[chasmo]

Superior to Best Medical Management

02/28/2007

Neurosurgery at an earlier stage of Parkinson disease: A randomized, controlled trial

WMM Schupbach, D Maltete, JL Houeto, S Tezenas de Montcel, L Mallet, ML Welter, M Garguilo, C Behar, AM Bonnet, V Czernecki, B Pidoux, S Navarro, D Dormont, P Cornu, Y Agid

Neurology 2007;68:267-271



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Patients with mild-to-moderate PD who receive DBS surgery have a better quality of life 18 months after surgery than patients receiving best medical management, according to this study.



Twenty PD patients with mild-to-moderate disease were enrolled. Patients were younger than age 55; had a disease duration of between 5 and 10 years; had Hoehn and Yahr scores less than or equal to 3; experienced motor fluctuations and off periods more than 25% of the waking day; and were employed. After entry, patients were pair-matched for age, disease duration, and UPDRS scores, and then randomized to receive STN DBS surgery or best medical management. Evaluations occurred at 6, 12, and 18 months post-surgery. The primary endpoint was change in overall quality of life as determined by the PDQ-39.



At 18 months, surgically treated patients had a 24% improved QoL, versus no change for medically treated patients. The surgically treated group did better on activities of daily living, stigmatization, and bodily discomfort subdomains of the scale. ADLs off medication also improved significantly in surgically treated patients, while those receiving medical management worsened. ADLs on medication did not differ between the groups. Motor scores off and on medication showed a similar pattern. Levodopa use decreased by 57% and motor complications improved by 83% in surgically treated patients, versus a 12% increase in levodopa and 15% motor complication worsening for medically treated patients.



Neuropsychological complications of surgery included transient depression (n=4, versus 3 in medically managed patients), transient hypomania (n=5), somatoform disorder (n=1). Anxiety and psychiatric morbidity improved as a whole for the surgically treated group.



The authors conclude, "Neurosurgery may thus be considered superior to medical management alone even in mild to moderate PD of < 10 years' duration, rather than as a last resort in very advanced stages of the disease. However, the advantages of STN stimulation must be weighed carefully against the risk with death or sequelae of cerebral hemorrhage reported in 0 to 5% of patients undergoing surgery."



In an accompanying editorial, David Riley and Andres Lozano write, "There is a trend toward early DBS in PD management, and this trial offers the best support of that trend to date..[U]ltimately the results indicate that earlier application of DBS represents an improvement over our current approach to management of PD."

[vlhperry]

Charlie, DBS saved my life. However, there are downsides. As you said, no more body MRI's to help discover other problems that may or may not be related to Parkinson's, such as torn rotator cuffs, or any other soft tissue damage. There is a risk the battery may unexpectedly stop and the patient will become seriously ill without associating his/her worse symptoms with DBS.

People who choose not to have DBS at any time should be allowed to make the choice without being pushed by those who were fortunate enough to find it helpful. I have read many posts by persons who were not helped by DBS. It is still a risky procedure and patients need to be given space to decide if it is the right procedure to try. The information is helpful and may help someone with their decision.

This is an exciting time to keep up with the research of the brain and how it works. More and more research is beginning to emerge painting a more accurate map of the effect of different toxins, proteins, mutations, and how they affect all the body, not just movement related disorders.

If I were a recently diagnosed patient, I probably would not choose to have DBS surgery. Although they say it is reverseable, they only refer to turning it on or off. The DBS itself would not be removed. It's very prescence in the body could prevent the patient from being involved in research projects that could present a permanent cure.

Love,
Vicky

[paula_w]

I don't like to be the rain on the parade and sorry for appearing a cynic. But this study was sponsored by Medtronic. Below is the disclosure from the full text.

This disclosure was sent around the pipeliner email list along with some very astute comments about the placebo effect. I can't take credit for this post - I'm just the messenger.

Placebo effect was a major issue in the GDNF arguments, with claims by researchers that it could last for years. Wouldn't someone with a DBS possibly have a placebo effect? What excludes DBS from the placebo effect?

DBS may save my life someday, but I've learned, sadly, that trust in what you read may not be earned or deserved. This attitude may be viewed as taking away hope. But I see it as improving the quality of what is done. In other words, reality gives me hope. And the reality of this treatment may be exactly what they are claiming.


DBS study.
> Here they are from the full text article.
>
> "Dr. Schüpbach was supported by grants from the
> Swiss National Science Foundation and the Swiss PD
> Association. The study was supported by Medtronic
> Europe.
> Disclosure: Medtronic sponsored the study and
> provided the stimulators. However, Medtronic had no
> influence on decisions concerning the study design;
> on the enrollment of patients; on the collection,
> analysis, and interpretation of data; on the writing
> of the report; and on the decision to submit the
> paper for publication."
>

Paula

[chasmo]

Paula;

the sample was only 20 patients too, which seems a bit small to me.

Vicki;

Regarding bad results, there are surgeons who simply are not that good. If you go with a proven program, and they are not that difficult to find, your chances of having a bad result are very low.

true enough about DBS being a disqualifer for experimental therapies. Which experimental therapy did you have in mind??
I wish medtronic would add a catheter to its leads, so we couljd be "pre-plumbed" so-to-speak. HAving said that, would you want to do without a DBS while waiting years for a new therapy to get approval?? I know I would not.
Those who are hanging on to the hope of a therapy that works, are simply kidding themselves, IMHO. I just do not see anything on the horizon. DBS remains our only option to classical drug therapies at this point. DBS works MUCH better than drug therapy, I think you'll agree.

Charlie

[Radioguy]

FWIW -- I'm currently in screening for a study very much like this one currenty recruiting in Nashville. I've been to Vanderbilt once already and met with the lead investigator, the study coordinator, the neurosurgeon and the bioethicist. I was very impressed and signed the consent.

I'm going back March 25-28 for the screening.

[jeanb]

Chasmo,

I agree more of us should consider this surgery earlier. Last week I spoke to a neurologist about DBS - he had it done early (both sides) and is doing well. He is on no meds (just dbs...). And he recommends the surgery early in the disease because it reduces stress on the brain. But for people later on in the disease - dbs has also been shown to be extremely helpful for severe dystonia - as well as many other symptoms.

I will keep it in mind - truly. But for now I am waiting for a clinical trial. If I were eligible for CERE-120 phase II now, i'd already have contacted Ceregene to sign me up. But I'm not. So I'll bide my time and sign up for their phase III trial -- assuming all goes well with the phase II.

[jeanb]

Radiguy,

Good for you for doing research and considering a clinical trial. Fewer than 1% of people with PD participate in clinical trials. (shocking but true!!)

As you can imagine, lack of trial participants adds to the time it takes to get drugs out of research -- through FDA approval -- and ultimately to us.

We need more people like you!!

[Radioguy]

Originally Posted by jeanb

Radiguy,

Good for you for doing research and considering a clinical trial. Fewer than 1% of people with PD participate in clinical trials. (shocking but true!!)

As you can imagine, lack of trial participants adds to the time it takes to get drugs out of research -- through FDA approval -- and ultimately to us.

We need more people like you!!

Thankee!

I work at NIH, and a large part of what I do is radio news releases on the importance of clinical research. What kind of hypocrite would I be if I didn't take a shot at something where I might be able to help?

Besides, I'm intrigued by the potential neuroprotective benefits of DBS. I'm only 52. (Yeah, that's right. I said "only.") If I can cut back on the meds and slow down the progression -- to me, it's worth the risks.

Of course, there's a 50 percent chance I get randomized to the control group. It's a flip of the coin.

[vlhperry]

Charlie, many genetic trials do not allow the patient to be on DBS.

I said in my first post, that if I were diagnosed with Parkinson's today, I would not go for a DBS right away. I would keep my options open. Many people posting negatively in this thread do not realize the affect their advocating for more patient involvement has been heard. I have seen many positive changes, espiecially on the Michael J. Fox website from being able to choose where your funds will be applied for research, to the National Parkinson's Foundation, where they have now included patient needs into their mission statement.

My neurologist is more receptive to my complaints and no longer just blows me off with "I've never heard of that being associated with PD." Don't be so negative Paula. You have had a positive effect. I agree that it is probably too late to help us, but you have PLOWED (forgive the pun) the way for those recently diagnosed. Charlie you have enlightened so many about DBS, but I still believe that it is a later option than an immediate one. I realize Medtronic is encouraging patients that it is better to have the surgery earlier than later, but patients need to have time to understand their disease and learn about how fast it progresses for themselves, and how severe their symptoms are before they approach such a serious decision to have surgery.

Charlie, have you heard of or met the new Director of the Minnesota Mayo Clinic. They have a young neurosurgeon on staff who has some interesting theories on how DBS actually works. Was told this by my neurologist at my check up last Thursday.

Love,
Vicky

[chasmo]

Originally Posted by vlhperry

Charlie, many genetic trials do not allow the patient to be on DBS.

Charlie, have you heard of or met the new Director of the Minnesota Mayo Clinic. They have a young neurosurgeon on staff who has some interesting theories on how DBS actually works. Was told this by my neurologist at my check up last Thursday.

Love,
Vicky

IIn most trials for anything, DBS is not allowed.

I think it is a unique decision for everyone. IF your life starts sucking like a Hoover.....its time to consider it!!!

No I haven't heard of him. Do you have a link to him??