[pegleg]

This is a study done in the UK. Fortunately, you can read the entire study for free (there is a fee for the full article).

Title:
Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

http://www.thelancet.com/journals/la...093-4/fulltext
Excerpts: The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39).

Conclusion: (My words) DBS plus your best medication regime makes for a better quality of life than medicine alone.
(I hope they didn't pay too much for this study; I could have told them that!)

My point I would like to discuss is this: What about placebo effect? Could it be that those that had the surgery (open-label means they knew they had the surgery) did better due to placebo effect??
This just doesn't seem like a really good study. Comments?

[LindaH]

Peggy, you are not alone in thinking this study has some problems. while looking up the full text of the DBS study, i came across another researcherwho published a critique of this study in the same online issue of Lancet Neurology.
Title: Deep brain stimulation for advanced Parkinson’s disease
Author: Maria C Rodriguez-Oroz
Clinica Universidad de Navarra, Centro de Investigación Médica
Aplicada, Pamplona 31008, Spain

Here are some o f the limitations of the DBS study that she identified:

The DBS study found :
“There was no diff erence between the two groups in cognition, as measured by the dementia rating scale-II (DRS-II). However, a more detailed neuropsychological study in a subgroup of patients showed that there was a decline in verbal fl uency and vocabulary in the surgery group compared with the medical therapy group.

As for trial design,” evaluators were not masked to treatment allocation.” Which means their judgements on rating participants symptoms could have been biased.

“The report of an improvement in dyskinesias and off periods was based
on results from the UPDRS complications of therapy subsection rather than on a more reliable source of information, such as diaries in which patients could make a note of their motor abilities every 30 min.”

Also,
“The investigators did not specify a standard defi nition of the on state; instead, assessment of whether a patient was in the on state was left to the judgment of neurologists at each centre. This raises concerns about the real motor state of the patients because there was no assessment of inter-rater variability. “

“Use of the DRS-II to assess cognitive ability might also be inadequate for patients with
Parkinson’s disease who are treated with DBS,4 because cognitive screening instruments are unlikely to be suffi ciently sensitive to postoperative changes”

And:
“There were more serious adverse events in the surgery group, which were mainly related to surgery.”


The dbs study will continue for 9 years – hopefully they will address these problems.
But for now if you're looking for guidance on deciding about DBS, I would look for other sources of information.

[lindylanka]

Peggy and Linda,
My neuro is one of the neuros mentioned in this study, a good man and head of the department at our regional hospital.

I am sure other UK members of this forum will recognize some of the names, and anyone interested in GDNF will recognize Steven Gill's name. These are doctors in the forefront of their field in the UK.

However this and other large scale studies being conducted over here give me some concern.

Beside the things you mention this study has other things that are challenging. The first is the randomization aspect, which is similar to another very large-scale study being done in NHS hospitals in the UK, where randomization is used, in medication options, which are divided into agonist and levodopa monotherapy treatment options. I am not sure the patients are always aware that they are even in a trial. This is very different from a study where patients volunteer for a trial. They are randomly offered a mode of treatment and presumably in the case of the trial you mention, as it is surgical, they consent, and are then given DBS,

But the choice of who it is offered to results from a computer randomization.......

Is this ethical, and does this mean that treatment options are not offered according to patient needs, but for study needs? Our system and a lack of patient awareness allows for this.

How aware is the patient that they are participating in a trial, or that it has been randomized in this way. When they are offered DBS do they know exactly what the trial basis is, and how they were chosen? Same questions for the other treatment options study .....

DBS was in a BBC news item on TV last week, heralded as an amazing 'new' treatment for PD, with a great big Medtronic ad in the background. It sort of coincided with big government meetings held in the newly built flagship hospital that is going to replace the one I go to in the run up to our elections.

It also seems as though there were a lot of adverse events related to surgery, perhaps they are discussed more fully in the complete article. 19% of 'serious surgery-related adverse events' seems high, but maybe I am being naive about this.

I share the other concerns that you have outlined.

Lindy


Also related to the above, and on a much more personal level.

I had an apomorphine challenge around 2005 as a day patient, there were two of us, very similar to look at, the other person was offered DBS then and there, she was more able than me and around 15 years younger, her challenge was timed perfectly and the apomorphine worked very well on her, it was administered to us both at the same time. By the time her testing was through mine was wearing off, and I was very sleepy, and performed badly in the testing. I often wondered whether she did get the DBS, and how she fared, and whether if I had been tested first that would have been me with that choice. She seemed both less advanced, and very young to go through the surgery. And of course I wondered why she was offered it in the first place..... We were both working and mums with young family. Though the testing was rigorous and the person conducting it was clearly extremely competent, the administration of the drug was not, it was sloppy.

All of this is a moot question as i would not have consented to DBS if I had qualified for a trial, but the result of the testing led to a three year question mark over my diagnosis, something that was not rectified till late 2007, and only then was my treatment, levodopa monotherapy changed, and entacapone added with great results. I attribute the fact that I have never been offered an agonist, and it has never been discussed, to this other larger study.)

[aftermathman]

a couple of years ago at the Royal College of Medicine in London.

They claimed that despite numerous surgeries DBS is still being labelled "under the counter" as a trial surgery not yet accepted as beneficial by NICE (national institute of clinical excellence).

This "10 year" study seems to be 9.9 years too long and little more than a Medtronic PR job or more likely another hoop for DBS to jump through to be accepted as mainstream in the UK by NICE despite the number of DBS surgeries.

Neil.

[pegleg]

Linda H. - thanks for your well-thought out comments. Lindy - I know you won't believe this, but my original comments were "blinded" (pun intended). I honestly did not look at any author's names - I just scanned the abstract, anc conclusion then posted my remarks. (One must be more careful).and aftermath, thank you for your post.

I want all of you reading this to know that I am THRILLED that there is a surgical procedure that indeed does help some people with Parkinson's (PWP) and that is a qualified "some".

As President Obama often says, "Here's the deal . . ." Deep Brain Stimulation (DBS) has been a godsend for many PWP, but it doesn't help everyone, Additionally, DBS has side effects (depression, loss of voice or garbled speech, worsening of balance, etc). not to mention site infection due to hardwear insertion, or incision. Maybe I hang with the unlucky folks, but I have noted more problems than helps. Yet almost 100% of those having DBS say they would d o it again.

I admit that the surgical procedure shows dramatic results. I've seen TV dramatize the surgery showing a very disabled lady who was wheelchair- bound. After DBS, she was able to get up and semi-run after surgery. People who are "successful" with DBS are often those who have severe dyskinesia and/or dystonia due to long-term levodopa therapy. And medications can definitely be reduced in most cases.

It should be noted (I think I'm right on this), that there was no "control" group in the DBS studies, other than a comparison symptomatically of the DBS group and the group that didn't have DBS.. And of course, there was to sham surgery control. So how did they compensate for placebo control?

Are you aware that DBS is very similar to ECT (electro-subcutaneous therapy) or sometimes called TMS (transcranial magnetic stimulation ) or what is commonly called "shock therapy" usually for bad cases of depression. And it works!

Now, my theory. Parkinson's is a bad case of not only deficient dopamine, but other brain chemicals necessary in keeping the person "happy." There's mixed up seritonin, and acetycholine, tyramine, and on and on. Well-being is highly important when you a re already dopamine-deficient. I contend that treating the well-being side of PWP is just as important as replacing the dopamine; and my theoory is that may be why we see the results we do with DBS.

I should know about how when you coontrol the clinical depression, you control the PD symptoms, oro least see improvement in motor skills. Depression brought on by (duh - stress) and my chemical imbalance are two of the major reasons I crashed and had to take early retirement. My well-being had well-went! lol

So the bottom line here is we need PsychCentral far more than we realize. And it's nothing to be ashamed of to need psychological, even psychiatric help. We're a chemical mess, then we go adding a little of thhis and a little that here and there, and then we have the ups and downs both in well-being and movement disorders.

Sorry to ramble on, but write this down today. If somebody else has alreaady said it, they didn't do a very good job of letting me know, but PD can be controlled much more easily if the depression that comes with the package deal is treated, also. Keep the well-being in check and PWP arew far less symptomatic.

Discussion? DBS in my opinion is good at controlling depresion, along with severe dyskinesia and dystonia. However, you might be able to take care of these with a holistic aapproach - eating dopamine-rich foods (e.g. fava beans), adding tyramine to your diet, and the other chemicals mentioned, and exercising to keep an oxygen-rich flow of blood to the brain.

Have we gotten onto somethhing here?
Peg

[lindylanka]

DBS also appears from footage shown to alleviate bradykinesia and rigidity in a dramatic way. Does this happen for everyone who has DBS? What was shown here on TV last week showed someone who travelled a lot more swiftly that I have been able to in years!

Peggy, you related DBS to shock therapy, and that drugs could be reduced after the procedure. And it is good for when dystonia and dyskinesia have become a big problem. These are side-effects of levo-dopa therapy as much as symptoms of PD. So is it the combination of the two that makes it something that patients are grateful for.... your outlining of the less beneficial side-effects of DBS indicate that there must be something powerfully anti-PD for so many to feel that they would do it again.

I too am happy for every single patient who genuinely benefits from treatment, no matter what it is.

I would be happier still if there was less hard sell, and more openness.
The side effects you describe are worrying, and so is the 19% in this study.
That is one in five almost....... so those people with the other experience, where are they, and what are their stories? Studies like this do not shed light on them.......

[LindaH]

I think someone asked what were the adverse events following dBS among the participants in this study – here is a list from the Lancet Neurology article

From: Deep brain stimulation plus best medical therapy versus best
medical therapy alone for advanced Parkinson’s disease
(PD SURG trial): a randomised, open-label trial
Published in:
www.thelancet.com/neurology Published online April 29, 2010 DOI:

“36 (19%) patients had serious surgery-related adverse events

Serious adverse events in first year after dbs
The first # is # of patients who experienced adverse event and had Dbs and second # is the number in study who experienced adverse event and was receiving PD meds only


Surgery-related 43 events in 36 patients 0 events in 12 patients*
Haemorrhage 4 (including 1 death)† 0
Infection 16 0
DBS-specifi c adverse events 13 events in 12 patients 0
Postoperative confusion 5 0
Neck pain 2 0
Seizures 2 0
Deteriorating control of Parkinson’s disease because battery was switched off
1 0
Psychosis 1 0
Unresponsive on operating table (possibly because of levodopa withdrawal) 1 0

Visual neglect from oedema 1 0
General surgery problems 10 events in 9 patients 0 events
Urinary retention 4 0
Pulmonary embolism 2 0
Anxiety attack 1 0
Diffi culty removing catheter 1 0
Postoperative hypotension 1 0
Pyrexia 1 0

Total: 96 events in 65 patients

The media reports rarely talk about the risks of brain surgery. And while i've been told many advanced patients have got their lives back - it's a personal risk/ benefit balance that each one needs to consider. It worries me that they seem to be encouraging more newly diagnosed PWP to undergo the surgery at a time while drugs are still working. The cynical side of me thinks "are they trying to implant as many devices as possible before dbs is replaced by a more advanced, safer treaetment?

[LindaH]

Lindy, you asked "does this mean that treatment options are not offered according to patient needs, but for study needs? Our system and a lack of patient awareness allows for this."
The answer is "yes" In our current system, the needs of a clinical trial come before patient neeeds. We are told we shouldn't enter a study, expecting any benefits or improvement in our symptoms. The benefits are few future patients. Very noble, but in reality i think unrealistic.
The informed consent document is supposed to explain these issues and also to advise patieints of other possible treatments that they could consider. It should explain exactly what the experimental treatments they will receive. In the U.S. this is backed by regulations that are supposed dto protect human subjects.
But how many people fully understand the informed consent documents they sign or are aware of the questions they should ask? Probably not very many.
The Parkinson's Pipeline Project has been workign with PDF to expand and better explain the rights of clinical trial participants. A working version is online at: http://pdpipeline.org/advocacy/rights.htm