precede the onset of motor manifestations; however, the lag time may be shorter. Recognition of a nonmotor preclinical phase spanning 20 or more years should guide the search for predictive biomarkers and the identification of risk or protective factors for Parkinson disease.

[soccertese]

Originally Posted by alongcamejones

Representing healthy sceptics: Medical Science research in the past has been inherently flawed, not robust, or vigorous and plagued by Massive Egos, has been shallow and narrow and has led to the prescription of vast amounts of unnecessary, expensive and dangerous drugs and has been easily manipulated by Big Pharm to research this and not that to prescribe this and not that. Most worringly, as a previous thread about MS proves, many neuros and medicos are unable to see the flaws in current treatments based on faulty diagnosis. They live in silos and will not consider they may be wrong.

Apart from that everything is fine, except I dont believe them about well.... lots of things, and I think thats reasonable based on the vast amount of info the internet has made available.

Jak

"Most worringly, as a previous thread about MS proves, many neuros and medicos are unable to see the flaws in current treatments based on faulty diagnosis. "

would you be more specific? parkinson's diagnosis involves identifying a specific set of symptoms, not doing laboratory analyses. they treat the symptoms, not the disease because they can't yet.
what flaws in current treatment? my conventional treatments reduce my symptoms, they may not be perfect but how are they flawed? please define flawed. i have tried iv glutathione, low dose naltrexone, chelation therapy, dozens of supplements and nothing has helped. i see a lot of promising treatments and research in the pipeline, a lot being done by non-pharma.

so i ask you, what specific pd research should be done that isn't being done, what treatments do you recommend that have independently been proven effective?? how should i treat my pd symptoms better than i currently am? and if if you do suggest something, please provide conclusive proof it works.

as anyone reading this board for awhile knows, most promising pd treatments have proven in larger trials to either not produce enough benefit and/or had too many side affects to not be approved by the FDA or couldn't be marketable. if i was a neuro i'd be skeptical of any new treatment that didn't have a peer reviewed clinical trial. heck, there is still a debate going on about the benefit of stents.