Hi all-

Forgive me for starting a new thread to respond to a comment by SteveI in the early thread "Early Detection of Huntington's Disease". Both to respond to Steve and to make a part of Dr Paulsen's paper more accessible (and to get a snappy new subject line) I'm copying below a portion of the paper near the end:

"When Does HD Begin?

If one were to ask the question, 'when does the disease begin?', the correct answer today would be that we do not know. We have not yet examined people with a CAG-expansion early enough in their lives to find a point when they appear to have no indication of HD. To date, we have found clinical and biological indicators of disease even in groups who are estimated to be more than 15 years from estimated clinical diagnosis.[10,23,41,50,79,123,124]

In light of the extensive findings demonstrating earlier detection of this brain disease years before its traditional diagnosis and the availability of an unequivocal genetic marker in the form of an expanded CAG tract, we must ask ourselves 'why do we not diagnose HD at an earlier time?' The formal diagnosis of HD is a controversial issue with important political, ethical, legal, social, medical and research implications. The identification of pre-HD individuals with varying degrees of risk to receive a clinical diagnosis of HD is appealing from a research perspective, because it could lead to more efficient clinical trials by using enriched samples (i.e., persons with a higher likelihood of clinical diagnosis during a brief time interval). In addition, it is clear that an increased uptake of predictive testing coupled with an augmentation in the propensity of individuals to volunteer for research may have the potential to expedite advances in pre-HD. At present, these limitations may explain why the study of pre-HD requires 33 sites in seven countries. Without considerable changes in the research and clinical arena for HD, clinical trials will require such excessive cost that our capacity to find treatments that make a difference for persons with HD will be diminished.

From a clinical standpoint, the early identification of disease could also have advantages, such as advanced planning for medical and legal decision making, initiating treatment plans and making lifestyle choices (e.g., childcare, work and living arrangements). However, earlier diagnosis must also be considered along with its potential risks, which might include increased stress, changes in social relationships and discrimination (e.g., loss of insurance coverage[125,126]). From a political perspective, efforts to alter the diagnostic criteria for HD will necessitate the addition of cognitive and psychiatric components, as well as the possibility of imaging criteria. For a disease that has benefited from monospecialty care for over a century, inclusion of additional criteria may present a challenge to healthcare professionals.

Earlier identification of disease is universally considered as useful when a treatment exists to slow or stop its progression. The argument is raised that until a prevention or treatment is found it is difficult to justify the importance of earlier detection. However, with regard to HD we need to ask the question 'treatment for what?' There may well be treatments for the HD symptoms of depression, irritability and cognitive decline, among others, that would benefit HD families. Short of a comprehensive treatment, HD families might benefit from acknowledging the way they feel about what is happening to them as the slowly progressive, insidious changes occur. At present, nobody in the prodrome of HD knows to ask about these symptoms or their treatment. Furthermore, possible treating physicians are not yet prepared to offer treatments for HD unless motor signs are evident that make them 99% confident of HD.

Historically, diagnosis in HD appears to have become code language for 'when should I tell the patient?' This was probably a combination of personal sensitivity combined with the pre-gene demand to be certain about diagnosis so that genetic studies could determine the locus. Unfortunately, hesitancy to diagnose HD remains. Truth telling in medicine has not always been seen as virtuous. The Hippocratic Oath instructed physicians "what I may see or hear in the course of the treatment or even outside of the treatment in regard to the life of men ... I will keep to myself". As late as the 1960s in the USA, over 90% of physicians said they would conceal the diagnosis of cancer from patients.[127] In the 1970s, truth-telling became a requirement for informed consent,[128] but patient advocacy groups still had to lobby for greater patient awareness and control over medical decision making. Breaking bad news emerged in the ethics literature as a requirement of professionalism and justice only recently.[129] It has been found that physician attitudes and communication styles can result in behaviors designed to dull the full impact of the news and avoid full statements of a diagnosis.[130,131] Although physicians continue to find it stressful to give a bad diagnosis, it has been reported that patients typically can address the news without increased anxiety and that avoidance of diagnosis can have adverse outcomes.[132]

Without adequate information regarding their condition, patients may have an impaired ability to formulate their own goals. According to standard theories of justice, all individuals have the right to make a rational life plan. Such a plan requires knowing one's aims and facing up to all possible information and circumstances in order to form the best course of action to achieve one's personal goals.[133] The goal of enabling patients to become full decision-making partners with the physician can only be met when the patient has the information necessary to understand the circumstances from which they must formulate a rational life plan. The main problem in withholding information in the case of a debilitating illness "is that the reluctance to make a candid disclosure of the diagnosis ... may violate basic moral and legal rights and may deprive patients and caregivers of some of the benefits of early disclosure of diagnosis".[130] For patients with an early diagnosis of HD, the withholding of information may mean the loss of an opportunity to seek early treatment or fulfill lifelong goals on a shortened timeline. To ensure the ability of our patients to make a rational life plan the earliest diagnosis may provide the best opportunity for the pursuit of these important individual aims."

Robi

Robi Blumenstein
CHDI Management/CHDI Foundation
robi.blumenstein@chdifoundation.org
www.chdifoundation.org

Great article. Thanks for taking the additional step to share it.

Can't wait for the day when I'm comfortable having it on my health record. But in the meantime I'm doing everything I can to fight this WITHOUT a doc (supplements but no prescription meds). And I've just emailed to participate in PREDICT as well as another MRI study they're doing locally for "pre-symptomatic" HD. (The study coordinator has assured me that there are good privacy protections in place, where no data will have my name + they're not obligated/allowed to release even if subpoenaed.)



Edited 1 time(s). Last edit at 03/24/2010 01:28PM by smiling sara.

Robi - HD "BEGINS", when you're conceived!!!

Being ignorant of your HD status in no way says you don't "have" it! Just like being ignorant that you have cancer, in no way means you don't have it!

The old "clinical testing" for HD was highly unreliable! Is one showing "symptoms"?

How do you define "symptoms"? I can't even begin to recount the people on here who have feared they might have symptoms. When the did the DNA test, they did not (thank god!)

jl

Thanks so much for sharing this! Some philosophical things to think about too.

According to my hubby's doc, a gene test only tells you that you carry the gene. Being symptomatic is the definative answer if you have HD.

Yes but that gets to the heart of what it means to be symptomatic. Clearly cellular dysfunction and cell death is happening 17 years before the current standards for clinical diagnosis. That would be okay if there were no cognitive problems and no psychiatric problems during that so called presymptomatic period, if the brain was truly able to compensate for the damage ALL THE TIME.

But we families know that that isn't true. My ex was diagnosed because of cognitive and psychiatric problems before he met the standard for enough movement impairment to be diagnosed clinically. Fortunately his neurologist thought that if he could no longer perform his job adequately any more despite previously doing so well that he won awards, then he was symptomatic and that was that. But not everyone is so lucky. Far too many people alienate family and friends and lose job after job before they meet the current clinical standards. Doctors aren't doing them any favor by falsely reassuring them that they are still well when they aren't by any meaningful standard.

And here's another problem. It is extremely hard to get a drug approved for delaying onset of a disease. How long are you going to run a trial with the current standards of clinical diagnosis? If there's a drug out there that helps the HD mice a lot if they get it early, then how can we do clinical trials with the current standards and find out if the drugs help? Give it to two groups of people who have no damage or dysfunction and then follow them for seventeen years!!!????!!!! Not enough money in the world to keep going like that to get our cocktail of treatments.

So the issue really is, are we strong enough as a community to see this disease on a 30 year continuum so we can help people early and get good treatments that might prevent the disease? In other words, can we regard this as a disease that starts very very slowly but starts nonetheless? Or are we going to keep to the current conceptions of a disease that starts abruptly and lasts 15 years so we can feel better for ourselves or our loved ones that all is well for a longer period of time?

This is an important question because doctors are doing this for US. I've heard them, they talk about the importance of not diagnosing HD before they absolutely have to because patients are so upset when they come to them. So if there is going to be change, we HD families have to be on board.



Edited 1 time(s). Last edit at 03/24/2010 09:12PM by Marsha.

Actually, MRO - the opposite is true.

Only the DNA test the definitive test of whether you
"have" HD - "symptoms" cannot! Other diseases can mock some of the "symptoms" of HD. None of those other diseases have that distinctive defective CAG count on the huntingin allele!

This is why families like mine had to put up with GENERATIONS ridicuous diagnoses - until we were FINALLY able to accurately test - after 1993!

My neurologist has extensive experience with BOTH HD - and Parkinson's. She KNOWS misdiagnoses can be made - if one relies totally on "clinical diagnoses"

This is why she DID do a clinical diagnosis - but didn't RELY on that!

Only the DNA test can tell you for sure!

jl

A DNA test only tells you if you are a carrier, not that you are symptomatic.

I am ready for a thirty year diaganosis Marsha, I am actually living it. Too bad I didn't figure it out ten years before diagnosis maybe I would be in a better position.

I agree with Maria about the gene test. Why would the discussion include possibly "preventing" the disease from beginning if there wasn't a time in someone's life that they didn't HAVE the disease even though they were gene positive? This has always been a clear and important distinction to me.

Changing our perspective to see this disease on a 30 year continuum is a very challenging leap for me to consider. I understand the importance of having the support of HD families and the potential breakthroughs it might provide at some point, but it would just be very hard. Another difficult adjustment to make among the sea of other adjustments that we all make on this journey. Just being honest.

I appreciate your honesty, Laura. I think that this generation has already had to be pioneers, with predictive gene testing, with clinical trials, with new family planning techniques. We're pioneers for HD families but also for other diseases as well. And now we are being asked to consider a new paradigm that will cause us to think about being sick or to think of our loved ones as sick (however early in the process) before there are early treatments ready. We have certainly been called upon to be courageous!

Great thought provoking topic. Delay diagnose causes untold hardship in some families and yet I often think that in some instances not knowing is a blessing of sorts early on, living life to the fullest without worry.
It seems to me that we never know what is ahead of us in life and can't always plan for what will happen.

Someone i know well has been showing symptoms for a couple of years now. i am no doctor of course, but seeing some completely different behavior and thought processes from someone is when i would say that symptoms began. This person refuses to test, because they say they already know they have it, and yet refuses to do anything else about anything, if you know what i mean. When asking for advice from anyone, it is never taken, and the bad judgements just continue. While this person may be just so worried about having it, they are causing their own symptoms, or whether they really have it, seems to be not helping them in either sense, since there is no improvement to their changes in lifestyle, no improvement in attitude, no proactive decsions that will make their life better in general - with or without HD. I really don't know what to do for this person, since they do not want to test, do not want to face it, i guess?

I mean, i understand that testing is not for everyone, i respect that. I do think that with all the positive help out there with testing and without, that this person would at least seek it, but no. After six family members total with HD, it seems evident that they have it, but who knows?? And you can't make anyone do something they do not want to do. I can see that this will go the hard way, and i was so hoping that it would not.

Hugs,
Suzanne

Laura we can either accept this change, embrace it and help move HD research forward in the process. Or we can sit around saying how hard it is and get nowhere fast. I know which one I'll be doing and it isn't a difficult choice for me. What ever helps us stop this disease quickest I'm all for.

[www.hdyo.org]

Robi and Marsha,
Thank you.

All this new information makes a lot of sense.

Paula

So there are both emotional, and insurance issues to diagnosing so early. Be nice if we could get rid of the insurance issues.

I also think it'll be better emotionally, when one of the more promising treatments in the pipeline comes through (like Huntexil or half dozen others). Even if there isn't long-term data available, the power to DO something will outweigh the emotional issues for more and more people. Except that without the long-term data, doctors may not be willing to HELP us do something (like prescribing Huntexil after FDA approval but before clinical diagnosis). And we'll still be limited to the supplements that we CAN get our hands on....

Seems like we need to find doctors that are willing to be this aggressive (like prescribing Memantine for HD now, or presribing SSRI's for pre-HD neuro-protection), share the news, and push other doctors to do the same....

As well as participating in every trial that is offered, that is practical for us.... And fund-raising so they can do more....



Edited 3 time(s). Last edit at 03/25/2010 08:36AM by smiling sara.

Marsha said: "Clearly cellular dysfunction and cell death is happening 17 years before the current standards for clinical diagnosis."

Well, exactly my point! After the great discovery of the DNA test in 1993 - I think those old "clinical test standards" should be thrown out the window for the inadequate tests they WERE for so many generations of HD families! I mean, the inadequacy can be richly demonstrated by the difficulty in even defining what are "symptoms" of HD - and what are symptoms of something else.

There are also the disagreements over WHICH "symptoms" occur FIRST. And WHEN!

That's because there are such vast differences! Some have "juvenile onset" - some have "median onset" (say, early adulthood). Others like me and my immediate family have "late onset" (late adulthood).

Clinical observations and diagnoses tend to be much more effective for the former - and much less so for the latter.

At any rate - by the time any suspicious "symptoms" show up in the latter - it's too late!

They've already HAD their families!

People may or not choose to get the DNA test before they have children. But should't they have that choice?

HD families didn't used to HAVE a choice! Now we do!

jl



Edited 1 time(s). Last edit at 03/25/2010 05:02PM by jl.

Laura said: "I agree with Maria about the gene test. Why would the discussion include possibly "preventing" the disease from beginning if there wasn't a time in someone's life that they didn't HAVE the disease even though they were gene positive? This has always been a clear and important distinction to me. "

JL: So is it to me - unfortunately we have reached opposite conclusions.


Laura also said: "Changing our perspective to see this disease on a 30 year continuum is a very challenging leap for me to consider. "

JL: Not for me, Laura - I have always seen HD over a "continuum of HUNDREDS of years", because that's how it's been in my (and other HD families!)

Marsha said, " I appreciate your honesty, Laura. I think that this generation has already had to be pioneers, with predictive gene testing, with clinical trials, with new family planning techniques. We're pioneers for HD families but also for other diseases as well. And now we are being asked to consider a new paradigm that will cause us to think about being sick or to think of our loved ones as sick (however early in the process) before there are early treatments ready. We have certainly been called upon to be courageous!"

jl: Well, actually, HD families are "pioneers for HD families" We've been struggling with misdiagnoses - and child-planning concerns for GENERATIONS! CENTURIES!

Again, DNA testing for HD has been a "great white hope" to US ever since (1) the autosomal-dominant nature of HD was discovered, (2) the MARKER was discovered, and (3) the actual GENE was found!

Look here, Marsha - I have no problem with studies that cover MORE than HD. Makes perfect sense to me! There are certainly similarities with other diseases that warrant checking out symptomatic "treatments"

But there are two extremely important DIFFERENCES - and they are autosomal-dominant inheritace - and a definitive DNA test.

We have people here who are at risk for HUNTINGTON'S - and are still in their child-bearing years!

Of course - there's the possibility that those at risk for HD can instead go on to have a different neurological disease.

BUT WHO CARES??? What matters to us is that nasty little huntingtin gene.

Whether our children will have (1) the vague outside chance of getting something unrelated, or (2) a 50% chance of getting HD!

Quite frankly, I've been much too busy dealing with HD in the family - and dealing with my OWN child-bearing - and other life-choices - to give anything else much of a thought!

I also don't think much about busses! HD is enough......

jl



Edited 1 time(s). Last edit at 03/28/2010 10:48PM by jl.

What I mean is that this kind of genetic testing is not only new to us, it's new altogether. There was no precedent for what kind of preparation would be needed and now as other genes for other diseases are being discovered, doctors and families are learning from our experiences.

We are also pioneering clinical trials for neuroprotection. There are no drugs approved for that purpose for any neurodegenerative disorder that I know of. So again, we're working out the details and that's why we have to be involved with advocacy about trial standards and the approval process.

And again, we're community working out the details of how to characterize a slow, neurodegenerative disease process, moving from the idea of abrupt onset to a slower, more subtle onset.

We didn't volunteer to be pioneers, but here we are all the same.

Well, of course, genetic testing has improved for all of us!

Those at risk for genetic disorders!

And those of us accused of crimes............

jl