Wendy,

You wrote: "Are there any studies that look at the benefits of having
DBS before vs
after levadopa treatment? Or is DBS only tried after levodopa no longer
is effective?"

The short answer is no. DBS has only had wide spread use for about the
last 5 years. There isn't a lot of longitudinal data on the long term
effectiveness of DBS itself. In fact, in a DBS symposium that I
attended, researchers were discussing whether the long term effect of
DBS will prove to be any better than Pallidotomy. DBS is now the
preferred method since it is theoretically reversable.  But no studies
have been done to prove whether or not DBS is more beneficial. One could
speculate that the DBS difference in target area in the basil ganglia
and the ability to adjust the stimulation parameters may give DBS a
longitudinal advantage, but that's pure speculation on my part and only
time will tell.

But it might be worthwhile to review some history. Prior to the
development and introduction of levodopa and other effecctive PD drugs
back in the 50's, Pallidotomies were routinely performed. Pallidotomy
fell out of favor with the introduction of levodopa. However, it made a
resurgence when it was found that it could help control the dyskinesias
(uncontrolled movements) associated with long term use of levodopa at
higher dosages. Since Pallidotomy makes lesions in the basil ganglia and
actually kills neurons, it once again fell out of favor when DBS became
available for the reasons mentioned above.

So levodopa is the best treatment that we have today for PD. Studies
have shown that neither Pallidotomy nor DBS can improve functional
performance beyond that provided by levodopa. In other words, you are
not restored to normal function with any of the interventions and the
effects of DBS and levodopa are not additive. The primary benefit of
Pallidotomy and DBS is to allow reduction in medication to avoid
dyskinesias while maintaining more function during the valleys of the
medication cycle.

Now, I'm going to introduce a little vocabulary to help you understand
what's going on with PD and the purpose of the interventions. Please
bare with me. The area of the brain affected in PD are the basil
ganglia. It's just a name. They're not something from Mars. Researchers
really don't know the function of the basil ganglia; however, they think
that it has something to do with the planning of movement. In normals,
activity starts in the basil ganglia prior to the intiation of movement,
stops during the movement, and then starts again just before the end of
the movement. In us PD types, the activity continues throughout the
movement.

The output of the basil ganglia is wired into the motor cortex. The
motor cortex actually controls the movement. So in normals, the basil
ganglia shut up and let the motor cortex do it's thing while in PD the
basil ganglia keep on babbling thus intefering with the motor cortex.

So why do the basil ganglia keep babbling in PD? Dopamine appears to
have a dampening action within the basil ganglia; thus, turning it off
when it is supposed to be quiet. Dopamine is produced in the substantia
nigra (just another funny name) which is part of the basil ganglia. When
you have 60-80% cell loss in the substantia nigra, symptoms of PD will
FIRST appear. So in the early stages of the disease(s), the cause of the
symptoms appears to be the resulting dopamine deficiency. So administer
levodopa and everything is cool.

Now for a few more 50 cent words. The striatum (caudate and putamen) and
globus pallidus (gp) are also part of the basil ganglia. The striatum
are the input structures of the basil ganglia and the globus pallidus is
the primary output structure. Dopamine is actually used by the neurons
in these areas. So it is produced in the substantia nigra and is stored
and used in the striatum and gp. As the disease progresses, we lose more
and more of the ability to store dopamine in these structures requiring
more frequent dosage to replenish it.

As more and more dopamine storage capacity is lost in the bg, a point is
reached where more and more neurons cannot be shut off. At that point a
Pallidotomy (describing a lesion in the g Pallidus) was performed to
knock off those misbehaving neurons. We now have DBS that essentially
appears to do the same thing.

So essentially DBS is shutting off the babbling. It's like if you can't
say something nice, don't say anything at all. So don't rudely interrupt
the motor cortex when it is doing it's thing.

But keep in mind that the surgical interventions only quiet those
neurons that are unruly at the time of the intervention. The disease
continues to progress and other neurons become unruly; thus, at least
Pallidotomy begins to lose it efficacy. As mentioned before, one my
argue that the DBS target area may provide a benefit of extended
efficacy beyond that of Pallidotomy.

So that leaves us with a lot of unanswered questions. How much of the
function in the basil ganglia can be shut down? What do you lose if you
shut them down completely? A research speaker at our support group
recently suggested that you may be able to shut the bg down completely
if you provide direct stimulation to the motor cortex by other means.

So the long answer to your original question is no you would not do DBS
surgery unless symptoms could not be effectively treated with levodopa.
The symptoms of many people with PD are effectively treated with
levodopa throughout the remainder of their life. Surgical interventions
have associated risk and at this point we don't have data to know the
long term efficacy of DBS. A local surgeon indicated that the
complication rate was less than 1% for DBS. That's pretty good unless
you are the 1 in 100 as was the case with a support group member in his
early 50's that passed away due to complications.  You also need to go
in for surgery on average every five years to have the battery replaced.

Hope I haven't bored you too much. I just think it is important to
understand the science so that you can make rational assessments about a
researchers comments concerning the potential of a given intervention.
In my opinion, there is a lot of research that needs to be done on what
PD is and how it progresses before we can have a lucid discussion about
the potential of a give cure.

Phil Gesotti - still humbled by the engineering of the human body and
our lack of knowledge about how it works

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