[Conductor71]

Originally Posted by indigogo

We'll all be a lot better if they focus on determining just exactly what Parkinson's is - and it's not just motor symptoms. It's much more - but what?

I was really struck by this post made by Carey; it parallels some ideas being tossed around on the PD Online Research site. Sorry, I'm too new here to post links, but if you Google the title and the author's name "Weiner", you'll get right to it. I apologize that some of you may have already discussed this, but I wanted to repost for those of us who are noobs.

Author: Weiner, William J.
Title: "There is no Parkinson Disease"
Journal: Archives of Neurology 2008 65(6)705-708

A few key excerpts from the article:

The difficulty of an accurate clinical diagnosis of Parkinson disease was highlighted by Hughes et al. Their study reported the pathologic findings in 100 consecutive patients clinically diagnosed as having Parkinson disease (the mean age at symptom onset was 64.5 years, and the mean disease duration at autopsy was 11.9 years). Of 100 patients diagnosed as having Parkinson disease, 76 had pathologic confirmation. The "misdiagnosed" cases included progressive supranuclear palsy, multiple system atrophy, Alzheimer disease, vascular nigral atrophy, postencephalitis, and healthy brain. This study illustrates the problems in clinical diagnosis. Of the patients misdiagnosed as having Parkinson disease, 67% had a marked initial response to levodopa treatment (>50% improvement). So much for levodopa responsiveness as a clinical criterion for the diagnosis of "true" Parkinson disease. Hughes et al, commenting on whether Parkinson disease is a clinically diagnosable specific entity, wrote, "Until biological markers or other techniques are developed, we must accept that diverse neuropathologic disorders may produce clinical syndromes indistinguishable from Lewy Body Parkinson's disease."

Furthermore..."Is it possible that recent neuroprotective trials for Parkinson disease have failed because numerous subtypes of Parkinson disease are lumped together? We know little about how these abnormal genes, their end products, or their mechanisms of action regarding cell degeneration and cell death operate. However, each of the abnormal genes identified thus far is speculatively linked to different biological mechanisms (eg, LRRK2 kinase activity and the parkin-ubiquitin-proteasome system)"


As someone who does not have what is now being studied as a possible major biomarker like diminished sense of smell, I wonder how many people might be further misdiagnosed or missed diagnosed if we don't start linking these broad based research avenues to genetic information that we do have?

I'm sure that the above article is not news, but I think it deserves to be a basis for redefining the whole PD research culture and standard clinical control measurements (over-reliance on placebo that by it's very nature is highly dubious because of its direct correlation to dopamine).

[reverett123]

I have been having another hard patch the last two weeks. How hard? Try crawling out of my bank on hands and knees last week and getting steadily worse since. Suspecting everything under the sun. Off almost all day yesterday. Today started the same with the addition that early morning curly toes didn't go away and were joined by full leg cramp on left side. After an hour and forty-five minutes of this normally ten minute experience, my wife forced two potassium tablets on me. Eight minutes later I was completely normal. This makes half-a-dozen times that potassium problems have crept up on me, even though I eat better than most.

The Linus Pauling Insitute says low potassium can cause:

"An abnormally low plasma potassium concentration is referred to as hypokalemia. Hypokalemia is most commonly a result of excessive loss of potassium, e.g., from prolonged vomiting, the use of some diuretics, some forms of kidney disease, or metabolic disturbances. The symptoms of hypokalemia are related to alterations in membrane potential and cellular metabolism. They include fatigue, muscle weakness and cramps, and intestinal paralysis, which may lead to bloating, constipation, and abdominal pain. Severe hypokalemia may result in muscular paralysis ..."

One would think this question was settled long ago. Well, guess again. There is virtually zero research on Medline about PD and potassium or even electrolytes. A total of nine hits on the former.

So, how many of us have a potassium absorption problem? No one knows. And no one is asking....

[indigogo]

Conductor - you are right - this is a huge problem. Many scientists and clinicians now refer to PD as a "syndrome" or perhaps a collection of diseases or one disease with subtypes. Doesn't really matter what they call it; it matters that they don't know. It is commonly said today that PD is "not just a movement disorder."

Patients are way ahead on this curve; we've known for a long time that we are not being treated for exactly what ails us. And we have very different symptoms - even the "defining" symptoms of PD, tremor and rigidity, don't occur among all patients.

It's one reason why clinical trials fail - the group of patients who have been dx'd with PD who are participating in any one trial may not all have the same disease.

MJFF is well aware of this conundrum; (others as well; I think it is partly due to us annoying and chatty patients; we pushed for increased research funding; we kept saying there's something wrong at scientific meetings and conferences) - it is why they are pushing their big biomarkers study. It means, of course, that it will take longer to find more treatments and a cure. But instead of a set back, I believe it is a result of more and better science - we have to know what we are dealing with if we are going to cure it. We are on a better track now than we were 5 years ago; still a long way to go.

This is a major reason patients need a closer connection to and better communication with scientists - they need to know the people they are trying to treat (many have never met a person with PD). And many clinicians still do think PD is only a movement disorder and never look beyond the tremor or stiffness that is presented.

There's lot's to do.

[bluedahlia]

Interesting you should mention potassium. Years ago I was speaking to a woman about Parkinson's, whose brother was a doctor in the Philippines. She told me to eat lots of potatoes. Does he know something we don't know?

http://www.vaughns-1-pagers.com/food...sium-foods.htm

As you can see, potassium is pretty high in potatoes.

Originally Posted by reverett123

I have been having another hard patch the last two weeks. How hard? Try crawling out of my bank on hands and knees last week and getting steadily worse since. Suspecting everything under the sun. Off almost all day yesterday. Today started the same with the addition that early morning curly toes didn't go away and were joined by full leg cramp on left side. After an hour and forty-five minutes of this normally ten minute experience, my wife forced two potassium tablets on me. Eight minutes later I was completely normal. This makes half-a-dozen times that potassium problems have crept up on me, even though I eat better than most.

The Linus Pauling Insitute says low potassium can cause:

"An abnormally low plasma potassium concentration is referred to as hypokalemia. Hypokalemia is most commonly a result of excessive loss of potassium, e.g., from prolonged vomiting, the use of some diuretics, some forms of kidney disease, or metabolic disturbances. The symptoms of hypokalemia are related to alterations in membrane potential and cellular metabolism. They include fatigue, muscle weakness and cramps, and intestinal paralysis, which may lead to bloating, constipation, and abdominal pain. Severe hypokalemia may result in muscular paralysis ..."

One would think this question was settled long ago. Well, guess again. There is virtually zero research on Medline about PD and potassium or even electrolytes. A total of nine hits on the former.

So, how many of us have a potassium absorption problem? No one knows. And no one is asking....

[bluedahlia]

Study Implicates Potassium Channel Mutations in Neurodegeneration and Mental Retardation

For release: Sunday, February 26, 2006

For the first time, researchers have linked mutations in a gene that regulates how potassium enters cells to a neurodegenerative disease and to another disorder that causes mental retardation and coordination problems. The findings may lead to new ways of treating a broad range of disorders, including Alzheimer's and Parkinson's diseases. The study was funded in part by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS).

"This type of gene has never before been linked to nerve cell death," says Stefan Pulst, M.D., of Cedars-Sinai Medical Center at the University of California, Los Angeles, who led the new study. The report will appear in the February 26, 2006, advance online publication of Nature Genetics.1

In the study, the researchers looked for the gene that caused a neurodegenerative movement disorder called spinocerebellar ataxia in a Filipino family. This disorder typically appears in adulthood and causes loss of neurons in the brain's cerebellum, resulting in progressive loss of coordination (ataxia). Dr. Pulst and his colleagues traced the disease in this family to mutations in a gene called KCNC3. The gene codes for one of the proteins that form potassium channels - pore-like openings in the cell membrane that control the flow of potassium ions into the cell. The researchers found a different KCNC3 mutation in a previously identified French family with a disease called spinocerebellar ataxia type 13, which causes childhood-onset ataxia, cerebellar degeneration, and mild mental retardation.

The KCNC3 gene codes for a type of potassium channel that normally opens and closes very quickly. This type of channel is particularly important in "fast-bursting neurons" that fire hundreds of times per second in the brain. "Fast-bursting neurons are like building blocks - they are used in the nervous system a lot," Dr. Pulst says. Among other places, these neurons are found in the brain's substantia nigra, where they aid in motor control, and in the hippocampus, where they play a role in learning. Previous studies have found abnormalities in the number of potassium channels in Parkinson's, Alzheimer's, and Huntington's diseases. Together with the new study, these findings suggest that potassium channel abnormalities may contribute to a wide variety of neurodegenerative diseases.

"This paper is a good example of how gene discovery is useful for giving clues about therapeutic targets and strategies, which is the most important goal of human gene discovery research in my view," says Katrina Gwinn-Hardy, M.D., the NINDS program director for Dr. Pulst's grant.

Read more.....

http://www.ninds.nih.gov/news_and_ev...m_20060226.htm

[Conductor71]

Originally Posted by bluedahlia

Study Implicates Potassium Channel Mutations in Neurodegeneration and Mental Retardation

For release: Sunday, February 26, 2006

Thanks for this, though it highlights why I am so utterly exasperated with the research paradigm. Looks like someone got funding for this in 2006. Where does it stand now? Another avenue closed off by lack of grant monies?

It seems like there are myriad approaches to tackling this disease, and the more we learn, the more we crowd out or overlook a possible cure. <sigh>

-Laura